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1.

Background

Biologics against tumor necrosis factor (anti-TNF) have dramatically changed the management of moderate-to-severe ulcerative colitis (UC). In pivotal clinical trials, golimumab showed efficacy as induction and maintenance therapy in anti-TNF naïve UC patients. However, confirmatory data on effectiveness in the real world setting are needed.

Aim

to summarize recent evidence on the effectiveness of golimumab in observational real-world studies.

Methods

A literature search was conducted using Medline, Embase, and congresses databases for English language articles or abstracts on the effectiveness of golimumab published between January 1, 2014 and May 15, 2018. Pooled short-term (6–14 weeks) and mid- and long-term (24–54 weeks) clinical response and remission rates were calculated.

Results

24 abstracts were included; of those 8 were published full-text articles and 16 were abstracts from medical conferences. Overall, pooled short-term clinical response and remission rates were 59.3% (range 35–85.5%; 13 studies; 1429 patients) and 35.9% (range 14–51.7%; 9 studies; 666 patients), respectively. Pooled mid- and long-term clinical response and remission rates were 60.3% (range 37.1–89.5%; 4 studies; 356 patients) and 39.2% (range 12–84%; 8 studies; 822 patients), respectively.

Conclusions

Results: of observational studies confirm that golimumab is an effective therapy for UC in clinical practice.  相似文献   

2.

Background

Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months.

Objective

We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw.

Methods

We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition.

Results

Sixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded.

Conclusions

It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.  相似文献   

3.

Background

Chronic hepatitis B virus (HBV) infection remains a primary cause of morbidity and mortality worldwide.

Aim

The study is aimed at updating the clinical and epidemiological profile of chronic HBV infection in Italy.

Methods

A cross-sectional multicenter prospective study enrolled consecutive HBsAg positive patients seen in 73 Italian centers in the period 2012–2015. Individual patient data were collected using an electronic platform and analyzed using standard statistical methods.

Results

Among 2877 HBsAg positive individuals (median age 49.8?years, 68% males), 27% were non-Italian natives (NINs); 20% had chronic infection, 58.5% chronic hepatitis and 21.5% cirrhosis. Among NINs, age was younger, male gender was less prevalent and liver disease less advanced than in Italians (all p?<?0.0001). HBeAg positive cases were 23.6% among NINs vs 8.2% in Italians (p?<?0.0001); HDV coinfections 11.1% vs 7.3% (p?=?0.006) and HCV coinfections 2.3% vs 4.2% (p?=?0.017), respectively. Anti-HDV or anti-HCV antibodies were detected more frequently in patients with cirrhosis. Fifty percent of NINs with cirrhosis were aged below 45?years.

Conclusion

The study offers an insight into the evolving burden of chronic hepatitis B virus infection in the near future and highlights new territories for public health interventions.  相似文献   

4.

Background

Anti-TNF therapies infliximab (IFX), adalimumab (ADA), and golimumab (GOL) are approved for treating moderate to severe ulcerative colitis (UC). In UC, only the switch from IFX to ADA has been investigated, reaching no more than 10–43% remission rates at 12 months.

Aim

Of the present study was to investigate disease outcome after a switch from subcutaneous (SC) agents to the intravenous (IV) agent (IFX).

Methods

In this retrospective multicentre study, we analysed the charts of UC patients unresponsive/intolerant or with secondary loss of response (LOR) to ADA or GOL who were switched to IFX. We evaluated clinical response and remission together with adverse events at 3, 6, and 12 months follow-up.

Results

Seventy-six patients were included; 38 patients started ADA and 38 started GOL for a mean therapy duration of 6?±?6 months. Indications for switch were adverse events in 3%, primary failure in 79%, and LOR in 18% of patients. Clinical remission was reached by 47%, 50%, and 77% of patients, respectively. Patients that switched for LOR did numerically, but not statistically, better than patients who switched for primary failure.

Conclusions

Our data show a superior remission rate in SC to IV anti-TNF switch in UC compared to the IV to SC switch reported in literature.  相似文献   

5.

Background

There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs).

Aim

To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking.

Methods

All subjects aged ≥18?years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014.

Results

The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p?<?0.01) but not in those positive for other HBV markers.

Conclusions

These findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker.  相似文献   

6.

Background

The growing number of gastric cancers together with improved survival resulted in an increasing population of survivors at risk of multiple primary cancers.

Aims

To estimate the 10-year risk and survival of third primary cancers (TPCs) among gastric first primary cancers (FPCs).

Methods

Gastric FPCs from the Portuguese North Region Cancer Registry, diagnosed in 2000-2006 (n?=?7409), were followed for a TPC (31/12/2012), and for all-cause death (31/12/2017). The cumulative incidence of TPCs was estimated. Patients with a TPC were matched (1:1, by sex, age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC?+?SPC patients without a TPC.

Results

Overall, 25 (0.3% of FPCs and 6.8% of SPCs) TPCs were diagnosed. The most common sites were tobacco-related, mainly including digestive organs. Among all FPCs, 10-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.4% (0.2–0.5%) and among SPCs 7.6% (4.4–10.8%). For TPCs, compared to matched patients, age-adjusted hazard ratio (95%CI) for death was 1.68 (0.77–3.67). The 10-year cumulative mortality of TPCs and matched patients was 92.6% and 67.9%, respectively.

Conclusions

A clustering of tobacco-related cancers was observed in TPCs, with a 10-year cumulative incidence of 0.4% among FPCs. TPCs had worse survival than patients without a TPC.  相似文献   

7.

Objective

Osteoarthritis causes severe pain and disability in joints, one of the most prevalent involved joints is the knee joint. There are several therapeutics ways to control pain and disability, but almost none of them are definite treatment. In this article, we tried to reveal the effect of weight loss on improving symptoms of knee osteoarthritis as an effective and permanent therapeutic approach.

Methods

We chose 62 patients with grade 1–2 (mild to moderate) knee osteoarthritis and divided them equally into case and control groups. Patients should not had used NSAIDs at least for 6 months before study initiation. Symptoms severity was measured by WOMAC and VAS questionnaires before and after 3 months follow up. Weight and BMI were recorded too. Case group was suggested to have weight loss diet of less fat and carbohydrates and control group did not have any limitation.

Results

Comparison of variables’ average of case and control groups was not logistically meaningful at the initiation and after the end of the study. But there was a meaningful correlation between variables’ changes and lifestyle change in both groups, especially in WOMAC and VAS scores. All variables in case group had statistically meaningful differences between their amounts at the beginning and after the end of the study, on the contrary of the control group.

Conclusion

In the comparison of our study with similar studies in the world. We deduced that weight loss can improve symptoms of knee osteoarthritis even in short time weight loss diet (3 months).

Trial registration number

ZUMS.REC.1394.94.  相似文献   

8.

Introduction and objectives

To assess the cost-effectiveness of edoxaban vs acenocoumarol in the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in Spain.

Methods

Markov model, adapted to the Spanish setting from the perspective of the National Health System, stimulating the progression of a hypothetical cohort of patients with NVAF throughout their lifetime, with different health states: stroke, haemorrhage, and other cardiovascular complications. Efficacy and safety data were obtained from the available clinical evidence (mainly from the phase III ENGAGE AF-TIMI 48 study). The costs of managing NVAF and its complications were obtained from Spanish sources.

Results

Edoxaban use led to 0.34 additional quality-adjusted life years (QALY) compared with acenocoumarol. The incremental cost with edoxaban was 3916€, mainly because of higher pharmacological costs, which were partially offset by lower costs of treatment monitoring and managing NVAF events and complications. The cost per QALY was 11 518€, within the thresholds commonly considered cost-effective in Spain (25 000-30 000 €/QALY). The robustness of the results was confirmed by various sensitivity analyses.

Conclusions

Edoxaban is a cost-effective alternative to acenocoumarol in the prevention of stroke and systemic embolism in patients with NVAF in Spain.  相似文献   

9.

Background

Endogenous β-endorphin is delivered exclusively from the pituitary gland in various stressful conditions and plays an essential role in the nervous system. Recently, a few studies demonstrated peripheral endogenous opioid secretion from immune cells at inflammatory sites. Here, we investigated the expression of β-endorphin, the most powerful endogenous opioid peptide, in peripheral tissues in response to systemic administration of lipopolysaccharide in mice.

Methods

Male C57BL/6N mice received intravenously administered lipopolysaccharide to induce an endotoxic shock-like condition. mRNA for proopiomelanocortin, a precursor of β-endorphin, was quantified in peripheral blood cells, liver and spleen. β-endorphin peptide was measured in the liver and spleen.

Results

Expression of proopiomelanocortin mRNA was detected in peripheral tissues after systemic administration of lipopolysaccharide. Lipopolysaccharide also induced β-endorphin expression in the liver and spleen.

Conclusion

Expression of proopiomelanocortin mRNA and β-endorphin was detected in peripheral tissues after systemic administration of lipopolysaccharide. These results provide new evidence that peripheral endogenous opioids can be produced not only as a result of local inflammation but also by severe systemic stress such as endotoxic shock. Further study is required to clarify the role of peripheral β-endorphin during endotoxic shock.  相似文献   

10.

Background

Men who have sex with men (MSM) account for the highest prevalence of HIV in Brazil. HIV testing allows to implement preventive measures, reduces transmission, morbidity, and mortality.

Methods

We conducted a cross-sectional study to evaluate HIV testing during lifetime, factors associated with the decision to test, knowledge about HIV transmission, and use of condoms between MSM from the city of Natal, northeast Brazil.

Results

Out of 99 participants, 62.6% had been tested for HIV during lifetime, 46.2% in the last year. The most frequent reported reason to be tested for HIV infection was curiosity (35.5%). Correct knowledge about HIV was observed in only 9.2% of participants. In multivariate analysis, age (PR 0.95; 95%CI, 0.91–0.99; p = 0.041) and previous syphilis test (PR 4.21; 95%CI, 1.52–11.70; p = 0.006) were associated with HIV testing.

Conclusions

The frequency of HIV testing among MSM from Natal is rather low, especially in younger MSM, and knowledge about HIV transmission is inappropriate.  相似文献   

11.

Background

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective.

Aims

The current study was aimed to investigate whether miR-494 influences epithelial-mesenchymal transition (EMT), tumor growth and metastasis of CCA.

Methods

The regulatory miRNAs of WDHD1 in CCA expression chip were predicted, followed by determination of the miR-494 and WDHD1 expression in normal cholangiocyte tissues and CCA tissues. The related protein levels were determined. CCA cell migration, invasion, viability, and cell cycle distribution and the dosage-dependent effect of miR-494 on CCA cell growth were subsequently detected. Finally, tumorigenicity and lymph node metastasis (LNM) were measured.

Results

Initially, miR-194 affected the CCA development via negatively regulating WDHD1 and miR-494 which were downregulated while WDHD1 was upregulated in CCA. In addition, miR-494 overexpression elevated E-cadherin expression while decreased expressions of WDHD1, N-cadherin, Vimentin, Snail, Twist and MMP-9. Finally, overexpressed miR-494 was observed to suppress EMT, cell viability, migration, invasion, arrest cell cycle progression, tumor formation, and LNM while accelerating cell apoptosis in vivo.

Conclusion

This study indicated that miR-494 overexpression suppresses EMT, tumor formation and LNM while promoting CCA cell apoptosis through inhibiting WDHD1 in CCA.  相似文献   

12.

Background

Mother-to-child-transmission (MTCT) is the main route of HIV-1 infection in children. Genetic studies suggest HLA-B alleles play an important role on HIV-1 transmission, progression, and control of HIV-1 infection.

Objective

To evaluate which polymorphisms of HLA-B are involved in HIV-1 MTCT.

Methods

Two independent reviewers performed a systematic review on search engines PubMed, Europe PMC, Cochrane, Scientific Electronic Library Online (SciELO), and Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs), using the following key terms: “HIV infection”, “HIV newborn”, “HLA polymorphisms”, “HLA-B”, and “Mother to child transmission”. All studies focusing on evaluation of HIV-1 MTCT, HIV infection evolution, and molecular analyses of HLA-B in children were selected.

Results

Nine studies fulfilled the inclusion criteria. Sixteen HLA-B alleles groups were associated with HIV-1 infection; seven of them (43.8%) were related to slow disease progression or reduced risk of MTCT, while six (37.5%) alleles groups were linked to a faster progression of HIV infection in children and to increased risk of MTCT. The available evidence suggest that HLA-B*57 group allele is associated with slow disease progression, while HLA-B*35 group allele is associated to increased risk of MTCT and rapid disease progression in infected children. The role of HLA-B*18, B*58 and B*44 are still controversial because they were associated to both, protection against MTCT, and to higher HIV replicative capacity, in different studies.

Conclusion

HLA-B*57 group allele can be protective against MTCT while HLA-B*35 groups alleles are consistently associated with HIV-1 MTCT.  相似文献   

13.

Introduction

Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by ventricular dilatation and impaired systolic function. Familial forms account for 30-50% of cases. Autosomal dominant inheritance is the predominant pattern of transmission. Causal genetic variants have been identified in several genes and molecular diagnosis has implications for genetic counseling and risk stratification.

Objective

We aimed to estimate the frequency of genetic variants and the molecular basis of DCM in Portugal.

Methods

We performed a multicenter study of unrelated patients, recruited between 2013 and 2014. Variants in 15 genes were screened using PCR with direct sequencing (next-generation sequencing with at least 30-fold coverage combined with Sanger sequencing).

Results

A total of 107 patients were included, 64 (60%) men, mean age at diagnosis 38±13 years, with 48 (45%) familial cases. In total, 31 rare variants in eight genes (mainly in MYBPC3, TNNT2 and LMNA) were identified, in 28 patients (26%). Only four variants had been previously described in association with DCM, 11 with hypertrophic cardiomyopathy, and nine variants were novel. Four variants were likely pathogenic and the remainder were of uncertain significance. We found no major differences in the main clinical and imaging characteristics between patients with or without rare variants and patients with likely pathogenic variants.

Conclusions

Our results reflect the complexity and diversity of DCM genetics. For better interpretation of the pathogenicity of the variants found and their causative roles in DCM, molecular cascade screening of families is imperative. Further insight into genotype-phenotype correlations and risk stratification is desirable.  相似文献   

14.

Objectives

To investigate the prevalence of human polyomavirus (BK and JC viruses) infection in peripheral blood mononuclear cells of healthy blood donors.

Methods

The study included 250 healthy blood donors. Five-milliliter blood was drawn into sterile EDTA tubes and PBMCs were isolated from whole blood. The isolated PBMCs were counted and stored at ?70 °C for future investigation. DNA was extracted and subjected to simple, sensitive and specific semi-nested PCR as well as QPCR using both general and specific primers for different assays.

Results

Of 250 blood samples, 66 (26.4%) were positive for BKV DNA (146–34,514 copies/106 cells). JC DNA was found in 45 (18%) blood samples (65–21,250 copies/106 cells). Co-infection with these viruses were found in 11 (4.4%) out of 250 blood samples.

Discussion

Our study provides important data on polyomavirus infection in peripheral blood mononuclear leukocytes in immunocompetent individuals. These data indicate significant differences between the prevalence of BKV and JCV infection in healthy blood donors. The prevalence of BK and JC virus infection is higher in the age range 30–39 years compared to other age ranges.  相似文献   

15.

Objective

To assess the prevalence of gallstone disease and identify associated risk factors in rheumatoid arthritis (RA) patients compared to the general population.

Methods

Eighty-four women with rheumatoid arthritis were included in the study. Each patient was assessed via a structured interview, physical examination, abdominal ultrasound and blood test including lipid profile. The prevalence of gallstone disease in rheumatoid arthritis was compared with data from a study of the Spanish population matched by age groups.

Results

Twenty-eight of the 84 women had gallstone disease (33.3%). RA women with and without gallstone disease were similar in most of the variables assessed, except for older age and menopausal status in the former. A greater prevalence of gallstone disease was seen in rheumatoid arthritis patients compared to the general population of the same age; however, the differences were significant only in women aged 60 or older (45.5% versus 23.1% respectively, P-value .008). The age-adjusted OR of developing gallstone disease in RA women compared with general population women was 2,3 (95% CI: 1.3–4.1). A significantly higher HDL3-c subfraction and higher apoA-I/HDL and HDL3-c/TC ratios were observed in patients with gallstone disease.

Conclusion

Women with rheumatoid arthritis may have a predisposition to gallstones that can manifest in middle or older age compared with women in the general population. This situation could be related to chronic inflammation and HDL metabolism.  相似文献   

16.

Background

The current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West.

Aims

This study aimed to develop an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF) as defined by the Asia Pacific Association for the Study of the Liver (APASL).

Methods

The nomogram was based on a retrospective study of 573 patients with ACHBLF, defined according to the APASL, at the Beijing Ditan Hospital. The results were validated using a bootstrapped approach to correct for bias in two external cohorts, including an APASL ACHBLF cohort (10 hospitals, N?=?329) and an EASL-CLIF ACHBLF cohort (Renji Hospital, N?=?300).

Results

Multivariate analysis of the derivation cohort for survival analysis helped identify the independent factors as age, total bilirubin, albumin, international normalized ratio, and hepatic encephalopathy, which were included in the nomogram. The predictive value of nomogram was the strongest compared with CLIF-C ACLF, MELD and MELD-Na and similar to COSSH-ACLF in both the derivation and prospective validation cohorts with APASL ACHBLF, but the CLIF-C ACLF was better in the EASL-CLIF ACHBLF cohort.

Conclusions

The proposed nomogram could accurately estimate individualized risk for the short-term mortality of patients with ACHBLF as defined by APASL.  相似文献   

17.
18.

Introduction and Aims

Remote magnetic navigation systems have demonstrated benefits in the ablation of difficult substrates. Their role in the ablation of atrioventricular nodal reentrant tachycardia (AVNRT), however, has only been studied in small patient series. The aim of this study was to compare the results of AVNRT ablation using magnetic navigation, in a center where every procedure is performed with this system, with manual ablation.

Methods

We selected 139 consecutive patients undergoing AVNRT ablation with magnetic navigation by a single operator between January 2009 and June 2016 and compared them to a group of 101 consecutive patients undergoing manual ablation in the same period by the same operator in another hospital. The methodology was the same in both groups. Success rates, complications, procedure time, radiofrequency time, total and operator fluoroscopy time, and recurrence rates were compared.

Results

There were no differences in success and complication rates. Procedure and total fluoroscopy times were not significantly different, but operator fluoroscopy time was significantly shorter with the magnetic navigation system (2.4±1.5 min vs. 7.2±4 min; p<0.001). The recurrence rate was higher in the manual group, although without statistical significance.

Conclusions

The ablation of AVNRT with magnetic navigation is feasible using the same methodology as for manual ablation. Success and complication rates were similar. Operator fluoroscopy time was significantly less with the magnetic navigation system.  相似文献   

19.

Objective

To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures.

Methods

Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated.

Results

396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16–0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010–0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations.

Conclusions

Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.  相似文献   

20.

Backgound

A significant proportion of hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive patients with non-Hodgkin lymphoma (NHL) undergoing rituximab-based chemotherapy (R-CT) may suffer hepatitis B virus (HBV) reactivation.

Aims

We wanted to assess efficacy and safety of lamivudine (LMV) prophylaxis to prevent this complication.

Methods

Eighty-five consecutive HBsAg negative/anti-HBc positive NHL patients (71 years, 100% serum HBV DNA undetectable, 74% anti-HBs positive) received LMV coadministered with R-CT and for 18 months after the end of R-CT. Serum ALT, HBsAg, anti-HBs and HBV DNA were assessed every 4 months during and after end of LMV.

Results

During 39 (2–108) months of study period, including 21 months of LMV and 27 additional months after LMV discontinuation, one patient (2%) had HBV reactivation, 31 months after stopping LMV and during administration of new immunosuppressive regimens, without LMV prophylaxis, owing to incomplete oncological response. A 50% decline of anti-HBs titers occurred in 22/63 (35%) patients, including 12 who became anti-HBs seronegative. Five (6%) patients had ALT increase during R-CT but none required R-CT discontinuation. Seventeen (20%) patients died, all for tumour progression.

Conclusion

LMV prophylaxis is safe and effective in preventing HBV reactivation in HBsAg negative/anti-HBc positive NHL patients receiving R-CT.  相似文献   

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