Publications

Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation in vivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-γ inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-γ suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host.

Autoimmunity is often familial, suggesting that inborn genetic variations might underlie its development. Curiously, autoimmunity has long been thought to be typically polygenic. Contrary to this prediction and consistent with growing discoveries of monogenic autoimmunity, Oftedal et al. discovered heterozygous dominant-negative AIRE mutations in patients with certain forms of autoimmunity.

BACKGROUND

The goal of targeted antiretroviral therapy initiation is to minimize disease progression among patients with human immunodeficiency virus while minimizing the therapeutic burden on these patients. We examine whether the effect of delaying therapy initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care.

METHODS

We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for therapy initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients 18 to 34, 35 to 44, and 45 to 65 years of age at study entry.

RESULTS

In the observed data, 10-year mortality was 13% (165 deaths). Mortality increased from 11% under therapy initiation at 500 cells/mm(3) to 12% at 350 cells/mm(3) (risk difference [RD]: 0.87; 95% confidence interval [CI]: .56, 2.17) and to 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying therapy became greater with age: RDs comparing the 350-cells/mm(3) threshold with the 500-cells/mm(3) threshold ranged from -0.03 (95% CI: -0.15, 1.76) for patients 18 to 34 years of age to 0.99 (95% CI: -.27, 1.98) for patients 35 to 44 and to 2.30 (95% CI: 1.29, 5.42) for patients 45 to 65.

CONCLUSIONS

Delaying therapy increased 10-year mortality in the full cohort. Subgroup analysis highlights that patients entering care at older ages may be more vulnerable to the consequences of delayed ART initiation than younger patients.

Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury.

BACKGROUND

Although an Observed Structured Clinical Examination (OSCE) has been used to evaluate patient interaction and general knowledge competencies of third-year students during their required surgical clerkships, whether surgical clerkship experience predicts satisfactory performance with a surgical patient in an OSCE environment has not been investigated.

OBJECTIVE

We hypothesized that completion of the third-year surgery clerkship would improve student ability to diagnose acute cholecystitis and recognize the further need for hospital admission and treatment.

DESIGN

An observational study design was used to determine student skills in evaluating a simulated surgical patient with abdominal pain from acute cholecystitis. The skills included key data gathering, physical examination, and information-sharing tasks.

SETTING

Tertiary care academic medical center.

PARTICIPANTS

Performance was compared between a cohort of 101 medical students who had completed the third-year surgical clerkship and 72 who had not. A secondary analysis compared performance for 91 students who had completed their third-year clerkship in sites near the University of California, San Francisco School of Medicine, and 10 who did so at a regional campus geographically distant from the medical school.

RESULTS

Of the 173 students who participated in the OSCE, only 42% correctly identified the diagnosis of acute cholecystitis, though 71% did suggest the possibility of a biliary process to the standardized patient. Most of the students who identified the condition as acute cholecystitis or gallbladder-related process had completed their third-year surgical clerkship (odds ratio [OR] = 3.26). Students who completed their surgical clerkship were also better able to recommend appropriate treatment for the patient (OR = 2.35), and recommend admission to the hospital or emergency department (OR = 2.00). Approximately one-third (35.3%) of all students documented a positive Murphy's sign, but only 6.4% identified the triad of leukocytosis, fever, and a Murphy's sign as diagnostic of acute cholecystitis and the need for surgical intervention. Student performance on the clinical examination did not differ depending on whether the students completed their clerkship at a Bay Area or regional hospital.

CONCLUSIONS

Student recognition of the key physical examination and laboratory findings diagnostic of acute cholecystitis was low, but students were better able to recommend further treatment for a patient with acute cholecystitis after completing the third-year surgical clerkship. Our study reveals areas where surgical educators can improve medical student ability to accurately diagnose acute cholecystitis and evaluate acute abdominal processes.