Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier.

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities.

An Automated Prognostic Model for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) constitutes a leading cause of cancer-related mortality despite advances in detection and treatment methods. While computed tomography (CT) serves as the current gold standard for initial evaluation of PDAC, its prognostic value remains limited, as it relies on diagnostic stage parameters encompassing tumor size, lymph node involvement, and metastasis. Radiomics have recently shown promise in predicting postoperative survival of PDAC patients; however, they rely on manual pancreas and tumor delineation by clinicians. In this study, we collected a dataset of pre-operative CT scans from a cohort of 40 PDAC patients to evaluate a fully automated pipeline for survival prediction. Employing nnU-Net trained on an external dataset, we generated automated pancreas and tumor segmentations. Subsequently, we extracted 854 radiomic features from each segmentation, which we narrowed down to 29 via feature selection. We then combined these features with the Tumor, Node, Metastasis (TNM) system staging parameters, as well as the patient's age. We trained a random survival forest model to perform an overall survival prediction over time, as well as a random forest classifier for the binary classification of two-year survival, using repeated cross-validation for evaluation. Our results exhibited promise, with a mean C-index of 0.731 for survival modeling and a mean accuracy of 0.76 in two-year survival prediction, providing evidence of the feasibility and potential efficacy of a fully automated pipeline for PDAC prognostication. By eliminating the labor-intensive manual segmentation process, our streamlined pipeline demonstrates an efficient and accurate prognostication process, laying the foundation for future research endeavors.

Nivolumab-Induced Colitis in a Patient With Esophageal Adenocarcinoma: A Case Report.

Nivolumab is an immune checkpoint inhibitor used in the treatment of several types of cancer. Among the adverse effects of this drug, immune-mediated colitis (IMC) has been described. However, in contrast to other checkpoint inhibitors, such as ipilimumab, drug-induced colitis due to nivolumab is not commonly reported. We report the case of a 59-year-old male who had undergone surgical resection for gastroesophageal junction adenocarcinoma, had been on nivolumab during the past five months, and presented with worsening diarrhea. Colonoscopy demonstrated local edema and mild colitis in a region of the colonic mucosa located 30 cm distal to the ileocecal valve. Biopsies revealed acute moderate colitis. The patient responded well to loperamide and dietary modifications. Although nivolumab rarely causes IMC, this occurrence requires proper management in order to avoid further complications.

Ceftriaxone Administration Associated with Lithiasis in Children: Guilty or Not? A Systematic Review.

Lithiasis is a known side effect of ceftriaxone administration in children. Sex, age, weight, dosage, and duration of intake have been reported as risk factors for the formation of calcification or stones in the bile and urine excretory systems of children who received ceftriaxone. The purpose of this systematic review is to investigate the reported effects of ceftriaxone administration in pediatric patients who were admitted to a hospital due to infection, the likelihood of gallstones, nephroliths, or precipitations in both the biliary and urinary systems, as well as investigate the relationship with their mother's history during pregnancy. Original studies and literature reviews from the PubMed database were included in the study. No time limit related to research or publication was set for the articles. The results were evaluated, aiming to understand the outcomes and identify any predisposing factors relevant to this side effect. Of the 181 found articles, 33 were appropriate for inclusion in the systematic review. The administered dose of ceftriaxone presented variability. Symptoms, such as abdominal pain and vomiting, were associated with ceftriaxone-related lithiasis in many cases. It was noted that most of the results were the outcomes of retrospective observation and not of prospective randomized research. Definitively, more randomized control studies with long-term outcomes are needed to identify the exact association between ceftriaxone and lithiasis in children.

Signaling pathways associated with bone loss in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized in many patients by extraintestinal manifestations. One of the most common comorbidities seen in IBD patients is a significant reduction in their bone mass. The pathogenesis of IBD is mainly attributed to the disrupted immune responses in the gastrointestinal mucosa and putative disruptions in the gut microbiomes. The excessive inflammation of the gastrointestinal tract activates different systems, such as the RANKL/RANK/OPG and the Wnt pathways linked with bone alterations in IBD patients, thereby suggesting a multifactorial etiology. The mechanism responsible for the reduced bone mineral density in IBD patients is thought to be multifactorial, and, so far, the principal pathophysiological pathway has not been well established. However, in recent years, many investigations have increased our understanding of the effect of gut inflammation on the systemic immune response and bone metabolism. Here, we review the main signaling pathways associated with altered bone metabolism in IBD.

Granulomatous Peritonitis Secondary to Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a rare, chronic, and progressive disease of the liver characterized by cholestasis due to multifocal bile duct strictures. PSC can lead to liver fibrosis, and in 10-20% of cases, it leads to cholangiocarcinoma and end-stage liver disease. However, the pathogenesis of the disease is not clearly understood. For the diagnosis of PSC, both imaging and liver biopsy can be used. No medical treatment has managed to prevent the progression of the disease. Consequently, in the case of late-stage disease, liver transplantation is considered the best treatment option. PSC may lead to different complications including bacterial cholangitis, cholangiocarcinoma, and cirrhosis. Nevertheless, to our knowledge, there are no reports of granulomatous peritonitis secondary to PSC. Granulomatous peritonitis may be a result of infectious, malignant, and idiopathic inflammatory diseases. It is also considered a rare postoperative complication, due to cornstarch from surgical glove powder, in laparoscopic procedures. Here, we report the case of a 39-year-old male patient with PSC, in which cholangiocarcinoma and peritoneal carcinomatosis were clinically suspected. Despite that, histological findings and staining methods of the surgically removed peritoneal masses demonstrated granulomatous peritonitis.

Efficacy and safety of endoscopic drainage of peripancreatic fluid collections: a retrospective multicenter European study.

Background: Endoscopic ultrasound (EUS)-guided transmural drainage allows treatment of symptomatic peripancreatic fluid collections (PFCs), with lumen-apposing metal stents (LAMS) and double pigtail plastic stents (DPPS) being the 2 most frequently used modalities. Methods: Consecutive patients undergoing PFC drainage in 10 European centers were retrospectively retrieved. Technical success (successful deployment), clinical success (satisfactory drainage), rate and type of early adverse events, drainage duration and complications on stent removal were evaluated. Results: A total of 128 patients-92 men (71.9%), age 57.2±11.9 years-underwent drainage, with pancreatic pseudocyst (PC) and walled-off necrosis (WON) in 92 (71.9%) and 36 (28.1%) patients, respectively. LAMS were used in 80 (62.5%) patients and DPPS in 48 (37.5%). Technical success was achieved in 124 (96.9%) of the cases, with no difference regarding either the type of stent (P>0.99) or PFC type (P=0.07). Clinical success was achieved in 119 (93%); PC had a better response than WON (91/92 vs. 28/36, P<0.001), but the type of stent did not affect the clinical success rate (P=0.29). Twenty patients (15.6%) had at least one early complication, with bleeding being the most common (n=7/20, 35%). No difference was detected in complication rate per type of stent (P=0.61) or per PFC type (P=0.1). Drainage duration was significantly longer with DPPS compared to LAMS: 88 (70-112) vs. 35 (29-55.3) days, P<0.001. Conclusions: EUS-guided drainage of PFCs achieves high percentages of technical and clinical success. Drainage using LAMS is of shorter duration, but the complication rate is similar between the 2 modalities.

Splenic Artery Ligation: An Ontable Bail-Out Strategy for Small-for-Size Remnants after Major Hepatectomy: A Retrospective Study.

It has been reported that the prevention of acute portal overpressure in small-for-size liver grafts leads to better postoperative outcomes. Accordingly, we aimed to investigate the feasibility of the technique of splenic artery ligation in a case series of thirteen patients subjected to major liver resections with evidence of small-for-size syndrome and whether the maneuver results in the reduction of portal venous pressure and flow. The technique was successful in ten patients, with splenic artery ligation alleviating portal hypertension significantly. Three patients required the performance of a portocaval shunt for the attenuation of portal hypertension. Portal inflow modulation via splenic artery ligation is a technically simple technique that can prove useful in the context of major hepatectomies as well as in liver transplantations and the early evaluation and modification of portal venous pressure post hepatectomy can be used as a practical tool to guide the effect of the intervention.

Severity of Pancreatic Leak in Relation to Gut Restoration After Pancreaticoduodenectomy: The Role of the Roux-en-Y Configuration.

Background: Pancreatic leak after pancreaticoduodenectomy and gut restoration via a single jejunal loop remains the crucial predictor of patients' outcome. Our reasoning that active pancreatic enzymes may be more disruptive to the pancreatojejunostomy prompted us to explore a Roux-en-Y configuration for the gut restoration, anticipating diversion of bile salts away from the pancreatic stump. Our study aims at comparing two techniques regarding the severity of postoperative pancreatic fistula (POPF) and patients' outcome. Methods: The files of 415 pancreaticoduodenectomy patients were retrospectively reviewed. Based on gut restoration, the patients were divided into: cohort A (n = 105), with gut restoration via a single jejunal loop, cohort B (n = 140) via a Roux-en-Y technique assigning the draining of pancreatic stump to the short limb and gastrojejunostomy and bile (hepaticojejunostomy) flow to long limb, and cohort C (n = 170) granting the short limb to the gastric and pancreatic anastomosis, whereas hepaticojejunostomy was performed to the long limp. The POPF-related morbidity and mortality were analyzed. Results: Overall POPF in cohort A versus cohorts B and C was 19% versus 12.1% and 9.4%, respectively (P = 0.01 A vs B + C). POPF-related morbidity in cohort A versus cohorts B and C was 10.5% versus 7.3% and 6.3%, respectively (P = 0.03 A vs B+C). POPF-related total hospital mortality in cohorts A versus B and C was 1.9% versus 0.8% and 0.59%, respectively (P = 0.02 A vs B+C). Conclusion: Roux-en-Y configuration showed lower incidence and severity of POPF. Irrespective of technical skill, creating a gastrojejunostomy close to pancreatojejunostomy renders the pancreatic enzymes less active by leaping the bile salts away from the pancreatic duct and providing a lower pH.

Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer.

Colorectal cancer represents a leading cause of cancer-related morbidity and mortality. Despite improvements, chemotherapy remains the backbone of colorectal cancer treatment. The aim of this study is to investigate the variation of circulating microRNA expression profiles and the response to irinotecan-based treatment in metastatic colorectal cancer and to identify relevant target genes and molecular functions. Serum samples from 95 metastatic colorectal cancer patients were analyzed. The microRNA expression was tested with a NucleoSpin miRNA kit (Machnery-Nagel, Germany), and a machine learning approach was subsequently applied for microRNA profiling. The top 10 upregulated microRNAs in the non-responders group were hsa-miR-181b-5p, hsa-miR-10b-5p, hsa-let-7f-5p, hsa-miR-181a-5p, hsa-miR-181d-5p, hsa-miR-301a-3p, hsa-miR-92a-3p, hsa-miR-155-5p, hsa-miR-30c-5p, and hsa-let-7i-5p. Similarly, the top 10 downregulated microRNAs were hsa-let-7d-5p, hsa-let-7c-5p, hsa-miR-215-5p, hsa-miR-143-3p, hsa-let-7a-5p, hsa-miR-10a-5p, hsa-miR-142-5p, hsa-miR-148a-3p, hsa-miR-122-5p, and hsa-miR-17-5p. The upregulation of microRNAs in the miR-181 family and the downregulation of those in the let-7 family appear to be mostly involved with non-responsiveness to irinotecan-based treatment.

Two Needle Passes Achieve Similar Diagnostic Yield Compared to Three Passes Regarding Diagnosis of Solid Pancreatic Lesions in Endoscopic Ultrasound-Guided Fine Needle Aspiration.

Current guidelines advocate 3-4 passes with a fine-needle aspiration (FNA) to achieve high rates of diagnostic samples for malignancy when performing endoscopic ultrasound (EUS)-guided sampling of solid pancreatic lesions, in the absence of on-site cytologic evaluation. The aim of this study is to compare 2 vs. 3 needle passes in EUS-FNA for solid pancreatic lesions in terms of incremental diagnostic yield and to identify factors associated with the procedure's outcome. In this retrospective study, 2 passes of EUS-FNA were found to have similar diagnostic yield compared to 3 passes for the diagnosis of solid pancreatic masses, suggesting that there might be no significant incremental tissue yield when 3 passes are performed.

COVID-19 in the endoscopy unit: How likely is transmission of infection? Results from an international, multicenter study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) significantly affected endoscopy practice, as gastrointestinal endoscopy is considered a risky procedure for transmission of infection to patients and personnel of endoscopy units (PEU). AIM: To assess the impact of COVID-19 on endoscopy during the first European lockdown (March-May 2020). METHODS: Patients undergoing endoscopy in nine endoscopy units across six European countries during the period of the first European lockdown for COVID-19 (March-May 2020) were included. Prior to the endoscopy procedure, participants were stratified as low- or high- risk for potential COVID-19 infection according to the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) joint statement, and contacted 7-14 d later to assess COVID-19 infection status. PEU were questioned regarding COVID-19 symptoms and/or infection via questionnaire, while information regarding hospitalizations, intensive care unit-admissions and COVID-19-related deaths were collected. The number of weekly endoscopies at each center during the lockdown period was also recorded. RESULTS: A total of 1267 endoscopies were performed in 1222 individuals across nine European endoscopy departments in six countries. Eighty-seven (7%) were excluded because of initial positive testing. Of the 1135 pre-endoscopy low risk or polymerase chain reaction negative for COVID-19, 254 (22.4%) were tested post endoscopy and 8 were eventually found positive, resulting in an infection rate of 0.7% [(95%CI: 0.2-0.12]. The majority (6 of the 8 patients, 75%) had undergone esophagogastroduodenoscopy. Of the 163 PEU, 5 [3%; (95%CI: 0.4-5.7)] tested positive during the study period. A decrease of 68.7% (95%CI: 64.8-72.7) in the number of weekly endoscopies was recorded in all centers after March 2020. All centers implemented appropriate personal protective measures (PPM) from the initial phases of the lockdown. CONCLUSION: COVID-19 transmission in endoscopy units is highly unlikely in a lockdown setting, provided endoscopies are restricted to emergency cases and PPM are implemented.

Single Dose of Sildenafil and Atorvastatin Increase Skin Survivability, but only Atorvastatin Increase Nitric Oxide in Rat Ischeamia Reperfusion Model.

Background: Ischeamia reperfusion injury is a frequent challenge during tissue reconstruction. Atorvastatin and Sildenafil, have been studied for their protective and/or therapeutic effects on various organ systems subjected to IRI. The aim of the present study was to compare a single dose of Atorvastatin and Sildenafil pretreatment on acute oxidative/nitrosative stress and the subsequent dermal flap necrosis. Materials and Methods: Forty-five Sprague-Dawley rats, were randomly allocated into three equal groups(n=15): Group A: Control rats treated with intraperitoneal saline, Group B: Sildenafil group, and Group C: atorvastatin group. All rats underwent flap elevation and inferior epigastric artery occlusion thirty minutes after drug administration. Myeloperoxidase activity, malondialdehyde levels and inducible nitric oxide synthase activity were evaluated 12 hours after reperfusion. Flap survivability was analysed 7 days after the procedure. Results: Statistically significant reduction was detected in sildenafil and atorvastation. Measurements of myelopyroxidase followed a similar pattern, interestingly malonadehyde levels measured to be significantly lower in the sildenafil group. Contrary, iNOS activity atorvastatin was significantly elevated in atorvastatin group. Conclusion: The single dose of atorvastatin or sildenafil increase flap survivability almost equally, however only atorvastatin enhances significantly iNOS expression.

The Carotenoid Compound of Saffron Crocetin Alleviates Effects of Ischemia Reperfusion Injury via a Mechanism Possibly Involving MiR-127.

Renal impairment is associated with high mortality rates in severely ill patients. The need to prevent and treat renal damage underlines the importance of understanding the pathophysiological mechanisms that characterize it. This could also enable early diagnosis and the design of alternative therapeutic approaches. The aim of this study is to investigate the effect of crocetin, a known antioxidant, on the prevention of renal damage due to ischemia-reperfusion injury and the investigation of the mechanisms involved. The present study was performed on C57BL/6 mice aged 10-12 weeks. The animals had access to water and food ad libitum. The experiment, as described in materials and methods, was completed at 24 h, in which case the kidneys were removed for further study, both at tissue morphology (with immunohistochemistry) and changes in the level of miRs' expression by qRT-PCR. Accordingly, using the automatic precision analyzer, the serum levels of the basic parameters currently used clinically for the monitoring of renal function were determined. The administration of crocetin, despite the short presence of the substance in the body, affects all the biochemical parameters analyzed (urea, creatinine, uric acid, and ions of Na, K, Cl, P, Mg and Ca), ​​causing significant decrease of their measured values. Crocetin also resulted in a significant limitation of the inflammation elements and the degree of epithelial damage. Furthermore, the administration of crocetin appears to restore levels of expression of miR21, miR127 and miR132.

Pancreatic intraductal papillary mucinous neoplasm masquerading as ampullary adenoma: a diagnostic puzzle.

Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cystic lesion, remaining mostly asymptomatic. An atypical presentation of such a lesion, initially thought to be an ampullary adenoma, is presented herein. A 78-year-old white male with painless jaundice was treated in a tertiary hospital. Imaging and endoscopic investigations pointed towards an ampullary adenoma obstructing and causing dilatation of both bile and pancreatic ducts. Endoscopic papillectomy was carried out and histology revealed tubulovillous adenoma. Follow-up duodenoscopy 3 months later showed a recurrent lesion with mucous leaking from the pancreatic duct. Cytology revealed mucin-rich atypical cells, consistent with main-duct IPMN. Pancreatoduodenectomy was performed, finally revealing main-duct IPMN protruding through Vater's ampulla. Cystic pancreatic lesions are increasingly found and IPMN is the most common of these. On the other hand, the management of ampullary adenomas has been revolutionized by endoscopic treatment and the advent of endoscopic papillectomy, with expanding indications. Meticulous clinical and imaging work up of these patients is essential to avoid suboptimal treatment. IPMN should be included in the differential diagnosis of ampullary adenomas, especially in the presence of a grossly dilated pancreatic duct.

A Duplicated Gallbladder in a Patient Presenting with Acute Cholangitis. A Case Study and a Literature Review.

Gallbladder duplication can present a clinical challenge primarily due to difficulties with diagnosis and identification. Recognition of this anomaly and its various types is important since it can complicate a gallbladder disease or a simple hepatobiliary surgical procedure. The case report of a 63-year-old woman who presented with cholangitis and underwent a successful laparoscopic management of symptomatic gallbladder duplication is described, emphasizing several important considerations. Using ERCP, MRCP and 3D reconstructions the two cystic ducts with one common bile duct were identified. A review of the literature in referral of this variant, its anatomical classifications and significance to clinical and surgical practice is included. In conclusion, gallbladder anomalies should be anticipated in the presence of a cystic lesion reported around the gallbladder when evaluating radiologic studies. In case of surgery, preoperative diagnosis is essential to prevent possible biliary injuries or reoperation if accessory gallbladder has been overlooked during initial surgery. Laparoscopic cholecystectomy remains feasible for intervention can be safely done and awareness is necessary to avoid complications or multiple procedures.

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.

Ischemic postconditioning decreases iNOS gene expression but ischemic preconditioning ameliorates histological injury in a swine model of extended liver resection.

BACKGROUND: Both pre- and postconditioning have been shown to protect the liver parenchyma from ischemia/reperfusion (I/R) injury during hepatectomy by altering the production of NO. However, to date there is no study to compare their effect on the inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) gene expression, who are the main modulators in the pathway of NO during the acute phase of I/R injury. METHODS: We designed a prospective experimental cohort comprising of three groups (sham group-SG, preconditioning-PrG and postconditioning group-PoG) and consisting of 10 animals per group. All animals underwent extended hepatectomy (70%) under prolonged warm ischemia either after preconditioning or followed by postconditioning or without any protective maneuver (SG). Following reperfusion blood samples and liver biopsies were obtained at the start of reperfusion (0 hours), at 6 and 12 hours post reperfusion. iNOS and eNOS gene expression was assessed on liver tissue by polymerase chain reaction (PCR); in addition, the extent of hepatocellular injury was histologically assessed. RESULTS: At the beginning of reperfusion iNOS expression was significantly reduced in the PoG in comparison to the SG (Kruskal-Wallis test, P=0.012; Mann-Whitney U test, P<0.0005 Bonferroni correction) and continued to remain at low levels until 6 hours post reperfusion (Kruskal-Wallis test, P=0.01; Mann-Whitney U test, P<0.0005-Bonferroni correction) This difference was eliminated by 12 hours. No significant differences were found in the expression of eNOS between groups and within time measurements. Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were found increased at the start of reperfusion; their levels continued to increase by 6 hours in all groups, however only in the PoG the increase attended statistical significance at 12 hours after reperfusion. ALT levels presented only minor alterations during the course of reperfusion. The PrG was found to have more intense hepatocellular injury at the start of reperfusion than the PoG however, that appeared to gradually settle by 12 hours in contrast to PoG where the hepatocellular injury continued to deteriorate. CONCLUSIONS: PoG appeared to decrease iNOS overexpression more effectively than PrG in comparison to animals who have undergone no protective maneuver (SG). However, PrG was more effective than PoG in ameliorating the hepatocellular injury observed at 12 hours after the ischemic insult.

The effect of transversus abdominis plane block on acute and chronic pain after inguinal hernia repair. A randomized controlled trial.

BACKGROUND: This prospective double-blind randomized study aimed at evaluating the short- and long-term postoperative analgesic efficacy of the ultrasound-guided tranversus abdominis plane (TAP) block in inguinal hernia repair under general anesthesia. METHODS: Sixty patients undergoing inguinal hernia repair were allocated to TAP block with either ropivacaine 0.75% 20 mL or placebo 20 mL. Postoperatively, they had access to a patient-controlled analgesia (PCA) device administering 1 mg doses of morphine as rescue analgesia. Pain was assessed at rest and during movement with the numeric rating scale (NRS) score 3,6 and 24 hs postoperatively. Other variables recorded were intraoperative dose of remifentanil required to maintain systolic arterial pressure within 20% of baseline, mg of morphine used in the Post Anesthesia Care Unit (PACU) and total dose of morphine administered via the PCA device. Six months after surgery, the occurrence of chronic pain was assessed with the NRS score at rest and during movement. Patients were also asked to fill in the DN4 questionnaire to estimate the development of neuropathic pain. RESULTS: Patients who were administered ropivacaine demonstrated significantly less pain at rest and on movement, as expressed by NRS scores in comparison to patients in the placebo group. The former group also required less remifentanil intraoperatively, less morphine during the PACU stay and had lower morphine consumption through the PCA device. Six months after surgery, pain scores at rest and during movement were comparable between the two groups. At the same time DN4 scores were low and comparable between the two groups. CONCLUSION: Ultrasound-guided TAP block provided better pain control than placebo in the acute setting after inguinal hernia repair. However, the incidence of chronic pain was low and not significantly affected by the performance of the block.

Immune-related intestinal pseudo-obstruction associated with nivolumab treatment in a lung cancer patient.

Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management.