Systematic Review and Meta-Analysis to Assess the Racial Disparities in the Outcomes of Carotid Endarterectomy in the United States.

OBJECTIVE: Race-based disparities in healthcare have been related to a myriad of prevailing factors among minorities in the United States. This study aims to study the race-based differences in the outcomes of carotid endarterectomy (CEA). METHODS: The PROSPERO database registered the review protocol (CRD42023428253). A systematic English literature review was performed using literature databases PubMed and Scopus from inception till June 2023. The review was designed on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and included studies reporting mortality, stroke or composite outcome of mortality and stroke after CEA for carotid artery disease, regardless of any degree of stenosis including both symptomatic and asymptomatic patients. The risk of bias was evaluated utilizing the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool. A pooled odds ratio (OR) for the overall mortality was computed, and a p-value of <0.05 was designated as statistically significant. Interstudy heterogeneity was evaluated by Q-metric and quantified using Higgins I2 statistics. RESULTS: Twelve studies were identified which included a total of 574,055 patients, who underwent CEA from 1998 to 2022. 11 out of 12 studies reported 30-day mortality as an outcome for patients undergoing CEA in which 52,4708 (92.5%) patients were white and 42797 (7.5%) were non-white. The overall pooled OR indicated a statistical significance in 30-day mortality between white and non-white patients undergoing CEA (OR: 1.73 [1.37-2.18], p=0.011) with substantial heterogeneity (I2 = 56.3%). 11 out of 12 studies reported stroke as an outcome for patients undergoing CEA in which 52,4708 (92.5%) patients were white and 42,801 (7.5%) were non-white. The overall pooled OR indicated no statistical significance in stroke between white and non-white patients undergoing CEA (OR:1.46 [1.28, 1.65], p = 0.111) with moderate heterogeneity (I2 = 35.9%). 5 out of 12 studies reported composite mortality or stroke as an outcome for patients undergoing CEA. The overall pooled OR indicated no statistical significance in composite mortality or stroke between white and non-white patients undergoing CEA (OR: 1.40 [1.24-1.59], p = 0.467) with no heterogeneity (I2 = 0.0%). CONCLUSION: Non-White patients have a relatively higher risk of mortality; however no significant difference was observed between the racial groups in terms of stroke or a composite outcome of mortality or stroke. The odds of mortality in Non-White patients have been persistent throughout recent studies.

Patients living farther from a tertiary care center are more likely to undergo peripheral arterial bypass for acute and chronic limb-threatening ischemia.

OBJECTIVE: The aim of this study was to assess the association between the proximity to the tertiary care hospital and the severity of peripheral arterial disease (PAD) at the time of lower extremity bypass (LEB) in a rural-urban mix region. METHODS: Patients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on a median distance from hospital (ie, Group I: ≥34 miles and Group II: <34 miles). Patients' demographic features, preoperative data including comorbidities, and medications were analyzed. A univariate analysis for the patient characteristics between the two study groups, along with evaluation of postoperative outcomes, and a multivariate predictive modeling to study the PAD stage as the indication of LEB was performed. A P-value of < .05 was set as a significant difference between the groups for all the analyses. RESULTS: There were 175 patients (49.9%) in Group I and 176 patients (50.1%) in Group II with a mean age of 65 ± 11.92 years (median, 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between study groups. It was observed that patients in Group I were more likely to be overweight or obese (71.3% vs 57%; P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%; P = .036) in comparison to Group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in Group I had 56% higher likelihood of LEB for chronic limb-threatening ischemia (adjusted odds ratio, 1.56; 95% confidence interval, 0.92-2.62; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (adjusted odds ratio, 5.07; 95% confidence interval, 1.42-18.13; P = .012) as compared with those in the Group II. CONCLUSIONS: Patients' proximity to a major tertiary hospital may have implications on the disease progression for patients with PAD and could also be related to inadequate vascular services in primary and secondary hospitals. Lack of preventive care and disease management in regions afar from a tertiary hospital could be other implicating factors and highlights the need for outreach programs, along with distribution of vascular specialists, to reduce geographical disparities and ensure equity in access to care.

Isolated diffuse intestinal ganglioneuromatosis presented as a redundant sigmoid colon: a case report.

Diffuse intestinal ganglioneuromtosis is a benign tumor of the enteric nervous system, that almost always occurs in children with systemic syndromes. Whereas isolated cases in adults are exceedingly rare. Case Presentation: A 38-year-old man presented with refractory chronic constipation. An abdominal computed tomography scan revealed a redundant sigmoid colon, then he underwent a sigmoid colectomy. Histopathologic examination showed diffuse ganglioneuromatosis. However, the patient was in good health 18 months after surgery. Clinical Discussion: Intestinal ganglioneuromas commonly occur in children with systemic syndromes such as multiple endocrine neoplasia type 2B and neurofibromatosis type 1. The most frequent symptoms are abdominal discomfort, constipation, ileus, weight loss, appendicitis, and obstruction in more severe cases. surgical resection is the standard management in diffuse ganglioneuromatosis. Conclusion: Although diffuse ganglioneuromatosis is uncommon, it should be considered in patients with refractory constipation.

Increased p53 expression induced by APR-246 reprograms tumor-associated macrophages to augment immune checkpoint blockade.

In addition to playing a major role in tumor cell biology, p53 generates a microenvironment that promotes antitumor immune surveillance via tumor-associated macrophages. We examined whether increasing p53 signaling in the tumor microenvironment influences antitumor T cell immunity. Our findings indicate that increased p53 signaling induced either pharmacologically with APR-246 (eprenetapopt) or in p53-overexpressing transgenic mice can disinhibit antitumor T cell immunity and augment the efficacy of immune checkpoint blockade. We demonstrated that increased p53 expression in tumor-associated macrophages induces canonical p53-associated functions such as senescence and activation of a p53-dependent senescence-associated secretory phenotype. This was linked with decreased expression of proteins associated with M2 polarization by tumor-associated macrophages. Our preclinical data led to the development of a clinical trial in patients with solid tumors combining APR-246 with pembrolizumab. Biospecimens from select patients participating in this ongoing trial showed that there was a suppression of M2-polarized myeloid cells and increase in T cell proliferation with therapy in those who responded to the therapy. Our findings, based on both genetic and a small molecule-based pharmacological approach, suggest that increasing p53 expression in tumor-associated macrophages reprograms the tumor microenvironment to augment the response to immune checkpoint blockade.

Structure of an endosomal signaling GPCR-G protein-ß-arrestin megacomplex.

Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by ß-arrestin (ß-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-ß-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine ß-arr to the core and phosphorylated tail, respectively, of a single active human chimeric ß2-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (ß2V2R). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and ß-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling.

Efficacy of Laparoscopy in Diagnosis and Treatment of Chronic Abdominal Pain of Unknown Origin.

Chronic abdominal pain of unknown origin is a challenging diagnosis encountered by clinicians. Patients often undergo an extensive workup and long periods of uncertainty without the establishment of a definitive diagnosis. Diagnostic laparoscopy is a relatively safe procedure that can be used as an effective diagnostic and therapeutic tool in treating this disease. This was a retrospective, single-institution study exploring the efficacy of diagnostic laparoscopy in treating chronic abdominal pain of unknown origin. More than 90 per cent of laparoscopies resulted in a positive finding, with adhesions being the most common. A total of 50 per cent of patients experienced resolution of symptoms on follow-up. Patients were overwhelmingly satisfied with their postoperative outcomes and willing to undergo the procedure again with their outcomes in mind.