Huaqing Zhao

Background: Pulmonary thromboendarterectomy (PTE) remains the preferred treatment for surgical accessible thrombus in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, residual pulmonary hypertension (PH) can persist post-PTE. Methods: A retrospective single-center analysis of patients that underwent PTE between 2013 and 2023. At 3-month follow-up, we performed a qualitative Echo-Doppler (DE) assessment and applied a semi-quantitative DE scoring system (DESS), assigning point values for six DE parameters: right ventricle (RV) size, RV shape (systolic base–apex ratio), RV function, septal position, tricuspid regurgitation (TR) and RV outflow tract notching (RVOTN). Higher scores suggested a more significant residual PH syndrome. Results: A total of 188 subjects (80%) did not require further PH intervention at ≥3 months (Group A); 48 (20%) required ongoing PH treatment (Group B). The pre-PTE median DESS was 10 and the post-PTE median DESS was 3.00 (range 0–16). The maximum DESS was 17. Using ROC analysis, post-PTE DESS strongly discriminated between Group A and B (AUC 0.76; 95% CI 0.65–0.89; p < 0.001). A post-PTE DESS of >6.5 differentiated Group A and B. Evidence of TR (OR 0.191, CI 0.103–0.279; p < 0.0001) and RV enlargement (OR 0.242; CI 0.153–0.330; p < 0.0001) at follow-up was associated with a need for additional PH interventions. Conclusions: Serial DE examination is a viable, noninvasive method to assess significant residual PH post-PTE.

Aim: Undergraduate medical education in point-of-care ultrasound remains limited. Common barriers to implementation include limited curricular space, financial constraints, and lack of instructors. This pilot study aims to assess the efficacy of a one-day symposium on medical students’ point-of-care ultrasound skills, knowledge, and confidence. Material and methods: The Philadelphia Ultrafest was a single-day educational symposium held in April 2023 for students attending one of seven Philadelphia-area medical schools. Utilizing pre- and post-conference assessments, instructors evaluated background attitudes towards ultrasound, experience level, self-reported confidence, and knowledge of ultrasonography. Pre- and post-test results were compared using McNemar’s or Symmetry Chi Squared analysis. Results: Sixty-six students completed the pre- and post- conference surveys. Before the conference, 62% of students correctly localized abdominal free fluid compared to 89% following the conference (p = 0.02). In identifying transducer type, the correct response rate increased from 78% to 98% (p = 0.004). Before the instruction, students had an average confidence rating of 5.4 out of 10 in their ability to identify organs on exam, compared to 7.7 after Ultrafest (p <0.001). Confidence levels in performing the focused assessment with sonography for trauma examination (3.3 pre vs. 6.7 post; p <0.001) and ultrasound-guided peripheral intravenous catheterization (3.4 pre vs. 6.5 post; p <0.001) also increased after Ultrafest as well. Conclusions: The results demonstrate enhanced sonographic knowledge and confidence following this one-day point-of-care ultrasound symposium. Future studies should evaluate the long-term outcomes of similar educational formats.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment. Neuroinflammatory processes, mediated by glial and immune cells, contribute to neuronal damage. Emerging evidence implicates innate immune mechanisms, including trained immunity and cell trans-differentiation, in AD pathogenesis, though their roles remain unclear. Objective: To investigate transcriptomic changes in the 3xTg-AD mouse model, focusing on trained immunity and cell trans-differentiation in disease mechanisms. Methods: RNA-sequencing was performed on brain tissue (cortex plus hippocampus) from 11-month-old female 3xTg-AD and wild-type mice (n = 3/group). Differentially expressed genes (fold change > 1.5, p < 0.05) were identified and followed by bioinformatics and knowledge-based transcriptomic profiling. Public AD datasets were also analyzed. Results: 3xTg-AD mice exhibited 316 upregulated and 412 downregulated genes. Downregulated genes included those for blood-brain barrier protein, while upregulated genes related to cerebrospinal fluid. Increased expression of proinflammatory markers, as well as genes related to cell differentiation, proliferation, activation, and adhesion. Upregulation of genes associated with cell migration and trans-differentiation suggests a potential role for inflammation and cellular plasticity. Additionally, genes involved in inflammasome pathways, immunometabolism, and trained immunity were upregulated. Mechanistically, these genes were modulated by knockdown of trained immunity promoter SET-7, overexpression of trained immunity inhibitor IL-37, and knockout of inflammasome genes IL-1 receptor, caspase-1, and pattern recognition receptor CD36. Conclusions: The finding underscore the potential role of trained immunity and cell trans-differentiation in AD, revealing a mechanistic framework in which danger-associated molecular patterns drive innate immune responses, inflammasome activation, and cell plasticity contribute to AD, offering therapeutic targets for neuroinflammation and cellular reprograming.

Background. Although COVID-19 is no longer a declared global health emergency, data remain limited on the impact of COVID-19 in lung transplant recipients. Methods. We identified lung transplant recipients who were diagnosed with COVID-19 from March 2020 through August 2022 in our institutional database and investigated clinical outcomes. We then analyzed outcomes based on date of COVID-19 diagnosis (first wave March 2020–October 2020; second wave November 2020–2021; third wave December 2021–September 2022) and compared these results. Results. Of the 210 lung transplant recipients (median age 67; 67% men) enrolled, 140 (67%) required hospital admission. Among admitted recipients, 35 (25%) were intubated and 7 (5%) were placed on extracorporeal membrane oxygenation. Overall survival was 67.1% at 1 y and 59.0% at 2 y post-COVID-19 diagnosis. COVID-19 led to mortality in all 5 patients diagnosed during their index admission for lung transplantation. Although overall survival was significantly better in recipients with COVID-19 during the third wave, in-hospital mortality remained high (first wave 28%, second wave 38%, and 28% third wave). Vaccination (partially vaccinated versus none and fully vaccinated versus none) was the only significant protective factor for hospital admission, and age 70 y and older and partially vaccinated (versus none or fully vaccinated) were independent risk factors for in-hospital mortality. Conclusions. Overall survival after COVID-19 infection in lung transplant recipients continues to improve; however, in-hospital mortality remains remarkably high. Vaccination appears to have been impactful in preventing hospital admission, but its impact on in-hospital mortality is still unclear. Further research is needed to better identify lung transplant recipients at high risk for mortality from COVID-19. Export

There are approximately 2.5 million cases of traumatic brain injury (TBI) in the U.S. each year. Post-traumatic epilepsy (PTE), a sequela of TBI, has been shown to occur in approximately 15% of TBI patients. Pre-disposing risk factors for the development of PTE include severe TBI and penetrating head injury. PTE is associated with poor functional outcomes, increased negative social factors, and mental illness. We conducted a retrospective chart review with a 5-year timeframe at an urban Level 1 Trauma Center. Patients with ICD-10-CM codes associated with TBI were identified. Patients were coded as TBI with or without PTE by the presence of codes associated with PTE. Datapoints collected included risk factors for PTE and encounters with neurologists. A total of 1886 TBI patients were identified, with 178 (9.44%) classified as TBI with PTE. The most significant risk factor associated with PTE was severe brain injury, with an odds ratio (OR) of 2.955 (95% CI [2.062,4.236]; p < 0.0001). Only 19 of 178 patients (10.7%) visited a neurologist beyond 6 months after TBI. Our results suggest the presence of a significant population of patients with PTE and the need for better follow-up.

To determine whether hyperlipidemia and chronic kidney disease (CKD) have a synergy in accelerating vascular inflammation via trained immunity (TI), we performed aortic pathological analysis and RNA-Seq of high-fat diet–fed (HFD-fed) 5/6 nephrectomy CKD (HFD+CKD) mice. We made the following findings: (a) HFD+CKD increased aortic cytosolic LPS levels, caspase-11 ( CASP11 ) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); (b) CASP11 ^–/– decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11–gasdermin D–mediated cytokine secretion; (c) CASP11 ^–/– decreased N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1B levels; (d) LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/ CASP11 (mouse) activation and increased N-GSDMD membrane expression; and (e) IL-1B served as the s econd-tier mechanism underlying HFD+CKD-promoted TI. Taken together, hyperlipidemia and CKD accelerated vascular inflammation by promoting 2-tier trained immunity.

Background: Pelvic venous obstruction (PVO), defined as greater than 50% stenosis or occlusion of pelvic veins, is a known risk factor for deep vein thrombosis (DVT). DVT is a known risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), but the prevalence of PVO in CTEPH is unknown. Methods: This cross-sectional study at Temple University’s tertiary referral center for Pulmonary Hypertension, Right Heart Failure, and CTEPH sought to identify the presence of PVO in patients with CTEPH who underwent cardiac catheterization, pulmonary angiography, and venography. Results: A total of 193 CTEPH patients were referred for pulmonary angiography, and among these, 148 underwent venography. PVO was identified in 65 (44%) patients. Lower extremity (LE) DVT was associated with PVO (p = 0.004). The severity of pulmonary hypertension was similar with and without PVO (mean pulmonary artery pressure 43.0 ± 10.3 mm Hg vs. 43.8 ± 12.4 mm Hg, p = 0.70), as was the need for pulmonary thromboendarterectomy (69.2% vs. 61.4%, p = 0.32). Conclusions: Pelvic vein obstruction is common and a novel clinical association in patients with CTEPH, particularly in patients with a history of LE DVT. PVO and its role in CTEPH warrants further study, including the potential role of revascularization to mitigate further risk.

Adenine nucleotide translocator (ANT) is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner membrane. It plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the cytoplasm. The isoform ANT1 predominately expresses in cardiac and skeletal muscles. Mutations or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular diseases. We aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-deficient mice. Hearts and quadriceps resected from age-matched wild type (WT) and ANT1-deficient mice were snap-frozen in liquid nitrogen. The Chance redox scanner was utilized to perform 3D optical redox imaging. Each sample underwent scanning across 3–5 sections. Global averaging analysis showed no significant differences in the redox indices (NADH, flavin adenine dinucleotide containing-flavoproteins Fp, and the redox ratio Fp/(NADH+Fp) between WT and ANT1-deficient groups. However, quadriceps had higher Fp than hearts in both groups ([ ] and 0.01, respectively). Furthermore, the quadriceps were also more oxidized (a higher redox ratio) than hearts in WT group ([ ]). NADH levels were similar in all cases. Our data suggest that under non-stressful physical condition, the ANT1-deficient muscle cells were in the same mitochondrial state as WT ones and that the significant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-deficient ones. Redox imaging of muscles under physical stress can be conducted in future.