The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.

IMPORTANCE Delays in initiation of postoperative radiotherapy (PORT) after surgery for head and neck squamous cell carcinoma (HNSCC) are common, predominantly affect racial minorities, and are associated with decreased survival. Details regarding the care processes that contribute to timely, equitable PORT remain unknown. OBJECTIVE To determine care processes associated with timely, equitable PORT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included patients 18 years or older undergoing surgery for HNSCC at the Medical University of South Carolina (MUSC), Charleston, followed by PORT (at MUSC or elsewhere) with or without chemotherapy from January 1, 2014, through December 31, 2016. Data were analyzed from September 15, 2017, through June 28, 2018. MAIN OUTCOMES AND MEASURES The main outcome measure was the proportion of timely, guideline-adherent initiation of PORT (≤6 weeks postoperatively). Secondary outcome measures included care processes associated with timely PORT. The association between process variables with timely PORT was explored using multivariable logistic regression analysis. Effect modification of the association between receipt of care processes and timely PORT by race was explored using interaction effects. RESULTS A total of 197 patients were included in the analysis; they were predominantly white (157 [79.7%]) and male (136 [69.0%]) with a mean age of 59 years (range, 28-89 years). Overall, 89 patients (45.2%) experienced a delay initiating PORT. African American patients had a 13.5% absolute increase in the rate of delayed PORT relative to white patients (21 of 37 [56.8%] vs 68 of 157 [43.3%]). The adjusted multivariable regression showed that the following care processes were associated with timely PORT: preoperative radiotherapy consultation (odds ratio [OR], 8.94; 95% CI, 1.64-65.53), PORT at MUSC (OR, 6.21; 95% CI, 1.85-24.75), pathology report within 7 postoperative days (OR, 4.14; 95% CI, 1.21-15.86), time from surgery to PORT referral of no longer than 10 days (OR, 12.14; 95% CI, 3.14-63.00), time from PORT referral to consultation of no longer than 10 days (OR, 10.76; 95% CI, 3.01-49.70), and time from PORT consultation to its start of no longer than 21 days (OR, 4.80; 95% CI 1.41-18.44). Analysis of interactions revealed no statistically significant differences between African American and white patients in receipt of key processes associated with timely PORT. CONCLUSIONS AND RELEVANCE Specific care processes are associated with guideline-adherent initiation of PORT. Novel strategies appear to be needed to ensure that these processes are performed for all patients with HNSCC, thereby facilitating timely, equitable PORT.

ObjectivesTo estimate the economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure in Canada.MethodsWe estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases associated with occupational and para-occupational asbestos exposure for calendar year 2011 based on the societal perspective. The key cost components considered are healthcare costs, productivity and output costs, and quality of life costs.ResultsThere were 427 cases of newly diagnosed mesothelioma cases and 1904 lung cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases. Our estimate of the economic burden is $C831 million in direct and indirect costs for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in quality of life costs based on a value of $C100 000 per quality-adjusted life year. This amounts to $C356 429 and $C652 369 per case, respectively.ConclusionsThe economic burden of lung cancer and mesothelioma associated with occupational and para-occupational asbestos exposure is substantial. The estimate identified is for 2331 newly diagnosed, occupational and para-occupational exposure cases in 2011, so it is only a portion of the burden of existing cases in that year. Our findings provide important information for policy decision makers for priority setting, in particular the merits of banning the mining of asbestos and use of products containing asbestos in countries where they are still allowed and also the merits of asbestos removal in older buildings with asbestos insulation.

There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, “transgenic” human anti-HIV T cell receptor (TCR). Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

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BackgroundWe report an unusual case of a 66-year-old female with a suspicious thoracic outlet mass presenting with severe biochemical hyperparathyroidism and classic hypercalcemic symptoms of renal and bone involvement.Case PresentationThere was clinical suspicion for parathyroid carcinoma, further supported by intra-operative findings. However, the final pathology described a primary hyperceullar parathyroid lesion with pathognomonic changes secondary to fine-needle aspiration (FNA) biopsy, along with a separate parathyroid lesion likely resulting from seeding along the needle tract. Upon further review, record of a remote FNA was discovered. This case highlights the complications associated with parathyroid FNA resulting in a diagnostic challenge and raising the possibility of malignancy.ConclusionsWe therefore recommend to take caution when there is a prior parathyroid FNA, as it can present with the risks of a secondary lesion from seeding and increase resemblance of malignancy both clinically and through pathologic diagnosis.