Clinical Efficacy, Safety, Tolerability, and Real-World Data of Patiromer for the Treatment of Hyperkalemia.

Hyperkalemia remains one of the most difficult consequences of disease state and treatment for patients with chronic kidney disease, heart failure, and diabetes. Controlling hyperkalemia can be difficult, but has become easier with the introduction of novel oral potassium binders. Patiromer was approved in 2015 for the treatment of hyperkalemia by the FDA in the United States. Several pivotal trials proved its efficacy, safety, and improved tolerability compared with previous hyperkalemia treatments. Additionally, many real-world publications and trials have given deeper insights into the capabilities of patiromer. We discuss improved disease state outcomes with combining patiromer with RAASi. This paper will also highlight new trials forthcoming that are highly anticipated to expand the possibilities in using patiromer to improve outcomes and populations.

Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus.

INTRODUCTION: The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained. METHODS: In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower ß-cell area and average islet size and density compared to non-T2DM controls (p < 0.05). RESULTS: Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and ß/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (p > 0.05 vs. Control). CONCLUSIONS: Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating ß-cell failure in PC can be important for our understanding of pathophysiology of PC.

Chemoradiotherapy for patients with locally advanced or unresectable extra-hepatic biliary cancer.

BACKGROUND: Although surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC. METHODS: This was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes. RESULTS: Forty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3-73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22-50%), 20% (95% CI: 11-36%), and 7% (95% CI: 2-20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12-36%), 27% (95% CI: 17-44%), 31% (95% CI: 20-48%), and 33% (95% CI: 22-50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy10 was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18-0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16-0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02-1.63, P=0.04). BED >59.5 Gy10 remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15-0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively. CONCLUSIONS: RT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.

Clinical spectrum of adult patients with annular pancreas: Findings from a large single institution cohort.

BACKGROUND AND AIMS: Annular pancreas (AnnP) is a rare congenital abnormality that results from the presence of a complete or partial ring of pancreatic tissue surrounding the descending portion of the duodenum. While the clinical presentation and management of AnnP in neonates and infants has been well described, the complete spectrum of clinical presentation of AP in adults is not very clear. We aimed to describe the clinical spectrum of presentation and management of adult patients with AnnP. METHODS: Using the electronic medical record, we identified 198 patients with radiologically and/or surgically confirmed AnnP evaluated at Mayo Clinic between 1995 and 2017. RESULTS: The mean age of the study population at diagnosis was 55.1 (±18.3) years (60% female). 60% of patients did not have symptoms attributable to pancreatic disease at the time of diagnosis and were diagnosed incidentally. Computed tomography (CT) was the most common modality (64%) of diagnosis. Among symptomatic patients, abdominal pain (50%), duodenal obstruction (31%) and acute pancreatitis (16%) were the most common symptoms (non-exclusive). While most patients with duodenal obstruction required surgery, all patients with acute pancreatitis could be managed conservatively in the absence of competing indications for intervention. CONCLUSION: AnnP may remain asymptomatic well into adulthood and be incidentally detected on abdominal imaging done for other indications. While surgery remains the mainstay of treatment in patients presenting with duodenal obstruction, a majority of these adult symptomatic patients with AnnP, including those with acute pancreatitis require no further treatment.