Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population

Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in NAFLD.Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of PCR.Results: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P < 0.01) and triglycerides(TGL)(TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4(rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase(ALT)(CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P < 0.01) and those who were more obese(32.2 vs 29.0 kg/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.

Preoperative albumin-bilirubin score is a prognostic factor for gastric cancer patients after curative gastrectomy

BACKGROUND Albumin-bilirubin(ALBI)score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular carcinomas.Currently,this liver function index has been used to predict prognosis in other neoplasms.However,the significance of ALBI score in gastric cancer(GC)after radical resection has not been elucidated.AIM To evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative treatment.METHODS Patients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective database.ALBI score was calculated as follows:(log10 bilirubin×0.660)+(albumin×-0.085).The receiver operating characteristic curve with area under the curve(AUC)was plotted to evaluate the ability of ALBI score in predicting recurrence or death.The optimal cutoff value was determined by maximizing Youden’s index,and patients were divided into low and high-ALBI groups.The Kaplan-Meier curve was used to analyze the survival,and the log-rank test was used for comparison between groups.RESULTS A total of 361 patients(235 males)were enrolled.The median ALBI value for the entire cohort was-2.89(IQR-3.13;-2.59).The AUC for ALBI score was 0.617(95%CI:0.556-0.673,P<0.001),and the cutoff value was-2.82.Accordingly,211(58.4%)patients were classified as low-ALBI group and 150(41.6%)as high-ALBI group.Older age(P=0.005),lower hemoglobin level(P<0.001),American Society of Anesthesiologists classification III/IV(P=0.001),and D1 lymphadenectomy P=0.003)were more frequent in the high-ALBI group.There was no difference between both groups in terms of Lauren histological type,depth of tumor invasion(pT),presence of lymph node metastasis(pN),and pathologic(pTNM)stage.Major postoperative complication,and mortality at 30 and 90 days were higher in the high-ALBI patients.In the survival analysis,the high-ALBI group had worse disease-free survival(DFS)and overall survival(OS)compared to those with low-ALBI(P<0.001).When stratified by pTNM,the difference between ALBI groups was maintained in stage I/II and stage III CG for DFS(P<0.001 and P=0.021,respectively);and for OS(P<0.001 and P=0.063,respectively).In multivariate analysis,total gastrectomy,advanced pT stage,presence of lymph node metastasis and high-ALBI were independent factors associated with worse survival.CONCLUSION The preoperative ALBI score is able to predict the outcomes of patients with GC,where high-ALBI patients have worse prognosis.Also,ALBI score allows risk stratification of patients within the same pTNM stages,and represents an independent risk factor associated with survival.

Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer

BACKGROUND Gastric cancer(GC)is still a prevalent neoplasm around the world and its main treatment modality is surgical resection.The need for perioperative blood transfusions is frequent,and there is a long-lasting debate regarding its impact on survival.AIM To evaluate the factors related to the risk of receiving red blood cell(RBC)transfusion and its influence on surgical and survival outcomes of patients with GC.METHODS Patients who underwent curative resection for primary gastric adenocarcinoma at our Institute between 2009 and 2021 were retrospectively evaluated.Clinicopathological and surgical characteristics data were collected.The patients were divided into transfusion and non-transfusion groups for analysis.RESULTS A total of 718 patients were included,and 189(26.3%)patients received perioperative RBC transfusion(23 intraoperatively,133 postoperatively,and 33 in both periods).Patients in the RBC transfusions group were older(P<0.001),and had morecomorbidities(P=0.014),American Society of Anesthesiologists classification III/IV(P<0.001),and lower preoperative hemoglobin(P<0.001)and albumin levels(P<0.001).Larger tumors(P<0.001)and advanced tumor node metastasis stage(P<0.001)were also associated with the RBCtransfusion group.The rates of postoperative complications(POC)and 30-d and 90-d mortalitywere significantly higher in the RBC transfusion group than in the non-transfusion group.Lowerhemoglobin and albumin levels,total gastrectomy,open surgery,and the occurrence of POC werefactors associated with the RBC transfusion.Survival analysis demonstrated that the RBCtransfusions group had worse disease-free survival(DFS)and overall survival(OS)compared withpatients who did not receive transfusion(P<0.001 for both).In multivariate analysis,RBCtransfusion,major POC,pT3/T4 category,pN+,D1 lymphadenectomy,and total gastrectomywere independent risk factors related to worse DFS and OS.CONCLUSIONPerioperative RBC transfusion is associated with worse clinical conditions and more advancedtumors.Further,it is an independent factor related to worse survival in the curative intentgastrectomy setting.

Transcranial Direct Current Stimulation Combined with Peripheral Neuromuscular Stimulation Improves Quality of Life, Fatigue, and Pain in a Patient with Rheumatoid Arthritis and Refractory Radicular Pain Related to Spinal Stenosis

Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS in patients with rheumatoid arthritis and with fatigue, poor quality of life, and refractory radicular pain associated with spinal stenosis. Case Presentation: An 85-year-old woman patient presented with rheumatoid arthritis in remission, refractory radicular pain-associated spinal stenosis, fatigue, and impaired quality of life. The patient underwent 16 daily sessions of tDCS intervention (2 mA, 20 min, positively and negatively charged electrodes were positioned at C1 and Fp2, respectively), in addition to simultaneous peripheral neuromuscular electrical stimulation (frequency of 100 Hz and amplitude of 500 μs). After the intervention, neither disease relapse nor clinical intercurrence occurred. Moreover, there was a significant and sustained improvement in her health-related quality of life, with a reduction in the level of pain and chronic fatigue. Conclusion: The present case report shows that tDCS is safe and may be an adjuvant tool for the treatment of pain and fatigue in patients with systemic autoimmune disease, as well as for improving quality of life. Further studies are required to corroborate this case report.

Transcranial direct current electrical stimulation in combination with aerobic exercise:A pilot study in post-COVID-19 systemic autoimmune rheumatic patients

BACKGROUND Systemic autoimmune rheumatic diseases(SARDs)are a group of diseases with multiorgan involvement and a high prevalence of chronic pain and fatigue.Patients with SARDs and post-coronavirus disease 2019(COVID-19)syndrome experience aggravation of symptoms.In this context,it is essential to establish strategies to reduce chronic pain and fatigue and improve quality of life.AIM To assess the efficacy of transcranial direct current stimulation(tDCS)for the treatment of fatigue and pain-associated post-COVID-19 syndrome in patients with SARDs.METHODS This study included nine patients with different types of SARDs.All patients had reverse transcription-polymerase chain reaction(RT-PCR)test confirmed COVID-19 as well as significant,persistent fatigue and pain that began to worsen after infection.Anodal tDCS was administered in five daily sessions(2mA,20 min).Concomitantly,patients were involved in aerobic exercise program.All participants were evaluated using specific questionnaires and strength assessment by handgrip and physical function by timed-up-and-go test and sit-to-stand test at baseline(within one week before tDCS protocol),and one week after tDCS protocol.During all procedures,the patients’treatments remained unchanged.RESULTS The sample comprised eight women and one man with a mean age of 48.7±9.6 years.After the tDCS protocol,pain and fatigue significantly improved on the visual analog scale(P<0.05).The physical function also improved 9.5±2.7 vs 6.8±0.8(P=0.001)for timed-up-go-test and 10.3±3.7 vs 15.1±4.0(P=0.037)for sit-to-stand test.None of the patients experienced any adverse events.CONCLUSION The present study showed that tDCS in combination with aerobic exercise was effective in improving physical function,and reducing fatigue/pain in SARDs patients with post-COVID-19 syndrome.

Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.

Gastric partitioning for the treatment of malignant gastric outlet obstruction

BACKGROUND Gastric outlet obstruction(GOO)is one of the main complications in stage IV gastric cancer patients.This condition is usually managed by gastrojejunostomy(GJ).However,gastric partitioning(GP)has been described as an alternative to overcoming possible drawbacks of GJ,such as delayed gastric emptying and tumor bleeding.AIM To compare the outcomes of patients who underwent GP and GJ for malignant GOO.METHODS We retrospectively analyzed 60 patients who underwent palliative gastric bypass for unresectable distal gastric cancer with GOO from 2009 to 2018.Baseline clinicopathological characteristics including age,nutritional status,body mass index,and performance status were evaluated.Obstructive symptoms were graded according to GOO score(GOOS).Surgical outcomes evaluated included duration of the procedure,surgical complications,mortality,and length of hospital stay.Acceptance of oral diet after the procedure,weight gain,and overall survival were the long-term outcomes evaluated.RESULTS GP was performed in 30 patients and conventional GJ in the other 30 patients.The mean follow-up was 9.2 mo.Forty-nine(81.6%)patients died during that period.All variables were similar between groups,with the exception of worse performance status in GP patients.The mean operative time was higher in the GP group(161.2 vs 85.2 min,P<0.001).There were no differences in postoperative complications and surgical mortality between groups.The median overall survival was 7 and 8.4 mo for the GP and GJ groups,respectively(P=0.610).The oral acceptance of soft solids(GOOS 2)and low residue or full diet(GOOS 3)were reached by 28(93.3%)GP patients and 22(75.9%)GJ patients(P=0.080).Multivariate analysis demonstrated that GOOS 2 and GOOS 3 were the main prognostic factors for survival(hazard ratio:8.90,95%confidence interval:3.38-23.43,P<0.001).CONCLUSION GP is a safe and effective procedure to treat GOO.Compared to GJ,it provides similar surgical outcomes with a trend to better solid diet acceptance by patients.

Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review

BACKGROUND Stroke is the second leading cause of death worldwide.There is a real need to develop treatment strategies for reducing neurological deficits in stroke survivors,and stem cell(SC)therapeutics appear to be a promising alternative for stroke therapy that can be used in combination with approved thrombolytic or thrombectomy approaches.However,the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time.Nonetheless,tracking SCs from their niche to the target tissues is a complex process.AIM To evaluate SC migration homing,tracking and therapeutic efficacy in the treatment of stroke using nanoparticles METHODS A systematic literature search was performed to identify articles published prior to November 2019 that were indexed in PubMed and Scopus.The following inclusion criteria were used:(1)Studies that used in vivo models of stroke or ischemic brain lesions;(2)Studies of SCs labeled with some type of contrast agent for cell migration detection;and(3)Studies that involved in vivo cellular homing and tracking analysis.RESULTS A total of 82 articles were identified by indexing in Scopus and Pub Med.Afterthe inclusion criteria were applied,35 studies were selected,and the articles were assessed for eligibility;ultimately,only 25 studies were included.Most of the selected studies used SCs from human and mouse bone marrow labeled with magnetic nanoparticles alone or combined with fluorophore dyes.These cells were administered in the stroke model(to treat middle cerebral artery occlusion in 74%of studies and for photothrombotic induction in 26%of studies).Fiftythree percent of studies used xenogeneic grafts for cell therapy,and the migration homing and tracking evaluation was performed by magnetic resonance imaging as well as other techniques,such as near-infrared fluorescence imaging(12%)or bioluminescence assays(12%).CONCLUSION Our systematic review provided an up-to-date evaluation of SC migration homing and the efficacy of cellular therapy for stroke treatment in terms of functional and structural improvements in the late stage.

Peroral endoscopic myotomy vs laparoscopic myotomy and partial fundoplication for esophageal achalasia: A single-center randomized controlled trial

BACKGROUND Achalasia is a rare benign esophageal motor disorder characterized by incomplete relaxation of the lower esophageal sphincter(LES). The treatment of achalasia is not curative, but rather is aimed at reducing LES pressure. In patients who have failed noninvasive therapy, surgery should be considered. Myotomy with partial fundoplication has been considered the first-line treatment for non-advanced achalasia. Recently, peroral endoscopic myotomy(POEM), a technique that employs the principles of submucosal endoscopy to perform the equivalent of a surgical myotomy,has emerged as a promising minimally invasive technique for the management of this condition.AIM To compare POEM and laparoscopic myotomy and partial fundoplication(LM-PF) regarding their efficacy and outcomes for the treatment of achalasia.METHODS Forty treatment-naive adult patients who had been diagnosed with achalasia based on clinical and manometric criteria(dysphagia score ≥ II and Eckardt score > 3) were randomized to undergo either LM-PF or POEM. The outcome measures were anesthesia time, procedure time, symptom improvement, reflux esophagitis(as determined with the Gastroesophageal Reflux Disease Questionnaire), barium column height at 1 and 5 min(on a barium esophagogram), pressure at the LES, the occurrence of adverse events(AEs), length of stay(LOS), and quality of life(QoL).RESULTS There were no statistically significant differences between the LM-PF and POEM groups regarding symptom improvement at 1, 6, and 12 mo of follow-up(P = 0.192, P = 0.242, and P = 0.242, respectively). However, the rates of reflux esophagitis at 1, 6, and 12 mo of follow-up were significantly higher in the POEM group(P = 0.014, P < 0.001, and P = 0.002, respectively). There were also no statistical differences regarding the manometry values, the occurrence of AEs, or LOS. Anesthesia time and procedure time were significantly shorter in the POEM group than in the LM-PF group(185.00 ± 56.89 and 95.70 ± 30.47 min vs 296.75 ± 56.13 and 218.75 ± 50.88 min,respectively;P = 0.001 for both). In the POEM group, there were improvements in all domains of the QoL questionnaire, whereas there were improvements in only three domains in the LM-PF group.CONCLUSION POEM and LM-PF appear to be equally effective in controlling the symptoms of achalasia,shortening LOS, and minimizing AEs. Nevertheless, POEM has the advantage of improving all domains of QoL, and shortening anesthesia and procedure times but with a significantly higher rate of gastroesophageal reflux.

Safety of Transcranial Direct Current Electrical Stimulation in Dermatomyositis: A Case Report

Transcranial direct current stimulation (tDCS) has emerged as a nonpharmacological tool in physical rehabilitation. There have currently no studies that evaluated the safety and efficacy of tDCS in patients with dermatomyositis. Case-report: Three adult women with dermatomyositis were allocated randomly to intervention (i-tDCS, one patient) or not (sham-tDCS, two patients) of three consecutive days of tDCS and evaluated in four periods: before-tDCS (PRE), 15 minutes after-tDCS (0th POST), 15 days after-tDCS (15th POST), and 30 days after-tDCS (30th POST). The tDCS was safe throughout the protocol, without disease relapsing or adverse effects related to tDCS. Furthermore, the tDCS increased the muscle torque and total work of dominant and non-dominant elbow flexors in the patient with i-tDCS, when compared to two patients with sham-tDCS. Conclusions: The tDCS was safe and appeared to influence long-term strength in the limb of the patient with stable dermatomyo-sitis.

Antipsychotics preserve telomere length in peripheral blood mononuclear cells after acute oxidative stress injury

Antipsychotics may prolong or retain telomere length,affect mitochondrial function,and then affect the metabolism of nerve cells.To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury,leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient.The mononuclear cells layer was resuspended in cell culture medium.Oxidative stress was induced with hydrogen peroxide in cultured leukocytes.Four days later,leukocytes were treated with aripiprazole,haloperidol or clozapine for 7 days.Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23%and 20%in peripheral blood mononuclear cells after acute oxidative stress injury.These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress.The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of Sao Paulo(FMUSP/CAAE approval No.52622616.8.0000.0065).

Triple-modal imaging of stem-cells labeled with multimodal nanoparticles, applied in a stroke model

BACKGROUND Mesenchymal stem cells(MSCs) have been widely tested for their therapeutic efficacy in the ischemic brain and have been shown to provide several benefits. A major obstacle to the clinical translation of these therapies has been the inability to noninvasively monitor the best route, cell doses, and collateral effects while ensuring the survival and effective biological functioning of the transplanted stem cells. Technological advances in multimodal imaging have allowed in vivo monitoring of the biodistribution and viability of transplanted stem cells due to a combination of imaging technologies associated with multimodal nanoparticles(MNPs) using new labels and covers to achieve low toxicity and longtime residence in cells.AIM To evaluate the sensitivity of triple-modal imaging of stem cells labeled with MNPs and applied in a stroke model.METHODS After the isolation and immunophenotypic characterization of human bonemarrow MSCs(hBM-MSCs), our team carried out lentiviral transduction of these cells for the evaluation of bioluminescent images(BLIs) in vitro and in vivo. In addition, MNPs that were previously characterized(regarding hydrodynamic size, zeta potential, and optical properties), and were used to label these cells,analyze cell viability via the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and BLI analysis, and quantify the internalization process and iron load in different concentrations of MNPs via magnetic resonance imaging(MRI),near-infrared fluorescence(NIRF), and inductively coupled plasma-mass spectrometry(ICP-MS). In in vivo analyses, the same labeled cells were implanted in a sham group and a stroke group at different times and under different MNP concentrations(after 4 h or 6 d of cell implantation) to evaluate the sensitivity of triple-modal images.RESULTS hBM-MSC collection and isolation after immunophenotypic characterization were demonstrated to be adequate in hBM samples. After transduction of these cells with luciferase(hBM-MSCLuc), we detected a maximum BLI intensity of 2.0 x10^8 photons/s in samples of 10~6 hBM-MSCs. Analysis of the physicochemical characteristics of the MNPs showed an average hydrodynamic diameter of 38.2 ±0.5 nm, zeta potential of 29.2 ± 1.9 mV and adequate colloidal stability without agglomeration over 18 h. The signal of iron load internalization in hBM-MSCLuc showed a close relationship with the corresponding MNP-labeling concentrations based on MRI, ICP-MS and NIRF. Under the highest MNP concentration, cellular viability showed a reduction of less than 10% compared to the control.Correlation analysis of the MNP load internalized into hBM-MSCLuc determined via the MRI, ICP-MS and NIRF techniques showed the same correlation coefficient of 0.99. Evaluation of the BLI, NIRF, and MRI signals in vivo and ex vivo after labeled hBM-MSCLuc were implanted into animals showed differences between different MNP concentrations and signals associated with different techniques(MRI and NIRF; 5 and 20 μg Fe/mL; P < 0.05) in the sham groups at 4 h as well as a time effect(4 h and 6 d; P < 0.001) and differences between the sham and stroke groups in all images signals(P < 0.001).CONCLUSION This study highlighted the importance of quantifying MNPs internalized into cells and the efficacy of signal detection under the triple-image modality in a stroke model.

A new heparin fragment decreases liver ischemia-reperfusion injury

To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca^(2+),showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1].

Expression profiles of gastric cancer molecular subtypes in remnant tumors

BACKGROUND Remnant gastric cancer(RGC)is a carcinoma arising in the stomach remnant after previous gastric resection.It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer(PGC).However,as it is less frequent,its profile regarding the current molecular classifications of gastric cancer has not been evaluated.AIM To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and RGC.METHODS Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels:Epstein-Barr virus in situ hybridization,immunohistochemistry for mismatch repair proteins(MutL homolog 1,MutS homolog 2,MutS homolog 6,and PMS1 homolog 2),p53 protein,and E-cadherin expression.Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients.RESULTS A total of 40 RGC patients were enrolled in this study.Compared to PGC,older age(P<0.001),male(P<0.001),lower body mass index(P=0.010),and lower hemoglobin level(P<0.001)were associated with RGC patients.No difference was observed regarding Lauren’s type and pathologic Tumor Node Metastasis stage between the groups.Regarding the profiles evaluated,EBV-positive tumors were higher in RGC compared to PGC(P=0.039).The frequency of microsatellite instability,aberrant p53 immunostaining,and loss of E-cadherin expression were similar between RGC and PGC.Higher rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC(P<0.001).According to the molecular classification,the subtypes were defined as EBV in nine(22.5%)cases,microsatellite instability in nine(22.5%)cases,genomically stable in one(2.5%)case,and chromosomal instability in 21(52.5%)cases.There was no significant difference in survival between molecular subtypes in RGC patients.CONCLUSION RGC was associated with EBV positivity and higher rates of co-altered expression profiles compared to PGC.According to the molecular classification,there was no significant difference in survival between the subtypes of RGC.

A PCR and RFLP-based molecular diagnostic algorithm for visceral leishmaniasis

Objective:To determine an algorithm for molecular diagnosis of visceral leishmaniasis(VL)by kinetoplast DNA(kDNA)(RV1/RV2)and internal transcriber spacer(ITS1)(LITSR/L5.8 S)polymerase chain reaction(PCR),complemented by ITS 1 PCR restriction fragment length polymorphism(RFLP),using peripheral blood or bone marrow aspirate from patients with suspected VL.Methods:Biological samples were submitted to the gold standard for the diagnosis of VL and molecular diagnosis represented by ITS 1 PCR,kDNA PCR,and ITS 1 PCR RFLP.The samples were obtained from seven groups:groupⅠ,82 samples from patients with confirmed VL;groupⅡ,16 samples from patients under treatment for VL;groupⅢ,14 samples from dogs with canine visceral leishmaniasis(CVL);groupⅣ,a pool of six experimentally infected sandflies(Lutzomya longipalpis);group V,18 samples from patients with confirmed tegumentary leishmaniasis(TL)and groupsⅥandⅦwere from control groups without VL.Results:The following gold standard and molecular examination results were obtained for each of the seven groups:groupⅠ:parasitologic and immunochromatographic tests showed a sensitivity of 76.3%(61 of 80)and 68.8%(55 of 80),respectively,and a sensitivity of 97.6%(80 of 82)and 92.7%(76 of 82)by ITS1 and kDNA PCR,respectively.After ITS1 PCR RFLP(HaeⅢ)analysis of the 80 positive samples,52.5%(42 of 80)generated three fragments of 180,70,and 50 bp,corresponding to the pattern of Leishmania infantum infantum;groupⅡ:negative for the parasitologic methods and positive for IrK39(100%,16 of 16),presented 12.5%(2 of 16)of positivity by ITS 1 PCR and 25.0%(4 of 16)by kDNA PCR;groupⅢ:positive in the parasitologic and serologic tests(100%,14 of 14),presented 85.7%(12 of 14)of positivity by ITS1 PCR and kDNA PCR.ITS1 PCR RFLP showed that 83.3%(10 of 12)of the canine samples contained parasites with profiles similar to L.infantum;groupⅣpresented amplifications by ITS1 PCR and kDNA PCR.ITS1 PCR products were analyzed by RFLP,generating a profile similar to that of L.infantum;groupⅤ:positive in the parasitologic examination(100%,18 of 18),presented 72.2%(13 of 18)of the samples by ITS1 PCR positive.A total of 69.2%(9 of 13)showed profiles corresponding to a Viannia complex by ITS1 PCR RFLP;and groupⅥand groupⅥwere negative by ITS 1 and kDNA molecular tests.Comparing the molecular results with the parasitologic and serologic diagnosis from groupⅠ,almost perfect agreement was found(κboth>0.80,P<0.001).ITS1 and RV1/RV2 PCR detected 90.2%(74 of 82)of the samples.Two samples positive by RV1/RV2 were negative by LITSR/L5.8 S,and six samples positive by LITSR/L5.8 S were negative by RV1/RV2.Therefore,these two systems complemented each other;they diagnosed 100%of the samples as belonging to the Leishmania genus.Conclusions:We suggest an algorithm for the molecular diagnosis of VL,which must consider previous parasitologic and serologic(immunochromatographic)diagnoses,and should combine kDNA and ITS1 to determine the Leishmania subgenus using RFLP as a complement method to define the L.infantum species.

Large primary hepatic gastrinoma in young patient treated with trisegmentectomy: A case report and review of the literature

Primary hepatic gastrinoma is a rare disease, with fewer than 40 cases reported in the medical literature. Because it is located in an organ in which metastases are common, its diagnosis is difficult. We report a case of a 19 years old male patient with a history of gastric ulcers since the age of nine. Following gastric surgery, an antrectomy and a vagotomy, there was some alleviation of symptoms. Subsequently, the patient reported various intermittent episodes of diarrhea, diffuse abdominal pain, and vomiting. The patient underwent tomography, which revealed the presence of a hepatic mass measuring 19.5 cm × 12.5 cm × 17 cm. Primary hepatic gastrinoma was diagnosed based on laboratory examinations that indicated hypergastrinemia and a positron emission tomography/magnetic resonance study with somatostatin analogue that confirmed the liver as the primary site. After hepatic trisegmentectomy(Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅷ), the patient's symptoms improved. The case is notable for the presence of a rare tumor with uncommon dimensions.

Status of bariatric endoscopy–what does the surgeon need to know? A review

BACKGROUND Obesity is a chronic and multifactorial disease with a variety of potential treatment options available.Currently,there are several multidisciplinary therapeutic options for its management,including conservative,endoscopic,and surgical treatment.AIM To clarify indications,technical aspects,and outcomes of bariatric endoscopy.METHODS Narrative review of current literature based on electronic databases including MEDLINE(PubMed),Cochrane Library,and SciELO.RESULTS Bariatric endoscopy is in constant development and comprises primary and revisional treatment options as well as management of surgical complications.Various devices act upon different mechanisms of action,which may be individualized to each patient.Despite favorable results for the endoscopic treatment of obesity,prospective randomized studies with long-term follow-up are required to fully validate primary and revisional endoscopic therapies.Regarding the management of bariatric surgery complications,endoscopic therapy may be considered the procedure of choice in a variety of situations.Still,as there is no standardized algorithm,local experience should be considered in decision-making.CONCLUSION The treatment of patients with obesity is complex,and a multidisciplinary approach is essential.Bariatric endoscopy has shown impressive results both in the treatment of obesity and its surgical complications,and therefore,must be part of the armamentarium in the fight against this disease.

Impact of an Exercise Training Program in a Patient with Relapsing Polychondritis: A Case Report

Background: Exercise training has demonstrating to be safe and promote benefits for several rheumatologic autoimmune diseases. However, no study has evaluated the safety and benefits of exercise in relapsing polychondritis. Aim: To evaluate the effectiveness of an exercise training program in a patient with relapsing polychondritis. Case presentation: A 67-year-old female patient with relapsing polychondritis in remission was submitted to a 12-week, twice weekly, aerobic and resistance training program. Aerobic capacity, muscle strength and function capacity, as well as body composition, were evaluated at baseline and after 12-weeks. Conclusions: Exercise training program demonstrated to be effective for increasing aerobic capacity, muscle strength and function, and for improving body composition in the patient. Further studies are necessary to confirm these findings.

Functional and Structural Arterial Vessel Features of Female Patients with Stable Dermatomyositis and Antisynthetase Syndrome

Introduction: Dermatomyositis (DM) and antisynthetase syndrome (ASS) show a high frequency of metabolic syndrome, which can be preceded by endothelial dysfunction and arterial stiffness. To date, only one study has evaluated these vessel parameters in DM, and no study of ASS exists. Therefore, the aim of the study was to assess the structural and functional arterial of arterial vessels in DM and ASS. Methods: This cross-sectional study enrolled 21 adult female patients (14 DM and 7 ASS) who were age-, gender- and ethnicity-matched to 12 healthy individuals. Patients using lipid lowering agents or prednisone at doses ≥ 0.25 mg/kg/day, and patients with uncontrolled systemic arterial hypertension, diabetes mellitus, cardiac insufficiency, and disease activity were excluded. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (PWV), and endothelial function was evaluated using dependent flow-mediated dilatation (FMD) of the brachial artery. Results: The mean age of patients with DM or ASS were 45.4 ± 8.6 and 44.0 ± 6.1 years, respectively (P = 1.000), and patients were predominantly of white ethnicity. Six DM patients and three ASS patients had systemic arterial hypertension, whereas 9 DM patients and six ASS patients had dyslipidemia. Endothelial baseline diameter, hyperemia diameter and FMD values were similar among the three groups (P > 0.05). Moreover, the median FMD values were also similar between the patients with DM and patients with ASS [8.3% (4.5% - 10.9%) vs. 6.0% (&minus;1.8% - 8.2%);P = 0.585]. The PWV values were comparable among the three groups (P = 0.253). In addition, no difference was observed between patients with DM and patients with ASS (7.4 ± 0.8 m/s vs. 7.4 ± 0.9 m/s;P = 1.000). Conclusions: Despite the high prevalence of dyslipidemia and systemic arterial hypertension, our female patients with stable DM and ASS had FMD and PWV values comparable to those of the control group.

Effects of Exercise Training on Endothelial Function,Arterial Structure,and Physical Conditioning in Patients with Systemic Autoimmune Myopathies:A Case Series Study

Introduction. Exercise training has been effective in improving endothelial function and decreasing arterial stiffness in several systemic autoimmune diseases. However, to date, no studies have assessed patients with systemic autoimmune myopathies (SAM). Methods. Five female patients with definite SAM (3 dermatomyositis and 2 polymyositis) who underwent a 12-week, twice-a-week, exercise training program were assessed prospectively. The following parameters were assessed: endothelial function measured by flow-mediated dilatation (FMD), carotid femoral by pulse wave velocity (PWV), disease status by International Myositis Assessment & Clinical Studies Group (IMACS) set score, the ventilatory anaerobic threefold (VAT), respiratory compensation point (RCP), maximum effort (ME), maximal oxygen uptake (VO2max) measured by ergospyrometer, and strength and muscle function. Results. Mean age of the patients and duration of disease were 43.9 and 10.5 years, respectively. The median FMD and PWV were 10.2% and 7.1 m/s. After exercise training, important FMD reduction was observed in 4 out of 5 patients, whereas the PWV parameters decreased in only 2 out of 5 patients. The exercise training was safe, without clinical intercurrences or disease relapses. Moreover, an increase in strength and functionality was observed. Concerning aerobic capacity, there was a decrease in the VAT and an increase in ME, without al-terations in the maximum oxygen consumption. Conclusions. In general, exercise training does not alter endothelial function and PWV values, but improves muscle strength and function and also, does not lead to disease reactivation (Clinical Trials (NCT03092167)).