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BACKGROUND/PURPOSE: Metal stents (MS) are recommended for preoperative biliary drainage (PBD) in patients with periampullary cancer, but whether MS are superior in terms of re-intervention and direct cost is debatable. This study aimed to compare the effects of MS and PS on the outcomes of patients with periampullary cancer. METHODS: For this random-effects meta-analysis, electronic databases were screened for randomized controlled trials (RCTs) published until January 2022. Subgroup analyses were performed basis on the center type and presence of NAC. RESULTS: In this meta-analysis, seven RCTs (440 participants) were included. MS reduced re-interventions (risk ratio [RR] = 0.42, 95% confidence interval [CI] = 0.25-0.72) and direct costs (mean difference = -474 USD, 95% CI = -656 to -292). PBD-related complications (RR = 0.74, 95% CI = 0.32-1.71) and postoperative complications (RR = 0.73, 95% CI = 0.45-1.17) did not differ between MS and PS. Compared PS, MS reduced postoperative complications in high-volume centers (RR = 0.64, 95% CI = 0.49-0.84) and PBD-related complications in patients receiving NAC (RR = 0.29, 95% CI = 0.08-1.08). CONCLUSIONS: Metal stents likely reduces re-interventions and direct costs. Further studies are needed to confirm the effects of MS on the outcomes.

<title>Abstract</title><sec> <title>Purpose</title> Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of osteopenia in digestive tract cancers remains to be defined. We aimed to review the prognostic value of preoperative osteopenia in patients with digestive cancers. </sec><sec> <title>Methods</title> Cohort studies evaluating the prognostic value of preoperative osteopenia in digestive cancers (colorectal, esophageal, hepatic, bile duct, and pancreatic cancer) were searched using electronic databases and trial registries. The exposure was defined as low BMD estimated by computed tomography at 11^th thoracic vertebra, while comparator was normal BMD. The primary outcomes were overall survival and recurrence-free survival for osteopenia. Random effect meta-analyses were performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence. </sec><sec> <title>Results</title> A total of 11 studies (2230 patients) were included. Osteopenia was an independent risk factor for overall survival (hazard ratio [HR] = 2.02, 95% CI = 1.47 to 2.78; <italic>I</italic>² = 74%), along with sarcopenia. Osteopenia also predicted poor recurrence-free survival (HR = 1.96, 95% CI = 1.36 to 2.81; <italic>I</italic>² = 85%). In subgroup analyses, osteopenia predicted prognosis in colorectal, esophageal, hepatic, and bile duct cancers, but not in pancreatic cancer. The certainty of the evidence was low due to inconsistency and publication bias. </sec><sec> <title>Conclusion</title> Osteopenia may be independently associated with poor prognosis in patients with digestive tract cancer. Further studies are needed to establish the relevance of osteopenia in the operative prognosis of these patients. </sec>

<sec><title>Introduction</title>This systematic review investigated the efficacy of a meal sequence, the carbohydrate-later meal pattern (CL), on type 2 diabetes mellitus (T2DM). </sec><sec><title>Research design and methods</title>We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov until April 2020 to perform meta‐analyses using random-effects models. Primary outcomes were hemoglobin A1c (HbA1c) and quality of life. Secondary outcomes were plasma concentrations of glucose, insulin and incretin 120 min after a meal, and any adverse outcomes. The revised Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of individual studies and the body of evidence, respectively. The present study was registered in the UMIN Clinical Trials Registry. </sec><sec><title>Results</title>We included 230 participants in eight trials, including both trials that examined long-term changes (more than 2 months and less than 2 years) and short-term changes (in 2-hour postprandial values). CL resulted in a slight to no difference in HbA1c (mean difference (MD), −0.21% in the intervention group; 95% CI −0.44% to+0.03%), plasma glucose (MD,+4.94 mg/dL; 95% CI −8.34 mg/dL to +18.22 mg/dL), plasma insulin (MD, −3.63 μIU/mL; 95% CI −11.88 μIU/mL to +4.61 μIU/mL), plasma GLP-1 (MD, +0.43 pmol/L; 95% CI −0.69 pmol/L to +1.56 pmol/L), and plasma GIP (MD, −2.02 pmol/L; 95% CI −12.34 pmol/L to +8.31 pmol/L). All of these outcomes were of low-certainty evidence or very low-certainty evidence. None of the trials evaluated quality of life or adverse events. </sec><sec><title>Conclusions</title>There was no evidence for the potential efficacy of recommending CL beyond standard dietary advice on T2DM. </sec><sec><title>Trial registration number</title>UMIN000039979. </sec>

Background Sarcopenia, as assessed by body composition, can affect morbidity and survival in several gastrointestinal cancer. However, the impact of sarcopenia, referring to both quantity and quality of skeletal muscle, in biliary tract cancer (BTC) is debatable. We aimed to investigate the impact of sarcopenia on morbidity and mortality in patients with BTC. Methods Electronic databases and trial registries were searched through July 2021 to perform random-effects meta-analyses. Study selection, data abstraction and quality assessment were independently performed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results Twenty-nine studies (4443 patients) were included; 28 used computed tomography and one used dual-energy X-ray absorptiometry to assess body composition. Eighteen studies reported the impact of pre-operative sarcopenia on postoperative outcomes; namely, sarcopenia increased postoperative complications (risk ratio = 1.23, 95% confidence interval [CI] = 1.07 to 1.41; I2 = 2%), and decreased recurrence-free survival (hazard ratio [HR] = 2.20, 95% CI = 1.75 to 2.75; I2 = 0%) in multivariable analyses. Low muscle quantity (HR = 2.26, 95% CI = 1.75 to 2.92; I2 = 66%) and quality (HR = 1.75, 95% CI = 1.33 to 2.29; I2 = 50%) decreased overall survival in multivariable analyses. The certainty of the evidence was low because of heterogeneity and imprecision. Conclusions In sarcopenia, low muscle quantity and quality by body composition conferred an independent risk of morbidity and mortality in patients with BTC. Further studies are needed to confirm these findings and mitigate risk.

Background/purpose: Previous systematic reviews have shown that radical antegrade modular pancreatosplenectomy (RAMPS) had favorable outcomes including prognosis. However, recent large studies have shown opposite results, thus necessitating clarification of RAMPS efficacy. We aimed to update existing evidence on the clinical outcomes of RAMPS for left-sided pancreatic cancer by comparing them to those of the conventional approach. Methods: Electronic databases and registries were searched until August 2021 to perform random-effect meta-analysis. Methodological quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The protocol was registered at protocols.io (dx.doi.org/10.17504/protocols.io.bxhfpj3n). Results: Thirteen cohort studies (1641 patients) and four ongoing randomized controlled trials (RCTs) were identified. RAMPS increased disease-free survival (HR 0.62, 95% CI = 0.42-0.91), but it had little effect on overall survival (hazard ratio [HR] 0.92, 95% confidence interval [CI] = 0.79-1.09) and recurrence-free survival (HR 0.72, 95% CI = 0.37-1.38) with low certainty of evidence. Conclusion: The meta-analysis of recent studies suggests that RAMPS may have little effect on clinical outcomes. These findings highlight the necessity of further studies, including RCTs to determine the efficacy and subsequent indication of RAMPS in clinical cases.

Postoperative pain is the main reason for delayed recovery after herniorrhaphy. Preoperative glucocorticoid administration may improve postoperative recovery. The present study assessed the efficacy of preoperative glucocorticoids in facilitating recovery after herniorrhaphy. Randomized controlled trials (RCTs) conducted up to January 2021 were searched in electronic databases and trial registries. Meta-analyses were performed using random effects models. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence. Seven RCTs (744 patients) were included in the meta-analysis. Preoperative glucocorticoid administration reduced patients’ pain on postoperative day 0 (standard mean diference [SMD]=− 0.73, 95% confidence interval [CI] − 1.45 to − 0.01; I2=94%). However, there was no marked diference in rescue analgesic use (risk ratio [RR]=− 0.06, 95% CI − 0.28 to − 0.16; I2=0%) or vomiting (RR=0.78, 95% CI 0.50–1.20; I2=30%) between preoperative glucocorticoid administration and control. The certainty of evidence was moderate because of inconsistencies or imprecision. No serious adverse effects were observed. Preoperative glucocorticoid administration reduced pain in patients following herniorrhaphy without increasing the occurrence of adverse events. Further studies will be required to confirm the efficacy of preoperative glucocorticoids.

Acoustic radiation force impulse (ARFI) elastography has been used to diagnose acute pancreatitis (AP). The present study aimed to assess the effectiveness of ARFI elastography in the diagnosis of AP. Studies examining the efficacy of ARFI elastography in AP were selected by searching MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrial.gov. until September 2021. Meta-analyses were performed using random effects models. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. Eight case-control studies (994 patients) were included in the meta-analysis. The ARFI-Virtual Touch Quantification value (or ARFI shear wave propagation velocity) of the AP patient group was 0.83 m/s higher (95% confidence interval [CI]: 0.36-1.3) than that in the control group (95% CI: 1.0-1.28). The sensitivity and specificity of ARFI elastography for diagnosing AP were 98.3% (95% CI: 92.6-96.6%) and 95.5% (95% CI: 87.5-98.5%), respectively. The results showed that physicians could use ARFI elastography to accurately diagnose patients with AP. Additional well-designed studies are necessary to validate the efficacy of ARFI elastography in patients with AP.

Background: Previous systematic reviews have not clarified the effect of postoperative coffee consumption on the incidence of postoperative ileus (POI) and the length of hospital stay (LOS). We aimed to assess its effect on these postoperative outcomes. Methods: Studies evaluating postoperative coffee consumption were searched using electronic databases until September 2021 to perform random-effect meta-analysis. The quality of evidence was assessed using the Cochrane risk-of-bias tool. Caffeinated and decaffeinated coffee were also compared. Results: Thirteen trials (1246 patients) and nine ongoing trials were included. Of the 13 trials, 6 were on colorectal surgery, 5 on caesarean section, and 2 on gynecological surgery. Coffee reduced the time to first defecation (mean difference (MD) −10.1 min; 95% confidence interval (CI) = −14.5 to −5.6), POI (risk ratio 0.42; 95% CI = 0.26 to 0.69); and LOS (MD −1.5; 95% CI = −2.7 to −0.3). This trend was similar in colorectal and gynecological surgeries. Coffee had no adverse effects. There was no difference in POI or LOS between caffeinated and decaffeinated coffee (p > 0.05). The certainty of evidence was low to moderate. Conclusion: This review showed that postoperative coffee consumption, regardless of caffeine content, likely reduces POI and LOS after colorectal and gynecological surgery.

Background: The prediction of at-home deaths has become an important topic in rural areas of Japan with an advanced aging society. However, there are no well-established predictors to explain how these factors influence intention. This study aims to investigate the possible predictors of at-home death for cancer patients in rural clinics in Japan. Methods: This is a nationwide cross-sectional survey. A self-administered questionnaire was sent to 493 rural clinics in Japan. The main outcome was the realization of at-home deaths for cancer patients. Results: Among the 264 clinics (54%) that responded to the survey, there were 194 clinics with the realization of at-home death. The use of a clinical pathway (adjusted odds ratio 4.19; 95% confidence interval 1.57–11.19) and the provision of organized palliative care (adjusted odds ratio 19.16; 95% confidence interval 7.56–48.52) were associated with the prediction of at-home death, irrespective of island geography or the number of doctors and nurses. Conclusions: Having a clinical pathway and systematizing palliative care could be important to determine the possibility of at-home deaths for cancer patients in rural clinics in Japan.

INTRODUCTION: There is no consensus regarding the range of immobilization in the conservative treatment of distal radius fractures (DRFs). Therefore, this systematic review and meta-analysis aimed to compare the clinical outcome of patients with DRFs treated conservatively with below- or above-elbow immobilization. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, two independent reviewers searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform in April 2020; a subsequent update search was conducted in April 2021. We identified all randomised controlled trials comparing two immobilization methods in DRFs. The primary outcome measures were the Disabilities of the Arm, Shoulder and Hand (DASH) or QuickDASH questionnaire scores in the short- and long-term (≤ and >six weeks, respectively) follow-up as well as the treatment failure rate. The secondary outcome measures were radiographic outcome, patient-rated wrist evaluation (PRWE) score, pain score and adverse events. Risk of bias was evaluated using the Cochrane Risk of Bias tool version 2. We used the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of evidence. RESULTS: The initial search revealed 1,775 records, and ten studies with 909 participants in total were included. There was no significant difference in DASH score in the short-term follow-up (4.99 lower, 95% confidence interval (CI): 10.45 lower to 0.46 higher; very low certainty) and treatment failure (risk ratio: 0.91, 95% CI: 0.59 to 1.40; low certainty). A clinically irrelevant but significant mean difference (0.83 lower, 95%CI: 1.64 lower to 0.03 lower; low certainty) was found in the DASH score in favour of below-elbow immobilization in the long-term follow-up. The overall risk of bias in DASH scores was high based on the measurement bias. Furthermore, there was no significant difference in secondary outcome measures. CONCLUSION: This meta-analysis did not demonstrate clinically meaningful difference between below- and above-elbow immobilization in terms of DASH score both in the short- and long-term follow-ups. However, overall certainty of evidence was considered very low, based on the very serious risk of bias, inconsistency and imprecision. Hence, there is a need for further higher quality research. TRIAL REGISTRATION NUMBER: UMIN000040134 (4/14/2020).

Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, to shed light on this issue, we performed a meta-analysis of data on PON1 activity in COPD. Electronic databases (MEDLINE, Embase and CENTRAL) were searched for available studies on PON1 activity in patients with stable COPD published before October 2021. A meta-analysis was performed using random-effects models. Twelve studies (12 studies on paraoxonase and three on arylesterase) were identified. Patients with COPD had lower levels of paraoxonase activity (standard mean difference [SMD] −0.77, 95% confidence interval [CI] −1.35 to −0.18) and arylesterase activity (SMD −1.15, 95% CI −1.95 to −0.36) in comparison to healthy controls. In subgroup analyses, paraoxonase activity was lower in patients of studies as consisted of mainly non-severe COPD (SMD −1.42, 95% CI −2.04 to −0.79) and, by contrast, slightly higher in patients of studies including severe COPD (SMD 0.33, 95% CI 0.02 to 0.64) in comparison to healthy controls. Arylesterase activity showed a similar trend. Overall, PON1 activity was lower in patients with COPD, suggesting that PON1-related antioxidant defense is impaired in COPD. Future studies are warranted.

Punch incision is an alternative to elliptical excision for treating epidermal inclusion cysts, but its efficacy has not been systematically reviewed. This study assessed the efficacy and safety of punch incision versus elliptical excision for epidermal inclusion cysts. Randomized controlled trials published through January 2021 that evaluated the performance of punch incision versus elliptical excision on epidermal inclusion cysts were identified through electronic databases and clinical registries. Version 2 of the Cochrane risk-of-bias tool for randomized trials tool was used. Review Manager software was used for the meta-analysis. Two trials (100 participants) were identified. The primary outcomes were recurrence rate (risk ratio, 2.40; 95% confidence interval [CI], 0.37–15.60 [favoring elliptical excision]), mean operative time (mean difference [MD], −5.28; 95% CI, −12.72 to 2.16 [favoring punch incision]), and mean postoperative wound length (MD, −11.67; 95% CI, −20.59 to −2.76 [favoring punch incision]). The evidence was low to moderate due to the small sample size and its considerable heterogeneity. The use of punch incision shortened the mean postoperative wound length and had comparable safety to that of elliptical excision.

Abstract For colonoscopy, bowel preparation, especially that using polyethylene glycol (PEG) or senna, is performed among children with gastrointestinal disorders; however, it is not fully grounded in evidence. This study reviewed via meta-analyses the approaches to bowel preparation for colonoscopy in children. Electronic databases and trial registries were searched until April 2021. Quality assessment was conducted using the Grading of Recommendations, Assessment, Development, and Evaluation method. In total, three randomized controlled trials (318 patients) were identified. PEG was observed as a preferred protocol of bowel preparation compared with senna (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.05-1.74; I2 = 15%). It was less painful than senna (RR 0.62, 95% CI 0.44-0.87; I2 = 0%). No serious adverse events were noted. Overall, the certainty of the evidence was low to moderate. PEG might be a preferred preparation agent for colonoscopy in children. Given the limited data, more studies are recommended.

Recently, underwater endoscopic mucosal resection (UEMR) without submucosal injection was introduced as a new replacement for conventional EMR (CEMR) and was reported to be useful for resecting large colonic polyps. Here, we aimed to assess the efficacy and safety of these two methods by a systematic review and meta-analysis. We comprehensively searched multiple databases until July 2021 to identify randomized controlled trials (RCTs) comparing UEMR with CEMR. The primary outcomes were the proportion of R0 resection and mean procedure time, and the secondary outcomes were the proportion of en bloc resection and all adverse events. Three reviewers independently searched for articles, extracted data, and assessed the risk of bias. We evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study was registered in www.protocols.io (Protocol Integer ID: 40849). We included six RCTs (1,374 polyps). We judged that a meta-analysis was not available, and the data were summarized narratively for the proportion of R0 resection. Regarding procedure time, UEMR likely resulted in a large reduction (mean difference = -64.3 seconds; 95% confidence interval (CI) = -122.5 to -6.0 seconds; I2 = 86%; moderate certainty of evidence). UEMR likely resulted in a large increase in en bloc resection (odds ratio = 1.85; 95% CI = 1.15 to 2.98; I2 = 60%; moderate certainty of evidence). Percentages of adverse events were 0-17% with CEMR and 0-16% with UEMR. In summary, UEMR might have higher efficacy than CEMR in the endoscopic resection of nonpedunculated colorectal polyps, with likely a large reduction in procedure time.

PURPOSE: This study aimed to determine the efficacy and safety of cement augmentation for internally fixed trochanteric fractures through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases to identify RCTs, published until July 2020 that examined the effects of cement augmentation of internal fixation of trochanteric fractures. The primary outcomes were reoperation and Parker Mobility Score, whereas the secondary outcomes were 1-year mortality rate, EuroQol 5 Dimension, fixation failures, and adverse events. We conducted meta-analyses of the outcome measures using the random-effects models. We evaluated the certainty of evidence based on the Cochrane risk-of-bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: We included three RCTs (326 participants). No significant effect was observed in favor of cement augmentation on all these outcomes. The certainty of evidence for fixation failures was very low and that for the other outcomes was low. The overall risk of bias for each outcome was high or of some concern in all included studies. CONCLUSIONS: The effect of cement augmentation of internal fixation of trochanteric fractures was uncertain for the clinical outcomes due to the low certainty of evidence. Further RCTs with a low risk of selection bias may present convincing conclusions on the efficacy and safety of cement augmentation. LEVEL OF EVIDENCE: Level 1.

BACKGROUND: The traditional radial approach (RA) is recommended as the standard method for coronary angiography (CAG), while a distal RA (DRA) has been recently used for CAG. AIM: To assess the efficacy and safety of the DRA vs RA during CAG. METHODS: The following databases were searched through December 2020: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov. Individual randomized-controlled trials for adult patients undergoing cardiac catheterization were included. The primary outcomes were the successful cannulation rate and the incidence of radial artery spasm (RAS) and radial artery occlusion (RAO). Study selection, data abstraction and quality assessment were independently performed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Three randomized control trials and 13 registered trials were identified. The two approaches showed similar successful cannulation rates [risk ratio (RR) 0.90, 95% confidence interval (CI): 0.72-1.13]. The DRA did not decrease RAS (RR 0.43, 95%CI: 0.08-2.49) and RAO (RR 0.48, 95%CI: 0.18-1.29). Patients with the DRA had a shorter hemostasis time in comparison to those with the RA (mean difference -6.64, 95%CI: -10.37 to -2.90). The evidence of certainty was low. CONCLUSION: For CAG, the DRA would be safer than the RA with comparable cannulation rates. Given the limited data, additional research, including studies with standard protocols, is necessary.

Introduction: Takayasu arteritis (TA) is a chronic vasculitis associated with an increased cardiovascular risk. The measurement of pulse wave velocity (PWV), carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD) are generally used for evaluating the cardiovascular risk. The application of these measurements to TA patients remains undetermined. Material and methods: Clinical studies that reported the PWV, CIMT and FMD levels in TA patients, which were published prior to 2021, were summarized using PubMed. Results: Fifteen studies were eligible. Overall, in TA patients, the PWV and CIMT levels were significantly higher and the FMD levels were significantly lower compared to controls. Part of the studies showed that the disease activity of TA was significantly associated with the PWV, CIMT or FMD levels. Conclusions: The PWV, CIMT and FMD measurements could be useful for evaluating the cardiovascular risk in TA patients. Further studies to determine the proper use of these measurements are warranted.

Oxidative stress is involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, reliable biomarkers of NAFLD in relation to oxidative stress are not available. While paraoxonase 1 (PON1) is an antioxidant biomarker, there appears to be mixed data on PON-1 in patients with NAFLD. The aim of this meta-analysis was to assess the current data on PON1 activity (i.e., paraoxonase and arylesterase) in patients with NAFLD. A PubMed, CENTRAL, and Embase search identified 12 eligible articles. In the meta-analysis, the paraoxonase activity was low in patients with NAFLD (mean difference (MD) −27.17 U/L; 95% confidence interval (CI) −37.31 to −17.03). No difference was noted in the arylesterase activity (MD 2.45 U/L; 95% CI −39.83 to 44.74). In a subgroup analysis, the paraoxonase activity was low in biopsy-proven nonalcoholic steatohepatitis (MD −92.11 U/L; 95% CI −115.11 to −69.11), while the activity in NAFLD as diagnosed by ultrasonography or laboratory data was similar (MD −2.91 U/L; 95% CI −11.63 to 5.80) to that of non-NAFLD. In summary, the PON1, especially paraoxonase, activity could be a useful biomarker of NAFLD. Further studies are warranted to ascertain the relevance of PON1 measurements in patients with NAFLD.

<title>Abstract</title>This letter was written to address two concerns about the results of the paper published by Zeynep et al. (BMC Health Qual Life Outcomes 18:265, 2020). First, the differences between the two groups in the environment with or without occupation may strengthen the primary outcome results. Second, lack of information on the complications and treatments of diabetes makes interpretation of the results difficult.

Introduction: Helicobacter pylori (H. pylori) infection is positively associated with cardiovascular diseases, but the involvement of lipids in this association remains unclear. The present study reviewed the changes in circulating lipid levels following H. pylori eradication. Methods: A PubMed database was searched until December 2020 to identify randomized control trials (RCTs) and non-RCTs investigating the effect of H. pylori eradication on the lipid levels in inverse variance-weighted, random-effects meta-analyses. Results: A total of 24 studies (four RCTs and 20 non-RCTs) with 5270 participants were identified. The post-eradication levels were increased for high-density lipoprotein cholesterol (HDL-C; mean difference (MD) 2.28 mg/dL, 95% confidence interval (CI) 1.90 to 2.66) and triglyceride (TG; MD 3.22 mg/dL, 95% CI 1.13 to 5.31) compared with the pre-eradication levels. H. pylori eradication resulted in little to no difference in the low-density lipoprotein-cholesterol levels (MD −2.33 mg/dL, 95% CI −4.92 to 0.26). In the analyses of RCTs only, the findings for elevated HDL-C levels, but not TG, were robust. Conclusions: H. pylori eradication increases the HDL-C levels. Further studies are needed to elucidate the effects of lipid changes following H. pylori eradication on cardiovascular diseases.

Background: Chronic spontaneous urticaria (CSU) is a disease with wheals and/or angioedema. Some drugs, especially antibiotics for Helicobacter pylori (H. pylori) eradication and the sulfone antibiotic dapsone, may be candidates for treating CSU. The present study assessed the efficacy of these antibiotic therapies for CSU. Methods: Databases (MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched until October 2020. Study selection, data abstraction and quality assessments were independently performed using the Grading of Recommendations Assessment, Development and Evaluation approach. The outcomes were the remission of CSU-related symptoms, activities and adverse events due to antibiotics for H. pylori eradication or dapsone. Results: Nine randomized controlled trials (RCTs; 361 patients) were included. The antibiotics for H. pylori eradication increased the remission rate (risk ratio (RR) = 3.99, 95% confidence interval (CI) = 1.31 to 12.14; I2 = 0%), but dapsone did not (RR = 1.15, 95% CI = 0.74 to 1.78). Antibiotics for H. pylori eradication (standard mean difference (SMD) = 1.49, 95% CI = 0.80 to 2.18; I2 = 69%) and dapsone (SMD = 7.00, 95% CI = 6.92 to 7.08; I2 = 0%) improved symptoms. The evidence of certainty was moderate. Dapsone was associated with mild adverse events, whereas H. pylori eradication was not. Conclusion: Antibiotics, especially those for H. pylori eradication, improved the remission rate and symptoms of CSU with few adverse events. Further studies are needed.

Introduction Helicobacter pylori (H. pylori) is a bacterium that causes chronic gastroduodenal infection and affects various systemic diseases. An increase in the blood level of C-reactive protein (CRP; a systemic inflammatory marker), at a low-grade chronic inflammation level, is observed in cases of infection. However, the effect of H. pylori eradication on CRP remains undetermined. Therefore, we aimed to see the circulating CRP levels in eradicated patients through a meta-analysis. Material and methods The PubMed database was searched from its inception to June 2020. Studies that described the CRP levels following H. pylori eradication were collected. A random-effects meta-analysis was then performed using an inverse variance with standardized mean difference. Results A total of 10 eligible studies (642 subjects in total) were available. The median age in the studies was 49.9 years old. The CRP level was 6.0 (median) mg/L before H. pylori eradication and 5.8 (median) mg/L after eradication. From the results of overall meta-analysis, there was found to be a significant reduction in the CRP levels with H. pylori eradication (standardized mean difference: -0.64; 95% confidence interval: -1.02 to -0.27). The result was not similarly confirmed in a subanalysis of the available randomized controlled trials. Conclusions Weak evidence exists in terms of the effects of H. pylori eradication on the reduced CRP levels. Further research is called for.

Background: Endoscopic submucosal dissection (ESD) for gastric cancer is increasingly performed worldwide due to its efficacy and safety. This study aimed to assess the evidence of the impact of early vs. delayed feeding after ESD on quality of care, which remains to be fully determined. Methods: Electronic databases (PubMed, the Cochrane Central Register of Controlled Trials, EMBASE) and the trial registries (the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched for studies performed prior to September 2020. Study selection, data abstraction, and quality assessment were independently performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Self-rated satisfaction and hospital stay were chiefly analyzed. Results: Two randomized controlled trials (239 patients) were included. The early and delayed post-ESD feeding groups had similar rates of post-ESD bleeding (risk ratio 1.90, 95% CI 0.42 to 8.63; I2 = 0%). Early post-ESD feeding resulted in increased patients' satisfaction in comparison to delayed post-ESD feeding (standard mean difference (MD) 0.54, 95% CI 0.27 to 0.81; I2 = 0%) and reduced the length of hospital stay (MD -0.83, 95% CI -1.01 to -0.65; I2 = 0%). Conclusion: Early post-ESD feeding was associated with increased patients' satisfaction and reduced hospital stay in comparison to delayed feeding, while the rate of complications did not differ to a statistically significant extent. As we must acknowledge the limited number of reviewed studies, various trials regarding the quality of care are further needed to determine the benefits of early feeding after ESD.

We report a case of an encapsulated fat necrosis without significant medical history. To differentiate from liposarcoma, it should be recognized that a half of abdominal encapsulated fat necrosis cases have a history of inflammation and surgery.

Early feeding after percutaneous endoscopic gastrostomy (PEG) placement is an accepted practice in the treatment of adult patients and the knowledge is clinically extrapolated in the treatment of children. To verify this treatment in children-as there are some specific features of PEG-related practices in children-the present study aimed to review meta-analyses of early feeding (within 4 h) after PEG placement in children. We searched the PubMed database for articles published until July 2020. A quality assessment was performed using the Grading of Recommendations, Assessment, Development, and Evaluation method. Three randomized controlled trials (208 patients) were eligible for inclusion. No patients died within 72 h. Early feeding resulted in little to no difference in the length of hospital stay (mean difference [MD] -7.47, 95% confidence interval [CI] -25.16 to 10.21; I2 = 95%) and vomiting events (risk ratio 0.84, 95% CI 0.55 to 1.31; I2 = 0%). In a subgroup analysis, early feeding without antibiotics reduced the length of hospital stay in one study (MD -21.60, 95% CI -22.86 to -20.34) but early feeding with antibiotics did not affect the length in two studies (MD 0.28, 95% CI -6.49 to 7.06; I2 = 0%). Overall, the certainty of the evidence was not very high. In summary, early feeding after PEG placement may be a safe alternative to delayed feeding in children. The findings in children seemed similar to those in adults, while there is a need for further studies that specifically investigate PEG placement-related practices in children.

Background and study aims  We aimed to assess the efficacy and safety of the starting position during colonoscopy. Patients and methods  We searched CENTRAL, MEDLINE, EMBASE, and the WHO International Clinical Trials Registry Platform through February 2019 to identify studies reporting the comparison between the right/supine/prone/tilt-down and left lateral starting position during colonoscopy. The primary outcomes were mean cecal insertion time and adverse events requiring medication. Two reviewers performed study selection and risk of bias assessment. We determined the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation method. This study was registered in PROSPERO (CRD42019124360). Results  We identified 10 randomized controlled trials (RCTs) (2083 participants), including three trials on right/tilt-down versus left, two trials on supine/prone versus left, respectively. Mean difference in mean cecal insertion time in supine versus left was -41.0 s (95 % confidence interval [CI] -57.3 to -24.7) in one study and in tilt-down versus left was - 37.3 s (95 % CI -72.1 to -2.4; I 2  = 58 %) in three studies; however, there were no statistically significant differences in prone/right versus left position (very low certainty of evidence). Four of eight studies noted adverse effects requiring medication (moderate certainty of evidence). One RCT applying the tilt-down position was terminated because of increased occurrence of oxygen desaturation. Conclusion  We could not conclusively determine the efficacy and safety of the starting position during colonoscopy because of low certainty of evidence. Further studies are needed to confirm the efficacy and safety of the starting potion during colonoscopy.

OBJECTIVES: There are two major methods for local anesthesia by lidocaine before upper gastrointestinal endoscopy: simple spray and viscous solution. We aimed to assess the efficacy and safety by meta-analysis between these two methods. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases through October 2019 to perform meta-analyses using random-effects models. The primary outcomes were participants' pain/discomfort, satisfaction, and anaphylactic shock. Three reviewers independently searched for articles, extracted data, and assessed the risk of bias. We evaluated the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study was registered in PROSPERO (CRD42020155611). RESULTS: We included seven randomized controlled trials (2667 participants). The participants' pain/discomfort may be similar between the lidocaine spray and viscous solution [standardized mean difference 0.03, 95% confidence intervals (CI) -0.37 to 0.42; I2  = 93%; low certainty of evidence]. The lidocaine spray probably increased participants' satisfaction compared with the viscous solution (relative risk 1.22; 95% CI, 1.02 to 1.47; I2  = 47%; moderate certainty of evidence). No anaphylactic shock occurred in four studies (low certainty of evidence). Four studies had high risks of selection bias. CONCLUSION: The use of lidocaine spray for local anesthesia provided better satisfaction scores than the viscous solution, and both methods have the same effect with regards to the control of discomfort and pain. Further studies in large multicenter randomized controlled trials with a pre-registration protocol are needed.

BACKGROUND: The cardiovascular relevance of isolated low levels of high-density lipoprotein cholesterol (HDL-C) is yet to be determined. Stroke often leads to long-term disability, and thus, not only stroke mortality but also stroke incidence is a topic of research. Although isolated low HDL-C level has been found to be a predictor for stroke mortality previously, whether it can predict stroke incidence is unknown. METHODS: In the Jichi Medical School cohort study, 11 025 community-living residents without a history of stroke were examined. Hazard ratios (HRs) for isolated and non-isolated low HDL-C levels were calculated relative to those for normal HDL-C levels in stroke patients using Cox's regression models. RESULTS: During the mean follow-up period of 10.7 years, 412 residents had their first-ever stroke. The multivariable-adjusted HRs for the levels of isolated and non-isolated low HDL-C were 1.11 (95% confidence interval, 0.85-1.44) and 1.35 (1.01-1.81), respectively, when compared to that for normal HDL-C. CONCLUSION: Low HDL-C levels with other dyslipidemias may contribute to the incidence of stroke, not isolated low HDL-C.

Background: Dynamic computed tomography (CT) angiography is useful for evaluating of hepatic vascularity. Although vasodilators increase hepatic blood flow, the utility of dynamic CT with vasodilators is unclear. Here we investigated the utility and safety of dynamic CT with vasodilators. Methods: A prospective case-control radiographic evaluation using abdominal dynamic CT with and without vasodilator was performed at a single center between October 2015 and September 2016. We compared the CT values in Hounsfield units of the aorta; celiac artery; and common, right, and left hepatic arteries in the arterial phase and the main trunk; right and left branches of the portal vein; and right, middle, and left hepatic veins in the portal phase with and without vasodilators. The region of interest was set in each element of the liver vasculature. Four radiological technologists independently and visually compared the scores of the portal vein (P-score) and hepatic vein (V-score) on a 5-point scale with and without vasodilators. Results: The CT values of arteries and veins using vasodilators were significantly higher than those without vasodilators. With and without vasodilators, the P-scores were 3.1 ± 1.2 and 4.0 ± 1.1 (P < 0.05) and the V-scores were 3.3 ± 1.4 and 4.3 ± 1.0 (P < 0.05). Only one patient with vasodilator use had transient hypotension and recovered immediately without medication. Conclusion: Dynamic CT with vasodilators can provides better visualization of vascular structures.

We aimed to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) concentration and the incident stroke subtypes. We enrolled 11 027 participants between the ages of 18 and 90 years without a history of stroke in 12 Japanese communities. Cox's regression models were used for stroke subtypes, adjusted for traditional risk factors, according to the categories based on HDL-C concentrations: 1.04 to 1.55 mmol/L, ≥1.56 mmol/L, and <1.03 mmol/L (as the reference). During a mean follow-up of 10.7 years, 412 stroke events had occurred. However, HDL-C was not significantly associated with the incidence of cerebral infarction and subarachnoid hemorrhage. High HDL-C concentration was associated with a decreased incidence of intracerebral hemorrhage in women (hazard ratio = 0.23; 95% confidence interval = 0.06-0.89), but not in men (hazard ratio = 0.73; 95% confidence interval = 0.27-1.97). Therefore, high HDL-C concentration might have a protective effect on the incidence of intracerebral hemorrhage, particularly in women.

Background: The importance of management of metabolic syndrome (MetS) for risk reduction of cardiovascular disease (CVD) has been recognized worldwide. Because of the comparatively unique characteristics of bodily figure/obesity and incident CVD in Japan, the relevance of MetS on CVD can be still discussed among Japanese people. The present study aimed to review briefly the relationship of MetS with CVD morbidity/mortality among general Japanese people. Methods: Population-based prospective cohort studies evaluating the predictive value of MetS on CVD morbidity/mortality via a PubMed search up to 2019 were summarized. Results: We identified two studies on morbidity that reported MetS to predict CVD morbidity. We identified three studies on mortality, and these studies showed an increased direction of hazard ratio (HR) of CVD mortality, while one study reported an insignificant prediction of MetS for CVD mortality. In the meta-analysis method, MetS significantly predicted CVD morbidity (HR=1.71 [95% confidence interval=1.34-2.18] in men and HR=1.89 [95% confidence interval=1.45-2.46] in women) as well as CVD mortality (HR=1.68 [95% confidence interval=1.37-2.06] in men and HR=1.73 [95% confidence interval=1.39-2.15] in women). Conclusion: Among general Japanese people, MetS can be a positive predictor of CVD morbidity/mortality. Since the studies are limited, more research is needed to establish the findings.

Introduction: Lipoprotein(a) (Lp[a]) is a risk factor of cardiovascular disease (CVD). Familial hypercholesterolemia (FH), which exhibits high low-density lipoprotein cholesterol (LDL-C) levels, is a risk factor of CVD. The relationship of Lp(a) with CVD has been characterized in populations specific to FH. Material and methods: Studies reporting on the relationship of Lp(a) with CVD among FH subjects via PubMed up to 2020 were reviewed. Results: Eight studies were identified as eligible. In the meta-analyses, a high Lp(a) level was significantly and predictively associated with CVD compared to a low Lp(a) level in 2 cross-sectional studies (odds ratio = 2.57; 95% confidence interval (CI): 1.16-5.73) and 6 cohort studies (risk/hazard ratio = 1.91; 95% CI: 1.50-2.43). The totally integrated relative risk of these studies was 1.97 (95% CI: 1.57-2.46). Conclusions: FH subjects with high Lp(a) levels can have a high CVD risk, and besides LDL-C, attention should be paid to Lp(a) levels in FH subjects.

Background: Metabolic syndrome (MetS) and cancer are major public health problems worldwide. The relationship between MetS and cancer death is of great interest. We examined the predictive value of MetS for cancer mortality in Japan. Methods: Study participants included 4495 men and 7028 women aged 18-90 years who were registered between 1992 and 1995 as part of the Jichi Medical School Cohort Study. We used a definition of MetS modified for the Japanese population. The primary outcome was cancer mortality. Additionally, the relationship between MetS and cancer-type specific mortality was examined. Analyses were conducted with Cox's regression models adjusted for age, smoking status, alcohol drinking status, marital status, educational attainment, physical activity, occupational category, and menopausal status (only in women). Results: During a mean follow-up of 18.5 years, 473 men and 297 women died from cancer. MetS was positively associated with cancer mortality in women (hazard ratio [HR], 1.69; 95% confidence interval [CI] 1.21-2.36), but not in men (HR, 1.21; 95% CI 0.90-1.62). Additionally, MetS was associated with a high risk of colorectal (HR, 3.48; 95% CI 1.68-7.22) and breast (HR, 11.90; 95% CI 2.25-62.84) cancer deaths in women. Conclusion: MetS was a significant predictor of cancer mortality in women.

Heparin-induced thrombocytopenia (HIT) is still a relatively uncommon condition and it is not well known how to administer argatroban during continuous hemodiafiltration (CHDF). A 72-year-old man required CHDF with heparin because of the oliguria and hyperpotassemia directly after the open repair of a juxtarenal abdominal aortic aneurysm. As the postoperative blood platelet count dropped and there was a thrombus in the CHDF circuit, HIT was suspected and nafamostat mesilate, but not heparin, was immediately administered for CHDF. As heparin-platelet factor 4 complex was positive, we diagnosed him with HIT and started argatroban while monitoring the activated clotting time (ACT), resulting in no further obstruction of the CHDF and an increase in the platelets. There was no disadvantage for administering nafamostat mesilate which we have commonly used instead of heparin, we should have used argatroban once we suspected HIT. It may be important to consider the history of heparin especially in administering heparin and it may be useful to monitor the ACT when initially starting argatroban for patients with HIT.