A 38-Year-Old Man With Persistent Fever and Progressive Shortness of Breath.

CASE PRESENTATION: A 38-year-old man presented to the ED complaining of persistent fever, dry cough, shortness of breath, and diarrhea for 7 days. He reported a history of OSA with inconsistent CPAP use, tobacco use of less than one pack per day, and daily e-cigarette use or "vaping." He denied any contact with ill people or recent travels and was up to date on recommended COVID-19 vaccinations. Prior to his presentation, he had been seen at an urgent care facility twice in the last week, where he was given IV fluids and prescribed steroids without improvement.

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.

A secretory form of Parkin-independent mitophagy contributes to the repertoire of extracellular vesicles released into the tumour interstitial fluid in vivo.

We characterized the in vivo interstitial fluid (IF) content of extracellular vesicles (EVs) using the GFP-4T1 syngeneic murine cancer model to study EVs in-transit to the draining lymph node. GFP labelling confirmed the IF EV tumour cell origin. Molecular analysis revealed an abundance of IF EV-associated proteins specifically involved in mitophagy and secretory autophagy. A set of proteins required for sequential steps of fission-induced mitophagy preferentially populated the CD81+/PD-L1+ IF EVs; PINK1, TOM20, and ARIH1 E3 ubiquitin ligase (required for Parkin-independent mitophagy), DRP1 and FIS1 (mitochondrial peripheral fission), VDAC-1 (ubiquitination state triggers mitophagy away from apoptosis), VPS35, SEC22b, and Rab33b (vacuolar sorting). Comparing in vivo IF EVs to in vitro EVs revealed 40% concordance, with an elevation of mitophagy proteins in the CD81+ EVs for both murine and human cell lines subjected to metabolic stress. The export of cellular mitochondria proteins to CD81+ EVs was confirmed by density gradient isolation from the bulk EV isolate followed by anti-CD81 immunoprecipitation, molecular sieve chromatography, and MitoTracker export into CD81+ EVs. We propose the 4T1 in vivo model as a versatile tool to functionally characterize IF EVs. IF EV export of fission mitophagy proteins has broad implications for mitochondrial function and cellular immunology.

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.

The Rising Physicians Program: A Novel Approach for Mentoring Medical Students.

INTRODUCTION: The transition to medical school is a particularly challenging time for new students as they are faced with significant academic responsibilities. Moreover, for many students at the Uniformed Services University they are adjusting to being on active duty in the military. Mentoring has been considered a way to help with the transition and professional development. Prior to 2015, there was no formal mentoring program for new students at the Uniformed Services University. MATERIALS AND METHODS: In order to address the demands and challenges facing matriculating medical students, the Rising Physicians Program was created. This student initiated program enabled pre-clerkship medical students to connect with residents at the Walter Reed National Military Medical Center via a secure database with resident profiles. Residents were recruited and voluntarily agreed to serve as mentors. Students were then able to access the database and reach out to mentors based on their specific goals. The program was introduced to students during orientation and student participation was completely voluntary. A survey was designed using best survey practices and sent to the 175 students participating in the program for the 2015 academic (class of 2019) year to determine participation and characteristics of the program. RESULTS: Sixty-four percent (112/175) of the students from the class of 2019 participated in the post-implementation survey. Fifteen percent of the class (26/175) reported participating in the voluntary mentoring program. The three most commonly used communication methods with mentors in precedence were in-person, e-mail, and text messages. The majority of the students found their interactions in this program were beneficial and did not get in the way of their academic performance. The most common topics of discussion were academics (20%), mentor's past experience (22%), military lifestyle (7%), medical school pathways (23%), and specialty selections (23%). Limitations of the program included a lack of U.S. Air Force mentors and mentors within certain residency specialties. CONCLUSIONS: The Rising Physician Program provides a near-peer mentoring model for new medical students. Students preferred to communicate with their mentors in person, but the flexibility of communication appears to be important. New students have a variety of academic and professional development concerns that could partially be addressed through mentoring by residents.

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.

Porphyromonas gingivalis stimulates IL-6 and IL-8 secretion in GMSM-K, HSC-3 and H413 oral epithelial cells.

Infection of oral epithelial cells with periodontopathogenic bacteria results in the production of pro-inflammatory cytokines involved in the initiation and progression of periodontal disease. The purpose of this study was to examine the release of interleukin (IL)-6 and IL-8 by oral epithelial cells after exposure to Porphyromonas gingivalis. Non-tumor-derived, immortalized human GMSM-K cells, and human oral squamous cell carcinoma, HSC-3 and H413 cells, were co-cultured with live and heat-inactivated P. gingivalis 2561 (ATCC 33277) and W83 (ATCC BAA-308™). IL-6 and IL-8 were quantified in the culture supernatants after 6 and 24 h. The basal levels of both cytokines and the responses to P. gingivalis were strongly dependent on cell type. GMSM-K cells produced less IL-8 than HSC-3 and H413 cells. Live P. gingivalis induced significant IL-6 and IL-8 secretion in GMSM-K and HSC-3 cells, and heat-inactivation of bacteria enhanced greatly IL-6 and IL-8 stimulation in these cells. Uninfected H413 cells produced high levels of IL-6 and IL-8, but were not responsive to live P. gingivalis; heat-inactivated P. gingivalis up-regulated IL-6 and IL-8 secretion in these cells. Since base-line secretion of IL-6 and IL-8, and responses to P. gingivalis depend on the cell type, conclusions on the responses to P. gingivalis should not be based on studies with a single cell type.

The effect of intraoperative mupirocin irrigation on Staphylococcus aureus within the maxillary sinus.

BACKGROUND: Antibiotic irrigations are occasionally used during endoscopic sinus surgery when gross mucosal infection is present. These irrigations are thought to flush out pathogenic bacteria and decrease the bacterial load within the mucosal surfaces. This treatment, however, has not been studied in vivo and it is unknown whether antibiotic rinses produce a quantitative reduction in pathologic bacteria within the sinus mucosa. The objective of this study was to determine the relative abundance of Staphylococcus aureus within the maxillary sinus and to evaluate the impact of intraoperative mupirocin irrigation on bacterial burden. METHODS: Sixteen patients with symmetric maxillary chronic rhinosinusitis were prospectively enrolled. After bilateral maxillary antrostomies, biopsies were taken of the maxillary sinus mucosa on both sides. In each patient, the right side was irrigated with 240 mL of normal saline (NS) and the left side was irrigated with 240 mL of NS mixed with 60 mg mupirocin. Repeat maxillary sinus mucosal biopsies were taken from each side 7 to 10 days postsurgery. Each biopsy was analyzed using quantitative polymerase chain reaction to determine the presence and relative amount of S. aureus. RESULTS: Mupirocin irrigations were found to significantly reduce the amount of S. aureus found within the maxillary sinus mucosa compared to NS alone. The average fold change between the pre- and posttreatment biopsies on the right and left was 9.05 and 97.42, respectively (p < 0.01). CONCLUSION: Intraoperative mupirocin irrigations significantly reduce the amount of S. aureus detected within the diseased sinus mucosa at up to 10 days postoperatively.