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We present a 49-year-old female with one year of intermittent fevers, chills, night sweats, and significant weight loss. Liver and lung biopsy showed evidence of a granulomatous process. Blood and liver biopsy cultures yielded growth of presumedMycobacterium interjectum, thought to be related to a disseminated long-term central venous catheter infection. She successfully received one year of combined antimicrobial therapy after catheter removal without recurrence of disease.M. interjectumhas been previously described as a cause of lymphadenitis in healthy children and associated with pulmonary disease in adults, although other localized infections have been reported. This is the first case described of a disseminatedM. interjectuminfection with bacteremia, hepatic and pulmonary involvement associated with a long-term catheter infection.

Objectives Rectovaginal fistulae (RVF) often represent surgical challenges, and treatment must be individualized. We describe outcomes after primary surgical repair stratified by fistula etiology and surgical approach. Methods This retrospective cohort study included women who underwent surgical management of RVF at a tertiary care center between July 1, 2001 and December 31, 2013. Cases were stratified according to the following etiology: cancer (RVF-C), inflammatory bowel disease or infectious (RVF-I), and other (RVF-O). Patients with prior surgical treatment of RVF were excluded. Surgical approaches included local (seton, plug), transvaginal or endorectal, abdominal, diversion alone, or definitive (completion proctocolectomy with permanent colostomy or pelvic exenteration). Recurrence-free survival was estimated using the Kaplan-Meier method, and comparisons between subgroups were evaluated based on fitting Cox proportional hazards models. Censoring occurred at last relevant clinical follow-up. Factors contributing to recurrence-free survival were evaluated including age, body mass index, smoking status, fistula etiology, ileostomy, and surgical approach. Results During the study period, 107 women underwent surgical repair of RVF. The most common fistula etiology was RVF-I (54.2%), followed by RVF-O (23.4%), and RVF-C (22.4%). Ninety-four women underwent fistula repair by the local (29.9%), transvaginal/endorectal (25.2%), abdominal approach (19.6%), or diversion alone (13.1%), whereas 13 underwent definitive surgery (12.2%). Recurrence-free survival was significantly different depending on surgical approach ( P < 0.001), but not etiology ( P = 0.71). Recurrence-free survival (95% confidence interval) at 1 year after surgery was 35.2% (21.8%–56.9%) for the local approach, 55.6% (37.0%–83.3%) for the transvaginal or endorectal approach, 95% (85.9%–100%) for the abdominal approach, and 33.3% (15%–74.2%) for those with diversion only. Conclusions Recurrence rates after RVF repair are high and did not differ by fistula etiology. Abdominal repair of RVF had significantly fewer recurrences.

Objective: Many patients are admitted to the ICU at or near the end of their lives. Consequently, the increasingly common debate regarding physician-assisted suicide and euthanasia holds implications for the practice of critical care medicine. The objective of this article is to explore core ethical issues related to physician-assisted suicide and euthanasia from the perspective of healthcare professionals and ethicists on both sides of the debate. Synthesis: We identified four issues highlighting the key areas of ethical tension central to evaluating physician-assisted suicide and euthanasia in medical practice: 1) the benefit or harm of death itself, 2) the relationship between physician-assisted suicide and euthanasia and withholding or withdrawing life support, 3) the morality of a physician deliberately causing death, and 4) the management of conscientious objection related to physician-assisted suicide and euthanasia in the critical care setting. We present areas of common ground and important unresolved differences. Conclusions: We reached differing positions on the first three core ethical questions and achieved unanimity on how critical care clinicians should manage conscientious objections related to physician-assisted suicide and euthanasia. The alternative positions presented in this article may serve to promote open and informed dialogue within the critical care community.

AbstractBackgroundThe targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC‐derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2.ResultsTranscriptome sequencing was performed on four replicates from each group (48 h untreated, 48 h trastuzumab and 48 h lapatinib) and differential gene expression analyses were performed on each treatment group relative to untreated cardiomyocytes. 517 and 1358 genes were differentially expressed, p < 0.05, respectively in cardiomyocytes treated with trastuzumab and lapatinib. Gene ontology analyses revealed in cardiomyocytes treated with trastuzumab, significant down‐regulation of genes involved in small molecule metabolism (p = 3.22 × 10−9) and cholesterol (p = 0.01) and sterol (p = 0.03) processing. We next measured glucose uptake and lactate production in iPSC‐derived cardiomyocytes 13 days post‐plating, treated with trastuzumab up to 96 h. We observed significantly decreased glucose uptake from the media of iPSC‐derived cardiomyocytes treated with trastuzumab as early as 24 h (p = 0.001) and consistently up to 96 h (p = 0.03).ConclusionsOur study suggests dysregulation of cardiac gene expression and metabolism as key elements of ERBB2 signaling that could potentially be early biomarkers of cardiotoxicity.

Lung cancer is the deadliest cancer in the United States, killing roughly one of four cancer patients in 2016. While it is well-established that lung cancer is caused primarily by environmental effects (particularly tobacco smoking), there is evidence for genetic susceptibility. Lung cancer has been shown to aggregate in families, and segregation analyses have hypothesized a major susceptibility locus for the disease. Genetic association studies have provided strong evidence for common risk variants of small-to-moderate effect. Rare and highly penetrant alleles have been identified by linkage studies, including on 6q23–25. Though not common, some germline mutations have also been identified via sequencing studies. Ongoing genomics studies aim to identify additional high penetrance germline susceptibility alleles for this deadly disease.