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The aim of this study was to evaluate the effect of gender on operative rates and outcomes in men and women with severe aortic stenosis. An institutional echocardiographic database was used to identify all adult patients with severe aortic stenosis from 2004 through 2005. Only patients with class I indication for aortic valve replacement (AVR) during the period of follow-up were included in the study. Three hundred sixty-two patients were identified with severe aortic stenosis and class I indication for AVR (52% women). Overall operative rate for the cohort was 72%. In patients who underwent AVR, Kaplan-Meier survival rates were the same for men and women. Sixty-four percent of women versus 81% of men underwent AVR (p <0.001). After adjusting for multiple covariates, women had a 2.1-fold lower odds of undergoing AVR compared to men (p = 0.02). After matching for age and Society of Thoracic Surgery risk score, women underwent AVR at a 19% lower relative rate compared to men (p = 0.03); when stratified by gender, there was no difference in reasons for not undergoing AVR. In conclusion, despite similar outcomes after surgery, women with severe aortic stenosis are less likely than men to undergo AVR. [ABSTRACT FROM AUTHOR]

Implantable cardiac devices, including cardiac pacemakers, are not without risk for infection, carrying a mortality and morbidity of around 5-15%. Gram positive organisms are most common in 91% of cases, whereas gram negative organisms are less common, found in 2% of cases secondary to gram negative organisms other than Pseudomonas aeruginosa . Here, we present a rare case of the gram-negative organism Proteus mirabilis leading to a pacemaker site infection., Competing Interests: Conflict of interest: Each author certifies that he/she, a member of his or her immediate family, has no commercial association (i.e., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted manuscript. The authors have not used Generative Artificial Intelligence or Artificial Intelligence associated technologies., (© 2025 Greater Baltimore Medical Center.)

Addison's disease is a rare, autoimmune condition leading to destruction of the adrenal gland. Autoimmune conditions are known to commonly co-occur. When Addison's disease presents in the setting of autoimmune thyroid disease and/or type 1 diabetes, this condition is termed autoimmune polyendocrine syndrome type II, a rare endocrinopathy found in roughly 1.4-4.5 per 100,000 individuals. Here, we describe a clinical case presenting with hypotension refractory to fluid resuscitation and electrolyte derangements later diagnosed as autoimmune polyendocrine syndrome type II., Learning Points: Primary adrenal insufficiency may present clinically as shock refractory to fluid resuscitation.Autoimmune polyglandular syndrome type 2 is a rare autoimmune condition occurring in 1.5-4.5 per 100,000 individuals.The presence of an underlying autoimmune condition should raise suspicion for multiple concurrent autoimmune conditions., Competing Interests: Conflicts of Interests: Each author certifies that he/she, a member of his or her immediate family, has no commercial association (i.e., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted manuscript. The authors have not used generative artificial intelligence or artificial intelligence associated technologies., (© EFIM 2024.)

The incidence and mortality of squamous cell carcinoma of the anus (SCCA) is on the rise, which highlights the unmet need for advances in treatment options. The landscape of treatment for this cancer is rapidly evolving with novel combination strategies including immunotherapy, radiation therapy and biomarker-guided therapy. This review article features an overview of recent advancements in both locoregional and metastatic SCCA. The recent focus on locoregional SCCA management is to tailor treatment according to tumor burden and minimize treatment-related toxicities. Mitomycin plus either infusional 5-fluorouracil (5-FU) or capecitabine is used for first-line chemoradiotherapy (CRT), and intensity-modulated radiotherapy (IMRT) is the preferred modality for radiation for locoregional anal cancer. Locally recurrent disease is managed with surgical resection. Systemic treatment is first-line for metastatic SCCA and immunotherapy with nivolumab and pembrolizumab being included as second-line agents. Current and future clinical trials are evaluating treatments for SCCA including immunotherapy alone or in combination regimens, radiotherapies, targeted treatments and novel agents. Another critical aspect of current research in SCCA is the personalization of CRT and immunotherapies based on molecular characterization and biomarkers such as the programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) and circulating tumor DNA.

Purpose: The purpose of this study is to determine whether bevacizumab is detectable in the breast milk of nursing mothers., Methods: Breast milk samples were collected from 2 patients receiving monthly intravitreal bevacizumab injections for choroidal neovascularization over the course of 16 months. Enzyme-linked immunosorbent assay and Western blot analysis was used to determine the levels of bevacizumab in the milk samples., Results: An enzyme-linked immunosorbent assay was developed using antibodies specific to bevacizumab in which the sensitivity threshold was 3 ng/mL. All breast milk samples assayed from the two patients actively undergoing treatment did not have detectable levels of bevacizumab. Samples collected 1.5 hours and 7 hours after an injection and 2 randomly chosen samples were negative by Western blot analysis., Conclusion: A sensitive assay to detect bevacizumab in breast milk samples assayed suggests that intravitreal injections do not result in detectable bevacizumab in breast milk.

Corneal transplantation is the oldest and one of the most successful transplant procedures with a success rate in many studies in excess of 90%. The high success rate is mainly attributable to the relatively immune-privileged status of the eye and the fact that the cornea is largely avascular. However, the success rate in patients with failed grafts is much lower such that regrafting is frequently the top indication for corneal transplantation in many centers. Neovascularization is the most important risk factor for rejection, as it allows access of the immune system to the donor tissue, compromising immune privilege of the graft/eye. We have developed a process to modify donor corneal tissue to prevent rejection by a single exposure to a gene therapy vector before surgery (EncorStat(®)). The vector used is based on clinically relevant equine infectious anemia virus (EIAV)-derived lentiviral platform and contains genes for two potently angiostatic genes, endostatin and angiostatin. We show that incubation of rabbit, primate, and human corneal tissue with the EIAV vector mediates strong, stable expression in the corneal endothelium. We have optimized this process to maximize transduction and, once this is complete, maximize the removal of free vector before transplant. Rabbit corneas treated with two different antiangiogenic expression vectors (EIAV-EndoAngio and to a lesser extent EIAV-Endo:k5) significantly suppressed neovascularization in a rabbit model of corneal rejection. As a result, corneal opacity, edema, and inflammatory infiltrates were reduced in these corneas. This study demonstrates that angiogenesis is a suitable target to prevent corneal rejection, and provides the first proof-of-concept data for the development of EncorStat, an ex vivo gene therapy treatment to prevent corneal rejection.

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4(216), which represses VEGF promoter activity. The TEAD4(216) isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4(216) protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4(216) isoform can competitively repress the stimulatory activity of the TEAD4(434) and TEAD4(148) enhancers. Synthesis of the native VEGF(165) protein and cellular proliferation is suppressed by the TEAD4(216) isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4(216) isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases.