Jefferson College

HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus's ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood-brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. Although modern ART regimens significantly reduce viral burden and HIV-related morbidity, they do not eliminate neurocognitive complications. Suboptimal CNS drug penetration and certain ART-associated toxicities contribute to CNS dysfunction, persistent neuroinflammation, and accelerated aging of the brain. As PLWH now experience increased life expectancy, prolonged exposure to ART and persistent low-level viral activity exacerbate chronic inflammation, immune activation, and metabolic dysregulation, collectively accelerating neurobiological aging. These pathological processes contribute to the development of HIV-associated neurocognitive disorders (HAND), which affect nearly half of virally suppressed PLWH. This review examines HIV-associated inflammation, neurotoxic pathways, and accelerated aging in PLWH in the modern ART era.

Buprenorphine (BUP) is widely used in the treatment of neonatal opioid withdrawal syndrome (NOWS). However, the most compounded formulation contains 30% ethanol, despite regulatory and clinical concerns regarding ethanol exposure in pediatric patients. Thus, this research aimed to develop an ethanol-free sublingual (SL) gel formulation of BUP that would be safe, stable, and suitable for NOWS. Multiple polymers were screened as gelling agents, with hydroxypropyl methylcellulose (HPMC) emerging as the ideal base polymer for the formulation due to its optimal pH, rheological characteristics, and stability. The formulated gels were stored at room temperature and refrigerated conditions for 30 days and evaluated for stability using pH, rheology, and liquid chromatography-mass spectrometry. BUP content was between 90-110% of the labeled amount of the dosage form (75 µg/mL) at all time-points, and the pH remained close to physiological values. Release studies demonstrated a drug release of 23-24% for SL gels without surfactants stored at room temperature and refrigerated conditions, respectively. Incorporation of non-ionic surfactants (Tween 20 and Tween 80) significantly increased drug release to 33% and 40%, respectively, reflecting enhanced solubilization and improved mucosal penetration. The ethanol-free formulation demonstrated physicochemical stability and favorable release characteristics suitable for neonatal administration. These findings represent a meaningful advance in the development of safer pediatric formulations for NOWS.

Recommended therapy for cervical and other pelvic cancers relies on external beam radiation therapy with brachytherapy. The total biologically equivalent dose in 2 Gy fractions delivered to the tumor ranges from 60 to 90 Gy. The addition of brachytherapy boosts tumor dose and substantially improves 5-year survival, but unavoidable radiation exposure of surrounding vaginal tissue often induces fibrotic scarring which constricts the vaginal vault and can result in complete occlusion. This condition is termed vaginal stenosis, a serious, chronic syndrome which leads to sexual dysfunction and may obstruct gynecological surveillance for cancer recurrence. Clinical management consists of self-administered vaginal dilation with hard plastic rods, an approach that is effective when applied consistently. However, many women are reluctant to use these dilators because the underlying rationale and the methodology are often inadequately presented, and dilator use can be painful and even injurious. Additional challenges with clinically managing vaginal stenosis include incompletely characterized radiation dosimetry, the absence of widely standardized diagnostic and assessment criteria, and an absence of innovative new therapeutics that are both well tolerated and efficacious. Accordingly, in the present review we begin by describing the pathogenesis of vaginal stenosis and focus on risk factors including irradiation modalities and methods and nonadherence to dilator use. Subsequently, in this context we address the key importance of standardized stenosis assessment and identify current inconsistencies in clinical reporting. Finally, within the above landscape we highlight potential innovations for protecting vaginal tissue and promoting vaginal recovery in pelvic radiotherapy patients.

Lyme disease (LD) cases have doubled globally. LD is a tick-borne illness caused by the Borrelia burgdorferi sensu lato (Bb). If untreated, Bb can disseminate to distal organs, causing carditis, arthritis, and meningitis. Currently, no FDA-approved human LD vaccine exists on the market. This study used two approaches to incorporate OspA into the rabies virus (RABV) vaccine vector. We used the RABV-glycoprotein tail (RVG tail) and the Hendra virus (HeV) glycoprotein tail (HVG tail) to incorporate OspA, creating BNSP333-OspA-RVG and BNSP333-OspA-HVG, respectively. Both vaccines produced type-1 biased anti-OspA antibodies, but only BNSP333-OspA-HVG induced neutralizing antibodies and protected against Bb infection. Furthermore, BNSP333-OspA-HVG was combined with an established LD vaccine, BNSP333-BBI39-dRVG, to study a multivalent LD vaccine. The single and multivalent vaccines produced robust type-1 biased humoral responses and induced protection against Bb after short-term and long-term tick challenge experiments. These findings contributed to the development of future LD vaccines.

Background: Patients with left ventricular assist devices (LVADs) experience high mortality and infection-related complications. While Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in various populations, their safety and efficacy in advanced heart failure patients on mechanical support remain understudied. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Using ICD-10 and procedural codes, adults with a diagnosis of LVAD (ICD-10: Z95.811) and a history of LVAD-related procedures were identified. Only GLP-1 RAs with proven cardiovascular outcomes -liraglutide, dulaglutide, semaglutide, and tirzepatide- were included. Patients exposed to GLP-1 RAs after LVAD placement formed the GLP1 RA group. Those without GLP-1 RA exposure comprised the control group. Propensity score matching (1:1) was performed on demographics, comorbidities (diabetes, chronic kidney disease, obesity, ischemic heart disease, atrial fibrillation), and medications. Outcomes were assessed over a 5-year follow up period from the index date. The primary outcome was all-cause mortality. Secondary outcomes included hospitalization, device infections, endocarditis, and MRSA/MSSA bloodstream infections. Results: After matching , 543 patients were included in each cohort. The GLP1 group showed significantly lower mortality (17.3% vs. 33.9%, HR 0.40, 95% CI: 0.31–0.51, p<0.001) and higher 5-year survival probability (70.3% vs. 45.6%). Hospitalization was also reduced (69.6% vs. 82.5%, HR 0.44, p<0.001), with longer median time to first admission (241 vs. 34 days). Bloodstream infections were significantly lower in GLP-1 users (20.4% vs. 26.5%, HR 0.61, p=0.001). Device-specific infections was similar in both cohorts (HR 0.86, p=0.13). Endocarditis showed a favorable trend among the GLP-1 RA group but did not reach statistical significance (HR 0.52, p=0.050), possibly due to limited statistical power. Conclusion: In this large real-world analysis, GLP-1 RA use in patients with LVADs was associated with significantly lower long-term mortality, reduced hospitalizations, and fewer bloodstream infections. Although device-specific infections were unaffected, these findings provide observational evidence suggesting possible cardiovascular and infection-related benefits of GLP-1 RAs in advanced heart failure populations. Prospective studies are warranted to confirm safety and efficacy in this unique cohort.

This prospective, multicenter study assessed the radiographic, clinical, and patient-reported outcomes for hallux valgus (HV) correction performed with an instrumented 1st tarsometatarsal (TMT) system through a mini-open incision (≤4cm) with a biplanar plating construct and early return to weightbearing. One hundred and five patients were treated, with 75 and 11 patients completing their 12- and 24-month visits, respectively. The median (min, max) length of the primary dorsal incision was 3.5 cm (3.0, 4.0). Patients underwent an early weightbearing protocol with mean (95 % CI) of 7.9 (6.7, 9.1) days to weightbearing in a CAM boot. Significant improvements from baseline in mean radiographic measurements for Hallux Valgus Angle (HVA), Intermetatarsal Angle (IMA), Tibial Sesamoid Position (TSP), and osseous foot width (OFW) were maintained through 12 months. Using recurrence definitions of greater than 15° and 20° postoperative HVA, recurrence rates were 5.5 % (95 % CI: 1.5 %, 13.4 %) and 0.0 % at 12 months and 0.0 % for both thresholds at 24 months, respectively. Significant improvements in patient-reported outcomes [Visual Analog Scale (VAS), Manchester-Oxford Foot Questionnaire (MOxFQ) and Patient-Reported Outcomes Measurement Information System (PROMIS)] were maintained through 12 and 24 months. A clinically meaningful assessment of the scar appearance was observed in the POSAS scores. One (1.0 %) patient in the overall treated cohort of 105 required reoperation for removal of hardware due to pain. The results of this prospective, multicenter study on a mini-open 1st TMT system demonstrated improvements in radiographic correction, low recurrence, early return to activity with low complication rates, and improvements in patient-reported outcomes.

Background: This study assessed the knowledge and preparedness of clinical-year medical students in the Western Region of Saudi Arabia regarding respiratory emergencies. The objective was to evaluate their understanding of critical respiratory conditions and identify gaps in education that may hinder effective patient management. By highlighting deficiencies in training, the study aimed to support the development of improved educational strategies to better equip future physicians for respiratory crises. Methods: A cross-sectional design was used, involving fourth- to sixth-year medical students from various Saudi universities. A structured digital questionnaire evaluated their knowledge on the recognition, diagnosis, investigation, and management of respiratory emergencies, including acute exacerbations of COPD, asthma, pulmonary embolism, chest trauma, and respiratory failure. Pre-clinical students, those studying abroad, and non-medical students were excluded. Data were analyzed using descriptive and inferential statistics, with knowledge levels classified on a three-point scale. Results: The findings revealed that while students generally recognized clinical signs and symptoms of conditions such as pulmonary embolism and acute respiratory failure, there were significant gaps in their understanding of appropriate diagnostic and initial management strategies. Certain demographic factors, including marital status, were associated with variations in knowledge levels. Conclusion: The study highlighted a concerning lack of preparedness among clinical-year students in handling respiratory emergencies, despite a high level of theoretical awareness. These findings underline the urgent need to strengthen medical curricula with focused education and practical training on respiratory emergency management to ensure competent and effective future physicians.