BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. METHODS: We performed a genomewide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer !10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. RESULTS: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P ¼ 5.88 Â 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P ¼ 6.60 Â 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone

A lthough guidelines are available for managing hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) 1,2 and our understanding of these diseases is growing, their incidence does not seem to be decreasing. 3 And the toll is high. About 10% of patients put on mechanical ventilation develop VAP, 3 and the mortality rate in VAP has been estimated at 13%. 4 Together, HAP and VAP accounted for 22% of hospital-acquired infections in a 2014 survey of 183 US hospitals. 5 Patients with VAP face a longer hospital course and incur higher healthcare costs than similarly ill patients without VAP. 1 This review discusses the diagnosis, management, and prevention of HAP and VAP using the 2016 guidelines from the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS), 1 as well as recent literature regarding controversial topics such as the role for procalcitonin testing and adjunctive inhaled aminoglycosides. ■ TERMSHAP is a new pneumonia (a lower respiratory tract infection verifi ed by the presence of a new pulmonary infi ltrate on imaging) that develops more than 48 hours after admission in nonintubated patients.VAP, the most common and fatal nosocomial infection of critical care, is a new pneumonia that develops after 48 hours of endotracheal intubation. Importantly, by the time of VAP onset, patients may have already been extubated.

Purpose: We explored differences in changes in medical student empathy in the third year of medical school between volunteers at JeffHOPE, a multisite medical student–run free clinic of Sidney Kimmel Medical College (SKMC), and nonvolunteers. Method: Volunteerism and leadership experience at JeffHOPE were documented for medical students in the Class of 2015 (n = 272) across their medical educations. Students completed the Jefferson Scale of Empathy at the beginning of medical school and at the end of the third year. Students who reported participation in other Jefferson-affiliated clinics (n = 44) were excluded from this study. Complete data were available for 188 SKMC students. Results: Forty-five percent of students (n = 85) volunteered at JeffHOPE at least once during their medical educations. Fifteen percent of students (n = 48) were selected for leadership positions involving weekly clinic participation. Nonvolunteers demonstrated significant decline in empathy in medical school (P = 0.009), while those who volunteered at JeffHOPE at least once over the course of their medical educations did not show any significant decline (P = 0.07). Conclusions: These findings suggest that medical students may benefit from volunteering at student-run free clinics to care for underserved populations throughout medical school.

Background: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-β-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. Methods: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. Results: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported β-lactam allergy (136/844 [16%] pre-and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients preand post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). Conclusion: Penicillin allergy skin testing adjudicates reported β-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Months after the first reports of a previously unknown pathogen isolated from patients with pneumonia in Wuhan, China, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). 1 Mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 can present with flu-like illness and progress to acute hypoxic respiratory failure. 2 Bilateral infiltrates on chest imaging, lymphopenia, and elevated inflammatory markers have been noted in those with COVID-19related pneumonia. 3 Increased incidence of severe disease is cited in the elderly and in those with comorbidities including cardiovascular disease, diabetes mellitus, and chronic respiratory disease. 4 Immunocompromised patients, including solid organ transplant recipients and people living with human immunodeficiency virus (HIV), merit particular attention. As has been described in the context of other ribonucleic acid respiratory viruses, altered host immunity may yield atypical illness presentations, delayed diagnosis, and rapid progression, as well as prolonged viral shedding propagating disease transmission. 5-8 Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes, as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with HIV. 9-12 Such patients may even be spared the robust inflammatory response that precipitates acute respiratory distress syndrome (ARDS) associated with COVID-19, complicating the management of iatrogenic immunosuppression.