Association of severe obesity with risk of conversion to open in laparoscopic cholecystectomy for acute cholecystitis.

Background: Obesity is a known risk factor for cholecystitis and is associated with technical complications during laparoscopic procedures. The present study seeks to assess the association between obesity class and conversion to open (CTO) during laparoscopic cholecystectomy (LC). Methods: Adult acute cholecystitis patients with obesity undergoing non-elective LC were identified in the 2017-2020 Nationwide Readmissions Database. Patients were stratified by obesity class; class 1 (Body Mass Index [BMI] = 30.0-34.9), class 2 (BMI = 35.0-39.9), and class 3 (BMI ≥ 40.0). Multivariable regression models were developed to assess factors associated with CTO and its association with perioperative complications and resource utilization. Results: Of 89,476 patients undergoing LC, 40.6 % had BMI ≥ 40.0. Before adjustment, class 3 obesity was associated with increased rates of CTO compared to class 1-2 (4.6 vs 3.8 %; p < 0.001). Following adjustment, class 3 remained associated with an increased likelihood of CTO (Adjusted Odds Ratio [AOR] 1.45, 95 % Confidence Interval [CI] 1.31-1.61; ref.: class 1-2). Patients undergoing CTO had increased risk of blood transfusion (AOR 3.27, 95 % CI 2.54-4.22) and respiratory complications (AOR 1.36, 95 % CI 1.01-1.85). Finally, CTO was associated with incremental increases in hospitalization costs (ß + $719, 95 % CI 538-899) and length of stay (LOS; ß +2.20 days, 95 % CI 2.05-2.34). Conclusions: Class 3 obesity is a significant risk factor for CTO. Moreover, CTO is associated with increased hospitalization costs and LOS. As the prevalence of obesity grows, improved understanding of operative risk by approach is required to optimize clinical outcomes. Our findings are relevant to shared decision-making and informed consent.

Association of uninsured status and rurality with risk of financial toxicity after pediatric trauma.

BACKGROUND: Pediatric traumatic injury is associated with long-term morbidity as well as substantial economic burden. Prior work has labeled the catastrophic out-of-pocket medical expenses borne by patients as financial toxicity. We hypothesized uninsured rural patients to be vulnerable to exorbitant costs and thus at greatest risk of financial toxicity. METHODS: Pediatric patients (<18 years) experiencing traumatic injury were identified in the 2016-2019 National Inpatient Sample. Patients were considered to be at risk of financial toxicity if their hospitalization cost exceeded 40% of post-subsistence income. Individual family income was computed using a gamma distribution probability density function with parameters derived from publicly available US Census Bureau data, in accordance with prior work. A multivariable logistic regression was developed to assess factors associated with risk of financial toxicity. RESULTS: Of an estimated 225,265 children identified for study, 34,395 (15.3%) were Rural. Rural patients were more likely to experience risk of financial toxicity (29.1 vs 22.2%, P < .001) compared to Urban patients. After adjustment, rurality (reference: urban status; adjusted odds ratio 1.45, 95% confidence interval 1.36-1.55) and uninsured status (reference: private; adjusted odds ratio 1.85, 95% confidence interval 1.67-2.05) remained linked to increased odds of risk of financial toxicity. Specifically among those with private insurance, Rural patients experienced markedly higher predicted risk of financial toxicity, relative to Urban. CONCLUSION: Our findings suggest a complex interplay between rural status and insurance type in the prediction of risk of financial toxicity after pediatric trauma. To target policy interventions, future studies should characterize the patients and communities at greatest risk of financial devastation among rural pediatric trauma patients.

Clinical and financial outcomes associated with the utilization of right internal mammary artery versus radial artery in multivessel coronary artery bypass grafting.

BACKGROUND: Multi-arterial coronary bypass grafting with the left internal mammary artery as a conduit has been shown to offer superior long-term survival compared to single-arterial coronary bypass grafting. Nevertheless, the selection of a secondary conduit between the right internal mammary artery and the radial artery remains controversial. Using a national cohort, we examined the relationships between the right internal mammary artery and the radial artery with acute clinical and financial outcomes. METHODS: Adults undergoing on-pump multivessel coronary bypass grafting with left internal mammary artery as the first arterial conduit were identified in the 2016 to 2020 Nationwide Readmissions Database. Patients receiving either the right internal mammary artery or the radial artery, but not both, were included in the analysis. Multivariable regression models were fitted to examine the association between the conduits and in-hospital mortality, as well as additional secondary outcomes. RESULTS: Of an estimated 49,798 patients undergoing multi-arterial coronary bypass grafting, 29,729 (59.7%) comprised the radial artery cohort. During the study period, the proportion of multi-arterial coronary bypass grafting utilizing the radial artery increased from 51.3% to 65.2% (nptrend <0.001). Following adjustment, the radial artery was associated with reduced odds of in-hospital mortality (adjusted odds ratio 0.44), prolonged mechanical ventilation (adjusted odds ratio 0.78), infectious complications (adjusted odds ratio 0.69), and 30-day nonelective readmission (adjusted odds ratio 0.77, all P < .05). CONCLUSION: Despite no definite endorsement from surgical societies, the radial artery is increasingly utilized as a secondary conduit in multi-arterial coronary bypass grafting. Compared to the right internal mammary artery, the radial artery was associated with lower odds of in-hospital mortality, complications, and reduced healthcare expenditures. These results suggest that whenever feasible, the radial artery should be the favored conduit over the right internal mammary artery. Nevertheless, future studies examining long-term outcomes associated with these vessels remain necessary.

Demystifying the association of center-level operative trauma volume and outcomes of emergency general surgery.

BACKGROUND: Recent studies have demonstrated a positive volume-outcome relationship in emergency general surgery. Some have advocated for the sub-specialization of emergency general surgery independent from trauma. We hypothesized inferior clinical outcomes of emergency general surgery with increasing center-level operative trauma volume, potentially attributable to overall hospital quality. METHODS: Adults (≥18 years) undergoing complex emergency general surgery operations (large and small bowel resection, repair of perforated peptic ulcer, lysis of adhesions, laparotomy) were identified in the 2016 to 2020 Nationwide Readmissions Database. Multivariable risk-adjusted models were developed to evaluate the association of treatment at a high-volume trauma center (reference: low-volume trauma center) with clinical and financial outcomes after emergency general surgery. To evaluate hospital quality, mortality among adult hospitalizations for acute myocardial infarction was assessed by hospital trauma volume. RESULTS: Of an estimated 785,793 patients undergoing a complex emergency general surgery operation, 223,116 (28.4%) were treated at a high-volume trauma center. Treatment at a high-volume trauma center was linked to 1.19 odds of in-hospital mortality (95% confidence interval 1.12-1.27). Although emergency general surgery volume was associated with decreasing predicted risk of mortality, increasing trauma volume was linked to an incremental rise in the odds of mortality after emergency general surgery. Secondary analysis revealed increased mortality for admissions for acute myocardial infarction with greater trauma volume. CONCLUSION: We note increased mortality for emergency general surgery and acute myocardial infarction in patients receiving treatment at high-volume trauma centers, signifying underlying structural factors to broadly affect quality. Thus, decoupling trauma and emergency general surgery services may not meaningfully improve outcomes for emergency general surgery patients. Our findings have implications for the evolving specialty of emergency general surgery, especially for the safety and continued growth of the acute care surgery model.

Interhospital Transfer for Emergency General Surgery: A Contemporary National Analysis.

BACKGROUND: Patients undergoing emergency general surgery (EGS) often require complex management and transfer to higher acuity facilities, especially given increasing national efforts aimed at centralizing care. We sought to characterize factors and evaluate outcomes associated with interhospital transfer using a contemporary national cohort. METHODS: All adult hospitalizations for EGS (appendectomy, cholecystectomy, laparotomy, lysis of adhesions, small/large bowel resection, and perforated ulcer repair) ≤2 days of admission were identified in the 2016-2020 National Inpatient Sample. Patients initially admitted to a different institution and transferred to the operating hospital comprised the Transfer cohort (others: Non-Transfer). Multivariable models were developed to consider the association of Transfer with outcomes of interest. RESULTS: Of ∼1 653 169 patients, 107 945 (6.5%) were considered the Transfer cohort. The proportion of patients experiencing interhospital transfer increased from 5.2% to 7.7% (2016-2020, P < .001). On average, Transfer was older, more commonly of White race, and of a higher Elixhauser comorbidity index. After adjustment, increasing age, living in a rural area, receiving care in the Midwest, and decreasing income quartile were associated with greater odds of interhospital transfer. Following risk adjustment, Transfer remained linked with increased odds of in-hospital mortality (AOR 1.64, CI 1.49-1.80), as well as any perioperative complication (AOR 1.33, CI 1.27-1.38; Reference: Non-Transfer). Additionally, Transfer was associated with significantly longer duration of hospitalization (ß + 1.04 days, CI + .91-1.17) and greater costs (ß+$3,490, CI + 2840-4140). DISCUSSION: While incidence of interhospital transfer for EGS is increasing, transfer patients face greater morbidity and resource utilization. Novel interventions are needed to optimize patient selection and improve post-transfer outcomes.

Trends, outcomes, and factors associated with in-hospital opioid overdose following major surgery.

Background: With the growing opioid epidemic across the US, in-hospital utilization of opioids has garnered increasing attention. Using a national cohort, this study sought to characterize trends, outcomes, and factors associated with in-hospital opioid overdose (OD) following major elective operations. Methods: We identified all adult (≥18 years) hospitalizations entailing select elective procedures in the 2016-2020 National Inpatient Sample. Patients who experienced in-hospital opioid overdose were characterized as OD (others: Non-OD). The primary outcome of interest was in-hospital OD. Multivariable logistic and linear regression models were developed to evaluate the association between in-hospital OD and mortality, length of stay (LOS), hospitalization costs, and non-home discharge. Results: Of an estimated 11,096,064 hospitalizations meeting study criteria, 5375 (0.05 %) experienced a perioperative OD. Compared to others, OD were older (66 [57-73] vs 64 [54-72] years, p < 0.001), more commonly female (66.3 vs 56.7 %, p < 0.001), and in the lowest income quartile (26.4 vs 23.2 %, p < 0.001). After adjustment, female sex (Adjusted Odds Ratio [AOR] 1.68, 95 % Confidence Interval [CI] 1.47-1.91, p < 0.001), White race (AOR 1.19, CI 1.01-1.42, p = 0.04), and history of substance use disorder (AOR 2.51, CI 1.87-3.37, p < 0.001) were associated with greater likelihood of OD. Finally, OD was associated with increased LOS (ß +1.91 days, CI [1.60-2.21], p < 0.001), hospitalization costs (ß +$7500, CI [5900-9100], p < 0.001), and greater odds of non-home discharge (AOR 2.00, CI 1.61-2.48, p < 0.001). Conclusion: Perioperative OD remains a rare but costly complication after elective surgery. While pain control remains a priority postoperatively, protocols and recovery pathways must be re-examined to ensure patient safety.

Social determinants as predictors of resection and long-term mortality in Black patients with non-small cell lung cancer.

BACKGROUND: Minorities diminished returns theory posits that socioeconomic attainment conveys fewer health benefits for Black than White individuals. The current study evaluates the effects of social constructs on resection rates and survival for non-small cell lung cancer (NSCLC). METHODS: Patients with potentially resectable NSCLC stage IA to IIIA were identified using the 2004 to 2017 National Cancer Database. Patients were stratified into quartiles based on population-level education and income. Logistic regression was used to predict risk-adjusted resection rates. Mortality was assessed with Cox proportional hazard modeling. RESULTS: Of the 416,025 patients identified, 213,643 (51.4%) underwent resection. Among White patients, the lowest income (adjusted odds ratio 0.76, 95% confidence interval 0.74-0.78, P < .01) and education quartiles (adjusted odds ratio 0.82, 95% confidence interval 0.79-0.84, P < .01) were associated with decreased odds of resection. The lowest education quartile among Black patients was not associated with lower resection rates. The lowest income quartile (adjusted odds ratio 0.67, 95% CI 0.61-0.74, P < .01) was associated with reduced resection. White patients in the lowest education and income quartiles experienced increased hazard of 5-year mortality (adjusted hazard ratio 1.13, 95% CI 1.11-1.15, P < .01 and adjusted hazard ratio 1.08, 95% CI 1.06-1.11, P < .01 respectively). In Black patients, there were no significant differences in 5-year survival between Black patients in the highest education and income quartiles and those in the lowest quartiles. CONCLUSION: Among Black patients with NSCLC, educational attainment is not associated with increased resection rates. In addition, higher education and income were not associated with improved 5-year survival. The diminished gains experienced by Black patients, compared to Whites patients, illustrate the presence of pervasive race-specific mechanisms in observed inequalities in cancer outcomes.

Persistent racial disparities in refusal of resection in non-small cell lung cancer patients at high-volume and Black-serving institutions.

BACKGROUND: Surgical resection is the standard of care for early-stage non-small cell lung cancer. Black patients have higher surgical refusal rates than White patients. We evaluated factors associated with the refusal of resection and subsequent non-small cell lung cancer outcomes. METHODS: We identified patients with non-small cell lung cancer stages IA to IIIA eligible for surgical resection (lobectomy or pneumonectomy) listed between 2004 and 2017 in the National Cancer Database. We stratified hospitals by the proportion of Black patients served and lung cancer resection volume. We used multivariable regression models to identify factors associated with refusal of resection and assessed 5-year mortality using Kaplan-Meier analysis and Cox proportional hazard modeling. RESULTS: Of 221,396 patients identified, 7,753 (3.5%) refused surgery. Black race was associated with increased refusal (adjusted odds ratio 2.06, 95% confidence interval 1.90-2.22). Compared to White race, Black race was associated with increased refusal across the highest (adjusted odds ratio 2.29, 95% confidence interval 1.94-2.54), intermediate (adjusted odds ratio 2.05, 95% confidence interval 1.78-2.37), and lowest (adjusted odds ratio 1.77, 95% confidence interval 1.58-1.99) volume tertiles. Similarly, Black race was associated with increased refusal across the highest (adjusted odds ratio 1.97, 95% confidence interval 1.78-2.17), intermediate (adjusted odds ratio 2.08, 95% confidence interval 1.80-2.40), and lowest (adjusted odds ratio 1.53, 95% confidence interval 1.13-2.06) Black-serving tertiles. However, surgical resection yielded similar 5-year survival for Black and White patients. CONCLUSION: Racial disparities in non-small cell lung cancer surgery refusal persist regardless of hospital volume or proportion of Black patients served. These findings suggest that a better understanding of patient and patient-provider level interventions could facilitate a better understanding of treatment decision-making.

Textbook outcomes in heart transplantation: A quality metric for the modern era.

BACKGROUND: Traditional quality metrics like one-year survival do not fully encapsulate the multifaceted nature of solid organ transplantation in contemporary practice. Therefore, investigators have proposed using a more comprehensive measure, the textbook outcome. However, the textbook outcome remains ill-defined in the setting of heart transplantation. METHODS: Within the Organ Procurement and Transplantation Network database, the textbook outcome was defined as having: (1) No postoperative stroke, pacemaker insertion, or dialysis, (2) no extracorporeal membrane oxygenation requirement within 72 hours of transplantation, (3) index length of stay <21 days, (4) no acute rejection or primary graft dysfunction, (5) no readmission for rejection or infection, or re-transplantation within one year, and (6) an ejection fraction >50% at one year. RESULTS: Of 26,885 heart transplantation recipients between 2011 to 2022, 9,841 (37%) achieved a textbook outcome. Following adjustment, textbook outcome patients demonstrated significantly reduced hazard of mortality at 5- (hazard ratio 0.71, 95% CI 0.65-0.78; P < .001) and 10-years (hazard ratio 0.73, CI 0.68-0.79; P < .001), and significantly greater likelihood of graft survival at 5- (hazard ratio 0.69, CI 0.63-0.75; P < .001) and 10-years (hazard ratio 0.72, CI 0.67-0.77; P < .001). Following estimation of random effects, hospital-specific, risk-adjusted rates of textbook outcome ranged from 39% to 91%, compared to a range of 97% to 99% for one-year patient survival. Multi-level modeling of post-transplantation rates of textbook outcomes revealed that 9% of the variation between transplant programs was attributable to inter-hospital differences. CONCLUSION: Textbook outcomes offer a nuanced, composite alternative to using one-year survival when evaluating heart transplantation outcomes and comparing transplant program performance.

Heparan Sulfate Proteoglycans (HSPGs) Serve as the Mediator Between Monomeric Tau and Its Subsequent Intracellular ERK1/2 Pathway Activation.

The conversion of soluble tau protein to insoluble, hyperphosphorylated neurofibrillary tangles (NFTs) is a major hallmark leading to neuronal death observed in neurodegenerative tauopathies. Unlike NFTs, the involvement of monomeric tau in the progression of tau pathology has been less investigated. Using live-cell confocal microscopy and flow cytometry, we demonstrate that soluble 0N4R monomers were rapidly endocytosed by SH-SY5Y and C6 glioma cells via actin-dependent macropinocytosis. Further, cellular endocytosis of monomeric tau has been demonstrated to be HSPG-dependent, as shown in C6 glial cells with genetic knockouts of xylosyltransferase-1-a key enzyme in HSPG synthesis-with a reduced level of tau uptake. Tau internalization subsequently triggers ERK1/2 activation and therefore, the upregulation of IL-6 and IL-1ß. The role of ERK1/2 in regulating the levels of pro-inflammatory gene transcripts was confirmed by inhibiting the MEK-ERK1/2 signaling pathway, which led to the attenuated IL-6 and IL-1ß expressions but not that of TNF-α. Moreover, as a key regulator of tau internalization, LRP1 (low-density lipoprotein receptor-related protein 1) levels were downregulated in response to monomeric tau added to C6 cells, while it was upregulated in HSPG-deficient cells, suggesting that the involvement of LRP1 in tau uptake depends on the presence of HSPGs on the cell surface. The subsequent LRP1 knockdown experiment we performed shows that LRP1 deficiency leads to an attenuated propensity for tau uptake and further elevated IL-6 gene expression. Collectively, our data suggest that tau has multiple extracellular binding partners that mediate its internalization through distinct mechanisms. Additionally, this study demonstrates the important role of both HSPGs and LRP1 in regulating cellular immune responses to tau protein monomers, providing a novel target for alleviating the neuroinflammatory environment before the formation of neurofibrillary tangles.

Enhanced Stress Resilience Training in Surgeons: Iterative Adaptation and Biopsychosocial Effects in 2 Small Randomized Trials.

OBJECTIVE: To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers. SUMMARY OF BACKGROUND AND DATA: Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown. METHODS: In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity"). RESULTS: Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls. CONCLUSIONS: This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.