The impact of chronic obstructive pulmonary disease on surgical outcomes after surgery for an acute abdominal diagnosis.

PURPOSE: The current study was undertaken to describe the independent contribution of chronic obstructive pulmonary disease (COPD) to the risk of postoperative morbidity and in-hospital mortality among patients undergoing surgery for an acute abdominal diagnosis. METHODS: Patients who underwent emergency abdominal procedures were identified from the electronic database of the Department of Visceral, Transplantation, Thoracic and Vascular Surgery of our institution. To evaluate differences in surgical risk associated with COPD, patients with COPD were matched for age, sex, and type of surgery with an equal number of controls who did not have COPD. Logistic regression was performed to evaluate the univariate and multivariate associations between the independent variables, including COPD and outcome variables. RESULTS: Between January 2012 and December 2022, 3519 patients undergoing abdominal emergency surgery were identified in our abdominal surgical department. After removing ineligible cases, 201 COPD cases with an equal number of matched controls remained for analysis. The prevalence of COPD after the exclusion of ineligible cases was 5.7%. There were statistically significant differences in the rate of postoperative pulmonary complications (PPCs [57.7% vs. 35.8%; P < 0.001]), ventilator dependence (VD [63.2% vs. 46.3%; P < 0.001]), thromboembolic events (TEEs [22.9% vs. 12.9%; P = 0.009]), and in-hospital mortality (41.3% vs. 30.8%; P = 029) for patients with and without COPD. Independent of other covariates, the presence of COPD was not associated with a significantly increased risk of in-hospital mortality (OR, 1.16; 95% CI 0.70-1.97; P = 0.591) but was associated with an increased risk of PPCs (OR, 2.49; 95% CI 1.41-4.14; P = 0.002) and VD (OR, 2.26; 95% CI 1.22-4.17; P = 0.009). CONCLUSIONS: Preexisting COPD may alter a patient's risk of PPCs and VD. However, it was not associated with an increased risk of in-hospital mortality.

Non-invasive assessment of steatohepatitis indicates increased risk of coronary artery disease.

INTRODUCTION: Fatty liver diseases (FLD), especially defined as metabolic dysfunction-associated FLD (MAFLD), is of growing importance for patients and health-care providers. Extrahepatic comorbidities, predominantly coronary artery disease (CAD), contribute to excess morbidity and mortality in FLD. Although the association of FLD and CAD is well known, underlying pathophysiological links are not fully understood. Non-invasive means of liver diagnostic enable a fast and thorough characterization of FLD. We therefore assessed the severity of FLD in a cohort of patients at risk of CAD. METHODS: Patients scheduled for coronary angiography were characterized by anthropometry, serum-based indices of liver fibrosis (NFS, FIB4), abdominal ultrasound and vibration controlled transient elastography (VCTE) including controlled attenuation parameter (CAP) and the Fibroscan-AST (FAST) score. Patients were stratified according to indication of therapeutic coronary intervention. RESULTS: 120 patients were recruited, MAFLD was found in 41%, while advanced fibrosis or cirrhosis were present in only 5%. Coronary vascular intervention was indicated in 42% (n = 50). Severity of steatosis assessed by CAP and risk of fibrosis defined by elevated liver stiffness (VCTE>8 kPa) and fibrosis indices were associated with the need for coronary intervention. FAST score, a marker of fibrotic steatohepatitis, was elevated in the intervention group (0.22 vs. 0.12, p<0.001). Multivariate regression analysis revealed FAST score as strongest predictor of CAD (OR 2.3 95%, CI 1.40-2.96). DISCUSSION: MAFLD is a frequent comorbidity in patients at CAD risk, but advanced liver disease has a low prevalence in patients undergoing elective coronary angiography. Therefore, a routine VCTE-based screening for FLD cannot be recommended in cardiac patients. The association of indicators of steatohepatitis with advanced CAD points to inflammatory processes as a conjoint mechanism of both diseases.

Primary-like Human Hepatocytes Genetically Engineered to Obtain Proliferation Competence as a Capable Application for Energy Metabolism Experiments in In Vitro Oncologic Liver Models.

Non-alcoholic fatty liver disease (NAFLD), characterized by lipid accumulation in the liver, is the most common cause of liver diseases in Western countries. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC); however, in vitro evaluation of hepatic cancerogenesis fails due to a lack of liver models displaying a proliferation of hepatocytes. Originally designed to overcome primary human hepatocyte (PHH) shortages, upcyte hepatocytes were engineered to obtain continuous proliferation and, therefore, could be a suitable tool for HCC research. We generated upcyte hepatocytes, termed HepaFH3 cells, and compared their metabolic characteristics to HepG2 hepatoma cells and PHHs isolated from resected livers. For displaying NAFLD-related HCCs, we induced steatosis in all liver models. Lipid accumulation, lipotoxicity and energy metabolism were characterized using biochemical assays and Western blot analysis. We showed that proliferating HepaFH3 cells resemble HepG2, both showing a higher glucose uptake rate, lactate levels and metabolic rate compared to PHHs. Confluent HepaFH3 cells displayed some similarities to PHHs, including higher levels of the transaminases AST and ALT compared to proliferating HepaFH3 cells. We recommend proliferating HepaFH3 cells as a pre-malignant cellular model for HCC research, while confluent HepaFH3 cells could serve as PHH surrogates for energy metabolism studies.

The effect of preoperative patient-reported anxiety on morbidity and mortality outcomes in patients undergoing major general surgery.

Excessive levels of anxiety may negatively influence treatment outcomes and likely increase patient suffering. We designed a prospective observational study to assess whether preoperative patient-reported anxiety affects major general surgery outcomes. We prospectively administered the State-Trait Anxiety Inventory (STAI) to measure preoperative anxiety in patients awaiting major general surgical procedures. Patients were grouped by STAI scores according to established cutoffs: no anxiety (STAI < 40) and anxiety (STAI ≥ 40). Four hundred patients completed the questionnaires and underwent surgery, with an average interval from questionnaire completion to surgery of 4 days. Applying a state anxiety (STAI-S) score ≥ 40 as a reference point, the prevalence of patient-reported anxiety was 60.5% (241 of 400). The mean STAI-S score for these patients was 50.48 ± 7.77. The mean age of the entire cohort was 58.5 ± 14.12 years. The majority of participants were male (53.8%). The distribution of sex by anxiety status showed that 53.5% of women and 46.5% of men had anxiety (p = 0.003). In the entire cohort, postoperative complications occurred in 23.9% and 28.6% of the no anxiety and anxiety groups, respectively. The difference was nonsignificant. In a subgroup of patients who underwent high-risk complex procedures (N = 221), however, postoperative complications occurred in 31.4% and 45.2% of the no anxiety and anxiety groups, respectively. This difference was significant at p = 0.004. Of the patients who were anxious, 3.3% (8 of 241) died during hospitalization following surgery, compared with 4.4% of the patients (7 of 159) who were not anxious (p = 0.577). In the multivariable analysis adjusted for covariates and based on the results of subgroup analysis, preoperative anxiety assessed by the STAIS score was associated with morbidity (OR 2.12, CI 1.14-3.96; p = 0.018) but not mortality. The majority of enrolled patients in this study were classified as having high- to very high-level preoperative clinical anxiety, and we found a significant quantitative effect of patient-reported anxiety on morbidity but not mortality after surgery.

Recipient obesity as a risk factor in kidney transplantation.

BACKGROUND: The aim of the study was to investigate the effect of recipient obesity on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: A total of 578 patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into normal weight (BMI 18.5-24.9 kg/m2; N = 304), overweight (BMI 25-29.9 kg/m2; N = 205) and obese (BMI ≥ 30 kg/m2; N = 69) groups. Their clinicopathological characteristics, outcomes, and survival rates were analyzed retrospectively. RESULTS: Obesity was associated with an increased rate of surgical complications such as wound infection (P < 0.001), fascial dehiscence (P = 0.023), and lymphoceles (P = 0.010). Furthermore, the hospital stay duration was significantly longer in the groups with obese patients compared to normal weight and overweight patients (normal weight: 22 days, overweight: 25 days, and obese: 33 days, respectively; P < 0.001). Multivariate analysis showed that recipient obesity (BMI ≥ 30) was an independent prognostic factor for delayed graft function (DGF) (OR 2.400; 95% CI, 1.365-4.219; P = 0.002) and postoperative surgical complications (OR 2.514; 95% CI, 1.230-5.136; P = 0.011). The mean death-censored graft survival was significantly lower in obese patients (normal weight: 16.3 ± 0.6 years, overweight: 16.3 ± 0.8 years, obese 10.8 ± 1.5 years, respectively; P = 0.001). However, when using the Cox proportional hazards model, the association between recipient obesity and death-censored renal graft failure disappeared, after adjustment for important covariates, whereas the principal independent predictors of graft loss were recipient diabetes mellitus and hypertension and kidneys from donors with expanded donor criteria. CONCLUSION: In conclusion, obesity increases the risk of DGF and post-operative surgical complications after primary KT. Appropriate risk-adapted information concerning this must be provided to such patients before KT. Furthermore, obesity-typical concomitant diseases seem to negatively influence graft survival and need to be considered after the transplantation of obese patients.

The impact of obesity on surgical outcomes in patients undergoing emergency laparotomy for high-risk abdominal emergencies.

BACKGROUND: Obesity has been shown to increase the rates of morbidity and occasionally mortality in patients undergoing nonbariatric elective surgery. However, little is known about the impact of obesity on outcomes after surgery for high-risk abdominal emergencies. METHODS: A single-center retrospective evaluation of outcomes in high-risk abdominal emergency patients categorized by body mass index (BMI) was conducted. Patient demographics, comorbidities, and operative details were analyzed. Patients with normal weight (BMI 18.5-24.9) served as comparators. Multivariable linear and logistic regression analyses were performed to assess the impact of obesity on surgical outcomes. RESULTS: In total, 886 patients with BMI < 18.5 (underweight; n = 50), 18.5-24.9 (normal weight; n = 306), 25-29.9 (overweight; n = 336) and ≥ 30 (obese; n = 194) based on the World Health Organization (WHO) weight classification criteria met the inclusion criteria. Compared to normal-weight patients, patients with overweight and obesity were older and more likely to be male. The rates of comorbidity (100% vs 91.2%, p = < 0.0001), morbidity (77.8% vs 65.6%, p = 0.003), and in-hospital mortality (44.8% vs 30.4%, p = 0.001) were all higher in patients with obesity than in normal-weight patients. Patients with obesity had an increased intensive care unit length of stay (ICU LOS) (13 days vs 9 days, p = 0.019) and hospital LOS (21.4 days vs 18.1 days, p = 0.081) and prolonged ventilation (39.1% vs 19.6%, p = 0.003). As BMI deviated from the normal range, the morbidity and mortality rates increased incrementally, with the highest morbidity (87.9%) and mortality (54.5%) rates observed in morbidly obese patients (BMI ≥ 40). CONCLUSIONS: Patients with obesity were the most likely to have coexisting conditions, experience postoperative complications, and die during the first admission following EL for high-risk abdominal emergencies.

Assessing differences in surgical outcomes following emergency abdominal exploration for complications of elective surgery and high-risk primary emergencies.

Irrespective of its etiology, emergency surgical abdominal exploration (EAE) is considered a high-risk procedure with mortality rates exceeding 20%. The aim of this study was to evaluate differences in outcomes in patients who required EAE due to complications of complex elective abdominal procedures and those who required EAE due to high-risk primary abdominal emergencies. Patients undergoing EAE for acute surgical complications of complex abdominal elective surgical procedures (N = 293; Elective group) and patients undergoing EAE for high-risk primary abdominal emergencies (N = 776; Emergency group) from 2012 to 2019 at our institution were retrospectively assessed for morbidity and mortality. Postoperative complications occurred in 196 patients (66.94%) in the elective group and 585 patients (75.4%) in the emergency group. The relatively low complication burden in the elective group was also evidenced by a significantly lower comprehensive complication index score (54.00 ± 37.36 vs. 59.25 ± 37.08, p = 0.040). The in-hospital mortality rates were 31% (91 of 293) and 38% (295 of 776) in the elective and emergency groups, respectively. This difference between the two groups was statistically significant (p = 0.035). In multivariate analysis, age, peripheral artery disease, pneumonia, thromboembolic events, ICU stay, ventilator dependence, acute kidney failure and liver failure were independent predictors of mortality. Our data show that patients undergoing EAE due to acute complications of major elective surgery tolerate the procedure relatively well compared with patients undergoing EAE due to primary high-risk abdominal emergencies.

In Vivo and In Vitro Characterization of Primary Human Liver Macrophages and Their Inflammatory State.

Liver macrophages (LMs) play a central role in acute and chronic liver pathologies. Investigation of these processes in humans as well as the development of diagnostic tools and new therapeutic strategies require in vitro models that closely resemble the in vivo situation. In our study, we sought to gain further insight into the role of LMs in different liver pathologies and into their characteristics after isolation from liver tissue. For this purpose, LMs were characterized in human liver tissue sections using immunohistochemistry and bioinformatic image analysis. Isolated cells were characterized in suspension using FACS analyses and in culture using immunofluorescence staining and laser scanning microscopy as well as functional assays. The majority of our investigated liver tissues were characterized by anti-inflammatory LMs which showed a homogeneous distribution and increased cell numbers in correlation with chronic liver injuries. In contrast, pro-inflammatory LMs appeared as temporary and locally restricted reactions. Detailed characterization of isolated macrophages revealed a complex disease dependent pattern of LMs consisting of pro- and anti-inflammatory macrophages of different origins, regulatory macrophages and monocytes. Our study showed that in most cases the macrophage pattern can be transferred in adherent cultures. The observed exceptions were restricted to LMs with pro-inflammatory characteristics.

The Value of Graft Implantation Sequence in Simultaneous Pancreas-Kidney Transplantation on the Outcome and Graft Survival.

BACKGROUND/OBJECTIVES: The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. MATERIAL AND METHODS: 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. RESULTS: Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3-17.1, p = 0.026) and five years (HR 3.7, 2.1-23.4, p = 0.040). CONCLUSION: Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.

The Effects of Oral Anticoagulant Exposure on the Surgical Outcomes of Patients Undergoing Surgery for High-Risk Abdominal Emergencies.

BACKGROUND: In chronic anticoagulant users undergoing surgery, bleeding and thromboembolism are common and serious complications. Many studies on mainly elective or minor emergency surgical procedures with low associated risks have focused on these outcomes. In comparison, patients undergoing high-risk emergency abdominal surgical procedures have not received sufficient attention. This study aimed to compare outcomes between oral anticoagulant users and nonusers who required emergency laparotomy for high-risk abdominal emergencies. METHODS: Patients who underwent surgery for abdominal emergencies at our institution between January 2012 and July 2019 were retrospectively reviewed. RESULTS: There were 875 patients, including 370 anticoagulant users and 505 nonusers. Of the 370 anticoagulant users, 189 (51.3), 77 (20.8%), 45 (12.2%), and 59 (15.9%) were prescribed antiplatelets, a vitamin k antagonist, a direct oral anticoagulant, and a combination drug regimen, respectively. The most common high-risk emergencies requiring surgery in both groups were perforated viscus (25.7% vs 40.9%), mesenteric ischemia with enteric necrosis (27% vs 12.8%), and bowel obstruction (17.6% vs 28.1%). The overall bleeding rate was higher (29.2% vs 22%, p = 0.015) in anticoagulant users than in nonusers, but the major bleeding rate was similar (17.8% vs 14.1%, p = 0.129) between the two groups. The rates of thromboembolic events and mortality were significantly higher in anticoagulant users than in nonusers (25.7% vs 9.7%, p < 0.0001 and 39.7% vs 31.1%, p = 0.01, respectively). Liver cirrhosis, peripheral arterial diseases, reoperation, and blood product transfusion were independent predictors of the overall risk of bleeding or TEEs, according to the multivariate analysis. In this model, liver cirrhosis had the largest overall effect on mortality, followed by pneumonia, thromboembolism, peripheral arterial disease, blood product transfusion, and atrial fibrillation. The use of oral anticoagulants was not an independent predictor of either bleeding or in-hospital mortality. The use of oral anticoagulants was associated with a decreased risk of all-cause in-hospital mortality. CONCLUSION: Based on our results, the continued use of oral anticoagulants is more protective than harmful considering the overall outcomes in this subset of patients.