Citations

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

Abstract Incretin‐based therapies, including glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and dual incretin agonists, are increasingly used for the management of diabetes, obesity, and cardiometabolic disease. Although their systemic benefits are well established, uncertainty remains regarding their safety in patients with neuroendocrine neoplasms (NENs), a biologically heterogeneous group of tumors with diverse molecular profiles. Preclinical studies suggest that GLP‐1 receptor activation may promote tumor growth in select receptor‐expressing models, although receptor expression varies widely across NEN subtypes and is often absent in common tumors such as ileal neuroendocrine tumors. Population‐level and retrospective clinical data have not demonstrated a consistent increase in oncologic risk but are limited by methodological constraints. In this expert consensus statement, the authors synthesize current evidence and provide a practical framework for the use of incretin mimetics in patients with NENs. The authors emphasize individualized risk assessment, shared decision‐making, and multi‐disciplinary collaboration, balancing potential but unquantified oncologic risks against substantial cardiometabolic benefits. Until prospective data are available, careful patient selection, dose optimization, and close clinical and radiologic surveillance remain essential to guide safe and effective use of these agents in this population.

ABSTRACT Background Few studies have examined pretransplant CD4 count and risk of post‐kidney transplant (KT) infection in persons with HIV (PWH). Methods This multi‐center, retrospective cohort study included adult PWH undergoing KT from 2004 to 2019. The primary outcome was infection in the first year post‐KT in PWH with pretransplant CD4 < 350 cells/µL versus CD4 ≥ 350 cells/µL. Relative risk was assessed using modified Poisson modeling. Restricted mean survival time analysis was used to assess 5‐year posttransplant outcomes. Results Of the 75 patients included, 27% had a pretransplant CD4 < 350 cells/µL. Those with CD4 < 350 versus CD4 ≥ 350 were more likely to be hospitalized for infection in the first year (55% versus 16%, p = 0.001). There were no significant differences in relative risk of infection in the first‐year posttransplant (RR: 1.31, p = 0.053), 5‐year overall survival (87.5% vs. 93%, p = 0.49) or 5‐year graft loss (29.4% vs. 23.1%, p = 0.61) betweengroups. Conclusion These findings suggest that pretransplant CD4 count alone may not reflect the true risk of post‐KT infection in PWH.

Aneuploidy is a hallmark of cancer often associated with inferior prognosis. Copy number gains of chromosome 8 (chr8) are recurrent in multiple cancers, including breast, prostate, colorectal cancers, and sarcomas such as malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are aggressive, hard-to-treat sarcomas frequently linked to the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. To investigate the role of chr8 gain in MPNST pathogenesis, we performed a CRISPR knockout screen and identified 58 essential genes on chr8, including PTK2, which encodes focal adhesion kinase (FAK). We evaluated FAK as a therapeutic target and tested small-molecule FAK inhibitors (FAKi) alone or combined with RAF/MEK inhibitors (RAF/MEKi), a class of agents relevant to NF1-deficient tumors with ERK pathway hyperactivation. Both pharmacological and genetic inhibition of FAK reduced MPNST cell proliferation in vitro and tumor growth in vivo. Combined FAKi and RAF/MEKi treatment further suppressed phosphorylation of FAK, STAT3, and AKT while increasing cleaved caspase-3 and PARP-1, indicating enhanced apoptosis. In MPNST patient-derived xenograft (PDX) models, combination therapy significantly reduced tumor growth, showing superior efficacy, particularly in chr8 gain MPNST-PDX. These results support FAK/RAF/MEK co-targeting as a promising therapeutic strategy for chr8 gain MPNST and related tumors.

Abstract Introduction Clozapine-induced constipation may occur in at least 60% of patients, with first-line options typically involving polyethylene glycol or sennosides. However, there may be adherence barriers to an over-the-counter bowel regimen due to the dosage form, lack of insurance coverage, or lack of benefit. One possible solution to address these adherence barriers may include prescribing a secretagogue laxative. However, there is limited literature supporting the use of secretagogue laxatives in clozapine-associated constipation. A case series is presented in which adherence barriers impeded the use of over-the-counter laxatives, and a secretagogue laxative was implemented to manage clozapine-induced constipation. Case Report In 4 cases, lubiprostone or linaclotide was initiated, either as monotherapy or in combination with over-the-counter laxatives. Reasons for secretagogue laxative initiation included: (1) reducing a complex over-the-counter laxative regimen, (2) a lack of insurance coverage of over-the-counter laxatives, (3) dissatisfaction with polyethylene glycol’s palatability, and (4) cognitive impairment leading to decreased adherence to polyethylene glycol. Discussion It is important that clozapine-induced constipation is managed adequately to prevent severe consequences of gastrointestinal hypomotility. In addition to timely initiation and titration of constipation pharmacotherapy, adherence should be assessed. When adherence barriers to the use of over-the-counter laxatives are present, the use of a secretagogue laxative may be an option, recognizing there is limited evidence to guide this decision. Conclusion In these cases, adherence barriers to over-the-counter laxatives were identified. A secretagogue laxative was implemented, well-tolerated, and able to be continued for the duration of follow-up.

Introduction Stressful experiences may generate persistent emotional distress that could interfere with daily life. Early intervention is key to reducing those emotional disturbances and potentially preventing the development of more severe pyschopathology. The present research consists of two studies that evaluate the effects of the PASER technique on levels of emotional disturbance. Methodology In study 1, a quasi-experimental repeated-measures within-group design was used, with four assessments conducted through the APEEM inventory in relation to a non-pathological stressful situation selected by each participant. The first three measurements were mediated solely by brief imaginal exposure (inherent to the APEEM instrument) in order to control for the cumulative effects of exposure and habituation over time. Following each of these assessments, a 15-min distractor task was administered. The fourth measurement was conducted after the group application of the PASER technique. In study 2, an experimental design was conducted, assessing the effects of the variables “measurement time point” (baseline and post-test), “sex” and “intervention condition” (control vs. PASER). Results The results showed a progressive reduction in emotional disturbance as time progressed in both studies. Participants receiving PASER exhibited a significantly greater reduction in emotional disturbance than those in the control condition. These findings support the effectiveness of PASER in reducing emotional disturbance beyond the effects attributable to repeated exposure and the passage of time. Conclusions These results suggest that PASER produces an effect greater than simple exposure-based desensitization, potentially promoting memory reconsolidation processes. Longitudinal studies are recommended to confirm the stability of these effects.

Background and Goals: Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with cirrhosis and ascites, with additional risks posed by multidrug-resistant organisms (MDRO). This real-world study evaluated clinical outcomes in patients with SBP and the impact of MDRO. Methods: This study identified US adults with SBP receiving guideline-recommended treatment with antibiotics and albumin from January 2012 to June 2022. Antibiotic utilization trends, health care resource utilization, and clinical outcomes [in-hospital and ICU mortality and hospital and ICU length of stay (LOS)] were assessed and stratified by MDRO status. Results: A total of 10,956 patients with 12,570 encounters were identified. Median age was 57.0 years (IQR=49.0 to 65.0), and 62.4% were male; suspected MDRO infections occurred in 15% of encounters. Third-generation cephalosporins were used in 71.6%, 49.2% had acute kidney injury, and 20.0% and 7.2% had hepatorenal syndrome and hepatic encephalopathy, respectively. Median hospital LOS was 7.2 days (IQR=4.3 to 12.9), with 17.7% in-hospital mortality. ICU care was required in 14.5% of encounters, with a median ICU LOS of 3.6 days (IQR=1.7 to 6.7) and ICU mortality of 29.7%. MDRO infections were associated with increased in-hospital mortality (OR=2.24, P <0.001) and decreased hazard of hospital discharge (ie, prolonged LOS; HR=0.43, P <0.001). Receiving albumin within 24 hours of admission was associated with a 72% higher hazard of hospital discharge (ie, shorter LOS; HR=1.72, P <0.001). Conclusion: This study highlights the clinical and resource burden of SBP, emphasizing the impact of MDRO infections and the importance of timely albumin administration concordant with clinical guidelines.