Summary Imatinib mesylate (IM) induces remission in chronic myelogenous leukemia (CML) patients but does not eliminate leukemia stem cells (LSC), which remain a potential source of relapse. Here we investigated the ability of HDAC inhibitors (HDACi) to target CML stem cells. Treatment with HDACi combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone, and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACi with IM markedly diminished LSC in a transgenic mouse model of CML. The interaction of IM and HDACi inhibited genes regulating hematopoietic stem cell maintenance and survival. HDACi treatment represents an effective strategy to target LSC in CML patients receiving tyrosine kinase inhibitors.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition among men of a wide age range, with detrimental effects on quality of life. The etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown, although progress has been made in these domains in recent years. A wide variety of pharmacologic and nonpharmacologic therapies have been studied in clinical trials, but most have shown limited efficacy in symptom alleviation. CP/CPPS is increasingly viewed as a condition that involves variable degrees of neuropathic pain. Medications such as gabapentin, pregabalin, memantine, and tricyclic antidepressants are often used in other neuropathic pain conditions and, therefore, are considered potential treatments for CP/CPPS. Few studies of these agents in patients with CP/CPPS have been reported, but future clinical trials should help to determine their utility and to characterize the pathogenetic mechanisms of pain in CP/CPPS. Combining treatment trials with biomarker, genomic, and imaging studies, in addition to epidemiologic and symptom-based assessments, will maximize the ability to probe disease etiology and pathogenesis, as well as identify effective treatment.

Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in part due to controversy regarding its definition, biological basis and diagnosis. Biomarkers are objective measures that may lead to improvements in our understanding of CFS by providing a more coherent and consistent approach to study, diagnosis and treatment of the illness. Such metrics may allow us to distinguish between CFS subtypes – each defined by characteristic biomarkers – currently conflated under the single, heterogeneous condition of CFS. These delineations, in turn, may guide more granular, focused, and targeted treatment strategies based on more precise characterizations of the illness. Here, we review potential CFS biomarkers related to neurological and immunological components of the illness, and discuss how these biomarkers may be used to move the field of CFS forward, emphasizing clinical utility and potential routes of future research.

RFA is an effective and durable treatment option for Barrett's-associated IMC. Greater than 80% of patients will achieve and maintain complete eradication of IMC at a mean of 2 years follow-up.

Radiofrequency ablation (RFA), with or without endoscopic mucosal resection (EMR), is a safe, effective, and durable treatment option for Barrett esophagus (BE)-associated dysplasia (DYS), but few studies have identified predictors of treatment failure in BE-associated intramucosal adenocarcinoma (IMC). The aim of this study was to determine the rate of IMC eradication when using RFA±EMR and to identify clinical and pathologic predictors of treatment failure. A retrospective review of medical records and a central review of index histologic parameters were performed for 78 patients who underwent RFA±EMR as the primary treatment for biopsy-proven IMC at 4 academic tertiary medical centers. Complete eradication (CE) (absence of IMC/DYS on first follow-up endoscopy) was achieved in 86% of patients, and durable eradication (DE) (CE with no recurrence of IMC/DYS until last follow-up) was achieved in 78% of patients, with significant variation between the 4 study sites (P=0.03 and 0.09 by analysis of variance for DE and CE, respectively). Use of EMR before RFA significantly reduced the risk for treatment failure for IMC/DYS (hazard ratio, 0.15; 95% confidence interval, 0.05-0.48; P=0.001), whereas IMC involving ≥50% of the columnar metaplastic area on index examination significantly increased the risk for treatment failure (hazard ratio, 4.24; 95% confidence interval, 1.53-11.7; P=0.005). Endoscopic and pathologic factors associated with treatment failure in BE-associated IMC treated with RFA±EMR may help identify the subset of IMC patients for whom a more aggressive initial approach may be justified.

A 44-year-old man is presented here with 14 years of chronic purulent sinusitis, a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with antifungal therapy resulted in symptom improvement, however he was unable to establish an effective long-term treatment regimen, resulting in debilitating symptoms. He had undergone extensive work-up without identifying a clear underlying etiology, although Candida species were cultured from the prostatic fluid. 100 genes involved in the cellular immune response were sequenced and a missense mutation was identified in the Ras-binding domain of PI3Kγ. PI3Kγ is a crucial signaling element in leukotaxis and other leukocyte functions. We hypothesize that his mutation led to his chronic infections and pelvic pain.

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Background Although the COVID‐19 pandemic increased social isolation among hospitalised patients given isolation precautions, visitor restrictions and curtailed interactions with healthcare teams, medical students had limited opportunities for involvement in the care of inpatients. Approach We designed a humanistic and narrative medicine intervention to engage medical students in combating social isolation in hospitalised patients during the COVID‐19 pandemic at a tertiary care teaching hospital. In our programme, medical students provided virtual social support to hospitalised patients via phone by providing assistance connecting with family members, having informal conversations and check‐ins and writing up patient life narratives. Evaluation From April 2020 to March 2021, we received 126 referrals of potentially isolated patients from inpatient medical teams. Fifty patients accepted and received our intervention, including 26 who completed life narratives. Feedback was positive, demonstrating benefit to medical students in learning about humanism and connecting with patients through their life stories. In addition, patients and medical teams felt more supported. We share key operational lessons and resources to facilitate the implementation of this intervention elsewhere. Implications Our intervention allows medical students to meaningfully contribute to the care of inpatients, support beleaguered inpatient teams and learn important lessons about humanism in medicine. This educational and patient care intervention holds promise in other settings, including beyond the COVID‐19 pandemic.