Podcasts about open label

JCO Editorial Fellow Peter Li and JCO Associate Editor Eileen O'Reilly discuss the ASCO 25 Simultaneous Publication paper "Tumor-Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Peter Li: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Peter Li, and I'm joined by JCO Associate Editor Dr. Eileen O'Reilly to discuss the Journal of Clinical Oncology article and abstract presentation "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Now, let's start with the relevance of the article. Eileen, can you explain this study to our listeners? Dr. Eileen O'Reilly: Thanks very much, Peter, for the invitation today to discuss this. Yes, so this is a positive phase 3 trial that was conducted in locally advanced, unresectable pancreas cancer. Patients were randomized to receive either gemcitabine and nab-paclitaxel, international standard, with or without tumor-treating fields. And this is a device like a battery pack that you would wear with a goal to wear that approximately 18 hours a day. And the primary endpoint of this study was overall survival, with key secondary endpoints of tumor response, progression-free survival, looking at pain-free survival, and distant progression-free survival. So, the primary endpoint was met with a median overall survival of 16.2 months compared to 14.2 months on the intervention versus control arm, with a hazard ratio of 0.82. And so that met the pre-specified boundary. There was not an increase in progression-free survival, but there was an increase in control of pain on the tumor-treating fields study. So, it was a large, global study, community, academic sites, randomized 570 people, and it supports what I think we've seen in other difficult-to-treat malignancies using tumor-treating fields, that there's a signal of interest. Dr. Peter Li: Can you speak to some of the strengths and weaknesses of this study? Dr. Eileen O'Reilly: So, strengths: it was a large study. It included community sites, it included academic sites. It included ECOG performance status 0, 1, and some patients with 2. The intent was locally advanced. It probably is fair to say that there were some patients who had more advanced disease based on early progression, based on relatively high CA 19-9 for a percentage of people. But likely that was, with random assignment, that would have presumably fallen out between the arms. The inclusion of patients with a lower performance status is nice to see in large phase 3 studies in pancreas cancer. So, they would be some of the strengths. So maybe some of the limitations are the fact that it's an open-label study - so, always some biases inherent in that. Acknowledging that the primary endpoint was overall survival, presumably that wouldn't be directly influenced by that. And there was an imbalance of women on the control arm, and women do fare a little better in this disease, so possibly kind of weighted one of the study arms a little bit. But nonetheless, I think it was a rigorously designed and rigorously conducted phase 3 trial. It's always hard to fully interpret the signal in locally advanced disease because of the fact that some patients go on to surgery, some patients have a treatment switch of cytotoxic therapy, some patients will go on to radiation. And the endpoint here of overall survival, to a degree, eliminates some of that. So, the benchmark, I think, was generally high here. Dr. Peter Li: Gotcha. And then with these findings and this positive study, how do you foresee this research being implemented and how it will impact clinical practice moving forward? Dr. Eileen O'Reilly: I think there'll be an educational need to introduce this approach to the community and to the pancreas cancer world. Again, there's a precedent in glioblastoma and data from other diseases, so there's some familiarity with this. I think people always want to understand how it works and why it works, and that's something that we'll look forward to hearing more about mechanistically, and also seeing how it can be built upon. And there's some intriguing data with the combination of tumor-treating fields and immunotherapy that's being evaluated in the PANOVA-4 study. So, we'll stay tuned to hear how that reads out in due course. But I think overall, it'll be educational and learning, managing the cutaneous impacts or some skin irritation effects from this, and building on this signal in locally advanced disease. Dr. Peter Li: Well, thank you so much, Eileen, for your time and for speaking about the JCO article, "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The FiltrateJoel TopfAC GomezSophia AmbrusoNayan AroraSpecial Guest Charles Edelstein, MD, PhD Professor, Medicine-Renal Med Diseases/HypertensionExtra-Special GuestMichelle Rheault, MD Professor of Pediatrics, University of MinnesotaEditing bySimon and Joel TopfThe Kidney Connection written and performed by by Tim YauShow NotesKDIGO ADPKD Guidelines:WebsiteGuideline PDFExecutive Summary PDFNephJC coverageConsortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)Hy's Law (Wikipedia) has three components:ALT or AST by 3-fold or greater above the upper limit of normalAnd total serum bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal)And no other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injuryMeeting this definition yields a very high risk of fulminant kidney failure (76% in one series)Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database (PubMed) Two of 957 patients on tolvaptan met Hy's law criteria. None had fulminant kidney failure.Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial (PubMed) Patients had a baseline urine volume on tolvaptan of 6.9 L/24 h. Urine volume decreased to 5.1 L/24 h with hydrochlorothiazide and to 5.4 L/24 h on metformin.TEMPO 3:4 Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease (NEJM)Reprise Trial Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease ( NEJM | NephJC )Unified ultrasonographic diagnostic criteria for polycystic kidney disease by Edelstein in JASN (PubMed)Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies (PubMed)Charles' draft choice Recommendation 4.1.1.1: We recommend initiating tolvaptan treatment in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ‡25 ml/min per 1.73 m2 who are at risk for rapidly progressive disease (1B).Sophia's draft choice Recommendation 1.4.2.1: We recommend employing the Mayo Imaging Classi cation (MIC) to predict future decline in kidney function and the timing of kidney failure (1B).Progression to kidney failure in ADPKD: the PROPKD score underestimates the risk assessed by the Mayo imaging classification (Frontiers of Science)AC's draft choice Recommendation 9.2.1: We recommend targeting BP to ≤ 50th percentile for age, sex, and height or ≤ 110/70 mm Hg in adolescents in the setting of ADPKD and high BP (1D).HALT-PKD Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease (NEJM)Nayan's draft choice Recommendation 6.1.2: We recommend screening for ICA in people with ADPKD and a personal history of SAH or a positive family history of ICA, SAH, or unexplained sudden death in those eligible for treatment and who have a reasonable life expectancy (1D).Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease (CJASN)Surgical Clipping Versus Endovascular Coiling in the Management of Intracranial Aneurysms (PubMed) Clipping is associated with a higher rate of occlusion of the aneurysm and lower rates of residual and recurrent aneurysms, whereas coiling is associated with lower morbidity and mortality and a better postoperative course.Joel's editorial pick Recommendation 6.1.1: We recommend informing adults with ADPKD about the increased risk for intracranial aneurysms (ICAs) and subarachnoid hemorrhage (1C).Joel's first draft pick The bring out your dead pick:Recommendation 4.3.1: We recommend not using mammalian target of rapamycin (mTOR) inhibitors to slow kidney disease progression in people with ADPKD (1C).Recommendation 4.4.1: We suggest not using statins specfiically to slow kidney disease progression in people with ADPKD (2D).Recommendation 4.5.1: We recommend not using metformin specifically to slow the rate of disease progression in people with ADPKD who do not have diabetes (1B).Recommendation 4.6.1: We suggest that somatostatin analogues should not be prescribed for the sole purpose of decreasing eGFR decline in people with ADPKD (2B).Perfect match: mTOR inhibitors and tuberous sclerosis complex (Orphanet Journal of Rare Diseases)Navitor Pharmaceuticals Announces Janssen Has Acquired Anakuria Therapeutics, Inc. (BioSpace) This is press release about acquiring the mTor1 inhibitor.Joel's second draft pick Recommendation 4.2.1.1: We suggest adapting water intake, spread throughout the day, to achieve at least 2–3 liters of water intake per day in people with ADPKD and an eGFR ≥ 30 ml/min per 1.73 m2 without contraindications to excreting a solute load (2D).Nayan's bonus draft Practice Point 4.7.1: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) should not be used to slow eGFR decline in people with ADPKD.Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan (KIReports)SMART Trial of GLP-1ra in non-diabetics: Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial (PubMed)Tubular SecretionsNayan: Landman on Paramount Plus (IMDB)Sophia: PassNayan: steps in with The Pitt on HBO (Wikipedia)Charles: The White Lotus, Yellowstone 1923, Poirot (IMDB)AC: The PittMichael Crichton's Estate Sends The Pitt to the Courtroom (Vulture)Joel: I Must Betray you by Ruta Sepetys (Amazon)

Is there a way to treat liver metastasis secondary to uveal melanoma without introducing systemic, treatment-related toxicity? Dr. Altan Ahmed (interventional radiologist at Moffitt Cancer Center) and Dr. Sid Padia (interventional radiologist at UCLA) join guest-host Dr. Kavi Krishnasamy to discuss HEPZATO, a novel device-based treatment for liver metastases from uveal melanoma. --- This podcast is supported by: RADPAD® Radiation Protection https://www.radpad.com/ --- SYNPOSIS Dr. Ahmed and Dr. Padia begin by exploring the design and setup of the HEPZATO clinical trials, while also speaking on patient selection criteria. The doctors then talk through the technical aspects of the intervention. After covering workflow and considerations related to procedure timing and coordination, the doctors go on to discuss drug dosing and optimizing treatment cycles. The episode concludes with current gaps in literature, current and future research aims, and potential future applications of the HEPZATO modality in treating other malignancies such as colorectal cancer. --- TIMESTAMPS 00:00 - Introduction 05:40 - Patient Selection Criteria 09:49 - Workflow 19:17 - Procedure Timing and Coordination 29:39 - Challenges and Considerations in Drug Dosing 32:39 - Optimizing Treatment Cycles and Patient Response 37:56 - Managing Post-Treatment and Adverse Effects 43:43 - Future Research and Gaps in Current Interventions 50:45 - Exploring New Applications for PHP Therapy 55:02 - Conclusion --- RESOURCES Hepzato: https://hepzatokit.com/ FOCUS Trial - Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study: https://pubmed.ncbi.nlm.nih.gov/38704501/ FOCUS phase 3 trial results: Percutaneous hepatic perfusion (PHP) with melphalan for patients with ocular melanoma liver metastases (PHP-OCM-301/301A): https://ascopubs.org/doi/pdf/10.1200/JCO.2022.40.16_suppl.9510 Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial: https://pubmed.ncbi.nlm.nih.gov/36624292/ Troponin Elevation in Patients Undergoing Percutaneous Hepatic Perfusion for Metastatic Uveal Melanoma: https://pmc.ncbi.nlm.nih.gov/articles/PMC11010739/ Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Ocular Melanoma Metastases Confined to the Liver: A Prospective Phase II Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC7801354/ Southampton group - Quality of life after melphalan percutaneous hepatic perfusion for patients with metastatic uveal melanoma: https://pmc.ncbi.nlm.nih.gov/articles/PMC10906212/ Leiden group - Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases: https://pubmed.ncbi.nlm.nih.gov/38587534/

Recorded live at the Critical Care Canada Forum 2024, this episode is part of our special Cardiac ICU Series.Dr. Rebecca Mathew, cardiologist and critical care specialist at the University of Ottawa Heart Institute, joins us to discuss the latest refractory cardiac arrest practice updates, including antiarrhythmic drugs, defibrillation strategies, and the role of ECPR.Chapters: • Defining refractory cardiac arrest • Antiarrhythmic drugs: amiodarone vs. lidocaine • Defibrillation strategies: vector change and double sequential defibrillation • Emerging therapies: stellate ganglion blocks and electrical storm management • ECPR: who qualifies and what the trials say • Equity and feasibility challenges in cardiac arrest management • ICU recovery clinics and patient-centered outcomes • Clinical trials: barriers to enrollment and the need for changeReferences: 1. ROC ALPS Trial: 1. Kudenchuk PJ, Brown SP, Daya M, et al. Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and Methodology Behind an Out-of-Hospital Cardiac Arrest Antiarrhythmic Drug Trial. American Heart Journal. 2014;167(5):653-9.e4. doi:10.1016/j.ahj.2014.02.010. PMID: 24766974.[1] 2. DOSE VF: Cheskes S, Drennan IR, Turner L, Pandit SV, Dorian P. The Impact of Alternate Defibrillation Strategies on Shock-Refractory and Recurrent Ventricular Fibrillation: A Secondary Analysis of the DOSE VF Cluster Randomized Controlled Trial. Resuscitation. 2024;198:110186. doi:10.1016/j.resuscitation.2024.110186. PMID: 38522736 3. ARREST: Yannopoulos D, Bartos J, Raveendran G, et al. Advanced Reperfusion Strategies for Patients With Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation (ARREST): A Phase 2, Single Centre, Open-Label, Randomised Controlled Trial. Lancet (London, England). 2020;396(10265):1807-1816. doi:10.1016/S0140-6736(20)32338-2. PMID: 33197396 4. INCEPTION: Ubben JFH, Suverein MM, Delnoij TSR, et al. Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest - A Pre-Planned Per-Protocol Analysis of the INCEPTION-trial. Resuscitation. 2024;194:110033. doi:10.1016/j.resuscitation.2023.110033. PMID: 37923112 Disclaimer:This episode is for educational purposes only and does not constitute medical advice. The views expressed are those of the hosts and guests and do not necessarily reflect their employers.

We are back with more exciting IDWeek 2024 content. In this episode, Breakpoints hostesses Drs. Erin McCreary, Julie Ann Justo, Jeannette Bouchard, and Megan Klatt highlight more of our favorite sessions and posters at IDWeek, this episode is a must listen if you are an IDWeek nerd like us! References: Perret et al. Application of OpenAI GPT-4 for the retrospective detection of catheter-associated urinary tract infections in a fictitious and curated patient data set. 10.1017/ice.2023.189 Wiemken et al. Assisting the infection preventionist: Use of artificial intelligence for health care–associated infection surveillance. 10.1016/j.ajic.2024.02.007 Leekha et al. Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study. 10.1136/bmjqs-2023-016831 Diekema et al. Are Contact Precautions "Essential" for the Prevention of Healthcare-associated Methicillin-Resistant Staphylococcus aureus? 10.1093/cid/ciad571 Martin et al. Contact precautions for MRSA and VRE: where are we now? A survey of the Society for Healthcare Epidemiology of America Research Network. 10.1017/ash.2024.350 Browne et al. Investigating the effect of enhanced cleaning and disinfection of shared medical equipment on health-care-associated infections in Australia (CLEEN): a stepped-wedge, cluster randomised, controlled trial. 10.1016/S1473-3099(24)00399-2 Protect trial: Decolonization in Nursing Homes to Prevent Infection and Hospitalization. 10.1056/NEJMoa2215254 Aldardeer et al. Early Versus Late Antipseudomonal β-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study. 10.1093/ofid/ofae059 Schmiemann et al. Effects of a multimodal intervention in primary care to reduce second line antibiotic prescriptions for urinary tract infections in women: parallel, cluster randomised, controlled trial. 10.1136/bmj-2023-076305 Vernacchio et al. Improving Short Course Treatment of Pediatric Infections: A Randomized Quality Improvement Trial. 10.1542/peds.2023-063691 Advani et al. Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria. 10.1001/jamanetworkopen.2024.2283 Saif et al. Clinical decision support for gastrointestinal panel testing. 10.1017/ash.2024.15 Bekker et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. 10.1056/NEJMoa2407001 Montini et al. Short Oral Antibiotic Therapy for Pediatric Febrile Urinary Tract Infections: A Randomized Trial. 10.1542/peds.2023-062598 Nielsen et al. Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark. 10.1016/S2352-4642(24)00133-0 Kaasch et al. Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial. 10.1016/S1473-3099(23)00756-9 AMIKINHAL: Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. 10.1056/NEJMoa2310307 PROPHY-VAP: Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. 10.1016/S2213-2600(23)00471-X AVENIR: Azithromycin to Reduce Mortality — An Adaptive Cluster-Randomized Trial. 10.1056/NEJMoa2312093 Thomas et al. Comparison of Two High-Dose Versus Two Standard-Dose Influenza Vaccines in Adult Allogeneic Hematopoietic Cell Transplant Recipients. 10.1093/cid/ciad458 Schuster et al. The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial. 10.1093/cid/ciad534 Mahadeo et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. 10.1016/S1470-2045(23)00649-6 Khoury et al. Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant. 10.1016/j.ajt.2024.04.009 Spec et al. MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses—A Multicenter, Open-Label, Randomized Comparative Trial. 10.1093/ofid/ofae010

It seems that open label placebo offered to people the possibility of gaining self awareness on their body and being more empowered in the way they manage their pain.” – Cláudia Carvalho, Ph.D In this episode, the host, Ana Melikian, dives into the fascinating world of placebo effects with guest Dr. Cláudia Carvalho, a board-certified… Continue reading Exploring Open-Label Placebos with Claudia Carvalho, Ph.D. The post Exploring Open-Label Placebos with Claudia Carvalho, Ph.D. appeared first on Ana Melikian, Ph.D..

Send us a Text Message.Diese Woche besprechen wir die Arbeit von Rahmel et al. zur ketogenen Ernährung in der Sepsis: Rahmel et al. An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis. Sci Transl Med. 16,eadn9285(2024).DOI:10.1126/scitranslmed.adn9285Mit im Studio dabei: Dr. Marie Koch, wissenschaftliche Mitarbeiterin der Klinik fr Anästhesiologie am UKHD. 

Struggling with ulcerative colitis flare-ups? This video explores a new study on Indigo Naturalis, a plant-based supplement. Researchers followed patients who achieved remission with Indigo Naturalis and found it very effective in preventing future flare-ups. Even those who relapsed after stopping the supplement saw success when restarting it. This is promising news, but remember, it's one study. Talk to your doctor before trying anything new. #NaturalTreatment #UlcerativeColitis #IndigoNaturalis Matsuno, Y., Umeno, J., Hirano, A., Fuyuno, Y., Nagasue, T., Fujioka, S., Kawasaki, K., Moriyama, T., & Torisu, T. (2024). MAINTENANCE EFFICACY OF ORAL INDIGO NATURALIS FOR ULCERATIVE COLITIS: A SINGLE-CENTER, OPEN-LABEL, RANDOMIZED, CONTROLLED STUDY. Inflammatory Bowel Diseases, 30(Supplement_1), S9. https://doi.org/10.1093/ibd/izae020.020 Matsuno, Y., Torisu, T., Umeno, J., Shibata, H., Hirano, A., Fuyuno, Y., Okamoto, Y., Fujioka, S., Kawasaki, K., Moriyama, T., Nagasue, T., Zeze, K., Hirakawa, Y., Kawatoko, S., Koga, Y., Oda, Y., Esaki, M., & Kitazono, T. (2022). One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: A real-world prospective study. Intestinal Research, 20(2), 260-268. https://doi.org/10.5217/ir.2021.00124 Alchepharma,Ralph Turchiano,citation,research,study,IndigoNaturalis,UlcerativeColitis,remission,maintenance therapy,herbal remedy,plant-based treatment,oral Indigo Naturalis,clinical trial,UC study,gut health,inflammatory bowel disease,flare-up prevention,mucosal healing,relapse rates,single-center study,open-label trial,randomized controlled trial,Mayo endoscopic subscore,dose-dependent effect,year-long study,safety profile,natural medicine --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support

Struggling with ulcerative colitis flare-ups? This video explores a new study on Indigo Naturalis, a plant-based supplement. Researchers followed patients who achieved remission with Indigo Naturalis and found it very effective in preventing future flare-ups. Even those who relapsed after stopping the supplement saw success when restarting it. This is promising news, but remember, it's one study. Talk to your doctor before trying anything new. #NaturalTreatment #UlcerativeColitis #IndigoNaturalis Matsuno, Y., Umeno, J., Hirano, A., Fuyuno, Y., Nagasue, T., Fujioka, S., Kawasaki, K., Moriyama, T., & Torisu, T. (2024). MAINTENANCE EFFICACY OF ORAL INDIGO NATURALIS FOR ULCERATIVE COLITIS: A SINGLE-CENTER, OPEN-LABEL, RANDOMIZED, CONTROLLED STUDY. Inflammatory Bowel Diseases, 30(Supplement_1), S9. https://doi.org/10.1093/ibd/izae020.020 Matsuno, Y., Torisu, T., Umeno, J., Shibata, H., Hirano, A., Fuyuno, Y., Okamoto, Y., Fujioka, S., Kawasaki, K., Moriyama, T., Nagasue, T., Zeze, K., Hirakawa, Y., Kawatoko, S., Koga, Y., Oda, Y., Esaki, M., & Kitazono, T. (2022). One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: A real-world prospective study. Intestinal Research, 20(2), 260-268. https://doi.org/10.5217/ir.2021.00124 Alchepharma,Ralph Turchiano,citation,research,study,IndigoNaturalis,UlcerativeColitis,remission,maintenance therapy,herbal remedy,plant-based treatment,oral Indigo Naturalis,clinical trial,UC study,gut health,inflammatory bowel disease,flare-up prevention,mucosal healing,relapse rates,single-center study,open-label trial,randomized controlled trial,Mayo endoscopic subscore,dose-dependent effect,year-long study,safety profile,natural medicine --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support

Date: November 20, 2023 Reference: Jones et al. Time to reflect on open-label placebos and their value for clinical practice. PAIN October 2023 Guest Skeptic: Dr. Caitlin Jones is a Postdoctoral Research Associate at Sydney University's institute for Musculoskeletal Health. Her research evaluates the benefits and harms of treatments for musculoskeletal conditions with a particular […] The post SGEM Xtra: Open Label Placebo first appeared on The Skeptics Guide to Emergency Medicine.

Drs Sandhya Srinivas and Tanya B. Dorff discuss metastatic hormone-sensitive prostate cancer, which patients are the best candidates for doublets vs triplets, and how we pick these patients. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988737). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Prostate Cancer https://emedicine.medscape.com/article/1967731-overview Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment https://pubmed.ncbi.nlm.nih.gov/37220335/ Triplet or Doublet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Updated Network Meta-Analysis Stratified by Disease Volume https://pubmed.ncbi.nlm.nih.gov/37055323/ PSMA PET in Imaging Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35155262/ Risks and Cancer Associations of Metachronous and Synchronous Multiple Primary Cancers: a 25-Year Retrospective Study https://pubmed.ncbi.nlm.nih.gov/34556087/ The Promise of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer: Going Beneath the Surface With Molecular Imaging https://pubmed.ncbi.nlm.nih.gov/35058322/ Gleason Score https://www.ncbi.nlm.nih.gov/books/NBK553178/ Luteinizing Hormone-Releasing Hormone (LHRH) Receptor Agonists Vs Antagonists: a Matter of the Receptors? https://pubmed.ncbi.nlm.nih.gov/23418666/ The Role of CYP17A1 in Prostate Cancer Development: Structure, Function, Mechanism of Action, Genetic Variations and Its Inhibition https://pubmed.ncbi.nlm.nih.gov/29372682/ Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial https://pubmed.ncbi.nlm.nih.gov/29384722/ Abiraterone for Prostate Cancer Not Previously Treated With Hormone Therapy https://pubmed.ncbi.nlm.nih.gov/28578639/ Abiraterone Plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/28578607/ Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP https://pubmed.ncbi.nlm.nih.gov/34928708/ Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35179323/ Abiraterone Plus Prednisone Added to Androgen Deprivation Therapy and Docetaxel in De Novo Metastatic Castration-Sensitive Prostate Cancer (PEACE-1): a Multicentre, Open-Label, Randomised, Phase 3 Study With a 2 × 2 Factorial Design https://pubmed.ncbi.nlm.nih.gov/35405085/

This week, please join author Sebastian Reinstadler and Senior Associate Editor Victoria Delgado as they discuss "Cardiac Magnetic Resonance Imaging Versus Computed Tomography to Guide Transcatheter Aortic Valve Replacement: A Randomized, Open-Label, Noninferiority Trial." For the episode transcript, visit:  https://www.ahajournals.org/do/10.1161/podcast.20231016.898440

In this episode, Domenica Lorusso, MD, PhD, and Alexandra Leary, MD, PhD, provide expert insights on key updates and new clinical trial data presented at the ESGO 2023 Congress for cervical, endometrial, and ovarian cancers, including:Long-Term Follow Up From Phase III SIENDO Study of Selinexor vs Pbo Maintenance in Patients With TP53wt Advanced/Recurrent Endometrial Cancer Global, Open-Label, Phase I/IIa of HER2-Targeting ADC (DB-1303) in Recurrent/Metastatic Endometrial CancerPhase III From KEYNOTE-826: Bevacizumab Subgroup Analysis Based on Protocol Specified Final Overall Survival ResultsPhase III ICON8B: Weekly DD-CT + Bev vs Q3W CT + Bev as First Line in High-Risk Epithelial Ovarian CancerHRD Testing on Cell-Free Tumor DNA From Peritoneal Fluid of Patients With Newly-Diagnosed Epithelial Ovarian CancerPresenters:Alexandra Leary, MD, PhDCo DirectorMedical Oncologist and Team LeaderGynecology Translational Research LabDepartment of MedicineGustave Roussy Cancer CenterParis, FranceDomenica Lorusso, MD, PhDAssociate ProfessorGynecologic Oncology DepartmentClinical Research UnitFondazione Policlinico Gemelli IRCCSRome, ItalyThis educational activity is supported by educational grants from AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, Genmab, and Seagen. Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/424E3Uq

Andrew Blauvelt, MD, FAAD interviewed by Jackie Dosal, MD, FAAD

Five years, 7 years, or 10 years: How long should follow-up last in melanoma? Dr Sapna Patel and Professor James Larkin discuss the challenges and opportunities. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989039). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Malignant Melanoma https://emedicine.medscape.com/article/280245-overview NCCN Guidelines. Melanoma: Cutaneous https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1492 Malignant Melanoma Staging https://emedicine.medscape.com/article/2007147-overview A Practical Guide to Understanding Kaplan-Meier Curves https://pubmed.ncbi.nlm.nih.gov/20723767/ SWOG Cancer Research Network https://www.swog.org/ Adjuvant Pembrolizumab Versus IFNα2b or Ipilimumab in Resected High-Risk Melanoma https://pubmed.ncbi.nlm.nih.gov/34764195/ Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/34818112/ Estimands — A Basic Element for Clinical Trials https://pubmed.ncbi.nlm.nih.gov/34857075/ Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/36856617/ Definitions of Additional Oncology Drug Endpoints https://www.ncbi.nlm.nih.gov/books/NBK137753/ Adjuvant Nivolumab Versus Ipilimumab in Resected Stage IIIB-C and Stage IV melanoma (CheckMate 238): 4-Year Results From a Multicentre, Double-Blind, Randomised, Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32961119/ Adjuvant Ipilimumab Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (EORTC 18071): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/25840693/ Adjuvant Pembrolizumab Versus Placebo in Resected Stage III Melanoma (EORTC 1325-MG/KEYNOTE-054): Distant Metastasis-Free Survival Results From a Double-Blind, Randomised, Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/33857412/ Pembrolizumab Versus Placebo as Adjuvant Therapy in Completely Resected Stage IIB or IIC Melanoma (KEYNOTE-716): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/35367007/ The Validity of Progression-Free Survival 2 as a Surrogate Trial End Point for Overall Survival https://pubmed.ncbi.nlm.nih.gov/34985773/ Neoadjuvant Talimogene Laherparepvec Plus Surgery Versus Surgery Alone for Resectable Stage IIIB-IVM1a Melanoma: A Randomized, Open-Label, Phase 2 Trial https://pubmed.ncbi.nlm.nih.gov/34608333/

Join experts Drs Kevin Kalinsky and Priyanka Sharma as they discuss their current approach to neoadjuvant therapy in triple negative breast cancer and how the SCARLET trial might change that. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/991256). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Pembrolizumab for Early Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/32101663/ Clinical and Biomarker Results of Neoadjuvant Phase II Study of Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer (TNBC) (NeoPACT) https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.513 CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/35044810/ NCCN Guidelines® Insights: Breast Cancer, Version 4.2023 https://pubmed.ncbi.nlm.nih.gov/37308117/ Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab https://classic.clinicaltrials.gov/ct2/show/NCT05812807 Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer https://clinicaltrials.gov/study/NCT05929768 Neoadjuvant Atezolizumab in Combination With Sequential Nab-Paclitaxel and Anthracycline-Based Chemotherapy Versus Placebo and Chemotherapy in Patients With Early-Stage Triple-Negative Breast Cancer (IMpassion031): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32966830/ Adjuvant Capecitabine for Breast Cancer After Preoperative Chemotherapy https://pubmed.ncbi.nlm.nih.gov/28564564/ Impact of Neoadjuvant Chemotherapy on Axillary Nodal Involvement in Patients With Clinically Node Negative Triple Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/25266871/ Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual HER2 Blockade for HER2-Positive Breast Cancer (TRAIN-2): A Multicentre, Open-Label, Randomised, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/30413379/

Exploring the science and data of microdosing, and briefing key drug interactions with the use of common used psychedelic therapies References: Cheung T. COMPASS Announces Positive Outcome of 25 mg COMP360 Psilocybin Therapy as Adjunct to SSRI Anti-depressant in Open-Label, Treatment-Resistant Depression Study. COMPASS Health. 13 Dec 2021 [press release]. Grinspoon P. The Popularity of Microdosing of Psychedelics: What Does the Science Say? Harvard Health. 19 Sept 2022. Gukasyan N, et al. Attenuation of Psilocybin Mushroom Effects During and After SSRI/SNRI Anti-depressant Use. Sage Journals. 2023 Jul; 37(7): 707-716 Malcolm B and Thomas K. Serotonin Toxicity of Serotonergic Psychedelics. Psychopharmacology. 2022;239: 1881-1891 Perez E, et al. The Psilocybin-Blunting Effects of SSRIs and Anti-depressants. Psychedelic Passage. 3 June 2022. Raison C, et al. Single Dose Psilocybin for Major Depressive Disorder. JAMA. 2023; 330(9): 843-853    

Drs Michael S. Saag and Rajesh Gandhi discuss HIV and Antiretroviral Therapy Guidelines. When to begin treatment, which treatment to choose, and how to treat the whole person, not just the HIV. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/986509). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources HIV Infection and AIDS https://emedicine.medscape.com/article/211316-overview Zidovudine (Rx) https://reference.medscape.com/drug/retrovir-zdv-zidovudine-342639 ddI and d4T Plus Protease Inhibitors https://pubmed.ncbi.nlm.nih.gov/11364012/ HIV-Protease Inhibitors https://pubmed.ncbi.nlm.nih.gov/9562584/ Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection https://pubmed.ncbi.nlm.nih.gov/26192873/ Early Symptomatic HIV Infection https://reference.medscape.com/article/211873-overview IAS-USA https://www.iasusa.org/ Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel https://pubmed.ncbi.nlm.nih.gov/36454551/ Integrase Strand Transfer Inhibitors Are Effective Anti-HIV Drugs https://pubmed.ncbi.nlm.nih.gov/33572956/ Dolutegravir (Rx) https://reference.medscape.com/drug/tivicay-tivicay-pd-dolutegravir-999861 Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy) https://www.medscape.com/viewarticle/941921_4 Dolutegravir/Lamivudine as a First-Line Regimen in a Test-and-Treat Setting for Newly Diagnosed People Living With HIV https://pubmed.ncbi.nlm.nih.gov/34115650/ Tenofovir DF (Rx) https://reference.medscape.com/drug/viread-tenofovir-df-342633 Tenofovir AF (Rx) https://reference.medscape.com/drug/vemlidy-tenofovir-af-1000007 Abacavir (Rx) https://reference.medscape.com/drug/ziagen-abacavir-342600 HLA B 5701 Testing https://www.ncbi.nlm.nih.gov/books/NBK560797/ Dolutegravir/Rilpivirine (Rx) https://reference.medscape.com/drug/juluca-dolutegravir-rilpivirine-1000216 Efficacy and Safety of Dolutegravir-Rilpivirine for Maintenance of Virological Suppression in Adults With HIV-1: 100-Week Data From the Randomised, Open-Label, Phase 3 SWORD-1 and SWORD-2 Studies https://pubmed.ncbi.nlm.nih.gov/31307948/ Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) https://clinicalinfo.hiv.gov/en/glossary/non-nucleoside-reverse-transcriptase-inhibitor-nnrti Cabotegravir/Rilpivirine: The Last FDA-Approved Drug to Treat HIV https://pubmed.ncbi.nlm.nih.gov/35596583/ Anticipating and Managing Drug Interactions: Pharmacokinetics of Long-Acting HIV Treatment and Prevention Formulations https://www.medscape.com/viewarticle/986504 Mpox Vaccination Basics https://www.cdc.gov/poxvirus/mpox/vaccines/index.html COVID-19 Treatment Guidelines https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals-including-antibody-products/summary-recommendations/ Mpox in People With Advanced HIV Infection: A Global Case Series https://pubmed.ncbi.nlm.nih.gov/36828001/ Information for Healthcare Providers: Tecovirimat (TPOXX) for Treatment of Mpox https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html HIV and Opioid Use Disorder: Screening Tools, Chronic Pain Management, and Access to Care in the Outpatient Setting https://www.medscape.com/viewarticle/986506

Join experts Drs Matt Sparks and Dawn Caster as they discuss the complexities around the management of lupus nephritis. What tools do we have now? What is on the horizon? Tune in to find out. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/991602). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Novel Aspects in the Pathophysiology and Diagnosis of Glomerular Diseases https://pubmed.ncbi.nlm.nih.gov/36535746/ Derivation and Validation of the Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus https://pubmed.ncbi.nlm.nih.gov/22553077 EULAR/ACR Classification Criteria for SLE https://pubmed.ncbi.nlm.nih.gov/31779843/ Sensitivity and Specificity of ANA and Anti-dsDNA in the Diagnosis of Systemic Lupus Erythematosus: A Comparison Using Control Sera Obtained From Healthy Individuals and Patients With Multiple Medical Problems https://pubmed.ncbi.nlm.nih.gov/24383972/ Podocyte Foot Process Effacement Precedes Albuminuria and Glomerular Hypertrophy in CD2-Associated Protein Deficient Mice https://pubmed.ncbi.nlm.nih.gov/34568396/  KDIGO 2023 Clinical Practice Guideline for the Management of Lupus Nephritis https://kdigo.org/wp-content/uploads/2023/03/KDIGO-2023-Lupus-Nephritis-Guideline_Public-Review_9-Mar-2023.pdf Management of Lupus Nephritis: A Systematic Literature Review Informing the 2019 Update of the Joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) Recommendations https://pubmed.ncbi.nlm.nih.gov/32699043/ Nonrenal Disease Activity Following Mycophenolate Mofetil or Intravenous Cyclophosphamide as Induction Treatment for Lupus Nephritis: Findings in a Multicenter, Prospective, Randomized, Open-Label, Parallel-Group Clinical Trial https://pubmed.ncbi.nlm.nih.gov/20039429/ Immunosuppressive Therapy in Lupus Nephritis: The Euro-Lupus Nephritis Trial, a Randomized Trial of Low-Dose Vs High-Dose Intravenous Cyclophosphamide https://pubmed.ncbi.nlm.nih.gov/12209517/ Voclosporin: A Novel Calcineurin Inhibitor for the Treatment of Lupus Nephritis https://pubmed.ncbi.nlm.nih.gov/35168373 Safety and Efficacy of Belimumab in Patients With Lupus Nephritis: Open-Label Extension of BLISS-LN Study https://pubmed.ncbi.nlm.nih.gov/36302567/ Anti-CD19 CAR T Cell Therapy for Refractory Systemic Lupus Erythematosus https://pubmed.ncbi.nlm.nih.gov/36109639/ Dapagliflozin in People With Chronic Kidney Disease https://pubmed.ncbi.nlm.nih.gov/37257897/ Empagliflozin in Patients With Chronic Kidney Disease https://pubmed.ncbi.nlm.nih.gov/36331190/

Drs Sapna Patel and Yana Najjar analyze the data and share their approach to frontline therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989035). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134 https://pubmed.ncbi.nlm.nih.gov/36166727/ Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial https://pubmed.ncbi.nlm.nih.gov/36049147/ Long-Term Outcomes of Patients With Active Melanoma Brain Metastases Treated With Combination Nivolumab Plus Ipilimumab (CheckMate 204): Final Results of an Open-Label, Multicentre, Phase 2 Study https://pubmed.ncbi.nlm.nih.gov/34774225/ Health-related Quality of Life With Nivolumab Plus Relatlimab Versus Nivolumab Monotherapy in Patients With Previously Untreated Unresectable or Metastatic Melanoma: RELATIVITY-047 Trial https://pubmed.ncbi.nlm.nih.gov/37167764/ Overall Survival With Combined Nivolumab and Ipilimumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/28889792/ Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial https://pubmed.ncbi.nlm.nih.gov/30811280/ Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915) https://pubmed.ncbi.nlm.nih.gov/36162037/ Single-Agent PD-1 Blockade Is "Treatment of Choice" for Desmoplastic Melanoma https://pubmed.ncbi.nlm.nih.gov/37071762/ Single-agent Pembrolizumab May Benefit Patients With Rare Type of Skin Cancer https://www.aacr.org/about-the-aacr/newsroom/news-releases/single-agent-pembrolizumab-may-benefit-patients-with-rare-type-of-skin-cancer/ Atezolizumab, Vemurafenib, and Cobimetinib as First-Line Treatment for Unresectable Advanced BRAFV600 Mutation-Positive Melanoma (Imspire150): Primary Analysis of the Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32534646/ Overall Survival Benefit With Tebentafusp in Metastatic Uveal Melanoma https://pubmed.ncbi.nlm.nih.gov/34551229/ Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis https://pubmed.ncbi.nlm.nih.gov/28056206/ Single-Agent Anti-PD-1 or Combined With Ipilimumab in Patients With Mucosal Melanoma: An International, Retrospective, Cohort Study https://pubmed.ncbi.nlm.nih.gov/35716907/ CheckMate 067: Long-Term Outcomes in Patients With Mucosal Melanoma. https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.10019 A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab Vs Ipilimumab + Nivolumab In BRAFV600-Mutant Melanoma Brain Metastases https://www.swog.org/clinical-trials/s2000

Drs Stanley Cohen and Philip Mease review the 2022 ACR meeting topics, including new treatments, trial data, and what they think are the most pressing unmet needs in the field. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984271). The topics and discussions are planned, produced, and reviewed independently of the advertisers. This podcast is intended only for US healthcare professionals. Resources Etanercept in the Treatment of Psoriatic Arthritis and Psoriasis: A Randomised Trial https://pubmed.ncbi.nlm.nih.gov/10972371/ Group for Research and Assessment of Psoriasis and Psoriatic Arthritis https://www.grappanetwork.org/ American College of Rheumatology (ACR) Convergence https://www.rheumatology.org/Annual-Meeting Bimekizumab Treatment in Biologic DMARD-Naïve Patients With Active Psoriatic Arthritis: 52-Week Efficacy and Safety Results From a Phase 3, Randomized, Placebo-Controlled, Active Reference Study https://acrabstracts.org/abstract/bimekizumab-treatment-in-biologic-dmard-naive-patients-with-active-psoriatic-arthritis-52-week-efficacy-and-safety-results-from-a-phase-3-randomized-placebo-controlled-active-reference-study/ Bimekizumab Treatment in Patients With Active Psoriatic Arthritis and Inadequate Response to Tumor Necrosis Factor Inhibitors: 16-Week Efficacy and Safety From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study https://acrabstracts.org/abstract/bimekizumab-treatment-in-patients-with-active-psoriatic-arthritis-and-inadequate-response-to-tumor-necrosis-factor-inhibitors-16-week-efficacy-and-safety-from-a-phase-3-randomized-double-blind-pla/ Bimekizumab Improvements in Efficacy on Disease Activity Assessed via Composite Endpoints in Biologic DMARD-Naïve and TNFi-IR Patients With Active PsA: Pooled 16-Week Results From Phase 3 Randomized, Placebo-Controlled Studies https://acrabstracts.org/abstract/bimekizumab-improvements-in-efficacy-on-disease-activity-assessed-via-composite-endpoints-in-biologic-dmard-naive-and-tnfi-ir-patients-with-active-psa-pooled-16-week-results-from-phase-3-randomized/ Bimekizumab Versus Adalimumab in Plaque Psoriasis https://pubmed.ncbi.nlm.nih.gov/33891379/ A Head-to-Head Comparison of the Efficacy and Safety of Ixekizumab and Adalimumab in Biological-Naïve Patients With Active Psoriatic Arthritis: 24-Week Results of a Randomised, Open-Label, Blinded-Assessor Trial https://pubmed.ncbi.nlm.nih.gov/31563894/ GRAPPA Treatment Recommendations: 2021 Update https://pubmed.ncbi.nlm.nih.gov/35293339/ Deucravacitinib Prescribing Information https://packageinserts.bms.com/pi/pi_sotyktu.pdf Safety and Efficacy of Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 Inhibitor, in Patients With Psoriatic Arthritis: 52-Week Results From a Randomized Phase 2 Trial https://acrabstracts.org/abstract/safety-and-efficacy-of-deucravacitinib-an-oral-selective-tyrosine-kinase-2-inhibitor-in-patients-with-psoriatic-arthritis-52-week-results-from-a-randomized-phase-2-trial/ Deucravacitinib Reduces Interferons, B Cell Pathways, and Serological Biomarkers of Systemic Lupus Disease Activity: Pharmacodynamic Analysis From the Phase 2 PAISLEY Study https://acrabstracts.org/abstract/deucravacitinib-reduces-interferons-b-cell-pathways-and-serological-biomarkers-of-systemic-lupus-disease-activity-pharmacodynamic-analysis-from-the-phase-2-paisley-study/ Nanobody: A Promising Toolkit for Molecular Imaging and Disease Therapy https://pubmed.ncbi.nlm.nih.gov/33464410/

For our last submission as the BTK Bariatric Surgery Team, we thought we would take a minute to review some recent landmark trials in bariatric surgery. Get caught up on the impact of bariatric surgery on obesogenic cancers and non-alcoholic steatohepatitis.  Journal articles: Association of Bariatric Surgery with Cancer Risk and Mortality in Adults with Obesity: https://pubmed.ncbi.nlm.nih.gov/35657620/.  Bariatric-Metabolic Surgery versus Lifestyle Intervention plus Best Medical Care in Non-Alcoholic Steatophepatitis (BRAVES): A Multicentre, Open-Label, Randomised Trial: https://pubmed.ncbi.nlm.nih.gov/37088093/. Ad referenced in episode: A team at the Brooke Army Medical Center is working to better define proficiency-based metrics for competency in commonly performed robotic general surgery procedures. If you are a general surgery resident or practicing surgeon who performs robotic assisted cholecystectomies or inguinal hernia repairs,  reach out to the PI, Robert Laverty, MD, at rblaverty@gmail.com for more information on how you could be compensated $500 per video submitted of each (up to $1000 per surgeon). Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more.   If you liked this episode, check out other bariatric episodes here: https://behindtheknife.org/podcast-category/bariatric/

In this JCO Article Insights episode, Emily Zabor interviews Dr. Gulam Manji from Columbia University Irving Medical Center. Dr. Manji provides insight into his editorial published in the April 10, 2023 JCO issue: "Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence?” (10.1200/JCO.23.00039). His editorial focuses on the JCO Original Report, “Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial” by Tempero, et al on the APACT Trial. TRANSCRIPT The guest on this podcast episode has no disclosures to declare.  Emily Zabor: Welcome to this JCO Article Insights episode for the April issue of JCO. This is Emily Zabor, one of JCO's editorial fellows. And today I am interviewing Dr. Manji from Columbia University on their editorial titled “Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence?” Dr. Manji, welcome to our podcast. You wrote this editorial to accompany the article, “Adjuvant Nab-Paclitaxel plus Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results from a Randomized Open-label Phase III Trial by Dr. Margaret Tempero and Colleagues.” That trial, called the APACT Trial, investigated the efficacy and safety of adjuvant nab-paclitaxel plus gemcitabine compared to gemcitabine alone in patients who had undergone resection for pancreatic ductal adenocarcinoma. So I wanted to ask if you could start by giving listeners a quick overview of the study design and the main findings from that trial. Dr. Gulam Manji: Yeah, sure, Emily. So, as you pointed out, it was a randomized phase III study in patients who had resected pancreatic carcinoma. The primary endpoint was independently assessed disease-free survival. Additional endpoints included investigator-assessed disease-free survival, overall survival, and safety. And we'll get back later on as far as the importance of investigator-assessed versus independently-assessed disease with survival because I think that that's the main point of discussion for today. The enrollment criteria were fairly stringent and included patients with macroscopic complete resection, ECOG performance status of either 0 or 1, and the peripheral tumor markers of CA 19-9 being less than 100. And patients were required to initiate adjuvant chemotherapy within 12 weeks. Patients received standard gemcitabine at 1000 milligrams per meter square, either with or without nab-paclitaxel of 125 milligrams per meter square once weekly for three weeks during every four-week cycle. Emily Zabor: Great. So I think that the main thing that we wanted to talk about today, and one of the main points you discuss in your editorial is the difference between the primary endpoint of independently assessed disease-free survival and the secondary endpoint of investigator-assessed disease-free survival. So can you describe the difference between those endpoints, how they were defined, and how they differed? Dr. Gulam Manji: Sure. So, independently-assessed DFS was determined by a radiologist who was blinded to treatment assignment, and new lesions followed RECIST 1.1 criteria. In contrast, the investigator-assessed recurrence was determined by the treating physicians using all available clinical information. So that could be abdominal pain, anorexia, probably elevation of peripheral tumor markers. And the other important aspect to the study is that the independent review was not performed in real-time to confirm investigator assessments. So patients who started subsequent therapy after recurrence by treating investigators were censured for the independently-assessed DFS analysis. So in this trial, 866 patients were randomized. And patients who are randomized to the experimental arm had a median independently assessed DFS of 19.4 months, while patients randomized to the control arm, which was gemcitabine alone, had a median DFS of 18.8 months. Now, when we compare that to the investigator-assessed DFS, the data looks quite different. Where the DFS was 16.6 months in the experimental arm compared to 13.7 months in the control arm. That is consistent with the five-year follow-up looking at the median overall survival, which was 41.8 months for the combination arm compared to 37.7 months for the gemcitabine alone arm. Emily Zabor: Okay, so there's some really interesting differences there. And I noticed that there were only 439 events according to the independently-assessed DFS versus 571 according to the investigator-assessed DFS. So that's a big difference in the number of events that I guess is coming from that additional censoring that was occurring due to the delay in the independently assessed endpoint. Is that right? Dr. Gulam Manji: Exactly. So you could envision a scenario where patients received chemotherapy and then on the investigator-assessed DFS, the investigators decided that the patient had recurred. However, that patient probably did not meet the RECIST or radiological criteria to determine that that patient had recurred. And hence, since it was not done in real-time, there was censoring that occurred for the independently-assessed DFS. So that's the reason why there was a difference in that number as you pointed out.  The decision to use independent DFS, disease-free survival, really was to remove investigator-associated bias and increase rigor to the study, which is commendable. However, unfortunately, that's not how we normally treat patients with aggressive cancer who have undergone surgical reception. And knowing that imaging modality is limited in identifying those patients, particularly in those that have peritoneal disease, or even more importantly, the patients who have recurrence within the surgical bed, I think is the issue.  Emily Zabor: Right. So the motivation behind selecting that endpoint was really good and well-motivated. Everybody wants to reduce bias and make sure we're taking out those kind of more subjective parts of identifying that. But it, unfortunately, missed some events as a result. Dr. Gulam Manji: Correct. I think that it delayed those events and that's what compromised the analysis because it was the limitations of the available modalities to determine when recurrence occurs. Emily Zabor: So how do these different definitions compare to other trials or previous trials? Dr. Gulam Manji: So previous trials that I'm aware of, it was the investigator-assessed DFS that had been used. And when you look at the data that was used in this trial, that concurs with what has historically been seen. And what I mean by that is that the original assumptions regarding DFS when this trial was being designed, used historical outcomes. Investigators see that DFS with adjuvant gemcitabine ranged anywhere from between 13.4 to 14.3 months. And the study had aimed to achieve a DFS improvement from 13.5 to 18.5 months. When you look at the investigator-assessed DFS, the ballpark of gemcitabine is very much in line with the previous historical data. So I think that the key discrepancy between the two DFS endpoints was likely a delay in accurately assessing disease recurrence when using the blinded radiological modality alone. And the second thing is, as you pointed out, a greater proportion of patients who were censored for independent assessments compared with those for investigator assessments was different. So that was between 40% versus 34%. So those two points, I think, were the key points that show the difference between independent versus investigator-assessed DFS and also that the independent-assessed DFS was not done in real-time. Emily Zabor: Yeah, that's really interesting and such a good point. And I think it really emphasizes how important it is to think carefully about these endpoint definitions in the design stage of these clinical trials and especially to think about when and why patients are getting censored and how that might impact the results.  So how do these results of this trial then, given the negative result of the primary endpoint, but that positive result on the secondary investigator-assessed endpoint, how do these fit in with other trials? And what do you think that means for patient treatment recommendations? Dr. Gulam Manji: Excellent point. So just to be clear, the APACT study did fail to meet its primary endpoint and hence gemcitabine and nab-paclitaxel were not indicated for patients in the adjuvant setting. The current standard of care are either modified FOLFIRINOX or gemcitabine combination with capecitabine. And those two regimens really remain a standard of care for patients. So what I do is for fit patients, I prefer modified FOLFIRINOX. However, in patients who are not as fit, gemcitabine in combination with capecitabine is the alternative.  Now, one could envision a scenario where gemcitabine and nab-paclitaxel may become relevant. It is, but only when I'm really pushed to do so, where I feel like there is no other regimen available optimally for a patient. And one could envision a scenario where you could have a patient who does not have the performance status to tolerate modified FOLFIRINOX and then you start that patient on gemcitabine in combination with capecitabine. However, I have experienced that that combination results in significant myelosuppression in patients in the United States. And then we have to do significant dose reductions or interruptions.  Now, in that case, where I feel like I'm reducing the dose of capecitabine to a point where the patient may not be potentially benefiting from that regimen, it's impossible to determine what dose would be efficacious when you're doing those dose reductions. That is the only scenario where I may be able to be pushed to consider gemcitabine and nab-paclitaxel, but only after also discussing with the patient the results of the current data and there being limited efficacy. Emily Zabor: That makes sense. So the treatment you would select would really depend on some patient characteristics and then how they do on the different treatments. Dr. Gulam Manji: Correct. Emily Zabor: So what do you think are the next steps for research in this area and in this disease?   Dr. Gulam Manji: I think that this clinical trial really demonstrated our inability to accurately pinpoint the time of disease recurrence using imaging modalities alone. And for patients who treat pancreas cancer, they would know that the recurrence patterns usually are either to the liver or to the peritoneum, or to the lung. However, in about 25% of the cases, the recurrence may be at the surgical site, and that's when things become tricky. After patients have undergone surgery, their scar tissue and the pancreas tumor is very dense, so it's difficult to determine that there's actually tumor growth. So that's where you really need help from other modalities. So should we get a PET scan? Is the patient symptomatic? Is a tumor marker going up in the absence of biliary obstruction? So all of those things need to be taken into account to truly pinpoint whether the patient has recurred or not. In peritoneal disease, you may need to ask the surgeons to help and have the patient undergo a laparoscopy to truly determine whether there is a peritoneal disease. And lastly, I think that incorporating ctDNA to better define whether there is a minimal residual disease will likely be a standard in the future. Emily Zabor: I see. Yeah, that makes sense. Incorporating some ctDNA biomarker information along with these really detailed clinical and possibly imaging assessments to determine recurrence seems like it would be really important in future trials to make sure you're capturing all of those recurrences accurately. Dr. Gulam Manji: Yeah, I think that that's critical before you can say that an adjuvant treatment is truly helping the patient. Emily Zabor: That's great. Well, I really learned a lot reading this article and speaking to you today. But before we end, is there anything else you'd like to share with our listeners?  Dr. Gulam Manji: Yeah, so I think we know that for a majority of patients who undergo curative resection, unfortunately, the disease recurs. And I think that that implies that, really, pancreas cancer is a systemic disease at the time of diagnosis. And despite aggressive adjuvant therapy, the median DFS, OS, and five-year survival rate show that we are impacting only a subset of patients with six additional months of chemotherapy. So I think that identifying predictive markers of response to systemic therapy, better selection of patients for surgery, perhaps using total upfront neoadjuvant therapy, an institution of maintenance therapy, and patients who are at high risk for recurrence, perhaps using ctDNA as a marker to determine who those high-risk patients are, all leads to help better design and identify patients who should really be treated systemically and patients who should undergo surgery. And lastly, with some glimmers of success from personalized vaccines may be on the horizon. And I'm hoping in the near future to treat minimal residual disease so that we can get the best outcome with minimal toxicity for our patients. Emily Zabor: That's great. That sounds like an exciting development for a disease that seems really tricky. Dr. Gulam Manji: Agreed. Emily Zabor: Well, thank you so much. It has been a pleasure speaking with you, Dr. Manji, and thank you so much for joining me today on this episode of JCO Article Insights.  This concludes the episode on the article “Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence?” Thank you for listening and please tune in for the next issue of JCO Article Insights.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Show Notes: Like, share and subscribe so you never miss an episode and leave a rating or review.  Guest Bio: Dr. Gulam Manji, MD, PhD is a medical oncologist at the Columbia University Irving Medical Center in New York.  Articles: Editorial: Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence? Original Report: Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial Find more articles from the April 10 issue.  

Drs Sumanta Pal and Scott Haake discuss the biology of kidney cancer and how to incorporate tissue biomarkers into prospective studies on renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984237). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources W. Kimryn Rathmell, MD, PhD, MMHC https://www.vumc.org/viiii/person/w-kimryn-rathmell-md-phd-mmhc Novel Emerging Biomarkers to Immunotherapy in Kidney Cancer https://pubmed.ncbi.nlm.nih.gov/34868351/ PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay https://pubmed.ncbi.nlm.nih.gov/32208115/ Oncogene-Specific Differences in Tumor Mutational Burden, PD-L1 Expression, and Outcomes From Immunotherapy in Non-Small Cell Lung Cancer https://pubmed.ncbi.nlm.nih.gov/34376553/ Multiomics in Primary and Metastatic Breast Tumors From the AURORA US Network Finds Microenvironment and Epigenetic Drivers of Metastasis https://pubmed.ncbi.nlm.nih.gov/36585450/ Avelumab Plus Axitinib Versus Sunitinib in Advanced Renal Cell Carcinoma: Biomarker Analysis of the Phase 3 JAVELIN Renal 101 Trial https://pubmed.ncbi.nlm.nih.gov/32895571/ Clinical Activity and Molecular Correlates of Response to Atezolizumab Alone or in Combination With Bevacizumab Versus Sunitinib in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/29867230/ Atezolizumab Plus Bevacizumab Versus Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (IMmotion151): A Multicentre, Open-Label, Phase 3, Randomised Controlled Trial https://pubmed.ncbi.nlm.nih.gov/31079938/ Insights Into the Genetic Basis of the Renal Cell Carcinomas From the Cancer Genome Atlas https://pubmed.ncbi.nlm.nih.gov/27330105/ Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study https://clinicaltrials.gov/ct2/show/NCT05361720

Drs Sumanta Pal and David A. Braun discuss the role of single-cell sequencing as a biomarker in renal cell carcinoma, how it is evolving, and how it might apply in other domains. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984238). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Single-Cell RNA Sequencing Technologies and Applications: A Brief Overview https://pubmed.ncbi.nlm.nih.gov/35352511/ Progressive Immune Dysfunction With Advancing Disease Stage in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/33711273/ Immune Checkpoint Inhibitors in Non-Conventional Histologies of Renal-Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/36758960/ Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/34261695/ Molecular Profiling in Early ER+ Breast Cancer to Aid Systemic Therapy Decisions https://pubmed.ncbi.nlm.nih.gov/36862337/ Dysbiosis of a Microbiota-Immune Metasystem in Critical Illness Is Associated With Nosocomial Infections https://pubmed.ncbi.nlm.nih.gov/36894652/ A Single-Cell Atlas Reveals Shared and Distinct Immune Responses and Metabolic Profiles in SARS-CoV-2 and HIV-1 Infections https://pubmed.ncbi.nlm.nih.gov/36992700/ Revealing the Vectors of Cellular Identity With Single-Cell Genomics https://pubmed.ncbi.nlm.nih.gov/27824854/ Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://pubmed.ncbi.nlm.nih.gov/32673417/

Episode 89: Alix Turoff MS, RD, CDN, CPT | Let's talk about Ozempic Show Notes: On this episode of the Alix Turoff Nutrition podcast, Alix is back with a new season! She starts the season off with a bang by talking about the medication that's on everyone's mind… Ozempic. She also discussed Mounjaro (tirzepatide). She's talking about everything from how these medications work, who they might be appropriate for, and the social media storm surrounding them. Research: Semaglutide for the treatment of obesity Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients with Type 2 Diabetes: The PIONEER 8 Trial Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension Safety of Semaglutide Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5 Semaglutide for the treatment of overweight and obesity: A review Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5 Clinical Impact of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist, on Obesity Management: A Review The Health at Every Size Paradigm and Obesity: Missing Empirical Evidence May Help Push the Reframing Obesity Debate Forward   Resources: Submit your questions for upcoming podcast episodes Get the 5 week Flexible Nutrition Starter Kit Apply for Alix's 12 week small group coaching program Apply for Alix's 1:1 coaching program Follow Alix on Instagram  Join Alix's private Facebook group Download your FREE Happy Hour Survival Guide Buy Alix's book on Amazon Shop my favorite products on Amazon Contact Alix via email   Be sure you're subscribed to this podcast to automatically receive your episodes!!!  If you enjoyed today's episode, I'd love it if you would take a minute to leave a rating and review! Subscribe to The Alix Turoff Nutrition Podcast Discount Codes: Built Bar: Use the code ALIX for 10% off your order Legion Athletics: Use the code Alix for 20% off your order  

Drs Michelle Kittleson and Biykem Bozkurt provide game-changing updates and insights on treating heart failure with reduced ejection fraction. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982148). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines https://pubmed.ncbi.nlm.nih.gov/35363499/ Effects of Enalapril on Mortality in Severe Congestive Heart Failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) https://pubmed.ncbi.nlm.nih.gov/2883575/ Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263228/ Safety, Tolerability and Efficacy of Up-titration of Guideline-Directed Medical Therapies for Acute Heart Failure (STRONG-HF): A Multinational, Open-Label, Randomised Trial https://pubmed.ncbi.nlm.nih.gov/36356631/

Drs Sumanta Pal and Martin Voss discuss second-line treatment of renal cell carcinoma, including current studies and agents used in the refractory setting. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968745). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma Treatment & Management https://emedicine.medscape.com/article/281340-treatment Comparative Effectiveness of Axitinib Versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61613-9/fulltext Cabozantinib Versus Everolimus in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/NEJMoa1510016 CANTATA: Primary Analysis of a Global, Randomized, Placebo (Pbo)-Controlled, Double-Blind Trial of Telaglenastat (CB-839) + Cabozantinib Versus Pbo + Cabozantinib in Advanced/Metastatic Renal Cell Carcinoma (mRCC) Patients (pts) Who Progressed on Immune Checkpoint Inhibitor (ICI) or Anti-Angiogenic Therapies. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4501 FDA Approves Tivozanib for Relapsed or Refractory Advanced Renal Cell Carcinoma https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma (TIVO-3): A Phase 3, Multicentre, Randomised, Controlled, Open-Label Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30735-1/fulltext Lenvatinib, Everolimus, and the Combination in Patients With Metastatic Renal Cell Carcinoma: A Randomised, Phase 2, Open-Label, Multicentre Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment (CONTACT-03) https://clinicaltrials.gov/ct2/show/NCT04338269 TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients With Metastatic Renal Cell Carcinoma https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(20)42472-X Kidney Cancer Research Summit https://kcrs.kidneycan.org/

Trials on heart failure, hypertension and lipid-lowering drugs, and the evolution of antithrombin and antiplatelet therapy are discussed in part 2 of cardiologists Bob Harrington and Mike Gibson's annual review. This podcast is intended for healthcare professionals only. To read a transcript or to comment, visit https://www.medscape.com/author/bob-harrington Lipid Lowering Safety, Tolerability and Efficacy of Up-Titration of Guideline-Directed Medical Therapies for Acute Heart Failure (STRONG-HF): A Multinational, Open-Label, Randomised, Trial https://doi.org/10.1016/S0140-6736(22)02076-1 Why Combination Lipid-Lowering Therapy Should Be Considered Early in the Treatment of Elevated LDL-C for CV Risk Reduction https://www.acc.org/latest-in-cardiology/articles/2022/06/01/12/11/why-combination-lipid-lowering-therapy-should-be-considered Incidental Coronary Artery Calcium: Opportunistic Screening of Prior Non-gated Chest CTs to Improve Statin Rates (NOTIFY-1 Project) https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.062746 Equivalent Impact of Elevated Lipoprotein(a) and Familial Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease https://doi.org/10.1016/j.jacc.2022.09.021 Comparative Effects of Low-Dose Rosuvastatin, Placebo and Dietary Supplements on Lipids and Inflammatory Biomarkers https://doi.org/10.1016/j.jacc.2022.10.013 Antihypertensive Drugs No Survival Advantage for Either Torsemide or Furosemide in HF: TRANSFORM-HF https://www.medscape.com/viewarticle/983611 Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events www.nejm.org/doi/full/10.1056/NEJMoa2212270 Antiplatelets Duration of Antiplatelet Therapy After Complex Percutaneous Coronary Intervention in Patients at High Bleeding Risk: A MASTER DAPT Trial Sub-analysis https://doi.org/10.1093/eurheartj/ehac284 PANTHER: Should Clopidogrel Become the 'New Aspirin' in CAD? https://www.medscape.com/viewarticle/980117 P2Y12 Inhibitor Versus Aspirin Monotherapy for Secondary Prevention of Cardiovascular Events: Meta-analysis of Randomized Trials https://doi.org/10.1093/ehjopen/oeac019 Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes https://doi.org/10.1056/nejmoa0904327 TCT-320 Pharmacokinetic and Pharmacodynamic Profile of PL-ASA, a Novel Phospholipid-Aspirin Complex Liquid Formulation, Compared to Enteric-Coated Aspirin at an 81-mg Dose – Results From a Prospective, Randomized, Crossover Study https://www.jacc.org/doi/10.1016/j.jacc.2021.09.1173 Pharmacokinetic and Pharmacodynamic Profile of a Novel Phospholipid Aspirin Formulation https://europepmc.org/article/pmc/pmc8773391 Antithrombins/Factor XI Rivaroxaban in Patients With a Recent Acute Coronary Syndrome https://www.nejm.org/doi/full/10.1056/nejmoa1112277 Genetically Determined FXI (Factor XI) Levels and Risk of Stroke https://doi.org/10.1161/strokeaha.118.022792 Factor XIa Inhibition With Asundexian After Acute Non-cardioembolic Ischaemic Stroke (PACIFIC-Stroke): an International, Randomised, Double-Blind, Placebo-Controlled, Phase 2b Trial https://doi.org/10.1016/s0140-6736(22)01588-4 Safety of the Oral Factor Xia Inhibitor Asundexian Compared With Apixaban in Patients With Atrial Fibrillation (PACIFIC-AF): a Multicentre, Randomised, Double-Blind, Double-Dummy, Dose-Finding Phase 2 Study https://doi.org/10.1016/S0140-6736(22)00456-1 A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction https://doi.org/10.1161/circulationaha.122.061612 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine Hear John Mandrola, MD's summary and perspective on the top cardiology news each week, on This Week in Cardiology https://www.medscape.com/twic Questions or feedback? Please contact news@medscape.net

Drs Sumanta Pal and Rana McKay discuss the use of biomarkers in treating patients with renal cell carcinoma to identify whose disease will recur and who will respond to therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968743). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma https://ascopubs.org/doi/10.1200/JCO.22.00219 The Detection of EpCAM+ and EpCAM­– Circulating Tumor Cells https://www.nature.com/articles/srep12270 Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768333/ ctDNA Guiding Adjuvant Immunotherapy in Urothelial Carcinoma https://www.nature.com/articles/s41586-021-03642-9 Clinical Activity and Molecular Correlates of Response to Atezolizumab Alone or in Combination With Bevacizumab Versus Sunitinib in Renal Cell Carcinoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721896/ Atezolizumab Plus Bevacizumab Versus Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (IMmotion151): A Multicentre, Open-Label, Phase 3, Randomised Controlled Trial https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(19)30723-8 Nivolumab Plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/nejmoa1712126 Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study https://clinicaltrials.gov/ct2/show/NCT05361720 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 Single-Cell RNA Sequencing of Human Kidney https://www.nature.com/articles/s41597-019-0351-8 Progressive Immune Dysfunction With Advancing Disease Stage in Renal Cell Carcinoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138872/

We're back with a new episode from the intestinal rehabilitation center at Cincinnati Children's Hospital. This time we're talking about peptides that enteroendocrine cells secretes with Drs. Helmrath and Wales. Hosts: Ellen Encisco, Cecilia Gigena Articles for further reading: Safety and Efficacy of Teduglutide in Pediatric Patients with Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study. https://aspenjournals.onlinelibrary.wiley.com/doi/full/10.1002/jpen.1690 Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome. https://pubmed.ncbi.nlm.nih.gov/27855998/ Experience With Teduglutide in Pediatric Short Bowel Syndrome: First Real-life Data https://pubmed.ncbi.nlm.nih.gov/32804906/ Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport. https://www.nature.com/articles/s41467-020-18536-z

This recording features audio versions of December 2022  Journal of Vascular and Interventional Radiology (JVIR) abstracts:Healthcare Disparities in Interventional Radiology ReadTransarterial Embolization of Neovascularity for Refractory Nighttime Shoulder Pain: A Multicenter, Open-Label, Feasibility Trial ReadUtilization of and Outcomes Associated with Intravascular Ultrasound During Deep Venous Stent Placement Among Medicare Beneficiaries ReadMidterm and Long-Term Outcomes Following Dedicated Endovenous Nitinol Stent Placement for Symptomatic Iliofemoral Venous Obstruction: Three- to 5-Year Results of the VIRTUS Study ReadCT-Guided Celiac Ganglion Block for Neurogenic Gastrointestinal Dysmotility ReadTransarterial Radioembolization for Hepatic Metastases of Pancreatic Adenocarcinoma: A Systematic Review ReadTransarterial Radioembolization Versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectible, Solitary Hepatocellular Carcinoma >/=3cm: A Propensity Score Matched Study ReadProstatic Artery Embolization Versus Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia: A Cost-Effectiveness Analysis ReadJVIR and SIR thank all those who helped record this episode:Host and audio editor:Daniel Kim, Edward Via College of Osteopathic Medicine, VirginiaAbstract readers:Daniel Kim, Edward Via College of Osteopathic Medicine, VirginiaRommell Noche, MS, Frank H. Netter MD School of Medicine at Quinnipiac University, ConnecticutLyanne Lu, University of California at Davis School of MedicineBridget Kowalczyk, Saint Louis University School of Medicine, MissouriDavid Clarfield, JVIR Managing EditorEric Cooper, University of Illinois College of Medicine, ChicagoSiddhi Hegde, Father Muller Medical College Hospital, India Benjamin Miller, Chicago Medical School, Illinois©  Society of Interventional RadiologySupport the show

Join Drs Cohen and Gibofsky as they step through a case of refractory psoriatic arthritis, discuss novel therapeutics, review latest clinical trials, and talk about the future in psoriatic arthritis. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/970786). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Psoriatic Arthritis Workup https://emedicine.medscape.com/article/2196539-workup#c6 GRAPPA Treatment Recommendations: 2021 Update https://www.jrheum.org/content/49/6_Suppl_1/52.long Methotrexate in Psoriasis and Psoriatic Arthritis https://www.jrheum.org/content/96/31 Psoriatic Arthritis Medication https://emedicine.medscape.com/article/2196539-medication#4 Effect of Secukinumab on the Different GRAPPA-OMERACT Core Domains in Psoriatic Arthritis: A Pooled Analysis of 2049 Patients https://www.jrheum.org/content/47/6/854 Three JAK Inhibitors Get Boxed Warnings, Modified Indications https://www.medscape.com/viewarticle/958024 Effect of Tofacitinib on Patient-Reported Outcomes in Patients With Active Psoriatic Arthritis and an Inadequate Response to Tumour Necrosis Factor Inhibitors in the Phase III, Randomised Controlled Trial: OPAL Beyond https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340607/ Upadacitinib in Patients With Psoriatic Arthritis and an Inadequate Response to Non-biological Therapy: 56-Week Data From the Phase 3 SELECT-PsA 1 Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524381/ Multicentre, Randomised, Open-Label, Parallel-Group Study Evaluating the Efficacy and Safety of Ixekizumab Versus Adalimumab in Patients With Psoriatic Arthritis Naïve to Biological Disease-Modifying Antirheumatic Drug: Final Results by Week 52 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509529/ Improvement in Patient-Reported Outcomes in Patients With Psoriatic Arthritis Treated With Upadacitinib Versus Placebo or Adalimumab: Results From SELECT-PsA 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572257/ Bimekizumab in Patients With Active Psoriatic Arthritis: Results From a 48-Week, Randomised, Double-Blind, Placebo-Controlled, Dose-Ranging Phase 2b Trial https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(19)33161-7 A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment https://clinicaltrials.gov/ct2/show/NCT04908189

In de aflevering van vandaag bespreken we alles omtrent hypernatriëmie. Een ondergewaardeerd probleem wat van groot belang is voor het welzijn en overleving van onze patiënt. Is een Natrium vanaf 143mmol/l  al schadelijk?Waarom verhoogd hypernatriëmie het risico op delier?Wat is het effect van hypernatriëmie op de hartfunctie en de beademingsduur?Wat is de behandeling van hypernatriëmie?Wat is het verschil tussen community acquired en IC-acquired hypernatriëmie?Wat is de link tussen hypernatriëmie en mortaliteit?Hoe snel mag je hypernatriëmie corrigeren?Wat is het effect van vrij water toediening?Moeten we wisselen van NaCl 0,9% naar Glucose 5%?- Sodium balance, not fluid balance, is associated with respiratory dysfunction in mechanically ventilated patients: a prospective, multicentre study- "Free water defecit calculation" - MdCalc- Hypernatremia in critically ill patients- ICU acquired hypernatremia treated by enteral free water – A retrospective cohort study- Hypernatremia in the Critically Ill Is an Independent Risk Factor for Mortality- The Development of Intensive Care Unit Acquired Hypernatremia Is Not Explained by Sodium Overload or Water Deficit: A Retrospective Cohort Study on Water Balance and Sodium Handling- Normal saline to dilute parenteral drugs and to keep catheters open is a major and preventable source of hypernatremia acquired in the intensive care unit- Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change- Renal Function is a Major Determinant of ICU-acquired Hypernatremia: A Balance Study on Sodium Handling- Saline versus 5% dextrose in water as a drug diluent for critically ill patients: a retrospective cohort study- Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot StudyBedankt voor het luisteren!Volg @intensiefdepodcast op InstagramVragen? intensiefdepodcast@gmail.com

https://psychiatry.dev/wp-content/uploads/speaker/post-9716.mp3?cb=1663478715.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Efficacy and safety of Lu AF35700 in treatment-resistant schizophrenia: A randomized, active-controlled trial with open-label extension – PubMed John M Kane etFull EntryEfficacy and safety of Lu AF35700 in treatment-resistant schizophrenia: A randomized, active-controlled trial with open-label extension – PubMed

Drs Sumanta Pal and Tian Zhang review the state of the data on adjuvant treatment with immunotherapy for patients with renal cell carcinoma, including where current clinical trials stand. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968737). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study https://clinicaltrials.gov/ct2/show/NCT03793166 The Role of Targeted Therapy in the Management of High-Risk Resected Kidney Cancer: What Have We Learned and How Will It Inform Future Adjuvant Trials https://journals.lww.com/journalppo/Abstract/2020/09000/The_Role_of_Targeted_Therapy_in_the_Management_of.3.aspx Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy https://www.nejm.org/doi/10.1056/NEJMoa1611406 Sutent (sunitinib) prescribing information https://labeling.pfizer.com/showlabeling.aspx?id=607 Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma (KEYNOTE-564) https://www.nejm.org/doi/full/10.1056/NEJMoa2106391 RAMPART: A Phase III Multi-arm Multi-stage Trial of Adjuvant Checkpoint Inhibitors in Patients With Resected Primary Renal Cell Carcinoma (RCC) at High or Intermediate Risk of Relapse https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520913/ A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy (IMmotion010) https://clinicaltrials.gov/ct2/show/NCT03024996 A Comparison of Sunitinib with Cabozantinib, Crizotinib, and Savolitinib for Treatment of Advanced Papillary Renal Cell Carcinoma: a Randomised, Open-Label, Phase 2 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687736/ A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney (CheckMate 914) https://clinicaltrials.gov/ct2/show/NCT03138512 PROSPER: Phase III RandOmized Study Comparing PERioperative nivolumab versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN EA8143). https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.TPS4596 Pembrolizumab as Post Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Results From 30-Month Follow-up of KEYNOTE-564 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.290 Leibovich RCC Model: Prediction of Progression After Radical Nephrectomy for patients With Clear Cell Renal Cell Carcinoma https://cancernomograms.com/nomograms/972 Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results From ASSURE, ECOG 2805 https://aacrjournals.org/clincancerres/article/21/18/4048/117759/Effects-of-Adjuvant-Sorafenib-and-Sunitinib-on

Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019 An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1 Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180 International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31 Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716 The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706 Twitter poll questions: What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877 What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305 What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057 Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/ OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf

Curious about tirzepatide and what it means for patients? Tirzepatide, a combination GLP-1 and GIP agonist, was just approved by the Food and Drug Administration for the treatment of diabetes. Tirzepatide has also gained attention for its weight-reducing effects. However, how does tirzepatide compare to other GLP-1 agonists? Is tirzepaide a GameChanger for type 2 diabetes management? Learn more with host, Geoff Wall.  The GameChanger Tirzepatide is the first in its class to hit the market and has been shown to be as or more effective than semaglutide in glycemic control and weight reduction.   Show Segments 00:00 – Introductions 01:15 – Type 2 Diabetes & Treatment 02:29 – Glucagon-like peptide-1 (GLP-1) Agonists 03:04 – Glucose-dependent insulinotropic polypeptide (GIP) Agonist   03:55 – Tirzepatide vs Semaglutide 14:27 -  Tirzepatide vs Insulin 21:15 – Retinopathy & Financial Considerations 22:30 – Closing Remarks  HostGeoff Wall, PharmD., BCPS, FCCP, CGP Professor of Pharmacy Practice, Drake University Internal Medicine/Critical Care, UnityPoint Health References and Resources Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes Once-Weekly Tirzeaptide Versus Once-Daily Insulin Degludec as Add-On to Metformin With or Without SGLT2 Inhibitors in Patients With Type 2 Diabetes (SURPASS-3): A Randomized, Open-Label, Parallel-Group, Phase 3 Trial  Efficacy and Safety of a Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide in Patients With Type 2 Diabetes (SURPASS-1): A Double-Blind, Randomised, Phase 3 Trial Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial Redeem your CPE or CME here CPE (Pharmacist)  CME (Physician)  Get a membership & earn CE for GameChangers Podcast episodes (30 mins/episode) Pharmacists: Get a membership Prescribers: Get a membership CE Information Learning Objectives Upon successful completion of this knowledge-based activity, participants should be able to: Describe the safety and efficacy of tirzepatide compared to GLP-1 agonists Discuss the use of tirzepatide compared to basal insulin for blood glucose control Select a patient who may be a candidate for tirzepatide therapy 0.05 CEU/0.5 HrUAN: 0107-0000-22-234-H01-P Initial release date: 06/27/2022 Expiration date: 06/27/2023 Additional CPE and CME details can be found here. 

Joseph Mikhael, MD, and Ashley Rosko, MD, discuss the role of comorbidities in multiple myeloma and stress the importance of shifting away from the sole use of age-based treatment decisions. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964338). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview International Myeloma Working Group Frailty Score Calculator http://www.myelomafrailtyscorecalculator.net/ R-MCI: Myeloma Comorbidity Index https://www.myelomacomorbidityindex.org/en_calc.html A Simplified Frailty Scale Predicts Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated in the FIRST (MM-020) Trial https://www.nature.com/articles/s41375-019-0539-0 Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline https://ascopubs.org/doi/full/10.1200/JCO.18.02096 Frailty in Older Adults: Evidence for a Phenotype https://academic.oup.com/biomedgerontology/article/56/3/M146/545770 Comprehensive Geriatric Assessment https://www.uptodate.com/contents/comprehensive-geriatric-assessment Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591827/

Joseph Mikhael, MD, and Peter Voorhees, MD, discuss frontline therapy for multiple myeloma and new options for both transplant-eligible and transplant-ineligible patients. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964337). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources International Myeloma Foundation https://www.myeloma.org/ Lenalidomide, Bortezomib, and Dexamethasone (RVD) Regimen for Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278911/pdf/i0018-5787-52-1-27.pdf Carfilzomib, Lenalidomide, and Dexamethasone Plus Transplant in Newly Diagnosed Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714092/ Maintenance With Daratumumab or Observation Following Treatment With Bortezomib, Thalidomide, and Dexamethasone With or Without Daratumumab and Autologous Stem-Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma (CASSIOPEIA): An Open-Label, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00428-9/fulltext Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone for Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial https://ashpublications.org/blood/article/136/8/936/454474/Daratumumab-lenalidomide-bortezomib-and Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of GRIFFIN After 24 Months of Maintenance https://ash.confex.com/ash/2021/webprogram/Paper149024.html Venetoclax or Placebo in Combination With Bortezomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (BELLINI): A Randomised, Double-Blind, Multicentre, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30525-8/fulltext Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone As Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial https://ash.confex.com/ash/2021/webprogram/Paper145097.html Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma https://ascopubs.org/doi/10.1200/JCO.21.01935 Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial https://www.thelancet.com/article/S1470-2045(20)30452-6/fulltext Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma The MANHATTAN Nonrandomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2778195 Carfilzomib or Bortezomib in Relapsed or Refractory Multiple Myeloma (ENDEAVOR): An Interim Overall Survival Analysis of an Open-Label, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30578-8/fulltext Carfilzomib With Cyclophosphamide and Dexamethasone or Lenalidomide and Dexamethasone Plus Autologous Transplantation or Carfilzomib Plus Lenalidomide and Dexamethasone, Followed by Maintenance With Carfilzomib Plus Lenalidomide or Lenalidomide Alone for Patients With Newly Diagnosed Multiple Myeloma (FORTE): A Randomised, Open-Label, Phase 2 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00535-0/fulltext Lenalidomide, Bortezomib, and Dexamethasone With Transplantation for Myeloma https://www.nejm.org/doi/full/10.1056/NEJMoa1611750

Dr. Justin Dunaway // #ClinicalTuesday // www.ptonice.com 

Drs Michael Saag and Constance Benson discuss antiretroviral therapy, maintenance, and switching. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/963238). The topics and discussions are planned, produced, and reviewed independently of our advertiser. This podcast is intended only for US healthcare professionals. Resources Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2021 Update https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf AIDS Clinical Trials Group https://actgnetwork.org/ Clarithromycin Therapy for Bacteremic Mycobacterium Avium Complex Disease https://www.acpjournals.org/doi/10.7326/0003-4819-121-12-199412150-00001?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed UC San Diego Medical Center https://healthlocations.ucsd.edu/san-diego/200-w.-arbor-drive-hospital Highlights from the Ryan White Clinical Conference https://www.hiv.gov/blog/long-acting-injectables-hold-promise-maintaining-viral-suppression-and-preventing-hiv Clinical Effectiveness of Integrase Strand Transfer Inhibitor–Based Antiretroviral Regimens Among Adults With Human Immunodeficiency Virus: A Collaboration of Cohort Studies in the United States and Canada https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492356/ Key Considerations and Recommendations for Early (Acute and Recent) HIV Infection https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/early-acute-and-recent-hiv-infection?view=full Rising Rates of Recent Preexposure Prophylaxis Exposure Among Men Having Sex with Men Newly Diagnosed With HIV: Antiviral Resistance Patterns and Treatment Outcomes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876422/ Long-acting Cabotegravir Plus Rilpivirine for Treatment in Adults With HIV-1 Infection: 96-week Results of the Randomised, Open-Label, Phase 3 FLAIR Study https://linkinghub.elsevier.com/retrieve/pii/S2352-3018(20)30340-4

Este é um podcast para médicos sob responsabilidade do Dr. Tiago Gil, médico anestesista CRMSP 157384 RQE 64871 A medicina é uma ciência que está em evolução e este podcast não deve ser utilizado como guia terapêutico. Esse episódio foi gravado como verdade até março de 2022 Referências Bibliográficas 1. Ekstrand J, Fattah C, Persson M, Cheng T, Nordanskog P, Åkeson J, et al. Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT). Int J Neuropsychopharmacol. 2021;1–11. 2. Veraart JKE, Smith-Apeldoorn SY, Spaans HP, Kamphuis J, Schoevers RA. Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review. J Affect Disord [Internet]. 2021;281(November 2020):82–9. Available from: https://doi.org/10.1016/j.jad.2020.11.123 3. Basso L, Bönke L, Aust S, Gärtner M, Heuser-Collier I, Otte C, et al. Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients. J Psychiatr Res [Internet]. 2020;123:1–8. Available from: https://doi.org/10.1016/j.jpsychires.2020.01.002

Drs Schapira and Gillespie begin this series by reviewing the current research on radiation options for early-stage breast cancer and how to discuss treatment options with patients. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/963162). The topics and discussions are planned, produced, and reviewed independently of our advertiser. This podcast is intended only for US healthcare professionals. Resources Radiation Therapy for the Whole Breast: Executive Summary of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline https://www.practicalradonc.org/article/S1879-8500(18)30051-1/fulltext Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526720/ Hypofractionated Breast Radiotherapy for 1 Week Versus 3 Weeks (FAST-Forward): 5-Year Efficacy and Late Normal Tissue Effects Results From a Multicentre, Non-inferiority, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext Partial-Breast Radiotherapy After Breast Conservation Surgery for Patients With Early Breast Cancer (UK IMPORT LOW trial): 5-Year Results From a Multicentre, Randomised, Controlled, Phase 3, Non-inferiority Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31145-5/fulltext External Beam Accelerated Partial Breast Irradiation Versus Whole Breast Irradiation After Breast Conserving Surgery in Women With Ductal Carcinoma In Situ and Node-Negative Breast Cancer (RAPID): A Randomised Controlled Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32515-2/fulltext Once Daily Versus Twice Daily External Beam Accelerated Partial Breast Irradiation: A Randomized Prospective Study https://www.redjournal.org/article/S0360-3016(20)34566-1/fulltext Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-term Results of the Randomized Phase III APBI-IMRT-Florence Trial https://ascopubs.org/doi/10.1200/JCO.20.00650 Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2422117 De-escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA) https://clinicaltrials.gov/ct2/show/NCT04852887 Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-term Follow-up of CALGB 9343 https://ascopubs.org/doi/10.1200/JCO.2012.45.2615 PRIME II Investigators. Breast-Conserving Surgery With or Without Irradiation in Women Aged 65 Years or Older With Early Breast Cancer (PRIME II): A Randomised Controlled Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71221-5/fulltext Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 https://jamanetwork.com/journals/jama/fullarticle/2653737 Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer (EORTC 10981-22023 AMAROS): A Randomised, Multicentre, Open-Label, Phase 3 Non-inferiority Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70460-7/fulltext Regional Lymph Nodes Radiation and Breast Cancer Related Lymphedema: Where We Stand https://www.redjournal.org/article/S0360-3016(21)00165-6/fulltext Event-Free Survival With Pembrolizumab in Early Triple-Negative Breast Cancer https://www.nejm.org/doi/10.1056/NEJMoa1910549

Drs Harrington and Gibson provide their annual roundup of what they consider the key cardiovascular trials of 2021. This podcast is intended for healthcare professionals only. To read a transcript or to comment, visit This podcast is intended for US healthcare professionals only. To read a full transcript of this episode or to comment please visit: https://www.medscape.com/viewarticle/963475 https://www.medscape.com/author/bob-harrington Antiplatelet Therapy Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease https://doi.org/10.1056/NEJMoa2102137 Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk https://doi.org/10.1056/NEJMoa2108749 Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI https://doi.org/10.1001/jama.2019.8145 Aspirin Versus Clopidogrel for Chronic Maintenance Monotherapy After Percutaneous Coronary Intervention (HOST-EXAM): An Investigator-Initiated, Prospective, Randomised, Open-Label, Multicentre Trial https://doi.org/10.1016/S0140-6736(21)01063-1 SGLT2 Inhibitors and GLP-1 Agonists Empagliflozin in Heart Failure with a Preserved Ejection Fraction https://www.nejm.org/doi/full/10.1056/NEJMoa2107038 Once-Weekly Semaglutide in Adults with Overweight or Obesity https://www.nejm.org/doi/full/10.1056/NEJMoa2032183 Cardiac Surgery and PCI Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke https://doi.org/10.1056/NEJMoa2101897 Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation https://doi.org/10.1056/NEJMoa2115961 Fractional Flow Reserve–Guided PCI as Compared with Coronary Bypass Surgery https://doi.org/10.1056/NEJMoa2112299 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine Hear John Mandrola, MD's summary and perspective on the top cardiology news each week, on This Week in Cardiology https://www.medscape.com/twic Questions or feedback? Please contact news@medscape.net

This episode features Benjamin Thomas (Palliative Care Service, Illawarra Shoalhaven Local Health District, Warrawong, NSW, Australia). Terminal delirium is a common symptom at the end of life, causing distress to patients and families. Traditional management for terminal delirium requires sedation, which limits interaction and rousability. This study is the first to report on the use of dexmedetomidine for the treatment of terminal delirium in palliative care, in a single arm open-label study. Dexmedetomidine, delivered by subcutaneous infusion, decreases delirium as measured by standardised tools, with increased patient interaction and rousability. Patients treated with dexmedetomidine are able to self-report comfort at the end of life, reassuring clinicians and families. Results from this study support further research into the use of dexmedetomidine in palliative care, particularly in comparison with standard care to determine efficacy. Family comfort with rousability at the end of life requires further exploration.

中国药监局 批准我国自主研发的长效GLP-1受体激动剂治疗2型糖尿病Cell子刊 4小时和6小时限时进食对体重和心血管代谢健康的影响Diabetes Obesity & Metabolism 严重低血糖与心血管事件发现的关系Gut 地中海饮食通过肠道菌群影响肥胖患者的胆固醇水平，不受能量的影响Nature子刊 光遗传学技术刺激脂肪产热来预防肥胖聚乙二醇洛塞那肽注射液（polyethylene glycol loxenatide）聚乙二醇洛塞那肽注射液（PEX168）是一种新型的、我国自主研发的、长效胰高血糖素样肽-1（GLP-1）受体激动剂，可促进葡萄糖依赖的胰岛素分泌，配合饮食控制和运动，单药或与二甲双胍联合，用于改善成人2型糖尿病患者的血糖控制。2019年5月中国国家药品监督管理局批准聚乙二醇洛塞那肽注射液上市，用于治疗2型糖尿病。《随机对照研究：聚乙二醇洛塞那肽注射液单药治疗中国人群2型糖尿病的疗效和安全性的3a期临床研究》Diabetes Obesity and Metabolism，2020年12月 (1)研究目的是评价聚乙二醇洛塞那肽注射液单药治疗中国2型糖尿病的疗效和安全性。这项多中心的、随机的、双盲的、安慰剂对照的3a期临床试验中，来自中日友好医院的研究人员招募了361名、糖化血红蛋白7.0%-10.5%、空腹血糖

中国药监局 批准我国自主研发的长效GLP-1受体激动剂治疗2型糖尿病Cell子刊 4小时和6小时限时进食对体重和心血管代谢健康的影响Diabetes Obesity & Metabolism 严重低血糖与心血管事件发现的关系Gut 地中海饮食通过肠道菌群影响肥胖患者的胆固醇水平，不受能量的影响Nature子刊 光遗传学技术刺激脂肪产热来预防肥胖聚乙二醇洛塞那肽注射液（polyethylene glycol loxenatide）聚乙二醇洛塞那肽注射液（PEX168）是一种新型的、我国自主研发的、长效胰高血糖素样肽-1（GLP-1）受体激动剂，可促进葡萄糖依赖的胰岛素分泌，配合饮食控制和运动，单药或与二甲双胍联合，用于改善成人2型糖尿病患者的血糖控制。2019年5月中国国家药品监督管理局批准聚乙二醇洛塞那肽注射液上市，用于治疗2型糖尿病。《随机对照研究：聚乙二醇洛塞那肽注射液单药治疗中国人群2型糖尿病的疗效和安全性的3a期临床研究》Diabetes Obesity and Metabolism，2020年12月 (1)研究目的是评价聚乙二醇洛塞那肽注射液单药治疗中国2型糖尿病的疗效和安全性。这项多中心的、随机的、双盲的、安慰剂对照的3a期临床试验中，来自中日友好医院的研究人员招募了361名、糖化血红蛋白7.0%-10.5%、空腹血糖

FDA 批准超速效赖脯胰岛素治疗糖尿病Diabetes Care 1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖Nature Review Cardiology SGLT2抑制剂：除血糖控制外的心血管益处机制Annals of Internal Medicine SGLT2抑制剂与糖尿病酮症酸中毒风险Cell ALK基因功能下调可以减肥超速效赖脯胰岛素（URLi）超速效赖脯胰岛素（URLi），在短效赖脯胰岛素的基础上改良的一种起效更快、持续时间更短的胰岛素，更大程度上模拟生理条件下、餐后胰岛素的释放曲线。超速效赖脯胰岛素与赖脯胰岛素相比，达到50%最大功效的时间分别为12.8分钟和25.4分钟，两者30分钟内的总暴露量分别为99.3pmol*h/L和34.8pmol*h/L。超速效赖脯胰岛素20分钟达到峰值，持续6小时。2020年6月，超速效赖脯胰岛素（LyumjevTM）已经被FDA批准上市。《PRONTO-T2D研究：超速效赖脯胰岛素与赖脯胰岛素在长效胰岛素基础上治疗2型糖尿病的3期临床研究》Diabetes Care，2020年6月 (1)评价赖脯胰岛素与超速效赖脯胰岛素（URLi）比较，在长效胰岛素基础上治疗2型糖尿病的疗效和安全性。共673位患者，在优化的、长效甘精胰岛素或长效德谷胰岛素的基础上，联合餐前赖脯胰岛素治疗8周后，患者随机分入餐前0-2分钟注射超速效赖脯胰岛素组、或普通赖脯胰岛素组。两种短效胰岛素均能改善患者糖化血红蛋白，治疗结束时糖化血红蛋白分别为6.92%和6.86%。在控制1小时和2小时餐后血糖的变化方面，超速效赖脯胰岛素优于赖脯胰岛素：餐后1小时两组差异为0.66 mmol/L，2小时两组差异为0.96 mmol/L。接受超速效赖脯胰岛素治疗的患者餐后30分钟至4.0小时内，餐后血糖偏移明显减少。两种治疗方法之间的总体治疗紧急不良事件，包括低血糖，发生率相似。结论：在2型糖尿病患者中，餐时注射的超速效赖脯胰岛素与餐前注射的赖脯胰岛素在控制糖化血红蛋白方面效果相当，但在餐后血糖控制方面优于赖脯胰岛素。《PRONTO-T1D研究：与赖脯胰岛素相比，超速效赖脯胰岛素改善了1型糖尿病患者餐后血糖控制》Diabetes Obesity Metabolism，2020年8月 (2)在一项为期26周的III期临床试验中，评估了超速效赖脯胰岛素（URLi）与赖脯胰岛素在成人1型糖尿病患者中的疗效和安全性。研究发现超速效赖脯胰岛素在控制糖化血红蛋白方面，不劣于赖脯胰岛素。餐时注射超速效赖脯胰岛素在减少餐时1小时和2小时餐后血糖方面明显更优秀：1小时两组血糖差异为1.55mmol/L， 2小时两组差异为1.73 mmol/L，餐后4小时低血糖发作降低37%（P = 0.013）。其他的不良反应发生率相似。结论：在1型糖尿病中，超速效赖脯胰岛素提供了良好的血糖控制，餐后血糖控制优于赖脯胰岛素。1型糖尿病的运动管理规律的运动对1型糖尿病儿童和青少年具有重要的健康和社交益处，应鼓励。有氧运动（步行、骑车）通常可降低血糖浓度，而无氧运动（全速跑、曲棍球、举重）通常会升高血糖，许多团体运动（足球、篮球、棒球）包含有氧和无氧运动。低血糖可能发生在运动期间或运动后不久，或者延迟至运动后数小时或睡眠时。高血糖可能发生在运动期间，或情绪激动时。建议运动前、运动30分钟、运动恢复期和睡前监测血糖。《1型糖尿病运动后血糖控制与残留的β细胞功能有关》Diabetes Care，2020年10月 (3)研究旨在评价剩余β细胞功能对1型糖尿病患者运动后血糖的影响。研究招募30名、1型糖尿病病史≥3年的参与者，首先盲法进行7天的自由生活数据采集；然后进行3小时混合餐试验评估C肽和胰高血糖素水平。使用C肽峰值将参与者分成极低C肽组（C肽浓度200 pmol/L）；最后，参与者完成45分钟在60%VO2峰值的运动，然后再进行48小时的连续血糖检测。在运动后12小时和24小时，高C肽组参与者中葡萄糖正常的时间显著高于其他两组的参与者（高C肽组：12小时 73.5%，24 h 76.3%；低C肽组：12小时43.6%，24小时52.3%；极低C肽组12小时40.6%，24小时 51.3%）。而且，高C肽组参与者中高血糖的时间显著低于其他两组，血糖的波动也更小（P < 0.01）。从运动前到运动后24小时连续血糖检测的结果发现：高C肽组的参与者血糖控制得更好了（正常血糖的时间增加了12.1%），但另外两组的血糖控制得更差了（正常血糖的时间减少了9.1%和16.2%）。结论：剩余的β细胞功能可能部分解释了1型糖尿病患者运动后血糖的个体间差异，量化C肽有助于为患者提供个性化、针对性的运动支持。《1型糖尿病与有氧运动：在长效基础胰岛素基础上，运动前单次口服果糖可降低运动性低血糖的风险》Diabetes Care，2020年8月 (4)虽然调整胰岛素是降低1型糖尿病患者运动相关性低血糖风险的既定策略，但对超长效基础胰岛素治疗的患者来说，这并不容易实现。目前的研究确定了1型糖尿病患者在运动前摄入果糖是否能降低因运动引起的低血糖的风险。研究中14名参与分别完成了两次60min的有氧自行车运动，一次在运动前30min服用20g果糖，一次不服用果糖。摄入果糖的情况下，患者60min平均只发生1次低血糖事件，而对照组在运动的约30分钟内发生6次低血糖事件，果糖将运动时低血糖的风险降低了87.8%。服用果糖的运动期间平均血糖为7.3mmol/L，对照组为5.5mmol/L。摄取果糖后30分钟内休息时，患者的乳酸水平较高，但运动期间即回到基线。结论：对于使用超长效胰岛素的1型糖尿病患者而言，运动前摄取果糖是一种简单可行、有效且耐受良好的策略，可以减轻运动引起的低血糖风险，同时避免高血糖。《1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖》Diabetes Care，2020年8月 (5)1型糖尿病中，心率变异性（HRV）降低可能是早期的自主神经功能障碍的一种表现；1型糖尿病患者，尤其是剧烈运动和长时间运动时，血糖会急剧变化，从而对心率变异性产生负面影响。本研究中，20名患有1型糖尿病的业余运动员9天骑行1500公里。研究出乎意料的发现，骑行的距离越长，高血糖时间越长，低血糖时间越短，同时夜间心率变异性越低；这可能和副交感神经张力降低有关。而且在这一过程中，胰岛素的使用没有改变，从饮食中摄入的碳水化合物也没有变化减少。结论：在患有1型糖尿病的运动爱好者中，长时间中高强度运动加重了高血糖，而高血糖与副交感神经及心脏功能相关；考虑潜在的对心脏的有害后果，未来的工作应该集中在理解和管理运动引起的高血糖现象。《1型糖尿病与中高强度运动：在运动前，采用长效胰岛素和胰岛素泵混合方案》Lancet Diabetes & Endocrinology，2020年6月 (6)使用持续皮下注射胰岛素泵（CSII）的1型糖尿病患者通常会在长时间运动前移除泵，但这种方法可能会增加高血糖和酮症的风险。该研究目的是评估一种混合方法的有效性和安全性，即通过胰岛素泵混合德谷胰岛素qd（一种长效胰岛素）提供每日必须的基础胰岛素治疗。这是一个单中心、开放标签、概念验证、随机交叉试验中，招募了平时规律使用胰岛素泵的1型糖尿病患者，开放标签分入单用胰岛素泵组和胰岛素泵联合长效胰岛素治疗组中，两组患者均在运动前60分钟停止胰岛素泵，运动后立即重新连接。与通常的胰岛素泵方案相比，混合胰岛素泵方案的参与者在中高强度运动后6小时内，血糖稳定（4-10mmol/L）的时间显著延长；在家运动时的高血糖持续时间更短。两种干预措施低血糖时间和低血糖事件方面没有显著差异。结论：清晨注射一次长效胰岛素和胰岛素泵的混合方案似乎对有规律运动习惯的1型糖尿病成人更加安全有效的。小羽点评：1型糖尿病病患者的残余β细胞功能和自主神经功能障碍均会影响患者运动后的血糖。β细胞残余功能越差，血糖波动越大；长时间中高强度的运动，副交感神经张力降低，引发高血糖。为了更高的减少运动后高血糖，可以采用长效胰岛素和胰岛素泵混合方案；为了减少运动相关低血糖时间，可以在运动前服用果糖。2型糖尿病的药物治疗-SGLT2抑制剂钠-葡萄糖协同转运蛋白2（SGLT2）表达于肾近端小管，介导约90%的滤过葡萄糖的重吸收。SGLT2抑制剂促进肾脏对葡萄糖的排泄，因此可降低血糖、降低血压和体重，通常不会导致低血糖。SGLT2最常见的副作用为外阴阴道假丝酵母菌感染及低血压。对于合并糖尿病肾病、心力衰竭和冠心病的患者，可考虑优先使用。在《内分泌科星期五 Episode 5》中，我们聊到了SGLT2抑制剂在1型糖尿病患者中的应用，不知道各位听众是否还记得。由于SGLT2抑制剂有增加1型糖尿病患者酮症酸中毒的风险，因此欧洲仅批准了SGTL2抑制剂用于BMI>27kg/m2的1型糖尿病患者。《队列研究：SGLT2抑制剂与糖尿病酮症酸中毒风险》Annals of Internal Medicine，2020年9月 (7)研究旨在评估SGLT-2抑制剂与DPP-4抑制剂相比，是否增加2型糖尿病患者酮症酸中毒的风险。研究纳入20757名新使用SGLT-2抑制剂的患者和20757名新使用DPP-4抑制剂的患者。在370 454人年的随访中，共发生了521例酮症酸中毒。与DPP-4抑制剂相比，SGLT-2抑制剂与酮症酸中毒风险增加相关。其中，达格列净的风险比为1.86；恩格列净的风险比为2.52；卡格列净的风险比3.58。这种关联性与年龄和性别无关，在曾接受过胰岛素治疗的人群中，这种风险风险似乎更低。结论：SGLT-2抑制剂使用后酮症酸中毒风险增加近3倍，不同药物的风险比略有不同。《SGLT2抑制剂：除血糖控制外的心血管益处机制》Nature Review Cardiology，2020年7月(8)SGLT2抑制剂除了控制血糖，也可以改善心血管和肾脏结局，且获益扩展到有射血分数降低的心功能不全的非糖尿病患者中。其中的机制可能包括：（1）早期尿钠与血浆体积减少、随之而来的血细胞比积升高、血管功能改善、血压降低和组织钠的变化都可能发挥作用；（2）减少脂肪组织介导的炎症反应和炎性细胞因子的生产，心脏和肾脏转向酮体代谢，减少氧化应激，降低尿酸，减少肾小球渗透压和蛋白尿，抑制晚期糖基化产物生成。《EMPEROR-Reduce研究：恩格列净治疗心衰患者的心血管和肾脏结局》New England Journal of Medicine，2020年8月 (9)这项双盲试验中，随机分配3730名II、III或IV型心衰、射血分数≤40%的患者，除推荐治疗外，随机接受恩格列净10mg qd或安慰剂治疗。随访16个月，恩格列净组和安慰剂组中，主要终点事件（心血管死亡和心衰住院）的发生率分别为19.4%和24.7%（风险比0.75，P < 0.001）。无论是否患有糖尿病，结果是一致的。两组中肾小球滤过率下降的幅度分别为-0.55ml/min和-2.28ml/min（P < 0.001）。应用恩格列净无并发症的生殖道感染发生率更高。结论：无论是否合并糖尿病，射血分数≤40%的心力衰竭患者加用恩格列净可以降低心血管死亡或心衰住院的风险。《DECLARE-TIMI 58研究的探索性分析：达格列净与2型糖尿病患者的心脏、肾脏和四肢的预后的关系》Circulation，2020年8月 (10)有研究显示SGLT2抑制剂增加2型糖尿病的截肢的风险。在这项探索性分析中，纳入了DECLARE-TIMI 58研究中的、17 160例2型糖尿病患者，6%患有外周动脉疾病PAD。主要疗效结果为MACE(心血管[CV]死亡、心肌梗死、卒中)、CV死亡/HHF和肾脏疾病进展。截肢、外周血管重建和肢体缺血不良事件由盲的审稿人进行现场报道和分类。患有外周动脉疾病的患者，死亡、心肌梗死、卒中（风险比1.23）、心血管死亡、心衰住院（风险比1.60）、肾脏疾病进展（风险比1.60）和截肢（风险比8.37）的风险显著升高。无论是否患有外周动脉疾病，服用达格列净后，心血管死亡、心衰在入院的相对风险均降低（风险比 0.86和0.82，p=0.79），肾脏疾病进展相对风险也降低（风险比0.78和0.76，P=0.84）。随访过程中，共记录到了560例患者的肢体缺血事件、和407例截肢事件。总体而言，使用达格列净与安慰剂相比，肢体缺血不良事件和截肢的风险没有统计学差异（风险比1.07和1.09）。结论：有外周动脉疾病的患者发生心血管死亡、心衰入院和肾脏结局的风险更高，使用达格列净能够获益；但与肢体缺血不良事件没有显著相关性。《VERTIS CV研究：埃格列净对2型糖尿病、冠心病患者的心血管事件结局的影响》New England Journal of Medicine，2020年9月 (11)这项多中心、双盲试验中，随机将8246名患有2型糖尿病和冠心病的患者，分配至埃格列净5mg qd、埃格列净15mg qd或安慰剂组。平均随访3年半，埃格列净组和安慰剂组均有11.9%的患者出现了不良心血管事件。埃格列净组和安慰剂组，分别有8.1%和9.1%的参与者死于心血管疾病或因心衰恶化住院（P=0.11），肾脏原因死亡、肾脏替代治疗或肌酐水平上升2倍的发生率也没有统计学差异。结论：在患有2型糖尿病和动脉粥样硬化性心血管疾病的患者中，埃格列净在主要不良心血管事件方面并不逊于安慰剂。胖基因《基础研究：在瘦的人群中定义ALK基因》Cell，2020年6月 (12)为研究肥胖的遗传易感性，但我们对健康的瘦的人群（BMI值最低的6个百分位数）进行了全基因组关联分析研究（GWAS），发现间变性淋巴瘤激酶（ALK）是一个候选的“瘦”基因。下丘脑神经元中的表达的ALK，通过交感神经对脂肪组织分解作用的影响，来控制能量的消耗。ALK突变可以增强机体的分解代谢能力，从而有效抵抗体重增加。在果蝇中，RNAi介导的ALK基因敲除，可以降低甘油三酯水平。在小鼠中，ALK基因缺失导致瘦的动物对饮食诱导的肥胖、和瘦素突变诱导的肥胖，均具有显著的抵抗能力。结论：这项遗传和机制实验确定ALK是一个胖基因，参与抵抗体重增加。小羽点评：ALK抑制剂已经用于癌症的治疗了。如果在可以关闭ALK或使ALK基因功能下调，那么是否能够帮助我们保持苗条，甚至减重呢？参考文献1.Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D. Diabetes Care. 2020.2.Klaff L, Cao D, Dellva MA, Tobian J, Miura J, Dahl D, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. 2020.3.Taylor GS, Smith K, Capper TE, Scragg JH, Bashir A, Flatt A, et al. Postexercise Glycemic Control in Type 1 Diabetes Is Associated With Residual β-Cell Function. Diabetes Care. 2020;43(10):2362-70.4.Kosinski C, Herzig D, Laesser CI, Nakas CT, Melmer A, Vogt A, et al. A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study. Diabetes Care. 2020.5.Lespagnol E, Bocock O, Heyman J, Gamelin FX, Berthoin S, Pereira B, et al. In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in a State of Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability. Diabetes Care. 2020.6.Aronson R, Li A, Brown RE, McGaugh S, Riddell MC. Flexible insulin therapy with a hybrid regimen of insulin degludec and continuous subcutaneous insulin infusion with pump suspension before exercise in physically active adults with type 1 diabetes (FIT Untethered): a single-centre, open-label, proof-of-concept, randomised crossover trial. Lancet Diabetes Endocrinol. 2020;8(6):511-23.7.Douros A, Lix LM, Fralick M, Dell'Aniello S, Shah BR, Ronksley PE, et al. Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Ann Intern Med. 2020;173(6):417-25.8.Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020.9.Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. New England Journal of Medicine. 2020;383(15):1413-24.10.Bonaca MP, Wiviott SD, Zelniker TA, Mosenzon O, Bhatt DL, Leiter LA, et al. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58. Circulation. 2020;142(8):734-47.11.Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-35.12.Orthofer M, Valsesia A, Magi R, Wang QP, Kaczanowska J, Kozieradzki I, et al. Identification of ALK in Thinness. Cell. 2020;181(6):1246-62 e22.

FDA 批准超速效赖脯胰岛素治疗糖尿病Diabetes Care 1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖Nature Review Cardiology SGLT2抑制剂：除血糖控制外的心血管益处机制Annals of Internal Medicine SGLT2抑制剂与糖尿病酮症酸中毒风险Cell ALK基因功能下调可以减肥超速效赖脯胰岛素（URLi）超速效赖脯胰岛素（URLi），在短效赖脯胰岛素的基础上改良的一种起效更快、持续时间更短的胰岛素，更大程度上模拟生理条件下、餐后胰岛素的释放曲线。超速效赖脯胰岛素与赖脯胰岛素相比，达到50%最大功效的时间分别为12.8分钟和25.4分钟，两者30分钟内的总暴露量分别为99.3pmol*h/L和34.8pmol*h/L。超速效赖脯胰岛素20分钟达到峰值，持续6小时。2020年6月，超速效赖脯胰岛素（LyumjevTM）已经被FDA批准上市。《PRONTO-T2D研究：超速效赖脯胰岛素与赖脯胰岛素在长效胰岛素基础上治疗2型糖尿病的3期临床研究》Diabetes Care，2020年6月 (1)评价赖脯胰岛素与超速效赖脯胰岛素（URLi）比较，在长效胰岛素基础上治疗2型糖尿病的疗效和安全性。共673位患者，在优化的、长效甘精胰岛素或长效德谷胰岛素的基础上，联合餐前赖脯胰岛素治疗8周后，患者随机分入餐前0-2分钟注射超速效赖脯胰岛素组、或普通赖脯胰岛素组。两种短效胰岛素均能改善患者糖化血红蛋白，治疗结束时糖化血红蛋白分别为6.92%和6.86%。在控制1小时和2小时餐后血糖的变化方面，超速效赖脯胰岛素优于赖脯胰岛素：餐后1小时两组差异为0.66 mmol/L，2小时两组差异为0.96 mmol/L。接受超速效赖脯胰岛素治疗的患者餐后30分钟至4.0小时内，餐后血糖偏移明显减少。两种治疗方法之间的总体治疗紧急不良事件，包括低血糖，发生率相似。结论：在2型糖尿病患者中，餐时注射的超速效赖脯胰岛素与餐前注射的赖脯胰岛素在控制糖化血红蛋白方面效果相当，但在餐后血糖控制方面优于赖脯胰岛素。《PRONTO-T1D研究：与赖脯胰岛素相比，超速效赖脯胰岛素改善了1型糖尿病患者餐后血糖控制》Diabetes Obesity Metabolism，2020年8月 (2)在一项为期26周的III期临床试验中，评估了超速效赖脯胰岛素（URLi）与赖脯胰岛素在成人1型糖尿病患者中的疗效和安全性。研究发现超速效赖脯胰岛素在控制糖化血红蛋白方面，不劣于赖脯胰岛素。餐时注射超速效赖脯胰岛素在减少餐时1小时和2小时餐后血糖方面明显更优秀：1小时两组血糖差异为1.55mmol/L， 2小时两组差异为1.73 mmol/L，餐后4小时低血糖发作降低37%（P = 0.013）。其他的不良反应发生率相似。结论：在1型糖尿病中，超速效赖脯胰岛素提供了良好的血糖控制，餐后血糖控制优于赖脯胰岛素。1型糖尿病的运动管理规律的运动对1型糖尿病儿童和青少年具有重要的健康和社交益处，应鼓励。有氧运动（步行、骑车）通常可降低血糖浓度，而无氧运动（全速跑、曲棍球、举重）通常会升高血糖，许多团体运动（足球、篮球、棒球）包含有氧和无氧运动。低血糖可能发生在运动期间或运动后不久，或者延迟至运动后数小时或睡眠时。高血糖可能发生在运动期间，或情绪激动时。建议运动前、运动30分钟、运动恢复期和睡前监测血糖。《1型糖尿病运动后血糖控制与残留的β细胞功能有关》Diabetes Care，2020年10月 (3)研究旨在评价剩余β细胞功能对1型糖尿病患者运动后血糖的影响。研究招募30名、1型糖尿病病史≥3年的参与者，首先盲法进行7天的自由生活数据采集；然后进行3小时混合餐试验评估C肽和胰高血糖素水平。使用C肽峰值将参与者分成极低C肽组（C肽浓度200 pmol/L）；最后，参与者完成45分钟在60%VO2峰值的运动，然后再进行48小时的连续血糖检测。在运动后12小时和24小时，高C肽组参与者中葡萄糖正常的时间显著高于其他两组的参与者（高C肽组：12小时 73.5%，24 h 76.3%；低C肽组：12小时43.6%，24小时52.3%；极低C肽组12小时40.6%，24小时 51.3%）。而且，高C肽组参与者中高血糖的时间显著低于其他两组，血糖的波动也更小（P < 0.01）。从运动前到运动后24小时连续血糖检测的结果发现：高C肽组的参与者血糖控制得更好了（正常血糖的时间增加了12.1%），但另外两组的血糖控制得更差了（正常血糖的时间减少了9.1%和16.2%）。结论：剩余的β细胞功能可能部分解释了1型糖尿病患者运动后血糖的个体间差异，量化C肽有助于为患者提供个性化、针对性的运动支持。《1型糖尿病与有氧运动：在长效基础胰岛素基础上，运动前单次口服果糖可降低运动性低血糖的风险》Diabetes Care，2020年8月 (4)虽然调整胰岛素是降低1型糖尿病患者运动相关性低血糖风险的既定策略，但对超长效基础胰岛素治疗的患者来说，这并不容易实现。目前的研究确定了1型糖尿病患者在运动前摄入果糖是否能降低因运动引起的低血糖的风险。研究中14名参与分别完成了两次60min的有氧自行车运动，一次在运动前30min服用20g果糖，一次不服用果糖。摄入果糖的情况下，患者60min平均只发生1次低血糖事件，而对照组在运动的约30分钟内发生6次低血糖事件，果糖将运动时低血糖的风险降低了87.8%。服用果糖的运动期间平均血糖为7.3mmol/L，对照组为5.5mmol/L。摄取果糖后30分钟内休息时，患者的乳酸水平较高，但运动期间即回到基线。结论：对于使用超长效胰岛素的1型糖尿病患者而言，运动前摄取果糖是一种简单可行、有效且耐受良好的策略，可以减轻运动引起的低血糖风险，同时避免高血糖。《1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖》Diabetes Care，2020年8月 (5)1型糖尿病中，心率变异性（HRV）降低可能是早期的自主神经功能障碍的一种表现；1型糖尿病患者，尤其是剧烈运动和长时间运动时，血糖会急剧变化，从而对心率变异性产生负面影响。本研究中，20名患有1型糖尿病的业余运动员9天骑行1500公里。研究出乎意料的发现，骑行的距离越长，高血糖时间越长，低血糖时间越短，同时夜间心率变异性越低；这可能和副交感神经张力降低有关。而且在这一过程中，胰岛素的使用没有改变，从饮食中摄入的碳水化合物也没有变化减少。结论：在患有1型糖尿病的运动爱好者中，长时间中高强度运动加重了高血糖，而高血糖与副交感神经及心脏功能相关；考虑潜在的对心脏的有害后果，未来的工作应该集中在理解和管理运动引起的高血糖现象。《1型糖尿病与中高强度运动：在运动前，采用长效胰岛素和胰岛素泵混合方案》Lancet Diabetes & Endocrinology，2020年6月 (6)使用持续皮下注射胰岛素泵（CSII）的1型糖尿病患者通常会在长时间运动前移除泵，但这种方法可能会增加高血糖和酮症的风险。该研究目的是评估一种混合方法的有效性和安全性，即通过胰岛素泵混合德谷胰岛素qd（一种长效胰岛素）提供每日必须的基础胰岛素治疗。这是一个单中心、开放标签、概念验证、随机交叉试验中，招募了平时规律使用胰岛素泵的1型糖尿病患者，开放标签分入单用胰岛素泵组和胰岛素泵联合长效胰岛素治疗组中，两组患者均在运动前60分钟停止胰岛素泵，运动后立即重新连接。与通常的胰岛素泵方案相比，混合胰岛素泵方案的参与者在中高强度运动后6小时内，血糖稳定（4-10mmol/L）的时间显著延长；在家运动时的高血糖持续时间更短。两种干预措施低血糖时间和低血糖事件方面没有显著差异。结论：清晨注射一次长效胰岛素和胰岛素泵的混合方案似乎对有规律运动习惯的1型糖尿病成人更加安全有效的。小羽点评：1型糖尿病病患者的残余β细胞功能和自主神经功能障碍均会影响患者运动后的血糖。β细胞残余功能越差，血糖波动越大；长时间中高强度的运动，副交感神经张力降低，引发高血糖。为了更高的减少运动后高血糖，可以采用长效胰岛素和胰岛素泵混合方案；为了减少运动相关低血糖时间，可以在运动前服用果糖。2型糖尿病的药物治疗-SGLT2抑制剂钠-葡萄糖协同转运蛋白2（SGLT2）表达于肾近端小管，介导约90%的滤过葡萄糖的重吸收。SGLT2抑制剂促进肾脏对葡萄糖的排泄，因此可降低血糖、降低血压和体重，通常不会导致低血糖。SGLT2最常见的副作用为外阴阴道假丝酵母菌感染及低血压。对于合并糖尿病肾病、心力衰竭和冠心病的患者，可考虑优先使用。在《内分泌科星期五 Episode 5》中，我们聊到了SGLT2抑制剂在1型糖尿病患者中的应用，不知道各位听众是否还记得。由于SGLT2抑制剂有增加1型糖尿病患者酮症酸中毒的风险，因此欧洲仅批准了SGTL2抑制剂用于BMI>27kg/m2的1型糖尿病患者。《队列研究：SGLT2抑制剂与糖尿病酮症酸中毒风险》Annals of Internal Medicine，2020年9月 (7)研究旨在评估SGLT-2抑制剂与DPP-4抑制剂相比，是否增加2型糖尿病患者酮症酸中毒的风险。研究纳入20757名新使用SGLT-2抑制剂的患者和20757名新使用DPP-4抑制剂的患者。在370 454人年的随访中，共发生了521例酮症酸中毒。与DPP-4抑制剂相比，SGLT-2抑制剂与酮症酸中毒风险增加相关。其中，达格列净的风险比为1.86；恩格列净的风险比为2.52；卡格列净的风险比3.58。这种关联性与年龄和性别无关，在曾接受过胰岛素治疗的人群中，这种风险风险似乎更低。结论：SGLT-2抑制剂使用后酮症酸中毒风险增加近3倍，不同药物的风险比略有不同。《SGLT2抑制剂：除血糖控制外的心血管益处机制》Nature Review Cardiology，2020年7月(8)SGLT2抑制剂除了控制血糖，也可以改善心血管和肾脏结局，且获益扩展到有射血分数降低的心功能不全的非糖尿病患者中。其中的机制可能包括：（1）早期尿钠与血浆体积减少、随之而来的血细胞比积升高、血管功能改善、血压降低和组织钠的变化都可能发挥作用；（2）减少脂肪组织介导的炎症反应和炎性细胞因子的生产，心脏和肾脏转向酮体代谢，减少氧化应激，降低尿酸，减少肾小球渗透压和蛋白尿，抑制晚期糖基化产物生成。《EMPEROR-Reduce研究：恩格列净治疗心衰患者的心血管和肾脏结局》New England Journal of Medicine，2020年8月 (9)这项双盲试验中，随机分配3730名II、III或IV型心衰、射血分数≤40%的患者，除推荐治疗外，随机接受恩格列净10mg qd或安慰剂治疗。随访16个月，恩格列净组和安慰剂组中，主要终点事件（心血管死亡和心衰住院）的发生率分别为19.4%和24.7%（风险比0.75，P < 0.001）。无论是否患有糖尿病，结果是一致的。两组中肾小球滤过率下降的幅度分别为-0.55ml/min和-2.28ml/min（P < 0.001）。应用恩格列净无并发症的生殖道感染发生率更高。结论：无论是否合并糖尿病，射血分数≤40%的心力衰竭患者加用恩格列净可以降低心血管死亡或心衰住院的风险。《DECLARE-TIMI 58研究的探索性分析：达格列净与2型糖尿病患者的心脏、肾脏和四肢的预后的关系》Circulation，2020年8月 (10)有研究显示SGLT2抑制剂增加2型糖尿病的截肢的风险。在这项探索性分析中，纳入了DECLARE-TIMI 58研究中的、17 160例2型糖尿病患者，6%患有外周动脉疾病PAD。主要疗效结果为MACE(心血管[CV]死亡、心肌梗死、卒中)、CV死亡/HHF和肾脏疾病进展。截肢、外周血管重建和肢体缺血不良事件由盲的审稿人进行现场报道和分类。患有外周动脉疾病的患者，死亡、心肌梗死、卒中（风险比1.23）、心血管死亡、心衰住院（风险比1.60）、肾脏疾病进展（风险比1.60）和截肢（风险比8.37）的风险显著升高。无论是否患有外周动脉疾病，服用达格列净后，心血管死亡、心衰在入院的相对风险均降低（风险比 0.86和0.82，p=0.79），肾脏疾病进展相对风险也降低（风险比0.78和0.76，P=0.84）。随访过程中，共记录到了560例患者的肢体缺血事件、和407例截肢事件。总体而言，使用达格列净与安慰剂相比，肢体缺血不良事件和截肢的风险没有统计学差异（风险比1.07和1.09）。结论：有外周动脉疾病的患者发生心血管死亡、心衰入院和肾脏结局的风险更高，使用达格列净能够获益；但与肢体缺血不良事件没有显著相关性。《VERTIS CV研究：埃格列净对2型糖尿病、冠心病患者的心血管事件结局的影响》New England Journal of Medicine，2020年9月 (11)这项多中心、双盲试验中，随机将8246名患有2型糖尿病和冠心病的患者，分配至埃格列净5mg qd、埃格列净15mg qd或安慰剂组。平均随访3年半，埃格列净组和安慰剂组均有11.9%的患者出现了不良心血管事件。埃格列净组和安慰剂组，分别有8.1%和9.1%的参与者死于心血管疾病或因心衰恶化住院（P=0.11），肾脏原因死亡、肾脏替代治疗或肌酐水平上升2倍的发生率也没有统计学差异。结论：在患有2型糖尿病和动脉粥样硬化性心血管疾病的患者中，埃格列净在主要不良心血管事件方面并不逊于安慰剂。胖基因《基础研究：在瘦的人群中定义ALK基因》Cell，2020年6月 (12)为研究肥胖的遗传易感性，但我们对健康的瘦的人群（BMI值最低的6个百分位数）进行了全基因组关联分析研究（GWAS），发现间变性淋巴瘤激酶（ALK）是一个候选的“瘦”基因。下丘脑神经元中的表达的ALK，通过交感神经对脂肪组织分解作用的影响，来控制能量的消耗。ALK突变可以增强机体的分解代谢能力，从而有效抵抗体重增加。在果蝇中，RNAi介导的ALK基因敲除，可以降低甘油三酯水平。在小鼠中，ALK基因缺失导致瘦的动物对饮食诱导的肥胖、和瘦素突变诱导的肥胖，均具有显著的抵抗能力。结论：这项遗传和机制实验确定ALK是一个胖基因，参与抵抗体重增加。小羽点评：ALK抑制剂已经用于癌症的治疗了。如果在可以关闭ALK或使ALK基因功能下调，那么是否能够帮助我们保持苗条，甚至减重呢？参考文献1.Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D. Diabetes Care. 2020.2.Klaff L, Cao D, Dellva MA, Tobian J, Miura J, Dahl D, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. 2020.3.Taylor GS, Smith K, Capper TE, Scragg JH, Bashir A, Flatt A, et al. Postexercise Glycemic Control in Type 1 Diabetes Is Associated With Residual β-Cell Function. Diabetes Care. 2020;43(10):2362-70.4.Kosinski C, Herzig D, Laesser CI, Nakas CT, Melmer A, Vogt A, et al. A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study. Diabetes Care. 2020.5.Lespagnol E, Bocock O, Heyman J, Gamelin FX, Berthoin S, Pereira B, et al. In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in a State of Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability. Diabetes Care. 2020.6.Aronson R, Li A, Brown RE, McGaugh S, Riddell MC. Flexible insulin therapy with a hybrid regimen of insulin degludec and continuous subcutaneous insulin infusion with pump suspension before exercise in physically active adults with type 1 diabetes (FIT Untethered): a single-centre, open-label, proof-of-concept, randomised crossover trial. Lancet Diabetes Endocrinol. 2020;8(6):511-23.7.Douros A, Lix LM, Fralick M, Dell'Aniello S, Shah BR, Ronksley PE, et al. Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Ann Intern Med. 2020;173(6):417-25.8.Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020.9.Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. New England Journal of Medicine. 2020;383(15):1413-24.10.Bonaca MP, Wiviott SD, Zelniker TA, Mosenzon O, Bhatt DL, Leiter LA, et al. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58. Circulation. 2020;142(8):734-47.11.Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-35.12.Orthofer M, Valsesia A, Magi R, Wang QP, Kaczanowska J, Kozieradzki I, et al. Identification of ALK in Thinness. Cell. 2020;181(6):1246-62 e22.

This poster was presented by Dr. Blauvelt and colleagues at the 2020 American Academy of Dermatology virtual annual meeting. This over is provided by Dr. Steve Feldman.

Ted Kaptchuk, professor of medicine at Harvard Medical school - and leading placebo researcher, has just published an analysis on bmj.com describing the effect of open label placebo - placebos that patient's know are placebos, but still seem to have some clinical effect. Ted joins us to speculate about what's going on in the body, what this means for designing a more effective placebo, and asking whether it's time to start honestly prescribing placebos in the clinic. Read his full analysis: https://www.bmj.com/content/363/bmj.k3889