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.

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.

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.

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.