Glyoxalase-I Is Upregulated in Acute Cerulein-Induced Pancreatitis: A New Mechanism in Pancreatic Inflammation?

Inflammation caused by oxidative stress (ROS) demonstrates an essential mechanism in the pathogenesis of acute pancreatitis (AP). Important sources for ROS comprise the reactive compound methylglyoxal (MGO) itself and the MGO-derived formation of advanced glycation end-products (AGEs). AGEs bind to the transmembrane receptor RAGE and activate NF-κB, and lead to the production of pro-inflammatory cytokines. MGO is detoxified by glyoxalase-I (Glo-I). The importance of Glo-I was shown in different models of inflammation and carcinogenesis. Nevertheless, the role of Glo-I and MGO in AP has not been evaluated so far. This study analyzed Glo-I in cerulein-(CN)-induced AP and determined the effects of Glo-I knockdown, overexpression and pharmacological modulation. Methods: AP was induced in C57BL6/J mice by i.p. injection of CN. Glo-I was analyzed in explanted pancreata by Western Blot, qRT-PCR and immunohistochemistry. AR42J cells were differentiated by dexamethasone and stimulated with 100 nM of CN. Cells were simultaneously treated with ethyl pyruvate (EP) or S-p-bromobenzylglutathione-cyclopentyl-diester (BrBz), two Glo-I modulators. Knockdown and overexpression of Glo-I was achieved by transient transfection with Glo-I siRNA and pEGFP-N1-Glo-I-Vector. Amylase secretion, TNF-α production (ELISA) and expression of Glo-I, RAGE and NF-κB were measured. Results: Glo-I was significantly upregulated on protein and mRNA levels in CN-treated mice and AR42J cells. Dexamethasone-induced differentiation of AR42J cells increased the expression of Glo-I and RAGE. Treatment of AR42J cells with CN and EP or BrBz resulted in a significant reduction of CN-induced amylase secretion, NF-κB, RAGE and TNF-α. Overexpression of Glo-I led to a significant reduction of CN-induced amylase levels, NF-κB expression and TNF-α, whereas Glo-I knockdown revealed only slight alterations. Measurements of specific Glo-I activity and MGO levels indicated a complex regulation in the model of CN-induced AP. Conclusion: Glo-I is overexpressed in a model of CN-induced AP. Pharmacological modulation and overexpression of Glo-I reduced amylase secretion and the release of pro-inflammatory cytokines in AP in vitro. Targeting Glo-I in AP seems to be an interesting approach for future in vivo studies of AP

Preoperative Endoscopy and Its Impact on Perioperative Management in Bariatric Surgery

BACKGROUND The role of preoperative upper-gastrointestinal endoscopy for bariatric surgery is still understood only with controversy. The aim of this study was to evaluate the prevalence of endoscopic findings and its impact on perioperative management. METHODS Patients who underwent bariatric surgery at our center between 2010 and 2013 were systematically analyzed from a prospective database. RESULTS Two hundred and twelve patients with a median body mass index of 50 kg/m(2) (range 29-87) underwent 216 bariatric procedures at our center between 2010 and 2013. All patients received preoperative upper endoscopy. In 159 cases (75%), the endoscopy was performed at our center. These cases were included in this study. In 37 cases (23%), no abnormal findings were detected. In 122 cases (76%), upper endoscopy revealed pathologies. No further treatment was necessary in 24 cases (15%). Medical treatment was changed in 81 cases (51%). The operation was delayed due to medical treatment and re-endoscopy in 13 cases (8%). The surgical approach was changed in 4 cases (3%). CONCLUSION Routinely performed preoperative endoscopy before bariatric surgery revealed a high prevalence of gastrointestinal diseases with a significant impact on perioperative management in two thirds of the cases. Therefore, we recommend routine gastroscopy about 2-4 weeks prior to surgery

Sonographic diagnosis and Endo-SPONGE assisted vacuum therapy of anastomotic leakage following posterior pelvic exenteration for ovarian cancer without using a protective stoma

Anastomotic leakage is a very significant complication after posterior pelvic exenteration and a major cause of postoperative morbidity and mortality. We present a patient who underwent an optimal debulking surgery for an advanced stage ovarian cancer (FIGO IIIC). On postoperative day 12, transvaginal ultrasound revealed an anastomotic dehiscence following an unsuspicious computer tomography scan the day before. The patient was successfully managed by transanal vacuum therapy without re-laparotomy within a period of 4 weeks after diagnosis. We conclude that high-resolution transvaginal ultrasound is a crucial method in the management of complications after surgery and even allow diagnosing leakages of colorectal anastomosis. In selected cases characterized by a small leak size and a local peritonitis confined to the pelvis a transanal vacuum therapy may avoid both surgical re-intervention and creating a secondary diverting stoma

Electronic properties of curved few-layers graphene: a geometrical approach

We show the presence of non-relativistic L\'evy-Leblond fermions in flat three- and four-layers graphene with AB stacking, extending the results obtained in [Curvatronics2017] for bilayer graphene. When the layer is curved we obtain a set of equations for Galilean fermions that are a variation of those of L\'evy-Leblond with a well defined combination of pseudospin, and that admit L\'evy-Leblond spinors as solutions in an approriate limit. The local energy of such Galilean fermions is sensitive to the intrinsic curvature of the surface. We discuss the relationship between two-dimensional pseudospin, labelling layer degrees of freedom, and the different energy bands. For L\'evy-Leblond fermions an interpretation is given in terms of massless fermions in an effective 4D spacetime, and in this case the pseudospin is related to four dimensional chirality. A non-zero energy band gap between conduction and valence electronic bands is obtained for surfaces with positive curvature.Comment: 16 pages, 4 figures. Matches the published version. Refined theory that describes the unique combination of isospin states ocurring in curved bilayer graphene sheet

The collateral caval shunt as an alternative to classical shunt procedures in patients with recurrent duodenal varices and extrahepatic portal vein thrombosis

Upper gastrointestinal bleeding episodes from variceal structures are severe complications in patients with portal hypertension. Endoscopic sclerotherapy and variceal ligation are the treatment options preferred for upper variceal bleeding owing to extrahepatic portal hypertension due to portal vein thrombosis (PVT). Recurrent duodenal variceal bleeding in non-cirrhotic patients with diffuse porto-splenic vein thrombosis and subsequent portal cavernous transformation represent a clinical challenge if classic shunt surgery is not possible or suitable. In this study, we represent a case of recurrent bleeding of duodenal varices in a non-cirrhotic patient with cavernous transformation of the portal vein that was successfully treated with a collateral caval shunt operation

Acute emergency care and airway management of caustic ingestion in adults: single center observational study

Background: Caustic ingestions are rare but potentially life-threatening events requiring multidisciplinary emergency approaches. Although particularly respiratory functions may be impaired after caustic ingestions, studies involving acute emergency care are scarce. The goal of this study was to explore acute emergency care with respect to airway management and emergency department (ED) infrastructures. Methods: We retrospectively evaluated adult patients after caustic ingestions admitted to our university hospital over a 10-year period (2005–2014). Prognostic analysis included age, morbidity, ingested agent, airway management, interventions (endoscopy findings, computed tomography (CT), surgical procedures), intensive care unit (ICU) admission, length of stay in hospital and hospital mortality. Results: Twenty-eight patients with caustic ingestions were included in the analysis of which 18 (64 %) had suicidal intentions. Ingested agents were caustic alkalis (n = 22; 79 %) and acids (n = 6; 21 %). ICU admission was required in 20 patients (71 %). Fourteen patients (50 %) underwent tracheal intubation and mechanical ventilation, of which 3 (21 %) presented with difficult airways. Seven patients (25 %) underwent tracheotomy including one requiring awake tracheotomy due to progressive upper airway obstruction. Esophagogastroduodenoscopy (EGD) was performed in 21 patients (75 %) and 11 (39 %) underwent CT examination. Five patients (18 %) required emergency surgery with a mortality of 60 %. Overall hospital mortality was 18 % whereas the need for tracheal intubation (P = 0.012), CT-diagnostic (P = 0.001), higher EGD score (P = 0.006), tracheotomy (P = 0.048), and surgical interventions (P = 0.005) were significantly associated with mortality. Conclusions: Caustic ingestions in adult patients require an ED infrastructure providing 24/7-availability of expertise in establishing emergent airway safety, endoscopic examination (EGD and bronchoscopy), and CT diagnostic, intensive care and emergency esophageal surgery. We recommend that - even in patients with apparently stable clinical conditions - careful monitoring of respiratory functions should be considered as long as diagnostic work-up is completed

Mutations in POLE and survival of colorectal cancer patients – link to disease stage and treatment

Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRCs), which are caused by exonuclease domain mutations (EDMs) in DNA polymerase ϵ (POLE). Data on the clinical implications of these findings as to whether these mutations define a unique CRC entity with distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE exonuclease domain in 431 well-characterized patients with microsatellite stable (MSS) CRCs of a population-based patient cohort. Mutation data were analyzed for associations with major epidemiological, clinical, genetic, and pathological parameters including overall survival (OS) and disease-specific survival (DSS). In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty-four mutations were identified in 46 of these samples (12.3%). Besides already reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding to amino acids 410–491) as well as in exon 9 and exon 11 (corresponding to aa 268–303 and aa 341–369). However, we did not see any significant associations of EDMs with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, KRAS, and BRAF mutations. While with a median follow-up time of 5.0 years, survival analysis of the whole cohort revealed nonsignificantly different adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82–2.25) and 1.44 (0.81–2.58) for OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup analysis for patients with stage III/IV disease receiving chemotherapy revealed a statistically significantly increased adjusted HR (1.87; 95%CI: 1.02–3.44). In conclusion, POLE EDMs do not appear to define an entirely new clinically distinct disease entity in CRC but may have prognostic or predictive implications in CRC subgroups, whose significance remains to be investigated in future studies

The collateral caval shunt as an alternative to classical shunt procedures in patients with recurrent duodenal varices and extrahepatic portal vein thrombosis

Upper gastrointestinal bleeding episodes from variceal structures are severe complications in patients with portal hypertension. Endoscopic sclerotherapy and variceal ligation are the treatment options preferred for upper variceal bleeding owing to extrahepatic portal hypertension due to portal vein thrombosis (PVT). Recurrent duodenal variceal bleeding in non-cirrhotic patients with diffuse porto-splenic vein thrombosis and subsequent portal. cavernous transformation represent a clinical challenge if classic shunt surgery is not possible or suitable. In this study, we represent a case of recurrent bleeding of duodenal varices in a non-cirrhotic patient with cavernous transformation of the portal vein that was successfully treated with a collateral caval shunt operation

The collateral caval shunt as an alternative to classical shunt procedures in patients with recurrent duodenal varices and extrahepatic portal vein thrombosis

Upper gastrointestinal bleeding episodes from variceal structures are severe complications in patients with portal hypertension. Endoscopic sclerotherapy and variceal ligation are the treatment options preferred for upper variceal bleeding owing to extrahepatic portal hypertension due to portal vein thrombosis (PVT). Recurrent duodenal variceal bleeding in non-cirrhotic patients with diffuse porto-splenic vein thrombosis and subsequent portal cavernous transformation represent a clinical challenge if classic shunt surgery is not possible or suitable. In this study, we represent a case of recurrent bleeding of duodenal varices in a non-cirrhotic patient with cavernous transformation of the portal vein that was successfully treated with a collateral caval shunt operation

Prognostic value of interleukin-1 receptor antagonist gene polymorphism and cytomegalovirus seroprevalence in patients with coronary artery disease

BACKGROUND: Chronic inflammatory stimuli such as cytomegalovirus (CMV) infection and various genetic polymorphisms determining the inflammatory response are assumed to be important risk factors in atherosclerosis. We investigated whether patients with stable coronary artery disease (CAD) and homozygous for allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene and seropositive for CMV represent a group particular susceptible for recurrent cardiovascular events. METHODS: In a series of 300 consecutive patients with angiographically defined CAD a prospective follow-up was conducted (mean age 57.9 years, median follow-up time 38.2 months). RESULTS: No statistically significant relationship was found between CMV serostatus and IL-1RN*2 (alone or in combination) and risk for future cardiovascular events (CVE). The hazard ratio (HR) for a CVE given positive CMV-serology and IL-1RN*2 was 1.07 (95% confidence interval (CI) 0.32–3.72) in the fully adjusted model compared to seronegative CMV patients not carrying the IL-1RN*2 allele. In this prospective cohort study involving 300 patients with angiographically defined CAD at baseline, homozygousity for allele 2 of the IL-1 RA and seropositivity to CMV alone and in combination were not associated with an increased risk for cardiovascular events during follow-up; in addition, combination of the CMV-seropositivity and IL-1RN*2 allele were not associated with a proinflammatory response CONCLUSION: Our study suggests that seropositivity to CMV and IL-1RA*2 genotype alone or in combination might not be a strong risk factor for recurrent cardiovascular events in patients with manifest CAD, and is not associated with levels of established inflammatory markers