Biermer Disease: Initial Presentation and Follow-Up of 66 Patients in Internal Medicine Department in Senegal

Pernicious anemia in black people, is little known. Through this study we assess its diagnostic and evolutive aspects, and compare vitamin therapy B12 intramuscular and oral. Sixty six Biermer disease patients followed (January 2000-June 2014) at Internal Medicine Department of Aristide Le Dantec University Teaching Hospital (Senegal) are included. They were 26 men and 46 women (gender ratio: 0.65), who had a mean age of 47.84 years ± 15.25 years. Patients consulted for anemia (65 cases), acquired melanodermia (36 cases), gastrointestinal symptoms (30 cases), peripheral neuropathy (27 cases), venous thrombosis (2 cases), acute depression (1 case). Macrocytosis was observed in 52 cases. The mean hemoglobin in the vitamin B12 intramuscular group (52 patients) or oral group (14 patients) was the inclusion: 6.55 g/dl ± 3.12 g/dl vs 6.52 g/dl ± 2.18 g/dl (p = 0.04);and at day 8 treatment: 8.69 g/dl ± 2.49 g/dl vs 8.85 g/dl ± 1.9 g/dl (p = 0.43). Neurological and vascular presentations are unusual in contrast to macrocytic anemia. Oral administration of vitamin B12, simple and effective should be recommended in country with limited resources.

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

Aspirin,other antiplatelet agents,and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases.A concomitant proton pump inhibitor(PPI)treatment is often prescribed in these patients,as gastrointestinal complications are relatively frequent.On the other hand,a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs;in particular,it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel,due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism.Previously,the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged.In contrast,it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel,new P2Y12 receptor antagonists.Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding,including advanced age,concurrent use of anticoagulants,steroids,or non-steroidal anti-inflammatory drugs,and Helicobacter pylori(H.pylori)infection.In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding,PPIs could be recommended,even if their usefulness deserves further data.H.pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease(with or without complication)treated with antithrombotic drugs.The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors,anticoagulants,and PPIs,discussing consequent clinical implications.

Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.

Non invasive tools for the diagnosis of liver cirrhosis

Liver cirrhosis(LC),the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis.This chronic progressive clinical condition,leads to liver cell failure and portal hypertension,which can favour the onset of hepatocellular carcinoma.Defining the phase of the natural history is crucial for therapeutic choice and prognosis.Liver biopsy is currently considered the best available standard of reference but it has some limits,so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis.Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications.They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores.Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound(US),US Doppler,contrast enhanced US andElastography.US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis,in this case Elastography is more reliable.This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

Promoter methylation status of hMLH1,MGMT,and CDKN2A/p16 in colorectal adenomas

AIM:To investigate aberrant DNA methylation of CpG islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma(tu-bular or villous/tubulovillous)patients,and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1(hMLH1),Cyclin-dependent kinase inhibitor 2A(CDKN2A/p16),and O-6-methylguanine DNA methyltransferase(MGMT),as well as their rela- tion to MSI. RESULTS:The frequency of promoter methylation for each locus increased in the sequence healthy tissue/adenoma/carcinoma.MGMT showed the highest frequency in each group.MGMT and CDKN2A/p16 presented a statistically significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas(tubular vs tubullovillous and villous adenomas).All patients with tubulovillous/villous adenomas,as well as all colorectal cancer patients,showed promoter methylation in at least one of the examined loci.These findings suggest a potentially crucial role for methylation in the polyp/adenoma to cancer progres- sion in colorectal carcinogenesis.MSI and methylation seem to be interdependent,as simultaneous hMLH1, CDKN2A/p16,and MGMT promoter methylation was present in 8/9 colorectal cancer patients showing the MSI phenotype. CONCLUSION:Methylation analysis of hMLH1,CD- KN2A/p16,and MGMT revealed specific methylation profiles for tubular adenomas,tubulovillous/villous adenomas,and colorectal cancers,supporting the use of these alterations in assessment of colorectal tumorigenesis.

Nanotechnology applications for the therapy of liver fibrosis

Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and,in the more advanced stages,for the limited available curative treatment options.In fact,when lesions of different etiologies chronically affect the liver,triggering the fibrogenesis mechanisms,damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications,expensive treatments and death in end-stage liver disease.Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis,the drugs used in liver fibrosis treatment still have a limited therapeutic effect.Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected.Hepatic stellate cells play a critical role in liver fibrogenesis,thus they are the target cells of antifibrotic therapy.The application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents(including drugs and nucleic acid)in the treatment of various pathologies,including liver disease.In this review,we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.

Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study

Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation(OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk(i.e., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT(i.e., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage,which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.

Current status of device-assisted enteroscopy: Technical matters, indication, limits and complications

Enteroscopy, defined as direct visualization of the smallbowel with the use of a fiberoptic or capsule endoscopy, has progressed considerably over the past severalyears. The need for endoscopic access to improvediagnosis and treatment of small bowel disease hasled to the development of novel technologies one ofwhich is noninvasive, the video capsule, and a type of invasive technique, the deviceassisted enteroscopy.In particular, the device-assisted enteroscopy consiststhen of three different types of instruments all able toallow, in skilled hands, to display partially or throug-hout its extension (if necessary) the small intestine.Newer devices, double balloon, single balloon and spiral endoscopy, are just entering clinical use. The aim of this article is to review recent advances in small bowelenteroscopy, focusing on indications, modifications toimprove imaging and techniques, pitfalls, and clinical applications of the new instruments. With new technologies, the trials and tribulations of learning new endo-scopic skills and determining their role in the diagnosisand treatment of small bowel disease come. Identification of small bowel lesions has dramatically improved.Studies are underway to determine the best strategy toapply new enteroscopy technologies for the diagnosisand management of small bowel disease, particularly obscure bleeding. Vascular malformations such as angiectasis and small bowel neoplasms as adenocar cinomaor gas trointestinal stromal tumors. Complete entero-scopy of the small bowel is now possible. However, because of the length of the small bowel, endoscopic examination and the rapeutic maneuvers require significant skill, radiological assistance, the use of deep sedation with the assistance of the anesthetist. Prospective ran-domized studies are needed to guide diagnostic testing and the rapy with these new endoscopic techniques.

Hypertransaminasemia in the course of infection with SARS-CoV-2:Incidence and pathogenetic hypothesis

In patients infected with severe acute respiratory syndrome coronavirus 2,the respiratory symptoms,such as fever,cough and dyspnea,are the most frequent clinical manifestations.These patients may also present with less well-defined symptoms like diarrhea,nausea,vomiting and/or abdominal discomfort both at the time of diagnosis and during the clinical course.In a few cases,these symptoms may also present before the appearance of respiratory symptoms.To penetrate the body,Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors,which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes.In several cases,viral RNA is detectable in the stool of patients with coronavirus disease 2019(COVID-19).The liver damage seems to show a multifactorial origin.About 2%-11%of patients with COVID-19 have known underlying hepatic pathologies.In 14%-53%of COVID-19 cases,there is an alteration of the indices of liver cytolysis and is more frequently observed in severe forms of COVID-19,especially during hospitalization.

Spectrum of final pathological diagnosis of gastric adenoma after endoscopic resection

AIM: To investigate how many discrepancies occur in patients before and after endoscopic treatment of referred adenoma and the reason for these results. METHODS: We retrospectively reviewed data from 554 cases of 534 patients who were referred from primary care centres for adenoma treatment and treated for endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) at Chungnam National University Hospital, from July 2006 to June 2009. Reendoscopy was examined in 142 cases and biopsywas performed in 108 cases prior to treatment. Three endoscopists (1, 2 and 3) performed all EMRs or ESDs and three pathologists (1, 2 and 3) diagnosed most of the cases. Transfer notes, medical records and endoscopic pictures of these cases were retrospectively reviewed and analyzed. RESULTS: Adenocarcinoma was 72 (13.0%) cases in total 554 cases after endoscopic treatment of referred adenoma. When the grade of dysplasia was high (55.0%), biopsy number was more than three (22.7%), size was no smaller than 2.0 cm (23.2%), morphologic type was depressed (35.8%) or yamada type Ⅳ (100%), and color was red (30.9%) or mixed-or-undetermined (25.0%), it had much more malignancy rate than the others (P < 0.05). All 18 cases diagnosed as adenocarcinoma in the re-endoscopic forceps biopsy were performed by endoscopist 1. There were different malignancy rates according to the pathologist (P = 0.027). CONCLUSION: High grade dysplasia is the most important factor for predicting malignancy as a final pathologic diagnosis before treating the referred gastric adenoma. This discrepancy can occur mainly through inappropriately selecting a biopsy site where cancer cells do not exist, but it also depends on the pathologist to some extent.

Results of gastroscope bacterial decontamination by enzymatic detergent compared to chlorhexidine

瞄准：比较功效酶与为胃的范围的 chlorhexidine 净化细菌的净化。方法：未来的使随机化的控制研究被承担评估这 2 个代理人的能力在一个胃的范围完成高级消毒。260 件样品的一个总数从 5 个不同胃的范围被收集。用手的清洗独立与这 2 个代理人为 10 min 被做(n = 130 各个) 。然后，所有标本经历了为 20 min 浸泡的 2% glutaraldehyde。在 70% 酒精被清洗以后，无菌的生理盐水被冲洗进每条胃的范围隧道，样品的 40 mL 是镇定的。样品被去请在膜以后的氧气的细菌的文化被过滤。比 200 cfu/mL 大的一个殖民地计数被认为重要。结果：积极文化率在酶的净化的手臂是 4.6% ， 3.1% 在 chlorhexidine 武装。假单胞菌属种类是从两个组(60%) 检测的主要有机体。多重有机体从 4 个标本被发现(酶的净化的手臂 = 1， chlorhexidine 手臂 = 3 ) 。结论：清洗答案的两种类型的污染率是相等的。

Surgical treatment of hepatocellular carcinoma in the era of COVID-19 pandemic:A comprehensive review of current recommendations

The new coronavirus disease 2019 (COVID-19) pandemic has resulted in a globalhealth emergency that has also caused profound changes in the treatment ofcancer. The management of hepatocellular carcinoma (HCC) across the world hasbeen modified according to the scarcity of care resources that have been divertedmostly to face the surge of hospitalized COVID-19 patients. Oncological andhepatobiliary societies have drafted recommendations regarding the adaptation ofguidelines for the management of HCC to the current healthcare situation. Thisreview focuses on specific recommendations for the surgical treatment of HCC (i.e., hepatic resection and liver transplantation), which still represents the bestchance of cure for patients with very early and early HCC. While surgery shouldbe pursued for very selected patients in institutions where standards of care aremaintained, alternative or bridging methods, mostly thermoablation and transarterialtherapies, can be used until surgery can be performed. The prognosis ofpatients with HCC largely depends on both the characteristics of the tumour andthe stage of underlying liver disease. Risk stratification plays a pivotal role indetermining the most appropriate treatment for each case and needs to balancethe chance of cure and the risk of COVID-19 infection during hospitalization.Current recommendations have been critically reviewed to provide a reference forbest practices in the clinical setting, with adaptation based on pandemic trendsand categorization according to COVID-19 prevalence.

Post-COVID-19 cholangiopathy:A systematic review

BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entailed various long-term complications,including post-infectious cholangiopathy.AIM To identify the available studies concerning post-coronavirus disease 2019(COVID-19)cholangiopathy.METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles(retrospective and prospective studies,cohort studies,case series and case reports)published between January 1,2020 and August 22,2022,using both MeSH terms and free-language keywords:cholangiopathy;COVID-19;post-COVID-19 cholangiopathy;SARS-CoV-2.RESULTS Thirteen studies fulfilled the inclusion criteria,which included 64 patients suffering from this condition.The patients were male in 82.8%of cases.Liver transplant was executed in 6 patients and scheduled in 7 patients,while 2 patients refused the surgical approach.Therefore in 23.4%of the cases,performing this procedure appeared to be necessary.CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient,inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.

Hepatocellular adenoma: An unsolved diagnostic enigma

Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in young and middle-aged women. Unlike other benign liver tumours, an HCA may be complicated by bleeding and malignant transformation. HCAs have been divided into four subtypes based on molecular and pathological features: hepatocyte nuclear factor 1α-mutated HCA, inflammatory HCA,β-catenin-mutated HCA, and unclassified HCA.β-cateninmutated HCA has the highest risk of haemorrhage or malignant transformation. In the latest upgrade of the guidelines regarding the management of benign liver tumours published in 2016 by the European Association for the Study of the Liver, magnetic resonance imaging (MRI) was recognized to be superior to all other imaging modalities in detecting HCAs and in being able to subtype HCAs up to 80%, with positive identification of 1α-mutated HCA or inflammatory HCA achievable with > 90% specificity. This review analyzed the imaging features of HCA using MRI with hepato-specific contrast agents, focusing on the limitations in the HCA characterization.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.

Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables

Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.

Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy

B cells lymphoma is one of the most challenging extrahepatic manifestations of hepatitis C virus(HCV). Recently, a new kind of B-cell lymphoma, named doublehit B(DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents(DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in oncohaematological diseases.

Interferon-a plus lamivudine vslamivudine reduces breakthroughs, but does not affect sustained response in HBeAg negative chronic hepatitis B

AIM: To investigate the efficacy of combination treatment of IFN-α and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAg-negative hepatitis B patients.METHODS: Fifty consecutive patients were randomly assigned to receive IFN-α-2b (5 MU thrice per week, n = 24) plus lamivudine (100 mg daily) or lamivudine only (n = 26) for 24 mo. Patients were followed up for further 6 mo. The primary outcome was the proportion with sustained virological response (undetectable serum HBV DNA concentrations) and or sustained biochemical response (transaminase levels within normal range) at 30 mo (6 mo after the end of therapy). Secondary end-points were timed from initial virological (biochemical) response to VBR (BBR, respectively) and the emergence of YMDD mutants across the two arms.RESULTS: Five of twenty-four (21%) patients in the combination arm vs 3/26 (12%) in the lamivudine arm had sustained response (i.e., normal serum transaminase levels and undetectable HBV DNA by PCR assay) 6 mo after treatment discontinuation. A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receiving combination treatment (10% vs46%, P= 0.01 and 14% vs46%, P= 0.03,respectively).Time from initial virologic response to virologic breakthrough (VBR) was greater among initial responders receiving combination treatment compared to those receiving lamivudine (22.9 mo vs 15.9 mo, respectively; P = 0.005).CONCLUSION: Our results demonstrate that IFN-α plus lamivudine combination therapy does not increase the sustained response, compared to lamivudine. However,combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development.

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis

BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

High-resolution computed tomography findings in humoral primary immunodeficiencies and correlation with pulmonary function tests

AIM To compare high-resolution computed tomography(HRCT) findings between humoral primary immunodeficiencies(hPIDs) subtypes; to correlate these findings to pulmonary function tests(PFTs).METHODS We retrospectively identified 52 consecutive adult patients with hPIDs who underwent 64-row HRCT and PFTs at the time of diagnosis. On a per-patient basis, an experienced radiologist recorded airway abnormalities(bronchiectasis,airway wall thickening, mucus plugging, tree-in-bud, and air-trapping) and parenchymal-interstitial abnormalities(consolidations, ground-glass opacities,linear and/or irregular opacities, nodules, and bullae/cysts) found on HRCT.The chi-square test was performed to compare the prevalence of each abnormality among patients with different subtypes of hPIDs. Overall logistic regression analysis was performed to assess whether HRCT findings predicted obstructive and/or restrictive PFTs results(absent-to-mild vs moderate-tosevere).RESULTS Thirty-eight of the 52 patients with hPIDs showed common variable immunodeficiency disorders(CVID), while the remaining 14 had CVID-like conditions(i.e., 11 had isolated IgG subclass deficiencies and 3 had selective IgA deficiencies). The prevalence of most HRCT abnormalities was not significantly different between CVID and CVID-like patients(P > 0.05), except for linear and/or irregular opacities(prevalence of 31.6% in the CVID group and 0 in the CVID-like group; P = 0.0427). Airway wall thickening was the most frequent HRCT abnormality found in both CVID and CVID-like patients(71% of cases in both groups). The presence of tree-in-bud abnormalities was an independent predictor of moderate-to-severe obstructive defects at PFTs(Odds Ratio, OR, of 18.75, P < 0.05), while the presence of linear and/or irregular opacities was an independent predictor of restrictive defects at PFTs(OR = 13.00; P < 0.05).CONCLUSION CVID and CVID-like patients showed similar HRCT findings. Tree-in-bud and linear and/or irregular opacities predicted higher risks of, respectively,obstructive and restrictive defects at PFTs.