Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis

Objective: This study aims to systematically examine the existing evidence regarding the clinical benefits of carbocysteine as an adjunctive treatment in acute bronchopulmonary and otorhinological processes. Design: Systematic review and meta-analysis. Data sources: An electronic search was conducted across PubMed, Cochrane Library, clinicaltrials.gov, and the European Clinical Trial Register, with the search dated to May 2023. Bibliographic references from other literature reviews and meta-analyses were also reviewed. The search was limited to randomized clinical trials published in any language and year. It was completed by cross-checking the references of the located articles. Methods: Inclusion criteria covered studies assessing systemic or inhaled carbocysteine, regardless of dosing regimen. Concomitant medication use was acceptable if balanced between intervention and control groups. Authors independently extracted data, resolving disagreements through consensus. Methodological quality assessment relied on critical reading of each study. Dichotomous variables were analyzed using odds ratio (OR), and a final effect size was calculated. Statistical significance was established when confidence intervals did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified studies, 4 met inclusion criteria. The meta-analysis for poor general condition yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs. 27.2% for placebo. On the seventh day, expectoration rates were 18.37% for carbocysteinevs 33.3% for placebo. Conclusions: The observed clinical benefits align with carbocysteine’s mucoactive and muco-regulatory properties, complemented by anti-inflammatory and antioxidant actions. Carbocysteine stands out among mucolytic agents. In the context of persistent infectious diseases, the study emphasizes the need for further exploration of carbocysteine’s therapeutic potential as an adjunctive treatment for acute respiratory infections. These findings underscore its significance in the evolving landscape of respiratory healthcare.

A systematic review of the efficacy of traditional Chinese medicine retention enema in the treatment of ulcerative colitis

The objective of this study is to summarize the efficacy and safety of traditional Chinese medicine(TCM)enema in the treatment of ulcerative colitis(UC).The randomized controlled trials on TCM enema intervention in the treatment of UC were searched in seven databases:PubMed,Embase,Web of Science,CBM,CNKI,Wanfang Database,and VIP Database from January 1,2013 to June 6,2022,and the data were analyzed using RevMan 5.3 software.A total of 18 studies involving 1514 UC patients were included.Meta analysis results showed that compared with conventional Western medicine,Chinese medicine enema had a significant effect on UC,and the clinical effective rate of the experimental group using Chinese medicine enema was 4.45 times that of the control group using conventional Western medicine(odds ratio=4.45,95%confidence interval[3.27,6.06]).Therefore,Chinese medicine enema is effective in the treatment of UC,and can significantly reduce related symptoms.

Adverse events with bismuth salts for Helicobacter pylori eradication:Systematic review and meta-analysis

AIM: To assess the safety of bismuth used in Helico- bacter pylori (H pylori) eradication therapy regimens. METHODS: We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched (up to October 2007) to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppres- sion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals (CI). RESULTS: We identified 35 randomised controlled tri- als containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth [relative risk (RR) = 1.01; 95% CI: 0.87-1.16], specific individual adverse events, with the exception of dark stools (RR = 5.06; 95% CI: 1.59-16.12), or adverse events leading to withdrawal of therapy (RR = 0.86; 95% CI: 0.54-1.37). CONCLUSION: Bismuth for the treatment of H pylori is safe and well-tolerated. The only adverse event oc- curring significantly more commonly was dark stools.

Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy(PDT) in non-resectable cholangiocarcinoma. METHODS Included studies compared outcomes with photodynamic therapy and biliary stenting(PDT group) vs biliary stenting only(BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubM ed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTS Ten studies(n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage(decrease in bilirubin level > 50% within 7days after stenting)in PDT vs BS group was 4.39(95%CI: 2.35-8.19).Survival period in PDT and BS groups were 413.04d(95%CI: 349.54-476.54) and 183.41(95%CI:136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99(95%CI: 4.15-9.82) and-3.93(95%CI:-8.63-0.77) respectively. Odds ratio for postintervention cholangitis in PDT vs BS group was 0.57(95%CI: 0.35-0.94). In PDT group, 10.51%(95%CI:6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups. CONCLUSION In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.

Outcomes of robotic vs laparoscopic hepatectomy:A systematic review and meta-analysis

AIM: To perform a systematic review and metaanalysis on robotic-assisted vs laparoscopic liver resections.METHODS: A systematic literature search was performed using Pub Med, Scopus and the Cochrane Library Central. Participants of any age and sex, who underwent robotic or laparoscopic liver resection were considered following these criteria:(1) studies comparing robotic and laparoscopic liver resection;(2) studies reporting at least one perioperative outcome; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measures were set for estimated blood loss, operative time, conversion rate, R1 resection rate, morbidity and mortality rates, hospital stay and major hepatectomy rates.RESULTS: A total of 7 articles, published between 2010 and 2014, fulfilled the selection criteria. The laparoscopic approach was associated with a significant reduction in blood loss and lower operative time(MD = 83.96, 95%CI: 10.51-157.41, P = 0.03; MD = 68.43, 95%CI: 39.22-97.65, P < 0.00001, respectively). No differences were found with respect to conversion rate, R1 resection rate, morbidity and hospital stay.CONCLUSION: Laparoscopic liver resection resulted in reduced blood loss and shorter surgical times compared to robotic liver resections. There was no difference in conversion rate, R1 resection rate, morbidity and length of postoperative stay.

The PCA3 test for guiding repeat biopsy of prostate cancer and its cut-off score： a systematic review and meta-analysis

The specificity of prostate-specific antigen （PSA） for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 （PCA3） may be more accurate in outcome prediction than other methods for the early detection of prostate cancer （PCa）. However, the results were inconsistent in repeated biopsies. Therefore, we performed a systematic review and meta-analysis to evaluate the role of PCA3 in outcome prediction. A systematic bibliographic search was conducted for articles published before April 2013, using PubMed, Medline, Web of Science, Embase and other databases from health technology assessment agencies. The quality of the studies was assessed on the basis of QUADAS criteria. Eleven studies of diagnostic tests with moderate to high quality were selected. A meta-analysis was carried out to synthesize the results. The results of the meta-analyses were heterogeneous among studies. We performed a subgroup analysis （with or without inclusion of high-grade prostatic intraepithelial neoplasia （HGPIN） and atypical small acinar proliferation （ASAP））. Using a PCA3 cutoff of 20 or 35, in the two sub-groups, the global sensitivity values were 0.93 or 0.80 and 0.79 or 0.75, specificities were 0.65 or 0.44 and 0.78 or 0.70, positive likelihood ratios were 1.86 or 1.58 and 2.49 or 1.78, negative likelihood ratios were 0.81 or 0.43 and 0.91 or 0.82 and diagnostic odd ratios （ORs） were 5.73 or 3.45 and 7.13 or 4.11, respectively. The areas under the curve （AUCs） of the summary receiver operating characteristic curve were 0.85 or 0.72 and 0.81 or 0.69, respectively. PCA3 can be used for repeat biopsy of the prostate to improve accuracy of PCa detection. Unnecessary biopsies can be avoided by using a PCa cutoff score of 20.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Single-incision laparoscopic appendectomy vs conventional laparoscopic appendectomy:Systematic review and meta-analysis

AIM: To assess the differences in clinical benefits and disadvantages of single-incision laparoscopic appendectomy(SILA) and conventional laparoscopic appendectomy(CLA).METHODS: The Cochrane Library,MEDLINE,Embase,Science Citation Index Expanded,and Chinese Biomedical Literature Database were electronically searched up through January 2013 to identify randomized controlled trails(RCTs) comparing SILA with CLA.Data was extracted from eligible studies to evaluate the pooled outcome effects for the total of 1068 patients.The meta-analysis was performed using Review Manager 5.2.0.For dichotomous data and continuous data,the risk ratio(RR) and the mean difference(MD) were calculated,respectively,with 95%CI for both.For continuous outcomes with different measurement scales in different RCTs,the standardized mean difference(SMD) was calculated with 95%CI.Sensitivity and subgroup analyses were performed when necessary.RESULTS: Six RCTs were identified that compared SILA(n = 535) with CLA(n = 533).Five RCTs had a high risk of bias and one RCT had a low risk of bias.SILA was associated with longer operative time(MD = 5.68,95%CI: 3.91-7.46,P < 0.00001),higher conversion rate(RR = 5.14,95%CI: 1.25-21.10,P = 0.03) and better cosmetic satisfaction score(MD = 0.52,95%CI: 0.30-0.73,P < 0.00001) compared with CLA.No significant differences were found for total complications(RR = 1.15,95%CI: 0.76-1.75,P = 0.51),drain insertion(RR = 0.72,95%CI: 0.41-1.25,P = 0.24),or length of hospital stay(SMD = 0.04,95%CI:-0.08-0.16,P = 0.57).Because there was not enough data among the analyzed RCTs,postoperative pain was not calculated.CONCLUSION: The benefit of SILA is cosmetic satisfaction,while the disadvantages of SILA are longer operative time and higher conversion rate.

Consequences of bullying victimization in childhood and adolescence:A systematic review and meta-analysis

AIM To identify health and psychosocial problems associated with bullying victimization and conduct a meta-analysis summarizing the causal evidence.METHODS A systematic review was conducted using Pub Med, EMBASE, ERIC and Psyc INFO electronic databases up to 28 February 2015. The study included published longitudinal and cross-sectional articles that examined health and psychosocial consequences of bullying victimization. All meta-analyses were based on qualityeffects models. Evidence for causality was assessed using Bradford Hill criteria and the grading system developed by the World Cancer Research Fund.RESULTS Out of 317 articles assessed for eligibility, 165 satisfied the predetermined inclusion criteria for meta-analysis.Statistically significant associations were observed between bullying victimization and a wide range of adverse health and psychosocial problems. The evidence was strongest for causal associations between bullying victimization and mental health problems such as depression, anxiety, poor general health and suicidal ideation and behaviours. Probable causal associations existed between bullying victimization and tobacco and illicit drug use. CONCLUSION Strong evidence exists for a causal relationship between bullying victimization, mental health problems and substance use. Evidence also exists for associations between bullying victimization and other adverse health and psychosocial problems, however, there is insufficient evidence to conclude causality. The strong evidence that bullying victimization is causative of mental illness highlights the need for schools to implement effective interventions to address bullying behaviours.

Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis

AIM To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width(RDW) in esophageal cancer(EC). METHODS We searched the PubM ed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible:(1) Studies including EC patients who underwent radical esophagectomy;(2) studies including patients with localized disease without distant metastasis;(3) studies including patients without preoperative neoadjuvant therapy;(4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes;(5) studies reporting association between the preoperative RDW and overall survival(OS)/disease-free survival(DFS)/cancer-specific survival(CSS); and(6) studies published in English.RESULTS A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio(HR) = 1.27, 95% confidence interval(CI): 0.97-1.57, P = 0.000] or DFS(HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13%(HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400(HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective(HR = 1.42, 95%CI : 1.16-1.69, P = 0.000).CONCLUSION Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.

Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis

BACKGROUND Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide.In clinical trials,Lactobacillus rhamnosus GG ATCC 53013(LGG)has been used to treat diarrhea.However,recent randomized controlled trials(RCTs)found no evidence of a beneficial effect of LGG treatment.AIM To evaluate the efficacy of LGG in treating acute diarrhea in children.METHODS The EMBASE,MEDLINE,PubMed,Web of Science databases,and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for metaanalyses and RCTs.The Cochrane Review Manager was used to analyze the relevant data.RESULTS Nineteen RCTs met the inclusion criteria and showed that compared with the control group,LGG administration notably reduced the diarrhea duration[mean difference(MD)-24.02 h,95%confidence interval(CI)(-36.58,-11.45)].More effective results were detected at a high dose≥1010 CFU per day[MD-22.56 h,95%CI(-36.41,-8.72)]vs a lower dose.A similar reduction was found in Asian and European patients[MD-24.42 h,95%CI(-47.01,-1.82);MD-32.02 h,95%CI(-49.26,-14.79),respectively].A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment[MD-15.83 h,95%CI(-20.68,-10.98)].High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea[MD-31.05 h,95%CI(-50.31,-11.80)]and the stool number per day[MD-1.08,95%CI(-1.87,-0.28)].CONCLUSION High-dose LGG therapy reduces the duration of diarrhea and the stool number per day.Intervention at the early stage is recommended.Future trials are expected to verify the effectiveness of LGG treatment.

Double versus single homologous intrauterine insemination for male factor infertility： a systematic review and meta-analysis

Male factor infertility affects 30%-50% of infertile couples worldwide, and there is an increasing interest in the optimal management of these patients. In studies comparing double and single intrauterine insemination （IUI）, a trend towards higher pregnancy rates in couples with male factor infertility was observed. Therefore, we set out to perform a meta-analysis to examine the superiority of double versus single IUI with the male partner＇s sperm in couples with male factor infertility. An odds ratio （OR） of 95% confidence intervals （CIs） was calculated for the pregnancy rate. Outcomes were analysed by using the ManteI-Haesel or DerSimonian-Laird model accordingto the heterogeneity of the results. Overall, five trials involving 1125 IUI cycles were included in the meta-analysis. There was a two-fold increase in pregnancies after a cycle with a double IUI compared with a cycle with a single IUI （OR. 2.0; 95% CI. 1.07-3.75; P〈O.03）. Nevertheless, this result was mainly attributed to the presence of a large trial that weighted as almost 50% in the overall analysis. Sensitivity analysis, excluding this large trial, revealed only a trend towards higher pregnancy rates among double IUI cycles （OR. 1.58; 95% CI. 0.59-4.21）, but without statistical significance （P=0.20）. Our systematic review highlights that the available evidence regarding the use of double IUI in couples with male factor infertility is fragmentary and weak. Although there may be a trend towards higher pregnancy rates when the number of IUIs per cycle is increased, further large and well-designed randomized trials are needed to provide solid evidence toide current clinical practice.

Active and passive smoking with breast cancer risk for Chinese females: a systematic review and meta-analysis

Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especially for Chinese females. Thus, we systematically searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases(PubMed, Embase, ScienceDirect, and Wiley) and three Chinese databases(CNKI, WanFang, and VIP). Fifty-one articles(3 cohort studies and 48 casecontrol studies) covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio(OR): 1.62; 95% confidence interval(CI): 1.39–1.85; I2 = 75.8%, P < 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer(OR: 1.04; 95% CI: 0.89–1.20; I2 = 13.9%, P = 0.248; n = 31). The OR of exposure to husband's smoking and to smoke in the workplace was 1.27(95% CI: 1.07–1.50) and 1.66(95% CI: 1.07–2.59), respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband's smoke(< 20 and ≥ 20 cigarettes per day), and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace(< 300 and ≥ 300 min of exposure per day). These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband's smoking.

Atropine 0.01% eye drops slow myopia progression: a systematic review and Meta-analysis

AIM: To evaluate the effects of atropine 0.01% on slowing myopia progression. METHODS: We searched for relevant studies in the Cochrane Library, PubMed, Embase, Ovid, CBM, CNKI, VIP and Wan Fang Data in Chinese. A supplementary search was conducted in OpenGrey(System for Information on Grey Literature in Europe), the ISRCTN registry, Clinical Trials.gov, and the WHO International Clinical Trials Registry Platform(ICTRP) from the dates of inception to June 30, 2018. RESULTS: Seven randomized controlled trials(RCTs) with a total of 1079 subjects were included(505 in the atropine 0.01% group and 574 in the control group). The results showed that the atropine 0.01% group exhibited significantly greater control of axial growth than the control group (MD=-0.12, 95%CI(-0.19,-0.06))There was also a statistically significant difference between the atropine 0.01% and control groups in the changes in axial length [MD=-0.14, 95%CI(-0.25,-0.03)], but the quality of evidence was low. There were no significant differences between the atropine 0.01% and control groups in the overall effect with respect to diopter value, change in diopter, distance vision and intraocular pressure (MD=0.08, 95%CI(-0.27, 0.42);MD=0.09, 95%CI(-0.17, 0.36);MD=-0.01, 95%CI(-0.02, 0.00);MD=0.08, 95%CI(-0.56,0.40))The sensitivity analysis showed that the conclusion of the Meta-analysis is relatively stable. With respect to adverse events, there were significant differences between the atropine 0.01% and control groups (OR=0.26, 95%CI(0.11, 0.61))CONCLUSION: Based on the available evidence, atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.

Meta-analysis and systematic review of colorectal endoscopic mucosal resection

AIM:To evaluate the proportion of successful complete cure en-bloc resections of large colorectal polyps achieved by endoscopic mucosal resection(EMR). METHODS:Studies using the EMR technique to resect large colorectal polyps were selected.Successful complete cure en-bloc resection was defined as one piece margin-free polyp resection.Articles were searched for in Medline,Pubmed,and the Cochrane Control Trial Registry,among other sources. RESULTS:An initial search identified 2620 reference articles,from which 429 relevant articles were selected and reviewed.Data was extracted from 25 studies(n =5221)which met the inclusion criteria.All the studies used snares to perform EMR.Pooled proportion of en-bloc resections using a random effect model was 62.85%(95%CI:51.50-73.52).The pooled proportion for complete cure en-bloc resections using a random effect model was 58.66%(95%CI:47.14-69.71).With higher patient load(>200 patients),this complete cure en-bloc resection rate improves from 44.19%(95%CI: 24.31-65.09)to 69.17%(95%CI:51.11-84.61). CONCLUSION:EMR is an effective technique for the resection of large colorectal polyps and offers an alternative to surgery.

Short-term clinical outcomes of laparoscopic vs open rectal excision for rectal cancer: A systematic review and metaanalysis

AIM To review evidence on the short-term clinical outcomes of laparoscopic(LRR) vs open rectal resection(ORR) for rectal cancer.METHODS A systematic literature search was performed using Cochrane Central Register, MEDLINE, EMBASE, Scopus, Open Grey and Clinical Trials.gov register for randomized clinical trials(RCTs) comparing LRR vs ORR for rectal cancer and reporting short-term clinical outcomes. Articles published in English from January 1, 1995 to June, 30 2016 that met the selection criteria were retrieved and reviewed. The Preferred Reporting Items for Systematic reviews and Meta-Analysis(PRISMA) statements checklist for reporting a systematic review was followed. Random-effect models were used to estimate mean differences and risk ratios. The robustness and heterogeneity of the results were explored by performing sensitivity analyses. The pooledeffect was considered significant when P < 0.05.RESULTS Overall, 14 RCTs were included. No differences were found in postoperative mortality(P = 0.19) and morbidity(P = 0.75) rates. The mean operative time was 36.67 min longer(95%CI: 27.22-46.11, P < 0.00001), the mean estimated blood loss was 88.80 ml lower(95%CI:-117.25 to-60.34, P < 0.00001), and the mean incision length was 11.17 cm smaller(95%CI:-13.88 to-8.47, P < 0.00001) for LRR than ORR. These results were confirmed by sensitivity analyses that focused on the four major RCTs. The mean length of hospital stay was 1.71 d shorter(95%CI:-2.84 to-0.58, P < 0.003) for LRR than ORR. Similarly, bowel recovery(i.e., day of the first bowel movement) was 0.68 d shorter(95%CI:-1.00 to-0.36, P < 0.00001) for LRR. The sensitivity analysis did not confirm a significant difference between LRR and ORR for these latter two parameters. The overall quality of the evidence was rated as high. CONCLUSION LRR is associated with lesser blood loss, smaller incision length, and longer operative times compared to ORR. No differences are observed for postoperative morbidity and mortality.

Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis

BACKGROUND Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir(TDF) and entecavir(ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.AIM To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.METHODS Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies(NRSs) using the keywords 'CHB', 'Tenofovir', and 'Entecavir', and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment,Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and24 mo.RESULTSNine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo[mean difference(MD) = 0.03 mg/dL;95%CI: 0.02-0.04;I2 = 0%], 12 mo(MD =0.05 mg/dL;95%CI: 0.02-0.08;I2 = 78%), and 24 mo(MD = 0.07 mg/dL;95%CI:0.01-0.13;I2 = 93%). The change in estimated glomerular filtration rate(eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo[standardized mean difference(SMD),-0.22;95%Cl:-0.36--0.08;I2 = 0%], 12 mo(SMD =-0.24;95%Cl:-0.43--0.05;I2 = 50%), and 24 mo(-0.35;95%Cl:-0.61--0.09;I2= 67%).CONCLUSION TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence.However, the differences are negligible.

Calcium supplementation for the prevention of colorectal adenomas: a systematic review and meta-analysis of randomized controlled trials

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched Pub Med, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the Clinical Trials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes(recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's riskof-bias. Between-study heterogeneity was assessed, and pooled risk ratio(RR) estimates with their 95% confidence intervals(95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat(NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas(fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; randomeffects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20(95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance(fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Effect of silymarin on biochemical indicators in patients with liver disease: systematic review with meta-analysis

AIM To evaluate the effect of silymarin on the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST) and gamma glutamyl transpeptidase(γGT) in patients with liver diseases. METHODS A systematic review with meta-analysis of ramdomized and controlled clinical trials was performed,evaluating the effects of sylimarin in patients with hepatic diseases,published by January 31,2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library,Pub Med/Medline,Scopus,Web of Science,Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes,with Liver Diseases who took oral silymarin supplementation,as extract or isolated,as well as Silymarin combined with other nutrients,were included. The trials should provide information about the intervention,such as dosages and detailing of the product used,besides the mean and standard deviation of serum levels of ALT,AST and γGT of the baseline and at the end of the intervention.RESULTS An amount of 10904 publications were identified. From those,only 17 were included in the systematic review and 6 in the meta-analysis,according to the used selection criteria. In this meta-analysis,the results indicated a reduction of 0.26 IU/m L(95%CI:-0.46-0.07,P = 0.007) at the level of ALT and 0.53 IU/m L(95%CI:-0.74-0.32,P = 0.000) at the serum levels of AST after using the silymarin,both,statistically significant,but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention,whether silymarin isolated or associated with other nutrients and the time of intervention(whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis. CONCLUSION Silymarin minimally reduced,but without clinical relevance,the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.

Endoscopic stenting for inoperable malignant biliary obstruction: A systematic review and meta-analysis

AIM: To analyze through meta-analyses the benefits of two types of stents in the inoperable malignant biliary obstruction.METHODS: A systematic review of randomized clinical trials(RCT) was conducted, with the last update on March 2015, using EMBASE, CINAHL(EBSCO), MEDLINE, LILACS/CENTRAL(BVS), SCOPUS, CAPES(Brazil), and gray literature. Information of the selected studies was extracted in sight of six outcomes: primarily regarding dysfunction, complication and reintervention rates; and secondarily costs, survival, and patency time. The data about characteristics of trial participants, inclusion and exclusion criteria and types of stents were also extracted. The bias was mainly assessed through the JADAD scale. This meta-analysis was registered in the PROSPERO database by the number CRD42014015078. The analysis of the absolute risk of the outcomes was performed using the software Rev Man, by computing risk differences(RD) of dichotomous variables and mean differences(MD) of continuous variables. Data on RD and MD for each primary outcome were calculated using the MantelHaenszel test and inconsistency was qualified and reported in χ2 and the Higgins method(I2). Sensitivity analysis was performed when heterogeneity was higher than 50%, a subsequent assay was done and other findings were compiled. Student's t-test was used for the comparison of weighted arithmetic means regarding secondary outcomes.RESULTS: Initial searching identified 3660 studies; 3539 were excluded through title, repetition, and/or abstract, while 121 studies were fully assessed and were excluded mainly because they did not compare self-expanding metal stents(SEMS) and plastic stents(PS), leading to thirteen RCT selected, with 13 articles and 1133 subjects meta-analyzed. The mean age was 69.5 years old, that were affected mostly by bile duct(proximal) and pancreatic tumors(distal). The preferred SEMS diameter used was the 10 mm(30 Fr) and the preferred PS diameter used was 10 Fr. In the metaanalysis, SEMS had lower overall stent dysfunction compared to PS(21.6% vs 46.8%, P < 0.00001) and fewer re-interventions(21.6% vs 56.6%, P < 0.00001), with no difference in complications(13.7% vs 15.9%, P = 0.16). In the secondary analysis, the mean survival rate was higher in the SEMS group(182 d vs 150 d, P < 0.0001), with a higher patency period(250 d vs 124 d, P < 0.0001) and a lower cost per patient(4193.98 vs 4728.65 Euros, P < 0.0985).CONCLUSION: SEMS are associated with lower stent dysfunction, lower re-intervention rates, better survival, and higher patency time. Complications and costs showed no difference.