Sex Differences in Ischemic Stroke Readmission Rates and Subsequent Outcomes After Coronary Artery Bypass Graft Surgery

Background and PurposePrior studies examining sex-related risk of readmission for ischemic stroke (IS) after coronary artery bypass grafting (CABG) did not adjust for preoperative comorbidities and used small study samples that were single-center or otherwise poorly generalizable. We assessed risk of readmission for IS after CABG for females compared to males in a nationwide sample.MethodsThe 2013 Nationwide Readmissions Database contains data on 49% of all U.S. hospitalizations. We used population weighting to determine national estimates. Using all follow-up data up to 1 year after discharge from CABG hospitalization, we estimated Kaplan-Meier cumulative risk of IS, stratified by sex, using the log-rank test for significance. We created Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for IS readmission, with sex as the main independent variable. We ran unadjusted models and models adjusted for age, vascular risk factors, estimated severity of illness and risk of mortality, hospital characteristics, and income quartile of patient's zip code.ResultsAn estimated 53,270 females and 147,396 males survived index CABG admission in 2013. There was a consistently elevated cumulative risk of readmission for IS after CABG for females versus males (log-rank p-value = 0.0014). In the unadjusted Cox model, the HR of IS in females vs. males was 1.35 (95% CI 1.12–1.62, p = 0.0015). The elevated risk for females remained after adjusting for severity of illness (1.30 [1.08–1.56], p = 0.0056) and risk of mortality (1.28 [1.07–1.54], p = 0.0086). This elevated risk persisted after adjusting for multiple vascular risk factors, hospital characteristics, and income quartile of patient's zip code (1.23 [1.02–1.48], p = 0.03).ConclusionsWe found a 23% increased risk of readmission for IS up to 1 year after CABG for females compared to males in a fully adjusted model utilizing a large, contemporary, nationwide database. Further research would clarify mechanisms of this increased risk among women.     

Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study

Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 10⁶ CD34⁺ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 10⁶ CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 10⁶ CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation.     

Acute Necrotising Pancreatitis Associated with Leptospirosis—A Case Report

Acute Necrotizing Pancreatitis is a rare complication of leptospirosis and this association carries a high mortality rate. Only few cases have been reported in literature. We hereby report one such case we encountered.     

RET,a targetable driver of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease, affecting about 40,000 individuals in the United States annually. We aimed to characterize the role of RET as a co-driver of pancreas tumorigenesis. To assess the role of RET as a co-driver of PDA, we generated a novel triple mutant transgenic mouse based on the cre-activated p53^R172H gene and a constitutively active RET ^M919T mutant (PRC). Survival analysis was performed using Kaplan–Meier analysis. Study of human PDA specimens and Pdx-1-Cre/Kras^G12D /p53^R172H (KPC) mice revealed that RET is upregulated during pancreas tumorigenesis, from inception through precursor lesions, to invasive cancer. We demonstrated that activation of RET is capable of inducing invasive pancreatic carcinomas in the background of the P53 inactivation mutation. Compared to KPC mice, PRC animals had distinct phenotypes, including longer latency to tumor progression, longer survival, and the presence of multiple macrometastases. Enhanced activation of the MAPK pathway was observed as early as the PanIN 2 stage. Sequencing of the exonic regions of KRAS in PRC-derived PDA cells revealed no evidence of KRAS mutations. RET can be an essential co-driver of pancreatic tumorigenesis in conjugation with KRAS activity. These data suggest that RET may be a potential target in the treatment of PDA.