Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers

Resveratrol(RSV),the primary polyphenol found in grapes,has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines,including IL-1β,IL-6,IL-1ra and TNFα.Considering the close association between chronic inflammation and cancer development,RSV’s immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation,proliferation,neovascularization,and migration.Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress.In addition to immunomodulation,RSV inhibits cancer development by expressing anti-oxidant effects,causing cell cycle arrest,stimulating the function of certain enzymes,and activating cell signaling pathways.The end outcome is one of the various forms of cell death,including apoptosis,pyroptosis,necroptosis,and more,as it has been observed in vitro.RSV has been shown to act against cancer in practically every organ,while its effects on colon cancer have been documented more frequently.It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol.The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV,with a particular emphasis on cancers of the digestive tract,as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Effect of patient COVID-19 vaccine hesitancy on hospital care team perceptions

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic posed new challenges in patient care worldwide.Vaccinations,which have proven efficacious in lowering the COVID-19 hospital burden,are still avoided by large populations.We,therefore,hypothesized that hospital care teams would have worse perceptions regarding the characteristics and care of patients with vaccine hesitancy.AIM To evaluate whether patient vaccine hesitancy affected the hospital care team(HCT)perceptions.METHODS We performed a prospective clinical study using structured questionnaires.We approached physicians and nurses with previous experience caring for COVID-19patients from 11 medical centers across Israel during the fourth COVID-19 surge(September and October 2021).The participants completed a questionnaire with the following parts:(1)Sociodemographic characteristics;(2)Assessment of anger(STAXI instrument)and chronic workplace stress(Shirom-Melamed burnout measure);and(3)Three tools to assess the effect of patient vaccine hesitancy on the HCT perceptions(the difficult doctor-patient relation questionnaire,the medical staff perception of patient’s responsibility questionnaire and the characterological derogation questionnaire).Results were evaluated according to each part of the questionnaire and the questionnaire as a whole.Associations between HCT perceptions and their baseline characteristics,anger or chronic workplace stress were assessed.RESULTS The HCT experienced their relationship with unvaccinated patients as more difficult(P<0.001,Cohen’s d=0.85),perceived unvaccinated patients as responsible for their medical condition(P<0.001,d=1.39)and perceived vaccinated patients as having a higher character value(P<0.001,d=1.03).Unvaccinated patients were considered selfish(P<0.001),less mature(P<0.001)and less satisfying to care for(P<0.001).The relationship with unvaccinated patients was more difficult among HCT with higher burnout(r=0.37,n=66,P=0.002).No correlations with baseline characteristics were found.All three study tools showed high internal consistency(αbetween 0.72 and 0.845).CONCLUSION Our results should raise awareness of the possible effects of vaccine hesitancy on HCT perceptions regarding unvaccinated patients.In order to minimize the potential negative impact on patient care,designated departments should promote specific patient-centered preparations.Further investigations should assess whether vaccine hesitancy directly affects patient quality of care.

Comparative analysis of the predictive power of different endothelial progenitor cell phenotypes on cardiovascular outcome

AIM: To compare the predictive power of different endothelial progenitor cell (EPC) phenotypic markers for future cardiovascular events. METHODS: Peripheral blood was collected from 76 consecutive patients with acute coronary syndromes (ACS) who underwent percutaneous coronary intervention in our institute. The various EPC phenotypes of peripheral blood mononuclear cells were CD34+CD133+, CD34+KDR+, and CD 133+KDR+. The outcome endpoint included cardiovascular mortality, recurrent ACS, and hospitalization for decompensated heart failure during a 24-mo follow-up period.RESULTS: CD34+CD133+ cells (P = 0.034), but not CD34+KDR+ (P = 0.35) or CD 133+KDR+ cells (P = 0.19), were found to predict recurrent ACS. We found no correlation between EPCs measured by any of the three phenotypic combinations of accepted CD markers and the total combination of these separate outcomes. CONCLUSION: The EPC CD34+CD133+ phenotype, but not the CD34+KDR+ or the CD 133+KDR+ phenotypes, is predictive of future adverse cardiovascular outcomes.

Co-occurrence of type 1 diabetes mellitus and celiac disease

The co-occurrence of celiac disease(CD) and type 1 diabetes(T1DM) has been reported as 5-7 times more prevalent than CD alone.The clinical presentation and natural history of CD in patients with T1 DM may vary considerably.Less than 10% of patients with T1 DM and CD show gastrointestinal symptoms.Therefore,experts support screening for CD in T1 DM patients,though there is no consensus as to the recommended frequency of screening.When stratified by time since CD diagnosis,longer follow-up and coexistence of CD are associated with significant increased risk of diabetic associated morbidity and mortality.Early CD diagnosis and treatment with a gluten-free diet are essential.

Virtual nonenhanced abdominal dual-energy MDCT:Analysis of image characteristics

AIM: To evaluate abdominal and pelvic image characteristics and artifacts on virtual nonenhanced (VNE) images generated from contrast-enhanced dual-energy multidetector computed tomography (MDCT) studies. METHODS: Hadassah-Hebrew University Medical Institutional Review Board approval was obtained; 22 patients underwent clinically-indicated abdominal and pelvic single-source dual-energy MDCT (Philips Healthcare, Cleveland, OH, USA), pre- and post-IV administration of Omnipaque 300 contrast (100 cc). Various solid and vascular structures were evaluated. VNE images were generated from the portal contrast-enhanced phase using probabilistic separation. Contrast-enhanced-, regular nonenhanced (RNE)-, and VNE images were evaluated with a total of 1494 density measurements. The ratio of iodine contrast deletion was calculated. Visualization of calcifications, urinary tract stones, and image artifacts in VNE images were assessed. RESULTS: VNE images were successfully generated in all patients. Significant portal-phase iodine contrast deletion was seen in the kidney (61.7%), adrenal gland (55.3%), iliac artery (55.0%), aorta (51.6%), and spleen (34.5%). Contrast deletion was also significant in the right atrium (RA) (51.5%) and portal vein (39.3%), but insignificant in the iliac vein and inferior vena cava (IVC). Average post contrast-to-VNE HU differences were significant (P < 0.05) in the: RA -135.3 (SD 121.8), aorta -114.1 (SD 48.5), iliac artery -104.6 (SD 53.7), kidney -30.3 (SD 34.9), spleen -9.2 (SD 8.8), and portal vein -7.7 (SD 13.2). Average VNE-to-RNE HU differences were significant in all organs but the prostate and subcutaneous fat: aorta 38.0 (SD 9.3), RA 37.8 (SD 16.1), portal vein 21.8 (SD 12.0), IVC 12.2 (SD 11.6), muscle 3.3 (SD 4.9), liver 5.7 (SD 6.4), spleen 22.3 (SD 9.8), kidney 40.5 (SD 6.8), and adrenal 20.7 (SD 13.5). On VNE images, 196/213 calcifications (92%) and 5/6 renal stones (84%) were visualized. Lytic-like artifacts in the vertebral bodies were seen in all studies. CONCLUSION: Iodine deletion in VNE images is most significant in arteries, and less significant in solid organs and veins. Most vascular and intra-abdominal organ calcifications are preserved.

Role of colonoscopy in patients with persistent acute diverticulitis

AIM： To identify patients with persistent acute diverticulitis who might benefit from an early colonoscopy during their first hospitalization. METHODS： All patients hospitalized between July 2000 and December 2006 for acute diverticulitis who underwent colonoscopy were included in the study. Patients were followed during hospitalization and after discharge. Patients were considered to have a persistent course of acute diverticulitis if symptoms continued after 1 wk of conventional treatment with 1V antibiotics, or if symptoms recurred within 2 mo after discharge. Patients were considered to benefit from an early colonoscopy if the colonoscopy was therapeutic or if it changed a patient＇s outcome. RESULTS： Three hundred and six patients were hospitalized between July 2000 and December 2006 with the diagnosis of acute diverticulitis. Two hundred and twenty four of these were included in the study group. Twenty three patients （10.3%） fulfilled the criteria for a persistent course of acute diverticulitis. Of them, four patients （17.4%） clearly benefited from an early colonoscopy; these patients＇ clinical course is described. None of the patients with a regular non-persistent course demonstrated any benefit from colonoscopy. CONCLUSION： Early colonoscopy detected other significant pathology, which accounted for the clinical presentation in 17% of patients with persistent acute diverticulitis. Therefore, we believe an early colonoscopy should be considered in all patients with a persistent clinical course.

Clinical characteristics of progressive nonarteritic anterior ischemic optic neuropathy

AIM:To study whether patients with progressive nonarteritic anterior ischemic optic neuropathy(NAION)present earlier than patients with stable NAION and to describe their clinical characteristics and visual outcome.METHODS:This was a retrospective chart review.All patients with NAION seen during the acute stage from January 2012 to December 2018 were reviewed.Patients were included if they had documented disc edema and follow up of at least 3 mo.Patients with progressive NAION were identified if they worsened in 2 out of 3 parameters:visual acuity≥3 Snellen lines;Color vision≥4 Ishihara plates;the visual field defect involved a new quadrant.The clinical characteristics,time from symptom onset to presentation,systemic risk factors and visual outcome were compared to patients with stable NAION.RESULTS:Totally 122 NAION cases met the inclusion criteria.Mean age was 58.1 y(range 22-74),70%were men.Twenty cases(16.4%)had progressive NAION.Patients with progressive NAION did not differ from stable NAION in their demographics,systemic risk factors or in their initial visual deficit.At last follow up,median visual acuity was 1.0 log MAR(IQR 0.64-1.55)in patients with progressive NAION,vs 0.18(IQR 0.1-0.63)in stable NAION(P<0.001).Median color vision testing was 0 plates correct(IQR 0-2.5%)vs 92%plates correct(IQR 50%-100%)in the stable NAION group(P<0.001).Patients with progressive NAION differed in the time from symptom onset to presentation(median 2 d vs 5 d,P=0.011).CONCLUSION:We find no identifiable risk factors associated with progressive NAION.Progressors arrive earlier for ophthalmological evaluation.

Late onset fulminant Wilson's disease:A case report and review of the literature

Wilson’s disease(WD)is an autosomal recessive inherited disorder of hepatic copper metabolism.WD can be present in different clinical conditions,with the most common ones being liver disease and neuropsychiatric disturbances.Most cases present symptoms at<40years of age.However,few reports exist in the literature on patients in whom the disease presented beyond this age.In this report,we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically,by genetic analysis of the ATP7B gene disclosing rare mutations(G1099S and c.1707+3ins T)as well as by high hepatic copper content.We also reviewed the relevant literature.The diagnosis of WD with late onset presentation is easily overlooked.The diagnostic features and the geneticbackground in patients with late onset WD are not different from those in patients with early onset WD,except for the age.Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early.

What is the best anti-vascular endothelial growth factor agent for the treatment of diabetic macular edema？ Review of the 2-year results of Diabetic Retinopathy Clinical Research Network ProtocolT

Diabetic macular edema(DME) remains a main concern in diabetic patients,due to potential visual impairment with any level of diabetic retinopathy.The first study to provide a treatment option for these patients was The Early Treatment Diabetic Retinopathy Study(ETDRS),

Flare-up of ulcerative colitis after systemic corticosteroids: A strong case for Strongyloides

Super-imposed infection with intestinal organisms can mimic a flare-up of underlying disease in patients with inflammatory bowel disease (IBD). We report a case of patient with long standing ulcerative colitis (UC), who presented with abdominal pain, diarrhea and low- grade fever after receiving systemic corticosteroids for an unrelated disorder. Despite a negative stool examination, a peripheral eosinophilia reappeared upon tapering down of a corticosteroid dose. Subsequently, duodenal biopsies showed evidence for Strongyloides, presumably acquired 20 years ago when the patient was residing in Brazil. The patient fully recovered following anti-helmintic therapy. This case underscores the importance of considering Strongyloides in the work-up of flaring-up IBD patients, even if a history of residing or traveling to endemic areas is in the distant past.

The Wingate anaerobic test cannot be used for the evaluation of growth hormone secretion in children with short stature

Purpose: To assess the growth hormone(GH) response to the Wingate anaerobic test(WAn T) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAn T would be similar to the GH response to a commonly used pharmacologic provocation test.Methods: Ten children(6 males and 4 females, age range 9.0–14.9 years) participated in the study. Each participant performed 2 tests: a standard all-out WAn T, cycling for 30 s against constant resistance, and a standardized pharmacologic test(clonidine or glucagon). Blood samples for GH were collected before and 10, 30, 45, and 60 min after the beginning of exercise. In addition, we collected pre-and post-exercise blood lactate levels.Results: There was a significant increase in GH levels after the WAn T, yet in 9 of 10 participants, this increase was below the threshold for GH sufficiency. Peak GH after the WAn T was significantly lower compared to the pharmacologic GH provocation tests(with 9 of 10 demonstrating GH-sufficient response).Conclusion: The traditional WAn T cannot be used as a GH provocation test. Further research is needed to develop anaerobic exercise protocols sufficient to promote GH secretion.

Effect of brimonidine tartrate on basophil activation in glaucoma patients

AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers.Blood samples were stimulated with brimonidine 0.15%,timolol 0.5%or brimonidine tartrate/timolol maleate 0.2%/0.5%.Premixed antibodies(CD63/FITC and aIgE/PE)were added for direct staining and whole-blood samples were lysed,fixed and analyzed by a flow cytometer.The basophil population was defined by high IgE cell expression.Degranulation was identified by the expression of the activation molecule CD63.RESULTS:Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine(2.58%,2.45%,respectively,P=0.72).There was a significant suppression of basophil activation when a combination of brimonidine-timolol(0.87%)was compared to timolol(2.27%;P=0.012)and to brimonidine alone(2.58%;P=0.017).CONCLUSION:The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction.Basophil activation was suppressed by the presence ofβ-blockers in patients hypersensitive to brimonidine and in healthy individuals.This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.

THE USE OF RELEASABLE SUTURES IN FILTRA-TION SURGERY REDUCES EARLY POST OPERA-TIVE COMPLICATIONS

Purpose: To evaluate the use of releasable sutures in filtration surgery by comparing the results and the rate of post-operative complications in eyes which underwent filtration surgery with and without releasable sutures. Methods: A retrospective evaluation of 74 eyes with glaucoma (COAG, CNAG, PXFG) of 74 patients who underwent filtration surgery in our department during 1999. All the patients included in the study had 6-12

<i>Chryseobacterium indologenes</i>Bacteremia: Clinical and Microbiological Characteristics of an Emerging Infection

Purpose: Since Chryseobacterium indologenes (C. indologenes) is a rare human pathogen, its clinical significance has not yet been fully established. C. indologenes contamination of medical devices involving fluids and of surgical implants has led to an increasing number of serious infectious reported in recent years, mainly in patients in extremes ages and an immunocompromised state. In this study, we describe the clinical and microbiological characteristics of seven adult patients with C. indologenes bacteremia treated in a tertiary medical center in Israel over a six-year period. Methods: Adult patients hospitalized in Rabin Medical Center, Israel, with a blood culture positive for C. indologenes during the period 2009-2014 were identified retrospectively and their medical records were reviewed. Results: Seven episodes of C. indologenes bacteremia in seven patients were identified during the study period. Five patients were females;the mean age was 76.8 years (41 - 92). Serious underlying conditions were present in all patients. All patients but one, presented after a recent invasive healthcare related intervention. Two patients required mechanical ventilation. Two patients died. All but one isolates were susceptible to ciprofloxacin. Conclusions: Despite our limited number of cases, to the best of our knowledge, our study serves as the largest cohort of adult patients with C. indologenes bacteremia reported in recent years.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice

AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

Severe Acute Respiratory Distress Syndrome in a Patient with Sickle-Cell Anemia Requiring Veno-Venous Extracorporeal Membrane Oxygenation Therapy: Case Report and Review of the Literature

Background: Sickle cell anemia is caused by a mutation in the beta globin gene, resulting in the production of sickle hemoglobin, which is less soluble than normal hemoglobin. The main disease features are related to hemolytic anemia and blood vessels occlusion, causing ischemia and infracts. Acute chest syndrome is one of its most dangerous manifestations, and may cause severe hypoxemia and acute respiratory failure. Conservative management is often successful, but in rare cases the syndrome may be refractory. Extracorporeal membrane oxygenation (ECMO) support may be life-saving in these extreme situations. Case Report: A 31-year-old male admitted to the intensive care unit (ICU) in our hospital due to acute chest syndrome and massive aspiration. Due to extreme hypoxemia and severe acute respiratory distress syndrome, veno-venous ECMO support was initiated with rapid improvement in both oxygenation and hemodynamic status. The patient was weaned of ECMO after 7 days. He was discharged 4 weeks later. Although initiation of ECMO in sickle cell patients is uncommon, in selected refractory cases it may be life-saving. Conclusion: Although initiation of ECMO therapy in sickle cell anemia patients is uncommon, and may be even controversial, in selected refractory cases it may be life-saving.

Significance of low level infliximab in the absence of anti-infliximab antibodies

AIM:To evaluate the prevalence of double negative(DN)sera and the mechanisms responsible for DN status.METHODS:Sera of inflammatory bowel disease patients treated with infliximab(IFX)were tested for drug/antibodies to infliximab(ATI)trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA(with labeled IFX as the detection antibody)and an antilambda ELISA(with anti-human lambda chain detection antibody).Repeat testing with lower than customary serum dilution(1:10)was performed.Patients with DN status were matched with IFX+/ATI-controls and were followed-up for subsequent development of nontransient ATI to investigate if DN status precedes ATI.RESULTS:Of 67 sera obtained at time of loss of response,only 6/67(9%)were DN by anti-lambda ELISA compared to 27/67(40%)with double antigen ELISA(P<0.001,Fisher’s Exact test).Of the latter27 sera,22%were also DN by anti-lambda ELISA,whereas 44%were actually IFX positive(IFX+ATI-),30%were ATI positive(IFX-ATI+)and 4%were double positive(IFX+ATI+).Re-testing using a 1:10 dilution converted most DN results into IFX+and/or ATI+status.Patients with DN status had shorter survival free of non-transient ATI compared with matched controls(log rank test,P<0.001).In 9/30(30%)of these patients,non transient ATI occurred before and after the event at which the DN serum was obtained,supporting the view that a DN result may represent aparticular time-point along the two curves of ATI titer rise and infliximab drug level decline.CONCLUSION:DN status may result from false negative detection of IFX or ATI by double antigen ELISA,suggesting a transitional state of low-level immunogenicity,rather than non-immunological clearance.

Effect of hepatic iron concentration reduction on hepatic fibrosis and damage in rats with cholestatic liver disease

AIM： TO assess the effect of iron reduction after phlebotomy in rats with ＂normal＂ hepatic iron concentration （HIC） on the progression of hepatic fibrosis, as a result of bile duct ligation （BDL）. METHODS： Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated. RESULTS： Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects. CONCLUSION： Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats. However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.

Evaluation of a Pediatric Mock Code Educational Training Program at a Large, Tertiary Care Pediatric Hospital

Background: Management of the acutely ill children represents one of the more complex clinical skills required of pediatric physicians. Our goal was to develop and evaluate a multidisciplinary pediatric mock code training program for the pediatric residents in our institution. Methods: We performed a before and after evaluation of pediatric residents. The residents were educated by attending five mock code scenarios, followed by debriefing. Before and after the five sessions, the residents completed a self-assessment questionnaire. Results: Residents reported a significant improvement in their comfort in all aspects of managing pediatric resuscitations, with notable improvement seen in running a resuscitation requiring airway management, managing fluid resuscitation and performing endotracheal intubation. The most prominent change was demonstrated in the comfort level of the overall management of a pediatric resuscitation. Conclusion: The pediatric mock code educational training program improved residents’ self-reported knowledge and comfort level in managing pediatric emergency situations.

Treatment of Hip Trochanteric Bursitis Using Hyaluronate Injections

Trochanteric bursitis is a common cause of musculoskeletal pain and often requires medical intervention and should be distinguished from sciatica and irradiating pain of pelvic and spinal origin. Previously, the etiology of the trochanteric pain syndrome was thought to be caused by inflammation. The current study was performed in order to assess the efficacy of trochanteric injections. Methods: 158 patients were treated for trochanteric bursitis (132 females/26 males, range 22 - 88 years). 59b were treated with corticosteroid injection, 60 with hyaluronate and 39 were injected using a combination of both. Patients were followed by the HOOS score for a minimum of 12 months. Results: Pre-operative HOOS scores were similar in all groups. Following injection, the HOOS score increased from 27 ± 4 to 66 ± 2 after six months and 77 ± 4 after a year. At 12-month follow-up, the average score of patients treated by corticosteroids injection was 44 ± 7 compared with 62 ± 8 for the hyaluronate injected group and 64 ± 6 for the combination injection group. Discussion: It appears that injection therapy is highly efficacious for treating trochanteric bursitis. The effect of hyaluronate or hyaluronate and steroid combination appears to be longer lasting than that of steroid alone.