The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Increased number of symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with prolonged time to return to full sports performance—AWAREⅧ

Purpose The aim of the study was to identify factors associated with prolonged time to return to full performance(RTFP)in athletes with recent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Methods Prospective cohort study with cross sectional analysis.A total of 84 athletes with confirmed SARS-CoV-2 infection assessed at a coronavirus disease 2019 recovery clinic gave a history of age,sex,type/level of sport,co-morbidities,pre-infection training hours,and 26 acute SARS-CoV-2 symptoms from 3 categories(“nose and throat”,“chest and neck”,and“whole body”/systemic).Data on days to RTFP were obtained by structured interviews.Factors associated with RTFP were demographics,sport participation,history of co-morbidities,pre-infection training history,and acute symptoms(type,number).Outcomes were:(a)days to RTFP(median,interquartile range(IQR))in asymptomatic(n=7)and symptomatic athletes(n=77),and(b)hazard ratios(HRs;95%confidence interval)for symptomatic athletes with vs.without a factor(univariate,multiple models).HR<1 was predictive of higher percentage chance of prolonged RTFP.Significance was p<0.05.Results Days to RTFP were 30 days(IQR:23–40)for asymptomatic and 64 days(IQR:42–91)for symptomatic participants(p>0.05).Factors associated with prolonged RTFP(univariate models)were:females(HR=0.57;p=0.014),endurance athletes(HR=0.41;p<0.0001),co-morbidity number(HR=0.75;p=0.001),and respiratory disease history(HR=0.54;p=0.026).In symptomatic athletes,prolonged RTFP(multiple models)was significantly associated with increased“chest and neck”(HR=0.85;p=0.017)and“nose and throat”(HR=0.84;p=0.013)symptoms,but the association was more profound between prolonged RFTP and increased total number of“all symptoms”(HR=0.91;p=0.001)and“whole body”/systemic(HR=0.82;p=0.007)symptoms.Conclusion A larger number of total symptoms and specifically“whole body”/systemic symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with prolonged RTFP.

Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

Outcomes following liver transplantation in intensive care unit patients

AIM:To determine feasibility of liver transplantation in patients from the intensive care unit (ICU) by estimating graft and patient survival.METHODS:This single center retrospective study included 39 patients who had their first liver transplant directly from the intensive care unit and 927 non-ICU patients who were transplanted from hospital ward or home between January 2005 and December 2010.RESULTS:In comparison to non-ICU patients,ICU patients had a higher model for end-stage liver disease (MELD) at transplant (median:37 vs 20,P < 0.001).Fourteen out of 39 patients (36%) required vasopressor support immediately prior to liver transplantation (LT) with 6 patients (15%) requiring both vasopressin and norepinephrine.Sixteen ICU patients (41%) were ventilator dependent immediately prior to LT with 9 patients undergoing percutaneous tracheostomy prior to transplantation.Twenty-five ICU patients (64%) required dialysis preoperatively.At 1,3 and 5 years after LT,graft survival was 76%,68% and 62% in ICU patients vs 90%,81% and 75% in non-ICU patients.Patient survival at 1,3 and 5 years after LT was 78%,70% and 65% in ICU patients vs 94%,85% and 79% in non-ICU patients.When formally comparing graft survival and patient survival between ICU and nonICU patients using Cox proportional hazards regression models,both graft survival [relative risk (RR):1.94,95%CI:1.09-3.48,P=0.026] and patient survival (RR:2.32,95%CI:1.26-4.27,P=0.007) were lower in ICU patients vs non-ICU patients in single variable analysis.These findings were consistent in multivariable analysis.Although not statistically significant,graft survival was worse in both patients with cryptogenic cirrhosis (RR:3.29,P=0.056) and patients who received donor after cardiac death (DCD) grafts (RR:3.38,P=0.060).These findings reached statistical significance when considering patient survival,which was worse for patients with cryptogenic cirrhosis (RR:3.97,P=0.031) and patients who were transplanted with DCD livers (RR:4.19,P=0.033).Graft survival and patient survival were not significantly worse for patients on mechanical ventilation (RR:0.91,P=0.88 in graft loss;RR:0.69,P=0.56 in death) or patients on vasopressors (RR:1.06,P=0.93 in graft loss;RR:1.24,P=0.74 in death) immediately prior to LT.Trends toward lower graft survival and patient survival were observed for patients on dialysis immediately before LT,however these findings did not approach statistical significance (RR:1.70,P=0.43 in graft loss;RR:1.46,P=0.58 in death).CONCLUSION:Although ICU patients when compared to non-ICU patients have lower survivals,outcomes are still acceptable.Pre-transplant ventilation,hemodialysis,and vasopressors were not associated with adverse outcomes.

Clues from a missense mutation of the adenosine A1 receptor gene associated with early-onset Parkinson’s disease

Parkinson’s disease (P D) is a com plex neu rodegenerative disorder for which ra re and common genetic variants contribute to disease risk,onset,and progression.The genetic contribution to PD can be classified mainly in,first,rare DNA variants that are highly penetrant and therefore causal,which are typically associated with monogenic PD;and second,more common risk polymorphic variants,which individually exert a small increase in the risk of the disease,which are usually identified in the most prevalent and apparently sporadic PD (Blauwendraat et al.,2020).

Ventricular Arrhythmia in the Fontan Circulation:Prevalence,Risk Factors and Clinical Implications

Objective:Sudden cardiac death(SCD)and malignant ventricular arrhythmia(VA)are increasingly recognized as important issues for people living with a Fontan circulation,but data are lacking.We sought to characterize the cohort who had sudden cardiac death,most likely related to VA and/or documented VA in the Australia and New Zealand Fontan Registry including risk factors and clinical outcomes.Methods:A retrospective cohort study was performed.Inclusion criteria were documented non-sustained ventricular tachycardia,sustained ventricular tachycardia,ventricular fibrillation,resuscitated cardiac arrest or SCD>30 days post-Fontan completion.Results:Of 1611 patients,20(1.2%)had VA;14(1.0%)had VA without SCD and 6(<1%)had SCD(6%of all deaths recorded in Registry;5 of those had documented VA at the time of arrest and 1 was presumed to be VA-associated).The median age at first VA was 20.5(14–32)years,10(50%)were females,and the median age at Fontan operation was 8(4–17)years.On univariable analysis,hypoplastic left heart syndrome(p=0.03)and older age Fontan operation(p<0.001)were associated with VA.Earlier Fontan era(p<0.003),atriopulmonary Fontan(p<0.001),pre-Fontan atrioventricular valve repair(p=0.013)pre-or post-Fontan atrial arrhythmia(p=0.010)were associated with SCD.Patients with VA had a 3 times higher risk of death or heart transplant(HR 3.27(1.19,8.98),p=0.02).Conclusions:A proportion of people living with a Fontan circulation have malignant VA.Routine VA screening in this cohort is essential.More data are needed to aid risk stratification.

Risk factors associated with the development of ischemic colitis

AIM:To ascertain the role of cardiovascular risk factors,cardiovascular diseases,standard treatments and other diseases in the development of ischemic colitis(IC).METHODS:A retrospective,case-control study was designed,using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003.IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible his-tology.Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy,excluding those with diagnosis of colitis.Cases were matched with controls(ratio 1:2),by age and sex.A conditional logistic regression was performed.RESULTS:A total of 483 patients(161 cases,322 con-trols)were included;mean age 75.67±10.03 years,55.9%women.The principal indications for colonos-copy in the control group were lower gastrointestinal hemorrhage(35.4%),anemia(33.9%),abdominal pain(19.9%)and diarrhea(9.6%).The endoscopic findings in this group were hemorrhoids(25.5%),diverticular disease(30.4%),polyps(19.9%)and colorectal cancer(10.2%).The following variables were associated with IC in the univariate analysis:arterial hypertension(P= 0.033);dyslipidemia(P<0.001);diabetes mellitus(P =0.025);peripheral arterial disease(P=0.004);heart failure(P=0.026);treatment with hypotensive drugs(P=0.023);angiotensin-converting enzyme inhibitors;(P=0.018);calcium channel antagonists(P=0.028);and acetylsalicylic acid(ASA)(P<0.001).Finally,the following variables were independently associated with the development of IC:diabetes mellitus[odds ratio(OR)1.76,95%confidence interval(CI):1.001-3.077,P=0.046];dyslipidemia(OR 2.12,95%CI:1.26-3.57,P=0.004);heart failure(OR 3.17,95%CI:1.31-7.68,P=0.01);peripheral arterial disease(OR 4.1,95%CI:1.32-12.72,P=0.015);treatment with digoxin(digitalis)(OR 0.27,95%CI:0.084-0.857,P=0.026);and ASA(OR 1.97,95%CI:1.16-3.36,P=0.012).CONCLUSION:The development of an episode of IC was independently associated with diabetes,dyslipid-emia,presence of heart failure,peripheral arterial dis-ease and treatment with digoxin or ASA.

Pre-illness changes in dietary habits and diet as a risk factor for inflammatory bowel disease: A case-control study

AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched healthy control group. METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis. RESULTS: Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.

Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

BACKGROUND Proton pump inhibitors(PPIs)are widely prescribed,often without clear indications.There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients.Furthermore,PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.AIM To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.METHODS Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017.PPI users were defined as cumulative defined daily dose(cDDD)≥28 within a landmark period,after hospitalisation for hepatic decompensation.Cox regression analysis for comparison was done after propensity score adjustment.Further risk of hepatic decompensation was analysed by Poisson regression.RESULTS Among 295 decompensated cirrhosis patients,238 were PPI users and 57 were non-users.PPI users had higher mortality compared to non-users[adjusted HR=2.10,(1.20-3.67);P=0.009].Longer PPI use with cDDD>90 was associated with higher mortality,compared to non-users[aHR=2.27,(1.10-5.14);P=0.038].PPI users had a higher incidence of hospitalization for hepatic decompensation[aRR=1.61,(1.30-2.11);P<0.001].CONCLUSION PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation.Longer PPI exposure with cDDD>90 increases the risk of mortality.

Colorectal cancer screening in countries of European Council outside of the EU-28

AIM: To provide an update on colorectal cancer(CRC) screening programmes in non-European Union(EU)-28 Council of Europe member states as of December 2015. METHODS: The mission of the Council of Europe is to protect and promote human rights in its 47 member countries. Its 19 non-EU member states are Albania, Andorra, Armenia, Azerbaijan, Bosnia and Herzegovina, Republika Srpska, Georgia, Iceland, Liechtenstein, Republic of Moldova, Monaco, Montenegro, Norway, Russian Federation, San Marino, Serbia, Switzerland, FYR of Macedonia, Turkey, and Ukraine(EU-19). The main data source were GLOBOCAN, IARC, WHO, EUCAN, NORDCAN, ENCR, volume X of the CI5, the ministerial and Public Health Agency websites of the individual countries, Pub Med, EMBASE, registries of some websites and the www.cochranelibrary.com, Scopus, www.clinicaltrials.gov, www.clinicaltrialsregister.eu, Research gate, Google and data extracted from screening programme results. RESULTS: Our results show that epidemiological data quality varies broadly between EU-28 and EU-19 countries. In terms of incidence, only 30% of EU-19 countries rank high in data quality as opposed to 86% of EU-28 states. The same applies to mortality data, since 52% of EU-19 countries as against all EU-28 countries are found in the high ranks. Assessment of the method of collection of incidence data showed that only 32% of EU-19 countries are found in the top three quality classes as against 89% of EU-28 countries. For the mortality data, 63% of EU-19 countries are found in the highest ranks as opposed to all EU-28 member states. Interestingly, comparison of neighbouring countries offering regional screening shows, for instance, that incidence and mortality rates are respectively 38.9 and 13.0 in Norway and 29.2 and10.9 in Sweden, whereas in Finland, where a national organised programme is available, they are respectively 23.5 and 9.3. CONCLUSION: Cancer screening should be viewed as a key health care tool, also because investing in screening protects the weakest in the population, decreases the social burden of cancer, and reduces all types of health care costs, including those for radical surgery, long-term hospitalisation, and chemotherapy.

High-risk esophageal varices in patients treated with locoregional therapy for hepatocellular carcinoma:Assessment with liver computed tomography

AIM:To assess the diagnostic performance of followup liver computed tomography(CT) for the detection of high-risk esophageal varices in patients treated with locoregional therapy for hepatocellular carcinoma(HCC).METHODS:We prospectively enrolled 100 patients with cirrhosis who underwent transcatheter arterial chemoembolization,radiofrequency ablation or both procedures for HCCs.All patients underwent upper endoscopy and subsequently liver CT.Three radiologists independently evaluated the presence of high-risk esophageal varices with transverse images alone and with three orthogonal multiplanar reformation(MPR) images,respectively.With endoscopic grading as the reference standard,diagnostic performance was assessed by using receiver operating characteristic(ROC) curve analysis.RESULTS:The diagnostic performances(areas under the ROC curve) of three observers with transverse images alone were 0.947 ± 0.031,0.969 ± 0.024,and 0.916 ± 0.038,respectively.The mean sensitivity,specificity,positive predicative value(PPV),and negative predicative value(NPV) with transverse images alone were 90.1%,86.39%,70.9%,and 95.9%,respectively.The diagnostic performances,mean sensitivity,specificity,PPV,and NPV with three orthogonal MPR images(0.965 ± 0.025,0.959 ± 0.027,0.938 ± 0.033,91.4%,89.5%,76.3%,and 96.6%,respectively) were not superior to corresponding values with transverse images alone(P > 0.05),except for the mean specificity(P = 0.039).CONCLUSION:Our results showed excellent diagnostic performance,sensitivity and NPV to detect high-risk esophageal varices on follow-up liver CT after locoregional therapy for HCC.

Clinical outcomes of tricuspid valve repair accompanying left-sided heart disease

AIM To determine whether the need for additional tricuspid valve repair is an independent risk factor when surgery is required for a left-sided heart disease.METHODS One hundred and eighty patients(68 ± 12 years,79 males) underwent tricuspid annuoplasty.Cox proportionalhazards regression model for multivariate analysis was performed for variables found significant in univariate analyses.RESULTS Tricuspid regurgitation etiology was functional in 154 cases(86%),organic in 16 cases(9%),and mixed in10 cases(6%),respectively.Postoperative mortality at 30 days was 11.7%.Mean follow-up was 51.7 mo with survival at 5 years of 73.5%.Risk factors for mortality were acute endocarditis [hazard ratio(HR) = 9.22(95%CI:2.87-29.62),P < 0.001],ischemic heart disease requiring myocardial revascularization [HR = 2.79(1.26-6.20),P = 0.012],and aortic valve stenosis [HR = 2.6(1.15-5.85),P = 0.021].Significant predictive factors from univariate analyses were double-valve replacement combined with tricuspid annuloplasty [HR = 2.21(1.11-4.39),P = 0.003] and preoperatively impaired ejection fraction [HR = 1.98(1.04-3.92),P = 0.044].However,successful mitral valve repair showed a protective effect [HR = 0.32(0.10-0.98),P = 0.046].Additionally,in instances where tricuspid regurgitation required the need for concomitant tricuspid valve repair,mortality predictor scores such as Euroscore 2 could be shortened to a simple Euroscore-tricuspid comprised of only 7 inputs.The explanation may lie in the fact that significant tricuspid regurgitation following leftsided heart disease represents an independent risk factor encompassing several other factors such as pulmonary arterial hypertension and dyspnea.CONCLUSION Tricuspid annuloplasty should be used more often as a concomitant procedure in the presence of relevant tricuspid regurgitation,although it usually reveals an overly delayed correction of a left-sided heart disease.

Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

AIM:To evaluate the rates of retinopathy without diabetes and diabetic retinopathy(DR),associated with some markers of oxidative stress,antioxidants and cardiometabolic risk factors.METHODS:We determined the prevalence of DR in 150type 2 diabetes mellitus(T2DM)patients,that of retinopathy in 50 non diabetics,the levels of body mass index(BMI),waist circumference(WC),blood pressure,lipids,8-isoprostane,8-hydroxydeoxyguanosine(8-oHdG),gamma-glutamyl transferase(GGT),oxidized low density lipoprotein(LDL)(OxLDL),thiobarbituric acid reacting substances(TBARS),reduced glutathione(GSH),superoxide dismutase(SOD),uric acid,creatinine,albumin,total antioxidant status(TAOS),zinc,selenium,magnesium,vitamin C,vitamin D,vitamin E,glucose,apolipoprotein B(ApoB).RESULTS:The prevalences of DR at 53y and Rtp at62y were 44%(n=66)and 10%(n=5),respectively.Thehighest levels of 8-isoprostane,8-OHdG,TBARS,SOD,and OxLDL were in DR.The lowest levels of vitamin D,vitamin C,TAOS,and vitamin E were in DR.In the casecontrol study discriminant analysis,the levels of vitamin C,vitamin D,ApoB,8-OHdG,creatinine,Zn,vitamin E,and WC distinguished significantly non-diabetics without DR(controls),T2DM patients without DR and T2DM patients with DR.CONCLUSION:Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2diabetics.Prevention of oxidative stress and abdominal obesity is needed.Supplementation in vitamin C,D,and E should be recommended as complement therapies of T2DM.

Hepatitis C virus and non-Hodgkin's lymphomas:Metaanalysisof epidemiology data and therapy options

Hepatitis C virus(HCV) is a global health problem affecting a large fraction of the world's population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell "benign" lymphoproliferative disorders, represents the most closely related as well as the most investigated HCVrelated extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin's lymphoma(NHL)] as well as hepatic malignancies(hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL's lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed.

Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2(PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs.METHODS: Tear samples were collected from 36 non-Sj?gren syndrome dry eye patients(10 males and 26 females, mean age 50.11±11.17 y). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time(TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay(ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction(MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores(R=0.608, P<0.001), however, they did not significantly associate with TBUT(R=0.153, P=0.373), Schirmer scores(R=-0.098, P=0.570), ocular surface staining scores(R=0.282, P=0.095), and stage of MGD(R=-0.107, P=0.535).Male sex was significantly negatively correlated with tear PGE2 levels.CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.

Cholecystectomy for asymptomatic gallstones:Markov decision tree analysis

Gallstones are a common public health problem,especially in developed countries.There are an increasing number of patients who are diagnosed with gallstones due to increasing awareness and liberal use of imaging,with 22.6%-80% of gallstone patients being asymptomatic at the time of diagnosis.Despite being asymptomatic,this group of patients are still at life-long risk of developing symptoms and complications such as acute cholangitis and acute biliary pancreatitis.Hence,while early prophylactic cholecystectomy may have some benefits in selected groups of patients,the current standard practice is to recommend cholecystectomy only after symptoms or complications occur.After reviewing the current evidence about the natural course of asymptomatic gallstones,complications of cholecystectomy,quality of life outcomes,and economic outcomes,we recommend that the option of cholecystectomy should be discussed with all asymptomatic gallstone patients.Disclosure of material information is essential for patients to make an informed choice for prophylactic cholecystectomy.It is for the patient to decide on watchful waiting or prophylactic cholecystectomy,and not for the medical community to make a blanket policy of watchful waiting for asymptomatic gallstone patients.For patients with high-risk profiles,it is clinically justifiable to advocate cholecystectomy to minimize the likelihood of morbidity due to complications.

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease

AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence.METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease(CD) in our center(1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy(median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients(follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype(B3) were postoperative risk factors. Previous perianal abscess/fistula(other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management(n = 49/161) prevented clinical(HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence(HR = 0.30, 95%CI: 0.13-0.70, P = 0.006).CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

Predictors of multiple injuries in individual distance runners:A retrospective study of 75,401 entrants in 4 annual races-SAFER XX

Background There are limited data on factors that predict an increased risk of multiple injuries among distance runners.The objective of this study was to determine risk factors that are predictive of individual runners with a high annual multiple injury risk(MIR).Methods A retrospective,cross-sectional study at 4 annual(2012-2015)Two Oceans 21.1 km and 56.0 km races in South Africa with 75,401 consenting race entrants.Running-related injury data were collected retrospectively through an online pre-race medical screening questionnaire.The average number of injuries for each runner every year was calculated by taking a runner's race entry history and injury history into account and categorizing entrants into 4 MIR categories(high,intermediate,low,and very low(reference)).Multiple logistic regression modeling(odds ratios)was used to determine whether the following factors were predictive of a high MIR(average>1 injury/year):demographics,training and racing,chronic-disease history(composite chronic disease score(CCDS)),and history of allergies.Results Of all entrants,9.2%reported at least 1 injury,and 0.4%of entrants were in the high MIR category;the incidence rate was 2.5 injuries per 10 runner-years(95%confidence interval(95%CI):2.4-2.7).Significant factors predictive of runners in the high MIR category were:running for>20 years:OR=2.0(95%CI:1.3-3.1;p=0.0010);a higher CCDS:OR=2.2(95%CI:2.0-2.4;p<0.0001);and a history of allergies:OR=2.8(95%CI:2.0-3.8;p<0.0001).Conclusion Runners who have been running recreationally for>20 years and those with multiple chronic diseases or a history of allergies were at higher risk of multiple running-related injuries.This high-risk group can be targeted for further study and possible injury-prevention interventions.

Usefulness of the Hook knife in flexible endoscopic myotomy for Zenker's diverticulum

AIM To investigate the outcome of flexible endoscopic myotomy performed with the Hook knife in patients with symptomatic Zenker's diverticulum(ZD).METHODS All consecutive patients treated for ZD at our institution between 7/2012 and 12/2016 were included.The flexible endoscopic soft diverticuloscope-assisted technique with endoclips placement and Hook knife myotomy were performed in all patients.Here we report a retrospective review of prospectively collected data.Demographics,dysphagia score(Dakkak and Bennett),associated symptoms and adverse events were collected pre-procedure,at 2 and 6 mo post-procedure,and at the end of the follow-up period.Clinical success was defined as at least 1-point improvement in dysphagia score and a residual dysphagia score≤1,with no need for reintervention.Dysphagia scores were compared before treatment and at end-of-follow-up using the Wilcoxon test.RESULTS Twenty-four patients were included.Mean size of ZD was 3.0 cm(range 2-8 cm).Mean number of sessions was 1.17/patient(range 1-3 sessions).Overall clinical success was 91.7%.Two adverse events(8.3%) occurred,and both were managed conservatively.No bleeding or perforation was reported.Mild pain was reported by 9 patients(37.5%).Median hospital stay was 1 d(range 1-6).Median follow-up was 19.5 mo(range 6-53).Mean ± SD dysphagia score was 2.25±0.89 before treatment and decreased to 0.41 ± 0.92 at end-of-follow-up(P<0.001).Regurgitation and cough dropped from 91.7% and 50% to 12.5% and 0% at the end of follow-up,respectively.Recurrence was observed in 3 patients,and all 3 were symptom-free after one more session.CONCLUSION The Hook knife,used in the soft diverticuloscope-assisted technique setting,is efficient and safe for treatment of ZD.

Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding

AIM: To compare outcomes of patients with nonvariceal upper gastrointestinal bleeding(NVUGIB) taking aspirin for primary prophylaxis to those not taking it.METHODS: Patients not known to have any vascular disease(coronary artery or cerebrovascular disease) who were admitted to the American University of Beirut Medical Center between 1993 and 2010 with NVUGIB were included. The frequencies of in-hospital mortality, re-bleeding, severe bleeding, need for surgery or embolization, and of a composite outcome defined as the occurrence of any of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics. We also compared frequency of in hospital complications and length of hospital stay between the two groups.RESULTS: Of 357 eligible patients, 94 were on aspirin and 263 patients were on no antithrombotics(controlgroup). Patients in the aspirin group were older, the mean age was 58 years in controls and 67 years in the aspirin group(P < 0.001). Patients in the aspirin group had significantly more co-morbidities, including diabetes mellitus and hypertension [25(27%) vs 31(112%) and44(47%) vs 74(28%) respectively,(P = 0.001)], as well as dyslipidemia [21(22%) vs 16(6%), P < 0.0001).Smoking was more frequent in the aspirin group [34(41%) vs 60(27%), P = 0.02)]. The frequencies of endoscopic therapy and surgery were similar in both groups. Patients who were on aspirin had lower inhospital mortality rates(2.1% vs 13.7%, P = 0.002),shorter hospital stay(4.9 d vs 7 d, P = 0.01), and fewer composite outcomes(10.6% vs 24%, P = 0.01). The frequencies of in-hospital complications and re-bleeding were similar in the two groups.CONCLUSION: Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes. Thus aspirin may have a protective effect beyond its cardiovascular benefits.