Weight Loss Outcomes in a Veterans Affairs Pharmacotherapy-based Weight Management Clinic.

Context: Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world reports on outcomes when AOMs have been used in veterans is limited. Objective: To analyze weight loss outcomes from a local Veterans Health Administration pharmacotherapy-based weight management clinic (WMC). Methods: This was a retrospective cohort study of veterans enrolled in a local WMC for 15 months from August 2016 through September 2018 and followed through November 2019. Patients were offered 1 of 5 available AOMs based on their comorbidities. Factors associated with weight loss (5% or more weight loss) were assessed. Key results: A total of 159 patients were seen in a WMC, 149 (93.7%) veterans were prescribed an AOM, and 129 returned for follow-up. Overall, 61/129 (47%) patients achieved 5% or greater weight loss and 28/129 (22%) achieved 10% or greater weight loss within 15 months. Clinically significant weight loss (%) over the first 15 months was achieved with phentermine/topiramate ER (-6.3%) and liraglutide (-7.5%), but not with orlistat (-3.9%) and lorcaserin (-3.6%). Comorbid obstructive sleep apnea was negatively associated with achieving ≥5% weight loss. Conclusion: Phentermine/topiramate ER and liraglutide were found to be effective AOMs among veterans. Further work is needed to mitigate barriers to AOM initiation given the continued rise in obesity.

PREVENT: A Randomized, Placebo-controlled Crossover Trial of Avexitide for Treatment of Postbariatric Hypoglycemia.

CONTEXT: Postbariatric hypoglycemia (PBH), characterized by enteroinsular axis overstimulation and hyperinsulinemic hypoglycemia, is a complication of bariatric surgery for which there is no approved therapy. OBJECTIVE: To evaluate efficacy and safety of avexitide [exendin (9-39)], a glucagon-like peptide-1 antagonist, for treatment of PBH. METHODS: A multicenter, Phase 2, randomized, placebo-controlled crossover study (PREVENT). Eighteen female patients with PBH were given placebo for 14 days followed by avexitide 30 mg twice daily and 60 mg once daily, each for 14 days in random order. The main outcome measures were glucose nadir and insulin peak during mixed-meal tolerance testing (MMTT) and hypoglycemic events captured by self-monitoring of blood glucose (SMBG), electronic diary, and blinded continuous glucose monitoring (CGM). RESULTS: Compared with placebo, avexitide 30 mg twice daily and 60 mg once daily raised the glucose nadir by 21% (P = .001) and 26% (P = .0002) and lowered the insulin peak by 23% (P = .029) and 21% (P = .042), corresponding to 50% and 75% fewer participants requiring rescue during MMTT, respectively. Significant reductions in rates of Levels 1 to 3 hypoglycemia were observed, defined, respectively, as SMBG <70 mg/dL, SMBG <54 mg/dL, and a severe event characterized by altered mental and/or physical function requiring assistance. CGM demonstrated reductions in hypoglycemia without induction of clinically relevant hyperglycemia. Avexitide was well tolerated, with no increase in adverse events. CONCLUSION: Avexitide administered for 28 days was well tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters, reinforcing the targeted therapeutic approach and demonstrating durability of effect. Avexitide may represent a first promising treatment for patients with severe PBH.

Prostate Cancer-Associated Disseminated Intravascular Coagulation with Excessive Fibrinolysis Treated with Degarelix.

Disseminated intravascular coagulation (DIC) with excessive fibrinolysis (XFL) is a rare and acute life-threatening variant of DIC in patients with prostate cancer. Patients present with coagulopathy, hypofibrinogenemia, and systemic bleeding. We describe a case of DIC XFL caused by prostate cancer (PC) successfully treated with a single injection of degarelix, a gonadotropin-releasing hormone (GnRH) receptor antagonist. This led to prompt control of the patient's coagulopathy within ten days of treatment. Our case highlights features of this rare and devastating hemorrhagic complication of PC along with a fast-acting and effective therapeutic drug option.

Neuroblastoma of the elderly, an oncologist's nightmare: case presentation, literature review and SEER database analysis.

Neuroblastoma is considered a pediatric malignancy as over 95% of cases are diagnosed in patients ≤10 years old. This cancer is extremely rare in elderly patients. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis in the USA between 1973-2007 that revealed only 35 elderly patients (>60 years of age) with neuroblastoma of whom only 2 patients had primary mediastinal neuroblastoma. There is a paucity of treatment and survival outcomes data for the elderly owing to the rarity of neuroblastoma in this population. Currently there are no standard guidelines or protocols for treatment of adult neuroblastoma. We report a rare and challenging case of an 86-year old patient presenting with mediastinal neuroblastoma and syndrome of inappropriate antidiuretic hormone secretion (SIADH) successfully treated with resection. Herein, we also provide a review of the literature and updated survival data on neuroblastoma based on results of our SEER database review.

Heart of lymphoma: primary mediastinal large B-cell lymphoma with endomyocardial involvement.

Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC) wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

MEKK3 initiates transforming growth factor beta 2-dependent epithelial-to-mesenchymal transition during endocardial cushion morphogenesis.

Congenital heart defects occur at a rate of 5% and are the most prevalent birth defects. A better understanding of the complex signaling networks regulating heart development is necessary to improve repair strategies for congenital heart defects. The mitogen-activated protein 3 kinase (MEKK3) is important to early embryogenesis, but developmental processes affected by MEKK3 during heart morphogenesis have not been fully examined. We identify MEKK3 as a critical signaling molecule during endocardial cushion development. We report the detection of MEKK3 transcripts to embryonic hearts before, during, and after cardiac cushion cells have executed epithelial-to-mesenchymal transition (EMT). MEKK3 is observed to endocardial cells of the cardiac cushions with a diminishing gradient of expression into the cushions. These observations suggest that MEKK3 may function during production of cushion mesenchyme as required for valvular development and septation of the heart. We used a kinase inactive form of MEKK3 (MEKK3(KI)) in an in vitro assay that recapitulates in vivo EMT and show that MEKK3(KI) attenuates mesenchyme formation. Conversely, constitutively active MEKK3 (ca-MEKK3) triggers mesenchyme production in ventricular endocardium, a tissue that does not normally undergo EMT. MEKK3-driven mesenchyme production is further substantiated by increased expression of EMT-relevant genes, including TGFbeta(2), Has2, and periostin. Furthermore, we show that MEKK3 stimulates EMT via a TGFbeta(2)-dependent mechanism. Thus, the activity of MEKK3 is sufficient for developmental EMT in the heart. This knowledge provides a basis to understand how MEKK3 integrates signaling cascades activating endocardial cushion EMT.