Warm Autoimmune Hemolytic Anemia Associated With Asymptomatic SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant coronavirus disease 2019 (COVID-19) are associated with several hematologic abnormalities, including immune thrombocytopenia, antiphospholipid syndrome, and autoimmune hemolytic anemia (AIHA). Initial case reports suggested immune dysregulation to be the underlying etiology of SARS-CoV-2-associated AIHA, as all reported cases involved patients with moderate to severe COVID-19, many of whom had underlying lymphoproliferative disorders. More recently, AIHA has been reported in patients with mildly symptomatic SARS-CoV-2 infection. Here, we detail a patient with asymptomatic SARS-CoV-2 infection who presented with severe, symptomatic anemia. Workup was consistent with warm autoimmune hemolytic anemia (WAIHA) secondary to SARS-CoV-2 infection.

Structure-guided discovery of a novel, potent, and orally bioavailable 3,5-dimethylisoxazole aryl-benzimidazole BET bromodomain inhibitor.

The bromodomain and extra-terminal (BET) family of proteins, consisting of the bromodomains containing protein 2 (BRD2), BRD3, BRD4, and the testis-specific BRDT, are key epigenetic regulators of gene transcription and has emerged as an attractive target for anticancer therapy. Herein, we describe the discovery of a novel potent BET bromodomain inhibitor, using a systematic structure-based approach focused on improving potency, metabolic stability, and permeability. The optimized dimethylisoxazole aryl-benzimidazole inhibitor exhibited high potency towards BRD4 and related BET proteins in biochemical and cell-based assays and inhibited tumor growth in two proof-of-concept preclinical animal models.

Tumour lysis syndrome: a rare side effect of imatinib therapy for GIST.

Tumour lysis syndrome (TLS) is a life-threatening complication wherein massive tumour cell lysis results in severe metabolic abnormalities. TLS generally follows chemotherapy of rapidly proliferating haematological malignancies; spontaneous TLS and TLS from treatment of solid tumours are infrequently reported. We present a rare case of TLS following treatment of a large gastrointestinal stromal tumour (GIST) in a 63- year-old man. Imatinib was started for tumour size reduction prior to surgical intervention and in 5 days the patient developed metabolic derangements consistent with TLS. Imatinib was held and fluids, allopurinol and rasburicase were started. All metabolic abnormalities resolved in 3 days. Imatinib was restarted, and he eventually underwent surgical intervention. This is the second case demonstrating successful reinitiation of imatinib following TLS when treating GIST. We highlight the importance of risk factor assessment and need for pre-emptive therapy to prevent TLS when using tyrosine kinase inhibitor therapy.

Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient.

Disseminated cutaneous varicella herpes zoster with visceral involvement is rare and seen almost exclusively in immunocompromised patients. We describe an unusual case of fulminant herpes zoster (HZ) in a healthy, immunocompetent 37-year-old woman. She initially presented to an urgent care centre with a classic HZ rash localised to her neck, and upper respiratory symptoms and was treated with prednisone and cephalexin. Within 1 week, the rash became diffuse and her clinical status rapidly deteriorated with development of severe acute respiratory distress syndrome. Varicella zoster infection was confirmed via skin biopsy, bronchial viral PCR and serology for varicella antibodies. She was successfully treated with intravenous acyclovir and aggressive supportive care. Though physicians readily recognise typical zoster infection, this case reminds clinicians that HZ infection can be fulminant and potentially life-threatening in younger, immunocompetent individuals. Early recognition and antiviral therapy is important to reduce morbidity and mortality.

Improved Resident Adherence to AAA Screening Guidelines via an Electronic Reminder.

The 2014 United States Preventive Services Task Force systematic review found abdominal aortic aneurysm (AAA) screening decreased related mortality by close to half. Despite the simplicity of screening, research suggests poor adherence to the recommended AAA screening guidelines. Using the quality improvement plan-study-do-act cycle, we retrospectively established poor adherence to AAA screening and poor documentation of smoking history in our resident clinic. An electronic reminder was prospectively implemented into our electronic medical record (EMR) with the goal of improving screening rates. After 1 year, a retrospective chart review was conducted. Comparisons of the pre- and post-electronic reminder intervention data were made using chi-square tests and odds ratios (OR). The purposeful AAA screening rate improved 27.8% during the intervention, 40.3% (95% confidence interval [CI]: 28.6-52.0%) versus 12.5% (95% CI: 3.1-21.9%), p = .002, suggesting patients were more likely to be screened as a result of the electronic reminder, OR = 4.73 (95% CI: 1.77-12.65). This improvement translates to a large effect size, Cohen's d = 0.86 (95% CI: 0.31-1.40). Electronic reminders are a simple EMR addition that can provide evidence-based education while improving adherence rates with preventive health screening measures.

Associations with resident physicians' early adoption of electronic cigarettes for smoking cessation.

BACKGROUND: Use of the electronic cigarette for nicotine delivery has increased dramatically in recent years. Information continues to emerge on its role as a smoking cessation aid, but little is known about resident physician use of the device in clinical practice. METHODS: In 2015, an electronic survey was administered to resident physicians in one healthcare system in Columbus, Ohio. The survey included questions about personal smoking exposure, knowledge, beliefs, attitudes about electronic cigarettes and early adoption of electronic cigarettes with patients. Data were dichotomised based on a 'stages of change' model that assessed resident physician adoption of electronic cigarettes for therapeutic use. Data were analysed through χ2 tests and logistic regression using ORs and 95% CIs. RESULTS: Of 338 residents, 142 (42%) responded. Of all residents, 25 (17.7%) reported that they have been recommending electronic cigarettes to their patients for the past 6 months or longer. In the multivariate model, residents ≥postgraduate year (PGY)-3 (OR=3.68, 95% CI 1.20 to 11.29), peer-reviewed article exposure (OR=6.65, 95% CI 1.56 to 28.38) and the view that addictive potential is definitely or somewhat less than traditional cigarettes (OR=5.05, 95% CI 1.48 to 17.24) were associated with recommendation of electronic cigarettes. CONCLUSIONS: Few residents report recommending electronic cigarettes to patients who smoke. These residents consider the electronic cigarette less addicting than traditional cigarettes, supporting harm reduction strategies over strict abstinence. Most residents require further evidence-based education on efficacy and long-term safety of electronic cigarettes before recommending to their patients.

Associations with resuscitation choice: Do not resuscitate, full code or undecided.

OBJECTIVE: To examine associations of individual exposure and knowledge of resuscitation mechanics and prognosis with specific decision: Do Not Resuscitate (DNR), Full Code (FC) or Undecided (UD). METHODS: Cross-sectional questionnaire at 3 sites: geriatric assessment center, internal medicine resident clinic, and inpatient palliative care service. RESULTS: 407 completed the questionnaire: 27% identified as DNR, 24% as FC and 49% as UD. Few (11.8%) respondents reported discussion of DNR status with their primary care doctor. DNR choice was associated with knowledge of DNR mechanics, OR=2.30 (95%CI: 1.23-4.30), physician discussion, OR=5.58 (95%CI: 2.39-13.04) and confidence in understanding own health problems, OR=2.89 (95%CI: 1.04-8.04). FC choice was associated with knowledge of FC mechanics, OR=2.01 (95%CI: 1.03-3.93) and media code exposure, OR=3.80 (95%CI: 1.46-9.92). Knowledge of resuscitation prognosis was negatively associated with FC, OR =0.48 (95%CI: 0.23-0.98). CONCLUSION: Many individuals lack knowledge or understanding of resuscitation procedure, its risks, and prognosis. Educational efforts, for both patients and healthcare professionals, are needed to improve individual knowledge needed for informed decision. PRACTICE IMPLICATIONS: Scheduled time for physician-patient discussion remains important for education about individual health conditions and risk/benefits related to resuscitation.

Disseminated Cladophialophora bantiana disease in a patient with prediabetes.

Cladophialophora bantiana, a dematiaceous fungus from the family Phaeohyphomycetes, is highly neurotropic and primarily reported as a rare cause of brain abscess. Pulmonary infection and disease outside the central nervous system is extremely rare, particularly in immunocompetent patients. We report an unusual case of disseminated cladosporiosis in a young man with a new diagnosis of prediabetes but no other identifiable risk factors for disease. Fungal cultures were positive for C. bantiana from brain abscess aspiration, vertebral bone cultures and subcarinal lymph node biopsy. Although the patient demonstrated initial good response to surgical debridement of brain abscesses plus antifungal therapy, he eventually expired from septic shock secondary to C. bantiana pneumonia and recurrent brain abscesses 2 years after initial diagnosis.

Bacterial foodborne infections after hematopoietic cell transplantation.

Diarrhea, abdominal pain, and fever are common among patients undergoing hematopoietic cell transplantation (HCT), but such symptoms are also typical with foodborne infections. The burden of disease caused by foodborne infections in patients undergoing HCT is unknown. We sought to describe bacterial foodborne infection incidence after transplantation within a single-center population of HCT recipients. All HCT recipients who underwent transplantation from 2001 through 2011 at the Fred Hutchinson Cancer Research Center in Seattle, Washington were followed for 1 year after transplantation. Data were collected retrospectively using center databases, which include information from transplantation, on-site examinations, outside records, and collected laboratory data. Patients were considered to have a bacterial foodborne infection if Campylobacter jejuni/coli, Listeria monocytogenes, E. coli O157:H7, Salmonella species, Shigella species, Vibrio species, or Yersinia species were isolated in culture within 1 year after transplantation. Nonfoodborne infections with these agents and patients with pre-existing bacterial foodborne infection (within 30 days of transplantation) were excluded from analyses. A total of 12 of 4069 (.3%) patients developed a bacterial foodborne infection within 1 year after transplantation. Patients with infections had a median age at transplantation of 50.5 years (interquartile range [IQR], 35 to 57), and the majority were adults ≥18 years of age (9 of 12 [75%]), male gender (8 of 12 [67%]) and had allogeneic transplantation (8 of 12 [67%]). Infectious episodes occurred at an incidence rate of 1.0 per 100,000 patient-days (95% confidence interval, .5 to 1.7) and at a median of 50.5 days after transplantation (IQR, 26 to 58.5). The most frequent pathogen detected was C. jejuni/coli (5 of 12 [42%]) followed by Yersinia (3 of 12 [25%]), although Salmonella (2 of 12 [17%]) and Listeria (2 of 12 [17%]) showed equal frequencies; no cases of Shigella, Vibrio, or E. coli O157:H7 were detected. Most patients were diagnosed via stool (8 of 12 [67%]), fewer through blood (2 of 12 [17%]), 1 via both stool and blood simultaneously, and 1 through urine. Mortality due to bacterial foodborne infection was not observed during follow-up. Our large single-center study indicates that common bacterial foodborne infections were a rare complication after HCT, and the few cases that did occur resolved without complications. These data provide important baseline incidence for future studies evaluating dietary interventions for HCT patients.

Infliximab-induced nonspecific interstitial pneumonia.

Infliximab has well-established complications including injection site and allergic reactions, cytopenias, induction of autoimmune and demyelinating diseases and malignancy, especially lymphoma. Pulmonary complications are well documented and include serious respiratory infections from tuberculosis, fungal and opportunistic pathogens. This has prompted a Food and Drug Administration black-box warning recommending close surveillance for these diseases. Nonspecific interstitial pneumonitis (NSIP) secondary to tumor necrosis factor-alpha inhibitor (TNF-alpha) therapy is less well described. Rarely, TNF-alpha inhibitor therapy has been reported to cause NSIP when used in conjunction with other immunosuppressive agents. Literature search revealed 12 independent patients with presumed infliximab-induced NSIP in 8 separate publications; all patients were on concomitant steroid sparing immunosuppressive agents, complicating cause and effect. The authors report a case in which infliximab is surmised to cause NSIP in the absence of other steroid sparing immunosuppressants in a young female with ulcerative colitis. Of importance, the patient was taking no additional steroid sparing immunomodulating agents. The diagnosis was based on clinical presentation and radiologic and histopathological data. Cessation of infliximab and high-dose steroid therapy resulted in complete resolution of the patient's presenting signs and symptoms.