HIV-1 Infection Results in Sphingosine-1-Phosphate Receptor 1 Dysregulation in the Human Thymus.

Regeneration of functional naïve T lymphocytes following the onset of human immunodeficiency virus (HIV) infection remains a crucial issue for people living with HIV (PLWH), even when adhering to antiretroviral therapy (ART). Thus far, reports on the impact of HIV-1 infection on the entry of thymic precursors and the egress of functional naïve T lymphocytes to and from the thymus are limited. We examined the impact of HIV-1 on Sphingosine-1-phosphate (S1P) signaling, which governs the egress of functional naïve thymocytes from the thymus to the periphery. Using in vitro experiments with primary human thymocytes and in vivo and ex vivo studies with humanized mice, we show that HIV-1 infection results in upregulation of the expression of S1P receptor 1 (S1PR1) in the human thymus. Intriguingly, this upregulation occurs during intrathymic infection (direct infection of the human thymic implant) as well as systemic infection in humanized mice. Moreover, considering the dysregulation of pro- and anti-inflammatory cytokines in infected thymi, the increased expression of S1PR1 in response to in vitro exposure to Interferon-Beta (IFN-ß) and Tumor Necrosis Factor-Alpha (TNF-α) indicates that cytokine dysregulation following HIV infection may contribute to upregulation of S1PR1. Finally, an increased presence of CD3hiCD69- (fully mature) as well as CD3hiCD69+ (less mature) T cells in the spleen during HIV infection in humanized mice, combined with earlier expression of S1PR1 during thymocyte development, suggests that upregulation of S1PR1 may translate to increased or accelerated egress from the thymus. The egress of thymocytes that are not functionally mature from the thymus to peripheral blood and lymphoid organs may have implications for the immune function of PLWH.

Predictors and outcomes of delayed plastic biliary stent removal following endoscopic retrograde cholangiopancreatography.

OBJECTIVE: Plastic biliary stents are commonly placed during endoscopic retrograde cholangiopancreatography (ERCP) and should be removed or replaced within 3 months to reduce the risk of stent obstruction. The aim of the study was to identify predictors and outcomes of patients who had delayed plastic biliary stent removal following ERCP. MATERIALS AND METHODS: Consecutive patients who received ERCP with plastic biliary stent placement at Loma Linda University Medical Center (10/2004-6/2013) were identified. Delayed removal was defined as presence of stent >3 months after index ERCP. Multivariable regression analysis to identify baseline characteristics associated with delayed removal was performed. Clinical outcomes of stent obstruction (e.g., cholangitis, hospitalization, intensive care) were also collected for those with delayed removal. RESULTS: Among 374 patients undergoing ERCP with plastic biliary stent, 71 (19%) had delayed stent removal. Patients who had anesthesia assistance (AOR = 3.8, 95%CI 1.2-11.4), non-English primary language (AOR = 3.0, 95%CI 1.5-6.2), and outpatient ERCP (AOR = 2.0, 95%CI 1.1-3.4) had increased while choledocholithiasis (AOR = 0.5, 95%CI 0.3-0.99) had lower odds of delayed stent removal. Among those with delayed removal, 13 (18%) were hospitalized for stent obstruction (5 (7%) had cholangitis, 8 (11%) were hospitalized for more than a week, and 3 (4%) required intensive care). CONCLUSIONS: Almost one-fifth of patients who underwent ERCP with plastic biliary stent placement had delayed removal with nearly one-fifth of these patients requiring hospitalization for stent obstruction. Targeting patients at risk by improving communication and ease of scheduling an ERCP may reduce preventable adverse events associated with delayed biliary stent removal.

Exploratory analysis to enhance operational efficiency of new patient screenings.

OBJECTIVE: The aims of this study were to 1) evaluate patient demographic data for new patient exams (NPE) and 2) analyze lead response time for checked-in and no-show appointments in predoctoral clinics in a dental school. METHODS: The data for the study were collected from the predoctoral clinics at Tufts University School of Dental Medicine (TUSDM) for patients with NPE appointments with American Dental Association's (ADA) diagnostic code of D100. A total of 26,826 appointments and 24,419 unique patients were reviewed from January 1, 2015 to December 31, 2019. Patient demographic variables such as age, gender, zip codes, and lead response time were analyzed. RESULTS: From 26,826 total number of appointments, 10,454 appointments were categorized as no-show appointments (38.97%). In the no-show appointments, the sex distribution was 59.93% female and 40.07% male, and in checked-in category, the sex distribution was 53.75% female and 46.25% male. As the lead response time increased over 5 days, the no-show rate increased to 49.79%. Approximately 55% of the entire NPE was from Greater Boston area. CONCLUSION: The association between lead time and no-show rate was shown that when lead time was reduced, no-show rate decreased. By identifying the no-show appointments and lead time, schools and clinics can improve operational efficiency, reduce financial loss, and maintain continuation of care by supporting patients who need access to care and creating secondary automated recall system to maximize communication and chair use.