KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression.

Background/Aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression. Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo. Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice. Conclusions: KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.

Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy.

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.

Development, reliability, and validity of the Posttraumatic Stress Disorder Interview for Vietnamese refugees: a diagnostic instrument for Vietnamese refugees.

The Posttraumatic Stress Disorder Interview for Vietnamese Refugees (PTSD-IVR) was created specifically to assess for the presence of current and lifetime history of premigration, migration, encampment, and postmigration traumas in Vietnamese refugees. The purpose of the present study was to describe the development of and investigate the interrater and test-retest reliability of the PTSD-IVR and its validity in relation to the diagnoses obtained from the Longitudinal, Expert, and All Data (LEAD; Spitzer, 1983) standard. Clinicians conducted the diagnosis process with 127 Vietnamese refugees using the LEAD standard and the PTSD-IVR. Assessment of the reliability and validity of the PTSD-IVR yielded good to excellent AUC (area under the receiver operating characteristic curve; .86, .87) and κ values (.66, .74) indicating the reliability of the PTSD-IVR and the agreement between the LEAD procedure and the PTSD-IVR. The results of the present study suggest that the PTSD-IVR performs successfully as a diagnostic instrument specifically created for Vietnamese refugees in their native language.

Machine learning-featured Secretogranin V is a circulating diagnostic biomarker for pancreatic adenocarcinomas associated with adipopenia.

Background: Pancreatic cancer is one of the most fatal malignancies of the gastrointestinal cancer, with a challenging early diagnosis due to lack of distinctive symptoms and specific biomarkers. The exact etiology of pancreatic cancer is unknown, making the development of reliable biomarkers difficult. The accumulation of patient-derived omics data along with technological advances in artificial intelligence is giving way to a new era in the discovery of suitable biomarkers. Methods: We performed machine learning (ML)-based modeling using four independent transcriptomic datasets, including GSE16515, GSE62165, GSE71729, and the pancreatic adenocarcinoma (PAC) dataset of the Cancer Genome Atlas. To find candidates for circulating biomarkers, we exported expression profiles of 1,703 genes encoding secretory proteins. Integrating three transcriptomic datasets into either a training or test set, ML-based modeling distinguishing PAC from normal was carried out. Another ML-model classifying long-lived and short-lived patients with PAC was also built to select prognosis-associated features. Finally, circulating level of SCG5 in the plasma was determined from the independent cohort (non-tumor = 25 and pancreatic cancer = 25). We also investigated the impact of SCG5 on adipocyte biology using recombinant protein. Results: Three distinctive ML-classifiers selected 29-, 64- and 18-featured genes, recognizing the only common gene, SCG5. As per the prediction of ML-models, the SCG5 transcripts was significantly reduced in PAC and decreased further with the progression of the tumor, indicating its potential as a diagnostic as well as prognostic marker for PAC. External validation of SCG5 using plasma samples from patients with PAC confirmed that SCG5 was reduced significantly in patients with PAC when compared to controls. Interestingly, plasma SCG5 levels were correlated with the body mass index and age of donors, implying pancreas-originated SCG5 could regulate energy metabolism systemically. Additionally, analyses using publicly available Genotype-Tissue Expression datasets, including adipose tissue histology and pancreatic SCG5 expression, further validated the association between pancreatic SCG5 expression and the size of subcutaneous adipocytes in humans. However, we could not observe any definite effect of rSCG5 on the cultured adipocyte, in 2D in vitro culture. Conclusion: Circulating SCG5, which may be associated with adipopenia, is a promising diagnostic biomarker for PAC.

Heart rate variability (HRV) and posttraumatic stress disorder (PTSD): a pilot study.

Exposure to combat experiences is associated with increased risk of developing Post Traumatic Stress Disorder. Prolonged exposure therapy and cognitive processing therapy have garnered a significant amount of empirical support for PTSD treatment; however, they are not universally effective with some patients continuing to struggle with residual PTSD symptoms. Heart rate variability (HRV) is a measure of the autonomic nervous system functioning and reflects an individual's ability to adaptively cope with stress. A pilot study was undertaken to determine if veterans with PTSD (as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist) would show significantly different HRV prior to an intervention at baseline compared to controls; specifically, to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD. The study also aimed at assessing the feasibility, acceptability, and potential efficacy of providing HRV biofeedback as a treatment for PTSD. The findings suggest that implementing an HRV biofeedback as a treatment for PTSD is effective, feasible, and acceptable for veterans. Veterans with combat-related PTSD displayed significantly depressed HRV as compared to subjects without PTSD. When the veterans with PTSD were randomly assigned to receive either HRV biofeedback plus treatment as usual (TAU) or just TAU, the results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD. However, the TAU had no significant effect on either HRV or symptom reduction. A larger randomized control trial to validate these findings appears warranted.

The impact of obesity on long-term survival after coronary artery bypass grafting.

BACKGROUND: Obesity is a well-known risk factor for coronary artery disease. The objective of our study was to examine the impact of obesity on long-term survival after coronary artery bypass grafting (CABG). MATERIALS AND METHODS: Using prospectively gathered data, we reviewed records of 1163 consecutive patients who underwent isolated primary CABG between 1997 and 2007. We compared outcomes of obese patients (body mass index [BMI] > or = 30 kg/m(2); n = 472) and non-obese patients (BMI < 30 kg/m(2); n = 691). Long-term survival was assessed by using Kaplan-Meier curves generated by log-rank tests and adjusted for confounding factors with Cox logistic regression analysis. RESULTS: Obese patients were slightly younger (60 +/- 8 versus 63 +/- 9y; P < 0.0001), were less likely to be current tobacco smokers (30% versus 41%; P < 0.0001), had a higher incidence of diabetes (51% versus 33%; P < 0.0001), and had a lower incidence of cerebral vascular disease (18% versus 24%; P = 0.009) than non-obese patients. The two groups of patients had similar 30-d rates of mortality (1.3% versus 1.5%; P = 0.8) and major adverse cardiac events (2.3% versus 2.5%; P = 0.9). Adjusted Cox regression survival curves were also similar between the two groups of patients (adjusted hazard ratio, 1.2; 95% confidence interval, 0.8-1.8; P = 0.28). CONCLUSIONS: Obese patients who underwent CABG had 30-d mortality rates and early outcomes similar to those of non-obese patients. Long-term survival was also similar between these two groups of patients after adjustment for confounding variables.

Impact of ACGME work-hour restrictions on the outcomes of coronary artery bypass grafting in a cohort of 600,000 patients.

BACKGROUND: Since the resident physician 80-h/wk restriction was implemented on July 1, 2003, little has been learned about the impact of this reform on patient outcomes after coronary artery bypass grafting (CABG). METHODS: Using the Nationwide Inpatient Sample database, we identified 614,177 patients who underwent isolated CABG from 1998 through 2007. Of the 374,947 patients who underwent CABG at a teaching hospital, 133,285 (36%) belonged to the post-reform group. Hierarchic logistic and multivariable regression models were used to assess the independent effect of the reform after adjusting for potential confounding factors. Outcomes assessed were operative morbidity and mortality, and length of stay. Outcomes of CABG patients at non-teaching hospitals were used to control for time bias. RESULTS: In teaching hospitals, after risk adjustment, the post-reform era was associated with lower mortality risk (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.56-0.63; P < 0.001) but greater operative morbidity (OR, 1.5; 95% CI, 1.43-1.58; P < 0.001). Although the implementation of work-hour reforms was correlated with shorter lengths of stay, there were fewer routine home discharges (OR, 0.73; 95% CI, 0.73-0.76; P < 0.001). Outcomes at non-teaching hospitals were similar, except that operative morbidity rates were lower during the post-reform era. CONCLUSIONS: The implementation of the resident work-hour reform in teaching hospitals did not affect mortality rates in CABG patients but was associated with increased morbidity. Further studies are needed to identify the reasons for the post-reform increase in postoperative complications at teaching hospitals.

Sarcopenia and Muscle Aging: A Brief Overview.

The world is facing the new challenges of an aging population, and understanding the process of aging has therefore become one of the most important global concerns. Sarcopenia is a condition which is defined by the gradual loss of skeletal muscle mass and function with age. In research and clinical practice, sarcopenia is recognized as a component of geriatric disease and is a current target for drug development. In this review we define this condition and provide an overview of current therapeutic approaches. We further highlight recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD+) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle. The last part of this review examines new therapeutic avenues for promising treatment targets. There is still no accepted therapy for sarcopenia in humans. Here we provide a brief review of the current state of research derived from various mouse models or human samples that provide novel routes for the development of effective therapeutics to maintain muscle health during aging.

Outcomes of coronary surgery at a Veterans Affairs hospital versus other hospitals.

BACKGROUND: The aim of this study was to compare outcomes of coronary artery bypass grafting (CABG) operations at a VA hospital and non-VA hospitals. MATERIALS AND METHODS: Using the 2004 Nationwide Inpatient Sample database, we identified 48,669 discharge records of patients who underwent CABG in non-VA hospitals and compared these patients' outcomes with those of 688 patients who underwent CABG at our VA hospital from 2002 to 2006. Student t- tests and chi(2) tests were used to identify significant intergroup differences. RESULTS: The VA patients were slightly younger than the non-VA patients (62 +/- 8 versus 66 +/- 11 y, P < 0.0001). The VA patients also had a higher prevalence of prior myocardial infarction (60.6% versus 34.6%), congestive heart failure (38.2% versus 22.1%), peripheral vascular disease (25.9% versus 7.2%), cerebral vascular disease (23.4% versus 5.9%), chronic obstructive pulmonary disease (32.3% versus 16.6%), and diabetes (41.7% versus 29.7%) (P < 0.0001 for all). Nonetheless, the in-hospital mortality rate was significantly lower in VA patients than in non-VA patients (1.6% versus 3.0%, P = 0.03). CONCLUSIONS: Despite the higher prevalence of comorbidities, patients who underwent CABG at a VA hospital had a significantly lower mortality rate than CABG patients in non-VA hospitals.

Associations among pain, PTSD, mTBI, and heart rate variability in veterans of Operation Enduring and Iraqi Freedom: a pilot study.

OBJECTIVE: The objective of the study was to determine if there is dysregulated autonomic nervous system activity as manifested by depressed heart rate variability (HRV) among veterans of Operations Enduring and Iraqi Freedom (OEF/OIF). PARTICIPANTS AND SETTING: The study used a convenience sample of OEF/OIF veterans (n = 28) seen at a Level II Polytrauma Network Site at the Michael E. DeBakey VA Medical Center. Participants were similar to other OEF/OIF veterans who received care at this site. DESIGN: Cross sectional study. MEASURES: Time domain analysis (standard deviation of beat-to-beat intervals [SDNN]) of HRV, diagnoses of mild traumatic brain injury and post-traumatic stress disorder (PTSD), and pain ratings from medical records. RESULTS: As a group, the sample evidenced markedly depressed HRV (as reflected by SDNN) as compared with available age and gender corrected normative data. Pain (71%), PTSD (57%), and mild traumatic brain injury (mTBI) (64%) were prevalent. Thirty-six percent had all three measures (P3). Pain and P3 were significantly and negatively associated with SDNN (r = -0.460, P = 0.014; r = -0.373, P = 0.05, respectively). CONCLUSIONS: These preliminary findings support the high prevalence of depressed HRV and P3 among veterans seen in a level II Polytrauma Center. The findings also suggest a possible synergistic effect of pain, PTSD, and mTBI on depressed HRV. The nature and implications of these relationships require additional research to elucidate.

Differentiating psychotic patients from nonpsychotic patients with the MMPI-2 and Rorschach.

The goal of this study was to examine the incremental validity and the clinical utility of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) and Rorschach (Rorschach, 1942) with regard to differential diagnosis in a sample of adult inpatients with a primary psychotic disorder or a primary mood disorder without psychotic features. Diagnostic efficiency statistics have suggested that the Rorschach Perceptual Thinking Index (PTI; Exner, 2000a, 2000b) was better than MMPI-2 scales in discriminating psychotic patients from nonpsychotic patients. We compared the 84% overall correct classification rate (OCC) for the PTI to an OCC of 70% for the MMPI-2 scales. Adding the MMPI-2 scales to the PTI resulted in a decrease in OCC of 1%, whereas adding the PTI to the MMPI-2 resulted in an increase in OCC of 14%. Sensitivity, specificity, positive predictive power, negative predictive power, and kappa were equal or higher with only the PTI in the model.

Reliability and Validity of the Vietnamese Depression Interview (VDI).

Current instruments used to aid in the diagnosis of psychological disorders have limited effectiveness with clients from Asian backgrounds. The Vietnamese Depression Interview (VDI) is a diagnostic instrument created to assess the presence of current and lifetime history of major depressive disorder specifically among Vietnamese refugees and immigrants. The purpose of the present study is to provide a description of the VDI, while also noting it as a reliable and valid means by which to assess depression in Vietnamese individuals. Using the Longitudinal, Expert, and All Data (LEAD; Spitzer in Compr Psychiatry 24:399-411, 1983) standard and the VDI, experienced clinicians conducted the diagnosis process with 127 Vietnamese refugees and immigrants. Assessment of the reliability and validity of the VDI yielded good to excellent AUC and kappa values, indicating the reliability of the VDI and the agreement between the LEAD procedure and the VDI. These study results imply that the VDI performs successfully as a diagnostic instrument specifically created for Vietnamese refugees and immigrants in their native language. Current and future contributions of the VDI with Vietnamese individuals are discussed.

Predictors of in-hospital complications after pericardiectomy: a nationwide outcomes study.

OBJECTIVE: Advances in medical care had caused a paradigm shift in the indications for pericardiectomy. We evaluated the current predictors of in-hospital complications for pericardiectomy. METHODS: Patients who underwent pericardiectomy between 1998 and 2008 were identified from the US Nationwide Inpatient Sample. Risk-adjusted logistic regression model was used to analyze the predictors of surgical outcomes. RESULTS: A total of 13,593 patients underwent pericardiectomy during this period. Pericardiectomy was performed for constrictive pericarditis (28%; n = 3851), pericardial calcification (15%; n = 2061), secondary malignancies (3%; n = 456), adhesive pericarditis (2%; n = 318), and other causes (40%; n = 5461). Unadjusted mortality and complication rates were approximately 8% and 48%, respectively. Fourteen percent of patients required blood transfusion. Only 62% were routinely discharged home. After risk adjustment, age, female gender, comorbidity index, and the primary diagnosis independently predicted in-hospital mortality and overall complication rates (P < .05). Calcific pericarditis was the only etiology associated with lower risk-adjusted mortality (odds ratio [OR], 0.48), operative complications (OR, 0.32), overall complications (OR, 0.32), incidence of transfusion (OR, 0.38), and highest routine discharge rates (OR, 1.84); P < .001 for all. Constrictive pericarditis had the highest requirement for cardiopulmonary bypass (OR, 6.41; P < .01) and incidence of bleeding complications (OR, 2.61; P < .01). CONCLUSIONS: Morbidity remains high for pericardiectomy. In addition to age, gender, and comorbidities, attention should be given to etiology during surgical planning or referral. This significantly influences the requirement for cardiopulmonary bypass, chances of bleeding complications, and transfusion requirements.

The impact of academic calendar cycle on coronary artery bypass outcomes: a comparison of teaching and non-teaching hospitals.

BACKGROUND: The commencement of new academic cycle in July is presumed to be associated with poor patient outcomes, although supportive evidence is limited for cardiac surgery patients. We sought to determine if the new academic cycle affected the outcomes of patients undergoing Coronary Artery Bypass Grafting. METHODS: A retrospective analysis was performed on 10-year nationwide in-hospital data from 1998-2007. Only patients who underwent CABG in the first and final academic 3-month calendar quarter were included. Generalized multivariate regression was used to assess indicators of hospital quality of care such as risk-adjusted mortality, total complications and "failure to rescue" (FTOR) - defined as death after a complication. RESULTS: Of the 1,056,865 CABG operations performed in the selected calendar quarters, 698,942 were at teaching hospitals. The risk-adjusted mortality, complications and FTOR were higher in the beginning of the academic year [Odds ratio = 1.14, 1.04 and 1.19 respectively; p < 0.001 for all] irrespective of teaching status. However, teaching status was associated with lower mortality (OR 0.9) despite a higher complication rate (OR 1.02); [p < 0.05 for both]. The July Effect thus contributed to only a 2.4% higher FTOR in teaching hospitals compared to 19% in non teaching hospitals. CONCLUSIONS: The July Effect is reflective of an overall increase in morbidity in all hospitals at the beginning of the academic cycle and it had a pronounced effect in non-teaching hospitals. Teaching hospitals were associated with lower mortality despite higher complication rates in the beginning of the academic cycle compared to non-teaching hospitals. The July effect thus cannot be attributed to presence of trainees alone. ULTRAMINI ABSTRACT: This study compares the July effect in teaching and non-teaching hospitals and demonstrates that this effect is not unique to teaching hospitals for CABG patients. In fact, teaching hospitals have somewhat better outcomes at the beginning of the academic cycle and the July effect is a much broader seasonal variation.

Impact of surgeon demographics and technique on outcomes after esophageal resections: a nationwide study.

BACKGROUND: Thoracic, cardiac, and general surgeons perform esophageal resections in the United States. This article examines the impact of surgeon subspecialty on outcomes after esophagectomy. METHODS: Esophagectomies performed between 1998 and 2008 were identified in the Nationwide Inpatient Sample. Surgeons were classified as thoracic, cardiac, or general surgeons if greater than 65% of their operative case mix was representative of their specialty. Surgeons with less than 65% of a specialty-specific case mix served as controls. Regression equations calculated the independent effect of surgeon specialty, surgeon volume, and operative approach (transhiatal versus transthoracic) on outcomes. RESULTS: Of the 40,589 patients who underwent esophagectomies, surgeon identifiers were available for 23,529 patients. Based on case mix, thoracic, cardiac, and general surgeons performed 3,027 (12.9%), 688 (2.9%), and 4,086 (17.4%) esophagectomies, respectively. Operative technique did not independently affect risk-adjusted outcomes-mortality, morbidity, and failure to rescue (defined as death after a complication). Surgeon volume independently lowered mortality and failure to rescue by 4% (p ≤ 0.002 for both), but not complications (p = 0.6). High-volume hospitals (>12 procedures/year) independently lowered mortality (adjusted odds ratio [AOR], 0.67, 95% confidence interval [CI], 0.46-0.96), and failure to rescue (AOR, 0.64; 95% CI, 0.44-0.94). Esophageal resections performed by general surgeons were associated with higher mortality (AOR, 1.87; 95% CI 1.02-3.45) and failure to rescue (AOR, 1.95; 95% CI, 1.06-3.61) but not complications (AOR, 0.97; 95% CI, 0.64-1.49). CONCLUSIONS: General surgeons perform the major proportion of esophagectomies in the United States. Surgeon subspecialty is not associated with the risk of complications developing but instead is associated with mortality and failure to rescue from complications. Surgeon subspecialty case mix is an important determinant of outcomes for patients undergoing esophagectomy.

Cirrhosis as a moderator of outcomes in coronary artery bypass grafting and off-pump coronary artery bypass operations: a 12-year population-based study.

BACKGROUND: Cirrhosis substantially affects morbidity and mortality in patients who undergo complex surgical procedures. However, cirrhosis is not included as a parameter in standardized perioperative cardiac risk assessment models. We sought to identify the impact of cirrhosis on coronary artery bypass grafting (CABG) and off-pump CABG (OPCAB) outcomes. METHODS: Using the 1998 to 2009 Nationwide Inpatient Sample databases, we identified 3,046,709 patients who underwent CABG procedures, 744,636 (24.4%) of which were OPCAB; 6,448 (0.3%) had cirrhosis. Using hierarchical multivariable regression models, we analyzed the impact of cirrhosis on in-hospital outcomes: mortality, morbidity, length of stay, hospital charges, and disposition. Severity of liver dysfunction was assessed by the Deyo-Charlson comorbidity index. RESULTS: In the overall CABG group, cirrhosis was independently associated with increased mortality (adjusted odds ratio [AOR] 6.9, 95% confidence interval [CI] 2.8 to 17), morbidity (AOR 1.6, 95% CI 1.3 to 2.0), length of stay (+1.2 days; p < 0.001), and hospital charges (+$22,491; p < 0.001). The prevalence of cirrhosis in the OPCAB group was 0.3% (n = 2,246); the OPCAB subgroup analysis revealed that the presence of cirrhosis did not affect mortality or morbidity unless there was severe liver dysfunction (mortality AOR 5.1, 95% CI 3.7 to 6.9; morbidity AOR 2.1, 95% CI 1.6 to 2.4). However, in the on-pump CABG patients, cirrhosis was associated with increased mortality and morbidity regardless of the severity of liver dysfunction. CONCLUSIONS: The impact of cirrhosis on perioperative outcomes and health care costs is significant; CABG should be performed on carefully selected cirrhotic patients and, whenever possible, without the use of cardiopulmonary bypass.

Gender as a moderator between having an anxiety disorder diagnosis and coronary artery bypass grafting surgery (CABG) outcomes in rural patients.

PURPOSE: This paper examines gender as a moderating variable between having an anxiety disorder diagnosis and coronary artery bypass grafting surgery (CABG) outcomes in rural patients. METHODS: Using the 2008 Nationwide Inpatient Sample (NIS) database, 17,885 discharge records of patients who underwent a primary CABG surgery were identified. Independent variables included age, gender, race, median household income based on patient's ZIP code, primary expected payer, the Deyo, Cherkin, and Ciol Comorbidity Index, and an anxiety comorbidity diagnosis. Outcome variables included in-hospital length of stay and patient disposition (routine and nonroutine discharge). A 2 × 2 analysis of variance and logistic regression analyses were used to assess the interaction between gender and an anxiety disorder diagnosis on in-hospital length of stay and patient disposition. FINDINGS: Twenty-seven percent of rural patients undergoing a CABG operation had a comorbid anxiety diagnosis. Rural patients who had nonroutine discharge were more likely to have comorbid anxiety diagnosis compared to rural patients who had a routine discharge. There was a significant interaction effect between having an anxiety diagnosis and gender on length of hospital stay but not for patient disposition. CONCLUSIONS: Three findings were noteworthy. First, anxiety disorder is prevalent in rural patients who are undergoing a CABG operation. Second, anxiety was a significant independent predictor of both length of hospital stay and nonroutine discharge for patients receiving CABG surgery. Last, having an anxiety disorder diagnosis increased hospital stay for both males and females; however, females seemed to be impacted more than males.

Outcomes of concomitant aortic valve replacement and coronary artery bypass grafting at teaching hospitals versus nonteaching hospitals.

OBJECTIVE: Hospitals with a high volume and academic status produce better patient outcomes than other hospitals after complex surgical procedures. Risk models show that concomitant aortic valve replacement and coronary artery bypass grafting pose a greater risk than isolated coronary artery bypass grafting or aortic valve replacement. We examined the relationship of hospital teaching status and the presence of a thoracic surgery residency program with aortic valve replacement/coronary artery bypass grafting outcomes. METHODS: By using the Nationwide Inpatient Sample database, we identified patients who underwent concomitant aortic valve replacement/coronary artery bypass grafting from 1998 to 2007 at nonteaching hospitals, teaching hospitals without a thoracic surgery residency program, and teaching hospitals with a thoracic surgery residency program. Multivariate analysis was performed to identify intergroup differences. Risk-adjusted multivariable logistic regression analysis was used to assess independent predictors of in-hospital mortality and complication rates. RESULTS: The 3 groups of patients did not differ significantly in their baseline characteristics. Patients who underwent aortic valve replacement/coronary artery bypass grafting had higher overall risk-adjusted complication rates in nonteaching hospitals (odds ratio 1.58; 95% confidence interval, 1.39-1.80; P < .0001) and teaching hospitals without a thoracic surgery residency program (odds ratio 1.42; 95% confidence interval, 1.26-1.60; P < .0001) than in thoracic surgery residency program hospitals. However, no difference was observed in the adjusted mortality rate for nonteaching hospitals (odds ratio 0.95; 95% confidence interval, 0.87-1.04; P = .25) or teaching hospitals without a thoracic surgery residency program (odds ratio 1.00; 95% confidence interval, 0.92-1.08; P = .98) when compared with thoracic surgery residency program hospitals. Robust statistical models were used for analysis, with c-statistics of 0.98 (complications) and 0.82 (mortality). CONCLUSION: Patients who require complex cardiac operations may have better outcomes when treated at teaching hospitals with a thoracic surgery residency program.