Ileus, Gastrointestinal Bleeding and Clostridium difficile Colitis after Hip and Knee Replacement - a Systematic Review.

INTRODUCTION: Major gastrointestinal complications after arthroplasty are rare, but can have detrimental effects on the patient and can substantially increase the overall cost of treatment. This systematic review provides an overview of ileus, gastrointestinal bleeding and C. difficile colitis after total hip and knee arthroplasty. MATERIALS AND METHODS: We followed the PRISMA guidelines and searched 3 databases for the period between 1 January 2000 and 31 December 2018. The manual search included references in retrieved articles. We extracted data on the cohort size, study level, arthroplasty procedure, complications and their incidence, and recommendations by the study. RESULTS: Twenty-five studies that analyzed these complications after total knee arthroplasty (TKA) and total hip arthroplasty (THA) were identified. These complications have an incidence of up to 2% each. According to some of the studies, an incidence of 0% is possible. While the risk factors for ileus varied greatly, those for C. difficile colitis were more consistent. There are some recommendations for reducing the incidence of ileus and C. difficile. This heterogeneity does not allow us to draw any conclusion regarding which thromboprophylaxis agent has the lowest incidence of gastrointestinal bleeding. CONCLUSION: The complications investigated in this systematic review are rare and have a reported incidence of up to 2% each. Even though there are some recommendations for reducing the complication rate, due to the complex nature of the arthroplasty setting, there is a need for further investigation of these risk factors and how they can be reduced.

Risk factors for ileus after hip and knee arthroplasty.

PURPOSE: Postoperative ileus (POI) is one of the complications that can occur after every surgical procedure including arthroplasty. It can have detrimental consequences for the patient and portrays an economic burden on health care systems. The risk factors for POI after arthroplasty described in the literature are scarce and include hip arthroplasty, male gender and previous abdominal surgery. The purpose of the study was to determine the risk factors for POI after hip and knee arthroplasty. METHODS: A retrospective review of 2760 patients undergoing primary hip and knee arthroplasty was performed. An in-depth analysis of patient history and physical operative and postoperative course was reviewed and statistically analyzed in a univariate and multivariate setting. RESULTS: Overall incidence of POI was 0.54%. History of myocardial infarction and chronic kidney disease were statistically significant risk factors for developing POI after arthroplasty with values of p = 0.023 and p = 0.004, respectively. Other risk factors included previous abdominal surgery (p < 0.001) and hip arthroplasty (p = 0.026). Age or gender correlations were not observed. CONCLUSIONS: Although postoperative ileus is an uncommon complication after joint arthroplasty, in addition to the known risk factors of male age, hip arthroplasty, and previous abdominal surgery, this study describes two previously unknown risk factors: chronic kidney disease and history of myocardial infarction. Patients with these risk factors should be monitored closely for developing postoperative ileus.

Intraoperative volume restriction in esophageal cancer surgery: an exploratory randomized clinical trial.

AIM: To investigate whether the fluid volume administered during esophageal cancer surgery affects pulmonary gas exchange and tissue perfusion. METHODS: An exploratory single-center randomized clinical trial was performed. Patients with esophageal cancer who underwent Lewis-Tanner procedure between June 2011 and August 2012 at the Department of Thoracic surgery "Jordanovac", Zagreb were analyzed. Patients were randomized (1:1) to receive a restrictive volume of intraoperative fluid (≤8 mL/kg/h) or a liberal volume (>8 mL/kg/h). Changes in oxygen partial pressure (Pao2), inspired oxygen fraction (FiO2), creatinine, and lactate were measured during and after surgery. RESULTS: Overall 16 patients were randomized and they all were analyzed (restrictive group n=8, liberal group n=8). The baseline value Pao2/FiO2 ratio (restrictive) was 345.01±35.31 and the value six hours after extubation was 315.51±32.91; the baseline Pao2/FiO2 ratio (liberal) was 330.11±34.71 and the value six hours after extubation was 307.11±30.31. The baseline creatinine value (restrictive) was 91.91±12.67 and the value six hours after extubation was 100.88±18.33; the baseline creatinine value (liberal) was 90.88±14.99 and the value six hours after extubation was 93.51±16.37. The baseline lactate value (restrictive) was 3.93±1.33 and the value six hours after extubation was 2.69±0.91. The baseline lactate value (liberal) was 3.26±1.25 and the value six hours after extubation was 2.40±1.08. The two groups showed no significant differences in Pao2/FiO2 ratio (P=0.410), creatinine (P=0.410), or lactate (P=0.574). CONCLUSIONS: Restriction of intraoperative applied volume does not significantly affect pulmonary exchange function or tissue perfusion in patients undergoing surgical treatment for esophageal cancer.

Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC).

Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (N = 23) and healthy tissues (N = 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (N = 225) and GTEx healthy donors' cohorts (N = 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (p < 0.001), LLGL1 (p = 0.0015), and SLC4A3 (p = 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (p = 0.0029) and LILRA5 (p = 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters.

Predictors of lower work ability among emergency medicine employees: the Croatian experience.

BACKGROUND: Worldwide research has indicated that emergency medicine employees and particularly ambulance personnel have symptoms related to traumatic events, and experience more chronic stressors in their work than workers in other health service settings. Unlike other countries which conducted similar studies, no specialty branch in emergency medicine exists in Croatia. STUDY OBJECTIVES: To identify possible predictors of low work ability, including occupational stress and quality of life, among emergency medicine employees. METHODS: A cross-sectional study was conducted from May 2010 till July 2010 in the Institute of Emergency Medicine in the City of Zagreb. Questionnaires were distributed to all employees with gathered total sample of 125 subjects (39 physicians, 38 medical nurses /technicians and 48 drivers). Data were collected using the socio-demographic questions, occupational stress assessment, work ability index (WAI) and WHO quality of life (WHOQOL-BREF) questionnaires. RESULTS: Emergency physicians were significantly more exposed to public criticism (p=0.008) but drivers had more exposure to hazards at workplace (p=0.001) regarding other employee groups. Binary logistic regression model showed two significant predictors of lower work ability (WAI score <37): lower physical WHO-BREF domain (OR=0.78; 95% CI 0.68 to 0.89; p<0.001) and the professional and intellectual demands (OR=1.09; 95% CI 1.01 to 1.19; p=0.043). CONCLUSION: Strenuous physical activity should be reduced in order to increase the overall work ability of the emergency medicine employees and better structural organisation and introduction of a residency in emergency medicine should significantly improve total work ability among emergency physicians.

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME.

AIM: To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS: Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 µg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 µg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS: BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability (as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening (obtained with L-NAME administration that was counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157-rats). CONCLUSION: Innate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy.

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.

BACKGROUND: Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. METHODS: Review of our research on BPC 157 in terms of brain-gut axis. RESULTS: BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. CONCLUSION: BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.

Hyperglycaemia in critical illness is a risk factor for later development of type II diabetes mellitus.

Hyperglycaemia caused by stress and inflammation is common during critical illness. We hypothesised that a latent glucose metabolism disturbance contributes to development of hyperglycaemia and that those patients have increased risk for diabetes. We included patients with sepsis, acute coronary syndrome and acute heart failure with no history of impaired glucose metabolism and divided them in the hyperglycaemia group (glucose ≥ 7.8 mmol/l) and normoglycaemia group. Patients were followed for 5 years. Follow-up was completed for 115 patients in the normoglycaemia group, of which 4 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 51 patients finished follow-up and 8 (15.7%) developed type 2 diabetes. Relative risk in 5-year period for patients with hyperglycaemia was 4.51 for development of type 2 diabetes. Patients with hyperglycaemia during critical illness who are not diagnosed with diabetes before or during the hospitalisation should be considered a population at increased risk for developing diabetes.

Hyperglycemia in sepsis is a risk factor for development of type II diabetes.

BACKGROUND: Hyperglycemia is frequent in sepsis, even in patients without diabetes or impaired glucose metabolism. It is a consequence of inflammatory response and stress, so its occurrence is related to severity of illness. However, not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesized the existence of latent disturbance of glucose metabolism that contributes to development of hyperglycemia and that those patients might have increased risk for diabetes. METHODS: Patients admitted with sepsis and no history of impaired glucose metabolism were included and divided in the hyperglycemia group (glucose >or=7.8 mmol/L) and normoglycemia group. Severity of sepsis was assessed. Surviving patients without diabetes at discharge were followed-up for 5 years to investigate risk for development of diabetes. RESULTS: Hyperglycemia was related to severity of sepsis. Follow-up was finished for 55 patients with hyperglycemia, of which 8 (15.7%) developed diabetes, and 118 patients with normoglycemia, of which 5 (4.2%) developed diabetes (P = .002). Relative risk for developing type 2 diabetes was 4.29 (95% CI, 1.35-13.64). CONCLUSION: Patients with hyperglycemia in sepsis who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes.