Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

BACKGROUND Helicobacter pylori(H.pylori)infection has been well-established as a significant risk factor for several gastrointestinal disorders.The urea breath test(UBT)has emerged as a leading non-invasive method for detecting H.pylori.Despite numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent limitations.These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H.pylori infection.AIM To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H.pylori infection in adult patients with dyspepsia.METHODS We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April 2022.Our search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference standard.We used the QUADAS-2 tool to assess the methodo-logical quality of the studies.We utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence intervals.We conducted subgroup analyses based on urea dosing,time after urea administration,and assessment technique.To investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess heterogeneity.Finally,we visually inspected a funnel plot and used Egger’s test to evaluate publication bias.endorsing both as reliable diagnostic tools in clinical practice.CONCLUSION In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic approach.Additionally,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enhance diagnostic precision.Nevertheless,it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P<0.01 and I²>50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-positive early-stage GML after bacterial eradication was 75.18%(95%CI:70.45%-79.91%).P-MA indicated the substantial heterogeneity in CR reported across studies(I2=92%;P<0.01).Meta-regression analysis identified statistically significant effect modifiers,including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.CONCLUSION Comprehensive synthesis of available evidence suggests that H.pylori eradication is effective as the sole initial therapy for early-stage GML.Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR,the present study is a relevant to informing clinical practice.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

Immunotherapy in glioblastoma treatment:Current state and future prospects

Glioblastoma remains as the most common and aggressive malignant brain tumor,standing with a poor prognosis and treatment prospective.Despite the aggressive standard care,such as surgical resection and chemoradiation,median survival rates are low.In this regard,immunotherapeutic strategies aim to become more attractive for glioblastoma,considering its recent advances and approaches.In this review,we provide an overview of the current status and progress in immunotherapy for glioblastoma,going through the fundamental knowledge on immune targeting to promising strategies,such as Chimeric antigen receptor T-Cell therapy,immune checkpoint inhibitors,cytokine-based treatment,oncolytic virus and vaccine-based techniques.At last,it is discussed innovative methods to overcome diverse challenges,and future perspectives in this area.

Helicobacter pylori infection in pregnant women:Gastrointestinal symptoms and pregnancy-related disorders

Helicobacter pylori(H.Pylori)is a gram-negative,flagellated and spiral-shaped bacterial pathogen that impacts approximately 46%among pregnant women globally and has been associated with various maternal-fetal complications.Iron deficiency anemia,fetal growth restriction,cardiovascular diseases,and insufficient nutrient absorption can be observed in pregnant women,as well as miscarriages and pregnancy-specific hypertensive disease,such as pre-eclampsia.Thus,the evidence supports the influence of H.pylori infection on fetal implantation/placentation failure,and positive strains of the cytotoxin-associated gene A of H.Pylori were reported as the most prevalent in these conditions.However,current knowledge indicates a relationship between this infection and the occurrence of hyperemesis gravidarum,characterized by frequent nausea and vomiting.Regarding the diagnosis of this bacterial infection,non-invasive approaches such as stool antigen test,urea breath test,and serological tests are more accepted during pregnancy,as they are easy to carry out and cost-effective.Finally,the bacteria eradication therapy should consider the risks and benefits for the pregnant woman and her child,with pharmacological intervention depending on the clinical presentation.

Pediatric multisystem inflammatory syndrome associated with COVID-19: Insights in pathogenesis and clinical management

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been a major challenge to be faced in recent years.While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019,children were thought to be exclusively asymptomatic or to present with mild conditions.However,around April 2020,there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children-multisystemic inflam-matory syndrome in children(MIS-C)-which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan involvement.The Centers for Disease Control and Prevention considers a suspected case of MIS-C an individual aged<21 years presenting with fever,high inflammatory markers levels,and evidence of clinically severe illness,with multisystem(>2)organ involvement,no alternative plausible diagnoses,and positive for recent SARS-CoV-2 infection.Despite its severity,there are no definitive disease management guidelines for this condition.Conversely,the complex pathogenesis of MIS-C is still not completely understood,although it seems to rely upon immune dysregu-lation.Hence,in this study,we aim to bring together current evidence regarding the pathogenic mechanisms of MIS-C,clinical picture and management,in order to provide insights for clinical practice and implications for future research directions.

Crohn's disease and clinical management today:How it does?

Crohn’s Disease(CD)is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature.Its etiology results from the interaction between genetic,enviromental and microbial factors.Regarding pathophysiology,it involves high levels of interleukin(IL)-12,IL-17,and Th1 profile,along with loss of tolerance mechanisms,an increase in pro-inflammatory interleukins,beyond the possibility to affect any part of the gastrointestinal tract.Its symptoms include abdominal pain,chronic diarrhea,weight loss,anorexia,and fatigue,as well as blood in the stool or rectum.Additionally,conditions comprising musculoskeletal,cutaneous,ocular,hepatic,and hematological alterations may be associated with this scenario and extra-intestinal presentation,such as erythema nodosum,anterior uveitis,osteoporosis,and arthritis can also occur.Today,clinical history,exams as fecal calprotectin,ileocolonocopy,and capsule endoscopy can be performed in the diagnosis investigation,along with treatments to induce and maintain remission.In this sense,anti-inflammatory drugs,such as corticosteroids,immunomodulators,and biological agents,as well as surgery and non-pharmacological interventions plays a role in its therapy.The aim of this review is to bring more current evidence to clinical management of CD,as well as to briefly discuss aspects of its pathophysiology,surveillance,and associated disorders.

Correction to“Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil”

Correction to“Freire de Melo F,Martins Oliveira Diniz L,Nélio Januário J,Fernando Gonçalves Ferreira J,Dórea RSDM,de Brito BB,Marques HS,Lemos FFB,Silva Luz M,Rocha Pinheiro SL,de Magalhães Queiroz DM.Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil.World J Exp Med 2022;12(5):100-103[PMID:36196438 DOI:10.5493/wjem.v12.i5.100]”.In this article,we identified an issue with the“Acknowledgments”section.Here,we then provide a recognition section for our supporting institutions.

Influence of Helicobacter pylori oncoprotein CagA in gastric cancer:A critical-reflective analysis

Gastric cancer is the fifth most common malignancy and third leading cancerrelated cause of death worldwide.Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3%of the world’s population and represents the main risk factor for the onset of gastric neoplasms.CagA is the most important virulence factor in H.pylori,and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions.Upon translocation and tyrosine phosphorylation,CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways,thereby disrupting cell proliferation,differentiation and apoptosis.All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes.In this sense,once gastric cancer sets in,its perpetuation is independent of the presence of the oncoprotein,characterizing a“hit-and-run”carcinogenic mechanism.Therefore,this review aims to describe H.pylori-and CagA-related oncogenic mechanisms,to update readers and discuss the novelties and perspectives in this field.

Role of nickel-regulated small RNA in modulation of Helicobacter pylori virulence factors

Helicobacter pylori(H.pylori)is a Gram-negative bacterium that infects about half of the world's population.H.pylori infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A(CagA).CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged H.pylori infection.In this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene expression.This function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial infections.Recent discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of H.pylori,including the oncoprotein CagA.Notably,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of CagA.In addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients without.With that in mind,this minireview approaches,in an accessible way,the most important and current aspects about the role of NikS in the control of virulence factors of H.pylori and the potential clinical repercussions of this modulation.

Oncolytic virus therapy in cancer: A current review

In view of the advancement in the understanding about the most diverse types of cancer and consequently a relentless search for a cure and increased survival rates of cancer patients,finding a therapy that is able to combat the mechanism of aggression of this disease is extremely important.Thus,oncolytic viruses(OVs)have demonstrated great benefits in the treatment of cancer because it mediates antitumor effects in several ways.Viruses can be used to infect cancer cells,especially over normal cells,to present tumor-associated antigens,to activate“danger signals”that generate a less immune-tolerant tumor microenvironment,and to serve transduction vehicles for expression of inflammatory and immunomodulatory cytokines.The success of therapies using OVs was initially demonstrated by the use of the genetically modified herpes virus,talimogene laherparepvec,for the treatment of melanoma.At this time,several OVs are being studied as a potential treatment for cancer in clinical trials.However,it is necessary to be aware of the safety and possible adverse effects of this therapy;after all,an effective treatment for cancer should promote regression,attack the tumor,and in the meantime induce minimal systemic repercussions.In this manuscript,we will present a current review of the mechanism of action of OVs,main clinical uses,updates,and future perspectives on this treatment.

From Helicobacter pylori infection to gastric cancer:Current evidence on the immune response

Gastric cancer(GC)is the result of a multifactorial process whose main components are infection by Helicobacter pylori(H.pylori),bacterial virulence factors,host immune response and environmental factors.The development of the neoplastic microenvironment also depends on genetic and epigenetic changes in oncogenes and tumor suppressor genes,which results in deregulation of cell signaling pathways and apoptosis process.This review summarizes the main aspects of the pathogenesis of GC and the immune response involved in chronic inflammation generated by H.pylori.

Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil

Qualitative antibody tests are an easy,point-of-care diagnostic method that is useful in diagnosing coronavirus disease 2019,especially in situations where reverse transcription-polymerase chain reaction is negative.However,some factors are able to affect its sensitivity and accuracy,which may contribute to these tests not being used as a first-line diagnostic tool.

COVID-19 neuropsychiatric repercussions:Current evidence on the subject

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the entire world,causing the coronavirus disease 2019(COVID-19)pandemic since it was first discovered in Wuhan,China in December 2019.Among the clinical presentation of the disease,in addition to fever,fatigue,cough,dyspnea,diarrhea,nausea,vomiting,and abdominal pain,infected patients may also experience neurological and psychiatric repercussions during the course of the disease and as a post-COVID-19 sequelae.Thus,headache,dizziness,olfactory and gustatory dysfunction,cerebrovascular disorders,neuromuscular abnormalities,anxiety,depression,and post-traumatic stress disorder can occur both from the infection itself and from social distancing and quarantine.According to current evidence about this infection,the virus has the ability to infect the central nervous system(CNS)via angiotensin-converting enzyme 2(ACE2)receptors on host cells.Several studies have shown the presence of ACE2 in nerve cells and nasal mucosa,as well as transmembrane serine protease 2,key points for interaction with the viral Spike glycoprotein and entry into the CNS,being olfactory tract and blood-brain barrier,through hematogenous dissemination,potential pathways.Thus,the presence of SARS-CoV-2 in the CNS supports the development of neuropsychiatric symptoms.The management of these manifestations seems more complex,given that the dense parenchyma and impermeability of brain tissue,despite protecting the brain from the infectious process,may hinder virus elimination.Still,some alternatives used in non-COVID-19 situations may lead to worse prognosis of acute respiratory syndrome,requiring caution.Therefore,the aim of this review is to bring more current points related to this infection in the CNS,as well as the repercussions of the isolation involved by the pandemic and to present perspectives on interventions in this scenario.

Molecular and serology methods in the diagnosis of COVID-19: An overview

Coronavirus disease-19(COVID-19)has become a pandemic,being a global health concern since December 2019 when the first cases were reported.Severe acute respiratory syndrome coronavirus 2,the COVID-19 causal agent,is aβ-coronavirus that has on its surface the spike protein,which helps in its virulence and pathogenicity towards the host.Thus,effective and applicable diagnostic methods to this disease come as an important tool for the management of the patients.The use of the molecular technique PCR,which allows the detection of the viral RNA through nasopharyngeal swabs,is considered the gold standard test for the diagnosis of COVID-19.Moreover,serological methods,such as enzyme-linked immunosorbent assays and rapid tests,are able to detect severe acute respiratory syndrome coronavirus 2-specific immunoglobulin A,immunoglobulin M,and immunoglobulin G in positive patients,being important alternative techniques for the diagnostic establishment and epidemiological surveillance.On the other hand,reverse transcription loop-mediated isothermal amplification also proved to be a useful diagnostic method for the infection,mainly because it does not require a sophisticated laboratory apparatus and has similar specificity and sensitivity to PCR.Complementarily,imaging exams provide findings of typical pneumonia,such as the ground-glass opacity radiological pattern on chest computed tomography scanning,which along with laboratory tests assist in the diagnosis of COVID-19.