Management of the Uninvolved Uterus and Adnexa During Routine Pelvic Peritonectomy in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Varies by Histology and Menopausal Status: An International Survey of Peritoneal Surface Malignancy Surgeons.

BACKGROUND: No guidelines exist regarding the management of the uninvolved uterus or adnexa (fallopian tubes and/or ovaries) in patients with peritoneal metastases (PM) from non-gynecologic malignancies. It is unclear whether salpingo-oophorectomy, hysterectomy, or both should be performed when a complete pelvic peritonectomy is otherwise warranted. METHODS: A 25-item electronic survey was sent to 225 surgeons worldwide who routinely perform cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Participants were recruited through listservs of expert groups. Individual surgeon approaches to the management of the grossly uninvolved uterus and adnexa in pre- and post-menopausal women with PM from low- and high-grade appendiceal neoplasms, colorectal cancer, and peritoneal mesothelioma were collected using a 5-point Likert scale. RESULTS: A total of 135 complete responses (60% response rate) were obtained from surgeons practicing in 27 countries. Respondents reported a median practice of 10 years (interquartile range [IQR] 6-15 years) and a median performance of 20 (IQR 12-30) CRS/HIPEC operations per year. Rates of salpingo-oophorectomy differed by histology and a woman's menopausal status, ranging from 29 to 42% in pre-menopausal women to 71-77% in post-menopausal women (P < 0.001). Notably, the number of surgeons who would perform a hysterectomy was lower, ranging from 12 to 27% for pre-menopausal women and from 32 to 44% for post-menopausal women, dependent on histology (P < 0.001). CONCLUSIONS: Surgeons are overall more aggressive with adnexal resection than with hysterectomy in both pre- and post-menopausal women with PM from non-gynecologic malignancies. Further prospective studies are required to determine the best approach to optimize surgical and oncologic outcomes while also accounting for the fertility and hormonal impact.

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.

Is Hyperthermic Intraperitoneal Chemotherapy Appropriate for Colon Cancer?

Colorectal cancer (CRC) with peritoneal metastases is a complex disease and its management presents significant clinical challenges. In well-selected patients at experienced centers, CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed with acceptable morbidity and is associated with prolonged survival. Based on the results of recent randomized controlled trials, HIPEC using oxaliplatin after CRS with shortened perfusion periods (30 minutes) is no longer recommended. There is a movement toward utilizing mitomycin C as a first-line intraperitoneal agent with extended perfusion times (90-120 minutes); however, there is currently little prospective evidence to support its widespread use.

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.

Factors Associated with Permanent Pacemaker Placement After Tricuspid Valve Operations.

BACKGROUND: Conduction abnormalities requiring permanent pacemaker (PPM) implantation are common after tricuspid valve operations, though incidence is variable. This study aims to investigate contemporary rates of and risk factors for PPM after tricuspid operations. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was used to identify patients with tricuspid repair or replacement from 2011 to 2020. Factors independently associated with risk of postoperative PPM during index hospital admission were examined using multivariable logistic regression with a complete case approach. Annualized hospital and surgeon volumes were calculated. RESULTS: We identified 71,937 patients undergoing tricuspid operations. Median patient age was 66 (53-74) years, 56% were female (n=40,590), and median ejection fraction was 56% (48%-60%). Tricuspid operations were concomitant in 87% (n=62,457), elective in 62% (n=44,393), and included repair in 86% (n=61,720). Overall postoperative incidence of PPM was 15% (n=10,857); 13% (n=8,304) after repair and 25% (n=2,553) after replacement; 4% (n=174) for isolated tricuspid repair and 24% (n=1,248) for isolated tricuspid replacement. Multivariable analysis showed baseline characteristics, endocarditis, concomitant operations, longer CPB time, tricuspid replacement, and lower hospital and surgeon tricuspid operative volumes were independently associated with greater risk for PPM. After adjustment, tricuspid replacement had 3.2 times greater PPM risk compared to tricuspid repair. CONCLUSIONS: Nationally, 15% of patients undergoing tricuspid operations required postoperative PPM implantation. PPM risk was increased with concomitant valve operations, tricuspid replacement, longer CPB time, and operations performed by less experienced surgeons and centers. Innovation is needed to decrease this significant morbidity.

Association of anesthesia handovers with perioperative and short-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Anesthesiologists transition patient care to combat clinician fatigue and accommodate shift limitations. Studies exploring the association of increased handovers with patient outcomes have conflicting findings. Here, we investigate the association of anesthesia handovers with perioperative outcomes in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a single institution from 2017 to 2022 were stratified by the number of anesthesia attending and nonattending (nurse anesthetist/resident) handovers (0-1 or ≥2). Primary outcomes were intensive care unit and hospital length of stay, in addition to 30-day serious morbidity. Logistic and negative binomial regression models were adjusted for covariates related to patient and case complexity. RESULTS: A total of 182 patients were included. Median operative time was 720 minutes (interquartile range, 540-900 minutes). Most cases had fewer than 2 attending handovers (n = 147, 81% vs ≥2 handovers n = 35, 19%) and 2 nonattending handovers (n = 120, 71% vs ≥2 handovers n = 53, 29%). In adjusted models, there were no differences in 30-day serious morbidity and intensive care unit or hospital length of stay between the attending handover groups (0-1 vs ≥2). Patients with ≥2 non-attending handovers had similar odds of 30-day serious morbidity compared with the 0-1 group (odds ratio, 1.613, 95% confidence interval, 0.733-3.550, P = .235), but a longer total hospital (incidence rate ratio, 1.301, 95% confidence interval, 1.071-1.579, P = .008) and intensive care unit length of stay (incidence rate ratio 1.548, 95% confidence interval, 1.038-2.049, P = .030). CONCLUSIONS: Multiple anesthesia handovers were not associated with an increased risk of serious morbidity for patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. However, increased handovers (≥2) between nonattending providers was associated with longer hospital and intensive care unit length of stays.

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.

'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.

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.