Racial and Ethnic Variations in Patients Undergoing Mitral and Tricuspid Valve Surgery.

INTRODUCTION: Prior investigations assessing the impact of race/ethnicity on outcomes after mitral valve (MV) surgery have reported conflicting findings. This analysis aimed to examine the association between race/ethnicity and operative presentation and outcomes of patients undergoing MV and tricuspid valve (TV) surgery. METHODS: We retrospectively analyzed 5984 patients (2730 female, median age 63 y) who underwent MV (n = 4,534, 76%), TV (n = 474, 8%) or both MV and TV (n = 976, 16%) surgery in a statewide collaborative from 2012 to 2021. The influence of race/ethnicity on preoperative characteristics, MV and TV repair rates, and postoperative outcomes was assessed for White (n = 4,244, 71%), Black (n = 1,271, 21%), Hispanic (n = 144, 2%), Asian (n = 171, 3%), and mixed/other race (n = 154, 3%) patients. RESULTS: Black patients, compared to White patients, had higher Society of Thoracic Surgeons predicted risk of morbidity/mortality (24.5% versus 13.1%; P < 0.001) and more comorbid conditions. Compared to White patients, Black and Hispanic patients were less likely to undergo an elective procedure (White 71%, Black 55%, Hispanic 58%; P < 0.001). Degenerative MV disease was more prevalent in White patients (White 62%, Black 41%, Hispanic 43%, Asian 51%, mixed/other 45%; P < 0.05), while rheumatic disease was more prevalent in non-White patients (Asian 28%, Hispanic 26%, mixed/other 25%, Black 17%, White 10%;P < 0.05). After multivariable adjustment, repair rates and adverse postoperative outcomes, including mortality, did not differ by racial/ethnic group. CONCLUSIONS: Patient race/ethnicity is associated with a higher burden of comorbidities at operative presentation and MV disease etiology. Strategies to improve early detection of valvular heart disease and timely referral for surgery may improve outcomes.

NOTCH3 and Pulmonary Arterial Hypertension.

NOTCH3 receptor signaling has been linked to the regulation of smooth muscle cell proliferation and the maintenance of smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (World Health Organization Group 1 idiopathic disease: PAH) is a fatal disease characterized clinically by elevated pulmonary vascular resistance caused by extensive vascular smooth muscle cell proliferation, perivascular inflammation, and asymmetric neointimal hyperplasia in precapillary pulmonary arteries. In this review, a detailed overview of the specific role of NOTCH3 signaling in PAH, including its mechanisms of activation by a select ligand, downstream signaling effectors, and physiologic effects within the pulmonary vascular tree, is provided. Animal models showing the importance of the NOTCH3 pathway in clinical PAH will be discussed. New drugs and biologics that inhibit NOTCH3 signaling and reverse this deadly disease are highlighted.

Neighborhood-Level Socioeconomic Disadvantage Predicts Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. PATIENTS AND METHODS: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). RESULTS: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS. CONCLUSIONS: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies.

Mortality risk prediction for primary appendiceal cancer.

BACKGROUND: Accurately predicting survival in patients with cancer is crucial for both clinical decision-making and patient counseling. The primary aim of this study was to generate the first machine-learning algorithm to predict the risk of mortality following the diagnosis of an appendiceal neoplasm. METHODS: Patients with primary appendiceal cancer in the Surveillance, Epidemiology, and End Results database from 2000 to 2019 were included. Patient demographics, tumor characteristics, and survival data were extracted from the Surveillance, Epidemiology, and End Results database. Extreme gradient boost, random forest, neural network, and logistic regression machine learning models were employed to predict 1-, 5-, and 10-year mortality. After algorithm validation, the best-performance model was used to develop a patient-specific web-based risk prediction model. RESULTS: A total of 16,579 patients were included in the study, with 13,262 in the training group (80%) and 3,317 in the validation group (20%). Extreme gradient boost exhibited the highest prediction accuracy for 1-, 5-, and 10-year mortality, with the 10-year model exhibiting the maximum area under the curve (0.909 [±0.006]) after 10-fold cross-validation. Variables that significantly influenced the predictive ability of the model were disease grade, malignant carcinoid histology, incidence of positive regional lymph nodes, number of nodes harvested, and presence of distant disease. CONCLUSION: Here, we report the development and validation of a novel prognostic prediction model for patients with appendiceal neoplasms of numerous histologic subtypes that incorporate a vast array of patient, surgical, and pathologic variables. By using machine learning, we achieved an excellent predictive accuracy that was superior to that of previous nomograms.

To close or not to close? Wound management in emergent colorectal surgery, an EAST multicenter prospective cohort study.

BACKGROUND: This study aimed to determine the clinical impact of wound management technique on surgical site infection (SSI), hospital length of stay (LOS), and mortality in emergent colorectal surgery. METHODS: A prospective observational study (2021-2023) of urgent or emergent colorectal surgery patients at 15 institutions was conducted. Pediatric patients and traumatic colorectal injuries were excluded. Patients were classified by wound closure technique: skin closed (SC), skin loosely closed (SLC), or skin open (SO). Primary outcomes were SSI, hospital LOS, and in-hospital mortality rates. Multivariable regression was used to assess the effect of wound closure on outcomes after controlling for demographics, patient characteristics, intensive care unit admission, vasopressor use, procedure details, and wound class. A priori power analysis indicated that 138 patients per group were required to detect a 10% difference in mortality rates. RESULTS: In total, 557 patients were included (SC, n = 262; SLC, n = 124; SO, n = 171). Statistically significant differences in body mass index, race/ethnicity, American Society of Anesthesiologist scores, EBL, intensive care unit admission, vasopressor therapy, procedure details, and wound class were observed across groups. Overall, average LOS was 16.9 ± 16.4 days, and rates of in-hospital mortality and SSI were 7.9% and 18.5%, respectively, with the lowest rates observed in the SC group. After risk adjustment, SO was associated with increased risk of mortality (OR, 3.003; p = 0.028) in comparison with the SC group. Skin loosely closed was associated with increased risk of superficial SSI (OR, 3.439; p = 0.014), after risk adjustment. CONCLUSION: When compared with the SC group, the SO group was associated with mortality but comparable when considering all other outcomes, while the SLC was associated with increased superficial SSI. Complete skin closure may be a viable wound management technique in emergent colorectal surgery. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

How To Do It: Mitral Valve Translocation.

Mitral valve translocation (MVT) is a novel procedure that was developed to treat patients with severe, symptomatic, secondary mitral regurgitation (MR). MVT enhances leaflet coaptation by insertion of an autologous pericardial patch interposed between the mitral annulus and the native mitral leaflets. The patch substantially increases total leaflet surface area and creates supranormal coaptation. In addition, it relieves leaflet tethering by transposing the native valve deeper into the ventricle and decreases the circumference of the annulus. The enhanced coaptation produced by MVT may protect against recurrent MR in patients with continued adverse left ventricular remodeling. The procedural steps include detachment of the intact native mitral valve at the annulus, placement of interrupted pledgeted sutures around the annulus to secure the proximal aspect of the patch, and attachment of the native valve to the distal aspect of the patch using running suture. Follow-up of patients who have undergoing MVT is ongoing, with satisfactory short-term results, including sustained MR grades of ≤mild and 14 mm coaptation at 12 months.

The epidemiology of firework-related injuries in the US, 2012-2022.

BACKGROUND: This study aimed to examine the epidemiology of firework-related injuries within a national population between 2012 and 2022, including the severity of injury by year, patient demographics, body region injured, firework type, and diagnosis category of injury. METHODS: Data were collected from the Consumer Product Safety Commission's National Electronic Injury Surveillance System, which is a representative nationwide database that collects data on consumer product-related injuries occurring in the US. Injury rates were calculated based on patient age, sex, body region injured, firework type, and diagnosis category. RESULTS: A total of 3219 injuries, representing an estimated 122,912 firework-related injuries, were treated in emergency departments within the US from 2012 to 2022. The overall incidence rate of firework-related injuries in the study rose by over 17% from 2012 [2.61 cases per 100,000 people (95% CI 2.03-3.20)] to 2022 and [3.05 cases per 100,000 people (95% CI 2.29-3.80)]. The rate of injuries was highest in adolescents and young adults (age 20-24; 7.13 cases per 100,000 people). Men experienced firework injuries at more than double the rate of women (4.90 versus 2.25 cases per 100,000 people). The upper extremities (41.62%), head/neck (36.40%), and lower extremities (13.78%) were the most commonly injured regions. Over 20% of cases in patients older than 20 were significant injuries requiring hospitalization. Aerial devices (32.11%) and illegal fireworks (21.05%) caused the highest rates of significant injury of any firework type. CONCLUSIONS: The incidence of firework-related injuries has risen over the past decade. Injuries remain the most common among adolescents and young adults. In addition, significant injuries requiring hospitalization occur most often during aerial and illegal firework use. Further targeted sale restrictions, distribution, and manufacturing regulations for high-risk fireworks are required to reduce the incidence of significant injury.

Influence of operative timing on perioperative outcomes of patients with the seatbelt sign.

Background: The seatbelt sign (SBS) is a pattern of bruising/contusions on the chest and abdominal wall following motor vehicle collisions. The aim of this analysis is to investigate the influence of time to surgery following identification of the SBS on perioperative outcomes. Methods: A retrospective review of the Trauma Quality Improvement Program database from 2017 to 2019 was performed. Patients included in this retrospective analysis were involved in motor vehicle collisions, experienced blunt abdominal trauma, presented with skin abrasions/contusions in the SBS distribution, were hemodynamically stable, and underwent laparotomy. Demographics, vital signs, injury severity score, Glasgow coma scale, preoperative CT scans (P-CT), and time from presentation to surgery were recorded. Time from presentation to surgery was subdivided by data quartiles as immediate (<1.3 h), early (1.3-4 h), and delayed (>4 h). The influence of operative timing on postoperative mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, and ventilator days was assessed in multivariate analyses. Results: A total of 1523 patients were included; 280 underwent immediate, 610 early, and 633 delayed surgery. Patients undergoing surgery in the early and delayed groups who received P-CT scans had shorter mean times to operation (4.52 h vs 5.24 h, p < 0.01). In multivariate analysis, patients who underwent delayed surgery stayed in the hospital 2.5 days longer (p < 0.001), spent 2.8 additional days in the ICU (p < 0.001), and spent 3.75 additional days on a ventilator (p < 0.001) than patients who received early surgery. Within the early and delayed surgical groups, P-CT was associated with lower mortality (OR 0.46 95 % CI 0.24-0.88, p < 0.01) in multivariate analysis. Conclusions: Early surgical intervention was associated with improved patient outcomes by reducing hospital and ICU LOS and ventilator days. Conducting P-CT reduced the time to surgery and mortality. Utilization of P-CT for screening hemodynamically stable patients with the SBS upon admission may expedite identification of the potential need for surgical management of abdominal injury.

Racial and ethnic variation in referral times for thoracic oncologic surgery in a major metropolitan area.

OBJECTIVE: The study objective was to understand the impact of race/ethnicity on access to thoracic surgical care for patients undergoing lung resection for cancer. METHODS: We performed a retrospective analysis on 206 consecutive patients who underwent lung resection for cancer (120 female, 86 male; median age 66 years), with respect to how race and ethnicity impact time to referral for thoracic surgery to a major healthcare center. Time between initial radiographic appearance of a lung nodule/mass 1 cm or greater to surgical referral and time from surgical referral to operation were evaluated for 121 White, 30 Asian, 26 Hispanic, 12 African American, and 17 mixed or other race patients. The impact of age, sex, median income of patient's household, national and state Area Deprivation Indices, insurance type, and distance between the patient's domicile and our hospital was evaluated. The influence of the referring physician's practice (hospital-based, hospital-affiliated, or private), internal or external referral, race/ethnicity, and level of specialization was also studied. RESULTS: African American, Asian, Hispanic, and mixed/other race patients had significantly longer wait times between initial radiographic finding of a lung nodule/mass 1 cm or greater and surgical referral compared with White individuals (median days: African American, 78; Asian, 95; Hispanic, 92; mixed or other, 65; White, 35). Multiple linear regression analysis demonstrated that race/ethnicity was the only significant predictor of prolonged time to surgical referral when adjusted for age, sex, median household income level, national and state Area Deprivation Indices, insurance type, and distance between patient's home and our hospital. The referring physician's type of practice and internal versus external referral were not significant. However, the physician's race/ethnicity and level of specialization had an impact on referral times, with nonspecialists referring patients sooner to thoracic surgery compared with specialists who ordered more workup tests. For all patient races/ethnicities, there was no difference in time between surgical referral and day of operation. CONCLUSIONS: Race and ethnicity have a major impact on the time from initial radiographic appearance of a lung nodule/mass 1 cm or greater to referral for surgical resection for cancer. This study suggests the need to develop strategies to reduce minority wait times and improve timely access to surgery for patients with thoracic malignancies. VIDEO ABSTRACT: Discussion of how race and ethnicity impact referral time to thoracic surgery discussed by Dr Moises Hernandez.

'From Gut to Heart': A rare case of Salmonella Typhimurium Bacteremia and native valve endocarditis.

Background: Salmonella species are very rarely associated with infective endocarditis, accounting for less than 0.01-2.9 % of total bacterial endocarditis cases. Since 1976, there have less than 90 reported cases of non-Typhoidal Salmonella bacteremia and endocarditis. Case presentation: We present the case of a 57-year-old homeless man with a past medical history significant only for polysubstance abuse. He presented to the emergency department with a 3-day history of severe, non-bloody diarrhea, nausea, chills, and oliguria. Due to the patient's history of substance use, screening laboratory tests were conducted and were positive for rapid plasma reagin, treponemal antibodies, and hepatitis C. For the profuse diarrhea and severe volume loss, C. difficile, stool white blood cells and stool ova and parasites were ordered but were ultimately negative. Both sets of blood cultures were found to be positive for Salmonella Typhimurium bacteremia. Further workup with transthoracic and transesophageal echocardiogram displayed small mobile masses attached to the aortic surface of the right and non-coronary cusps, confirming endocarditis on the aortic valve. Treatment included penicillin-G once a week for 3 weeks for latent syphilis and ceftriaxone and levofloxacin for bacteremia and endocarditis. Conclusions: Patients with Salmonella typically present early with gastrointestinal symptoms, but clinicians should consider cardiovascular imaging if blood cultures are found to be positive in order to potentially identify and promptly treat highly fatal Salmonella endocarditis.

Panniculus morbidus resection complicated by multiple gastrointestinal hernias: A case report.

Introduction: Prevalence of obesity and obesity-related complications are steadily rising in the United States. Panniculus morbidus is a rare end stage complication of abdominal obesity characterized by excess abdominal skin and subcutaneous tissue induced by severe lymphedema. The resulting pannus can limit a patient's mobility, impair activities of daily living including hygiene maintenance and subject the skin and soft tissue to intertrigo, cellulitis and chronic skin ulcerations. Case presentation: We present the case of a 39-year-old female with a BMI of 57 kg/m2 who presented for evaluation of primary umbilical and ventral hernias, as well as a large pannus causing significant abdominal and back pain. A massive panniculectomy with hernia repair was performed to correct the gastrointestinal herniation and panniculus. Clinical discussion: Panniculus morbidus is a debilitating complication of longstanding obesity. Massive panniculectomy is one of the only treatments available to restore functional status and facilitate future weight loss. Ventral and umbilical hernias commonly accompany panniculus morbidus and can pose a challenge to repair. Conclusion: This case demonstrates that both panniculus morbidus and multiple primary gastrointestinal hernias can be effectively managed with a panniculectomy and concomitant hernia repair with onlay mesh, all together safely improving patient ambulation, weight loss and quality of life.

Racial and ethnic variation in emergent surgical care and outcomes during the COVID-19 pandemic: post hoc analysis of an EAST MCT.

Objectives: The COVID-19 pandemic highlighted concerns regarding the equity of medical care. We evaluated associations between race/ethnicity, timing of hospital presentation and outcomes of acute appendicitis (AP) and acute cholecystitis (AC) during the initial pandemic peak. Methods: Analysis was performed on a prospective, observational, multicenter study of adults with AP or AC. Patients were categorized as pre-pandemic (pre-CoV: October 2019-January 2020) or during the first pandemic peak (CoV: April 2020 through 4 months following the end of local pandemic restrictions). Patient demographics, American Association for the Surgery of Trauma (AAST) imaging/pathology grade, duration of symptoms before triage, time from triage to intervention and hospital length of stay were collected. Results: A total of 2165 patients (1496 pre-CoV, 669 CoV) were included from 19 centers. Asian and Hispanic patients with AC had a longer duration of symptoms prior to presentation during CoV than pre-CoV (100.6 hours vs 37.5 hours, p<0.01 and 85.7 hours vs 52.5 hours, p<0.05, respectively) and presented later during CoV than Black or White patients (34.3 and 37.9 hours, p<0.01). During CoV, Asian patients presented with higher AAST pathology grade for AP compared with pre-CoV (1.90 vs 1.26, p<0.01). Asian and Hispanic patients presented with higher AAST pathology grade for AC during CoV versus pre-CoV (2.57 vs 1.45, p<0.01, and 1.57 vs 1.20, p<0.05, respectively). Patients with AC and an AAST pathology grade of ≥3 were at higher odds of postoperative complications (OR 4.4, 95% CI 1.0 to 18.4) and AP (OR 2.8, 95% CI 1.3 to 6.0). Asian and Hispanic patients with AC had a higher risk of postoperative complications compared to White patients (Asian: OR 3.9, 95% CI 1.2 to 12.7; Hispanic: OR 3.3, 95% CI 1.2 to 8.9). Conclusion: Asian and Hispanic patients had a longer duration of symptoms before hospital presentation during the initial COVID-19 peak, had higher odds of postoperative complications and more advanced pathologic disease. Level of evidence: III, Prognostic/epidemiological.

JAGGED-NOTCH3 signaling in vascular remodeling in pulmonary arterial hypertension.

Within the pulmonary arterial tree, the NOTCH3 pathway is crucial in controlling vascular smooth muscle cell proliferation and maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (PAH) is a fatal disease without cure, characterized by elevated pulmonary vascular resistance due to vascular smooth muscle cell proliferation in precapillary arteries, perivascular inflammation, and asymmetric neointimal hyperplasia. Here, we show that human PAH is characterized by overexpression of the NOTCH ligand JAGGED-1 (JAG-1) in small pulmonary artery smooth muscle cells and that JAG-1 selectively controls NOTCH3 signaling and cellular proliferation in an autocrine fashion. In contrast, the NOTCH ligand DELTA-LIKE 4 is minimally expressed in small pulmonary artery smooth muscle cells from individuals with PAH, inhibits NOTCH3 cleavage and signaling, and retards vascular smooth muscle cell proliferation. A new monoclonal antibody for the treatment of PAH, which blocks JAG-1 cis- and trans-induced cleavage of the NOTCH3 receptor in the pulmonary vasculature, was developed. Inhibition of JAG-1-induced NOTCH3 signaling in the lung reverses clinical and pathologic pulmonary hypertension in two rodent models of disease, without toxic side effects associated with nonspecific NOTCH inhibitors. Our data suggest opposing roles of NOTCH ligands in the pulmonary vasculature in pulmonary hypertension. We propose that selectively targeting JAG-1 activation of NOTCH3 may be an effective, safe strategy to treat PAH.

A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan.

Background: Aging is associated with increased levels of reactive oxygen species and inflammation that disrupt proteostasis and mitochondrial function and leads to organism-wide frailty later in life. ARA290 (cibinetide), an 11-aa non-hematopoietic peptide sequence within the cardioprotective domain of erythropoietin, mediates tissue protection by reducing inflammation and fibrosis. Age-associated cardiac inflammation is linked to structural and functional changes in the heart, including mitochondrial dysfunction, impaired proteostasis, hypertrophic cardiac remodeling, and contractile dysfunction. Can ARA290 ameliorate these age-associated cardiac changes and the severity of frailty in advanced age? Methods: We conducted an integrated longitudinal (n = 48) and cross-sectional (n = 144) 15 months randomized controlled trial in which 18-month-old Fischer 344 x Brown Norway rats were randomly assigned to either receive chronic ARA290 treatment or saline. Serial echocardiography, tail blood pressure and body weight were evaluated repeatedly at 4-month intervals. A frailty index was calculated at the final timepoint (33 months of age). Tissues were harvested at 4-month intervals to define inflammatory markers and left ventricular tissue remodeling. Mitochondrial and myocardial cell health was assessed in isolated left ventricular myocytes. Kaplan-Meier survival curves were established. Mixed ANOVA tests and linear mixed regression analysis were employed to determine the effects of age, treatment, and age-treatment interactions. Results: Chronic ARA290 treatment mitigated age-related increases in the cardiac non-myocyte to myocyte ratio, infiltrating leukocytes and monocytes, pro-inflammatory cytokines, total NF-κB, and p-NF-κB. Additionally, ARA290 treatment enhanced cardiomyocyte autophagy flux and reduced cellular accumulation of lipofuscin. The cardiomyocyte mitochondrial permeability transition pore response to oxidant stress was desensitized following chronic ARA290 treatment. Concurrently, ARA290 significantly blunted the age-associated elevation in blood pressure and preserved the LV ejection fraction. Finally, ARA290 preserved body weight and significantly reduced other markers of organism-wide frailty at the end of life. Conclusion: Administration of ARA290 reduces cell and tissue inflammation, mitigates structural and functional changes within the cardiovascular system leading to amelioration of frailty and preserved healthspan.