SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

Comparative evaluation of the clinical presentation and epidemiology of the 2022 and previous Mpox outbreaks: a rapid review and meta-analysis.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarised and compared the findings from published observational studies on the clinical presentation and epidemiology of the 2022 and previous outbreaks of Mpox. METHODS: We registered a review protocol with the Open Science Framework (osf.io/j3kb7). We searched MEDLINE, Embase, CENTRAL, CINAHL and Scopus databases, and relevant websites up to August 30, 2022. Retrieved literature citations were screened for eligibility, and summary clinical presentation and epidemiological data from the included studies were pooled, when possible, using an inverse variance, random-effects model. RESULTS: Seventy-nine studies met the eligibility. Irrespective of outbreak, fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat were potentially highly relevant Mpox manifestations, while conjunctivitis, cough, and possibly reactivation of varicella zoster virus may be part of the clinical presentation. The mean incubation period for the 2022 outbreaks was 7.4 d (6.4-8.4 d, I2 64.2%; 4 studies: 270 cases) and for previous outbreaks, 12.9 d (10.4-15.5 d; one study: 31 cases), p < .001. None of the male cases from previous outbreaks was reported to have sex with men (MSM) whereas almost all reported male cases from the 2022 outbreak were MSM. Concomitant sexually transmitted infections and perianal lesions were reported only among male cases from the 2022 outbreak, with the cases mostly presenting with genital lesions. CONCLUSIONS: The 2022 Mpox outbreaks appear to be mostly among MSM and have a lower incubation period compared with previous outbreaks.Key messages79 studies met the review's inclusion criteria.The 2022 Mpox outbreaks appear to have shorter incubation period compared with previous outbreaks.Established clinical presentation of Mpox includes fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat.Almost all reported cases from the 2022 Mpox outbreaks were men who had sex with men (MSM).Concomitant sexually transmitted infections and perianal lesions were only reported among cases from the 2022 Mpox outbreaks.A significantly higher proportion of Mpox cases from the 2022 outbreaks had genital lesions compared with cases from previous outbreaks.The 2022 Mpox outbreaks appear to be mostly among MSM.

SAGES/AHPBA guidelines for the use of minimally invasive surgery for the surgical treatment of colorectal liver metastases (CRLM).

BACKGROUND: Colorectal liver metastases (CRLM) occur in roughly half of patients with colorectal cancer. Minimally invasive surgery (MIS) has become an increasingly acceptable and utilized technique for resection in these patients, but there is a lack of specific guidelines on the use of MIS hepatectomy in this setting. A multidisciplinary expert panel was convened to develop evidence-based recommendations regarding the decision between MIS and open techniques for the resection of CRLM. METHODS: Systematic review was conducted for two key questions (KQ) regarding the use of MIS versus open surgery for the resection of isolated liver metastases from colon and rectal cancer. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Additionally, the panel developed recommendations for future research. RESULTS: The panel addressed two KQs, which pertained to staged or simultaneous resection of resectable colon or rectal metastases. The panel made conditional recommendations for the use of MIS hepatectomy for both staged and simultaneous resection when deemed safe, feasible, and oncologically effective by the surgeon based on the individual patient characteristics. These recommendations were based on low and very low certainty of evidence. CONCLUSIONS: These evidence-based recommendations should provide guidance regarding surgical decision-making in the treatment of CRLM and highlight the importance of individual considerations of each case. Pursuing the identified research needs may help further refine the evidence and improve future versions of guidelines for the use of MIS techniques in the treatment of CRLM.

Preoperative oral fluoroquinolone antibiotics in elective colorectal surgery to prevent surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Preoperative treatment with oral neomycin combined with erythromycin or metronidazole is recommended to decrease the risk of surgical site infections (SSIs) in elective colorectal surgery. However, oral neomycin is not commercially available in Canada, and therefore it is not routinely used. Fluoroquinolones are widely available and have excellent activity against aerobic Gram-negative bacteria. The aim of this systematic review was to identify, critically appraise and summarize the evidence on the efficacy and safety of preoperative use of oral fluoroquinolone antibiotics for the prevention of SSIs in adult patients undergoing elective colorectal resection. METHODS: Following Cochrane guidelines, we included English-language randomized controlled trials (RCTs) comparing oral fluoroquinolones plus routine preoperative intravenous antibiotics against intravenous antibiotics alone from MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials( Ovid) and ClinicalTrials.gov. RESULTS: We included 3 RCTs (1136 patients). Risk of bias was uncertain in 2 trials and high in 1 trial. Preoperative oral fluoroquinolones led to significantly decreased total SSIs (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.32-0.57, I 2 = 0%), superficial incisional (RR 0.38, 95% CI 0.22-0.68, I 2 = 32%), deep incisional (RR 0.19, 95% CI 0.06-0.65, I 2 = 0%) and organ/space SSIs (RR 0.34, 95% CI 0.12-0.90, I 2 = 33%). There was also a significant reduction in anastomotic leaks (RR 0.22, 95% CI 0.06-0.87, I 2 = 0%). No antibiotic-related adverse events were reported. CONCLUSION: This review suggests that preoperative oral fluoroquinolones with intravenous antibiotics are superior to intravenous antibiotics alone for preventing SSIs after colorectal surgery. If neomycin is unavailable, oral fluoroquinolones should be considered as a reasonable alternative. Future trials are required to further compare the relative efficacy of oral antibiotic regimens.

Self-Management Programs for Chronic Non-Cancer Pain: A Rapid Review of Randomized Trials.

BACKGROUND: The body of evidence regarding self-management programs (SMPs) for adult chronic non-cancer pain (CNCP) is steadily growing, and regular updates are needed for effective decision-making. OBJECTIVES: To systematically identify, critically appraise, and summarize the findings from randomized controlled trials (RCTs) of SMPs for CNCP. METHODS: We searched relevant databases from 2009 to August 2021 and included English-language RCT publications of SMPs compared with usual care for CNCP among adults (18+ years old). The primary outcome was health-related quality of life (HR-QoL). We conducted meta-analysis using an inverse variance, random-effects model and calculated the standardized mean difference (SMD) and associated 95% confidence interval (CI) and statistical heterogeneity using the I2 statistic. RESULTS: From 8538 citations, we included 28 RCTs with varying patient populations, standards for SMPs, and usual care. No RCTs were classified as having a low risk of bias. There was no evidence of a significant improvement in overall HR-QoL, irrespective of pain type, immediately post-intervention (SMD 0.01, 95%CI -0.21 to 0.24; I2 57%; 11 RCTs; 979 participants), 1-4 months post-intervention (SMD 0.02, 95%CI -0.16 to 0.20; I2 48.7%; 12 RCTs; 1160 participants), and 6-12 months post-intervention (SMD 0.07, 95%CI -0.06 to 0.21; I2 26.1%; 9 RCTs; 1404 participants). Similar findings were made for physical and mental HR-QoL, and for specific QoL assessment scales (e.g., SF-36). CONCLUSIONS: There is a lack of evidence that SMPs are efficacious for CNCP compared with usual care. Standardization of SMPs for CNCP and better planned/conducted RCTs are needed to confirm these conclusions.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

Minimally invasive versus open hepatectomy for the resection of colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: While surgical resection has a demonstrated utility for patients with colorectal liver metastases (CRLM), it is unclear whether minimally invasive surgery (MIS) or an open approach should be used. This review sought to assess the efficacy and safety of MIS versus open hepatectomy for isolated, resectable CRLM when performed separately from (Key Question (KQ) 1) or simultaneously with (KQ2) the resection of the primary tumor. METHODS: PubMed, Embase, Google Scholar, Cochrane CENTRAL, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov databases were searched to identify both randomized controlled trials (RCTs) and non-randomized comparative studies published during January 2000-September 2020. Two independent reviewers screened literature for eligibility, extracted data from included studies, and assessed internal validity using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed using risk ratios (RR) and mean differences (MD). RESULTS: From 2304 publications, 35 studies were included for meta-analysis. For staged resections, three RCTs and 20 observational studies were included. Data from RCTs indicated MIS having similar disease-free survival (DFS) at 1-year (RR 1.03, 95%CI 0.70-1.50), overall survival (OS) at 5-years (RR 1.04, 95%CI 0.84-1.28), fewer complications of Clavien-Dindo Grade III (RR 0.62, 95%CI 0.38-1.00), and shorter hospital length of stay (LOS) (MD -6.6 days, 95%CI -10.2, -3.0). For simultaneous resections, 12 observational studies were included. There was no evidence of a difference between MIS and the open group for DFS-1-year, OS-5-year, complications, R0 resections, blood transfusions, along with lower blood loss (MD -177.35 mL, 95%CI -273.17, -81.53) and shorter LOS (MD -3.0 days, 95%CI -3.82, -2.17). CONCLUSIONS: Current evidence regarding the optimal approach for CRLM resection demonstrates similar oncologic outcomes between MIS and open techniques, however MIS hepatectomy had a shorter LOS, lower blood loss and complication rate, for both staged and simultaneous resections.

Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis.

The effectiveness of T cell-mediated rejection (TCMR) therapy for achieving histological remission remains undefined in patients on modern immunosuppression. We systematically identified, critically appraised, and summarized the incidence and histological outcomes after TCMR treatment in patients on tacrolimus (Tac) and mycophenolic acid (MPA). English-language publications were searched in MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Ovid), CINAHL (EBSCO), and Clinicaltrials.gov (NLM) up to January 2021. Study quality was assessed with the National Institutes of Health Study Quality Tool. We pooled results using an inverse variance, random-effects model and report the binomial proportions with associated 95% confidence intervals (95% CI). Statistical heterogeneity was explored using the I2  statistic. From 2875 screened citations, we included 12 studies (1255 participants). Fifty-eight percent were good/high quality while the rest were moderate quality. Thirty-nine percent of patients (95% CI 0.26-0.53, I2 77%) had persistent ≥Banff Borderline TCMR 2-9 months after anti-rejection therapy. Pulse steroids and augmented maintenance immunosuppression were mainstays of therapy, but considerable practice heterogeneity was present. A high proportion of biopsy-proven rejection exists after treatment emphasizing the importance of histology to characterize remission. Anti-rejection therapy is foundational to transplant management but well-designed clinical trials in patients on Tac/MPA immunosuppression are lacking to define the optimal therapeutic approach.

Interventions to improve early cancer diagnosis of symptomatic individuals: a scoping review.

OBJECTIVES: To summarise the current evidence regarding interventions for accurate and timely cancer diagnosis among symptomatic individuals. DESIGN: A scoping review following the Joanna Briggs Institute's methodological framework for the conduct of scoping reviews and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SOURCES: MEDLINE (Ovid), CINAHL (EBSCOhost) and PsycINFO (Ovid) bibliographic databases, and websites of relevant organisations. Published and unpublished literature (grey literature) of any study type in the English language were searched for from January 2017 to January 2021. ELIGIBILITY AND CRITERIA: Study participants were individuals of any age presenting at clinics with symptoms indicative of cancer. Interventions included practice guidelines, care pathways or other initiatives focused on achieving predefined benchmarks or targets for wait times, streamlined or rapid cancer diagnostic services, multidisciplinary teams and patient navigation strategies. Outcomes included accuracy and timeliness of cancer diagnosis. DATA EXTRACTION AND SYNTHESIS: We summarised findings graphically and descriptively. RESULTS: From 21 298 retrieved citations, 88 unique published articles and 16 unique unpublished documents (on 18 study reports), met the eligibility for inclusion. About half of the published literature and 83% of the unpublished literature were from the UK. Most of the studies were on interventions in patients with lung cancer. Rapid referral pathways and technology for supporting and streamlining the cancer diagnosis process were the most studied interventions. Interventions were mostly complex and organisation-specific. Common themes among the studies that concluded intervention was effective were multidisciplinary collaboration and the use of a nurse navigator. CONCLUSIONS: Multidisciplinary cooperation and involvement of a nurse navigator may be unique features to consider when designing, delivering and evaluating interventions focused on improving accurate and timely cancer diagnosis among symptomatic individuals. Future research should examine the effectiveness of the interventions identified through this review.

Guidelines for the performance of minimally invasive splenectomy.

BACKGROUND: Minimally invasive splenectomy (MIS) is increasingly favored for the treatment of benign and malignant diseases of the spleen over open access approaches. While many studies cite the superiority of MIS in terms of decreased morbidity and length of stay over a traditional open approach, the comparative effectiveness of specific technical and peri-operative approaches to MIS is unclear. OBJECTIVE: To develop evidence-based guidelines that support clinicians, patients, and others in decisions on the peri-operative performance of MIS. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) including methodologists used the Grading of Recommendations Assessment, Development and Evaluation approach to grade the certainty of evidence and formulate recommendations. RESULTS: Informed by a systematic review of the evidence, the panel agreed on eight recommendations for the peri-operative performance of MIS for adults and children in elective situations addressing six key questions. CONCLUSIONS: Conditional recommendations were made in favor of lateral positioning for non-hematologic disease, intra-operative platelet administration for patients with idiopathic thrombocytopenic purpura instead of preoperative administration, and the use of mechanical devices to control the splenic hilum. Further, a conditional recommendation was made against routine intra-operative drain placement.

Remdesivir for coronavirus disease 2019 (COVID-19): a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: In view of many unanswered clinical questions regarding treatment of COVID-19 with remdesivir, we systematically identified, critically appraised and summarized the findings from randomized controlled trials (RCTs) of remdesivir for COVID-19. METHODS: We searched relevant databases/websites (up to September 2020) and selected English-language RCT publications of remdesivir for COVID-19. We conducted meta-analysis using an inverse variance, random-effects model in addition to trial sequential analysis (TSA) for the efficacy outcomes: all-cause mortality, viral burden and clinical progression. Safety outcomes were diarrhoea, nausea, and vomiting. We calculated the relative risk (RR) and 95% confidence interval (CI) for all outcomes. Statistical heterogeneity was calculated using the I2 statistic. RESULTS: We included five RCTs (7540 participants) from 7237 citations. Most (80%) were of an unclear to high risk of bias. There was no evidence of a significant improvement with remdesivir (100 mg, 10 days) regarding all-cause mortality (RR 0.94, CI 0.82-1.07; I2 = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99-1.18; I2 = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40-1.66; I2 = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28-6.03; I2 = 0%; 2 RCTs; 630 patients). TSA showed that the required information size was not reached for firm conclusions to be drawn. CONCLUSIONS AND RELEVANCE: There is insufficient evidence to support the use of remdesivir for treatment of COVID-19. More high-quality RCTs are needed for a stronger evidence. Until then, remdesivir should remain an experimental drug for COVID-19.

Integration of geriatric assessment into clinical oncology practice: A scoping review.

Sixty percent of newly diagnosed cancers occur in older adults and more complex planning is required to sustain quality care for older populations. Individualized care incorporating geriatric assessment can predict early mortality and treatment toxicity for older cancer patients. We mapped and summarized the available evidence on the integration of geriatric assessment into clinical oncology practice, and ascertained which domains have been implemented. We systematically searched bibliographic databases and trial registries for reports of clinical studies, clinical practice guidelines, systematic and non-systematic reviews, and grey literature published in English. We gathered data on study characteristics, geriatric domains and strategies evaluated, and relevant study objectives and findings. From a total of 10,124 identified citations, 38 articles met our eligibility criteria, 3 of which were clinical practice guidelines. Nearly half of these articles came from the United States. Domains of the geriatric assessment implemented in studies ranged from 1 to 12, with varied combinations. We identified 27 studies on strategies for implementing geriatric assessment and 24 studies on feasibility of implementing geriatric assessment, into clinical oncology practice. We also identified 3 main geriatric assessment models: 2 from the United States and 1 from Australia. Furthermore, we identified 2 reviews that reported varied components of geriatric assessment models. There is increasingly robust evidence to implement formal geriatric assessment in oncology practice. There remains a great deal of variation in the tools recommended to address each of the domains in a geriatric assessment, with only 1 guideline (American Society of Clinical Oncology guideline) settling on a specific best practice. Protocol registration: Open Science Framework osf.io/mec93.

Does a Delay in Anterior Cruciate Ligament Reconstruction Increase the Incidence of Secondary Pathology in the Knee? A Systematic Review and Meta-Analysis.

OBJECTIVE: Previous systematic reviews looking at timing of anterior cruciate ligament reconstruction (ACLR) examined the functional outcomes and range of motion; however, few have quantified the effect of timing of surgery on secondary pathology. The goal of this study was to analyze the effects of early ACLRs versus delayed ACLR on the incidence of meniscal and chondral lesions. DATA SOURCES: We searched MEDLINE, EMBASE, and CINAHL on March 20, 2018, for randomized control trials (RCTs) that compared early and delayed ACLR in a skeletally mature population. Two reviewers independently identified trials, extracted trial-level data, performed risk-of-bias assessments using the Cochrane Risk of Bias tool, and evaluated the study methodology using the Detsky scale. A meta-analysis was performed using a random-effects model with the primary outcome being the total number of meniscal and chondral lesions per group. RESULTS: Of 1887 citations identified from electronic and hand searches, we included 4 unique RCTs (303 patients). We considered early reconstruction as <3 weeks and delayed reconstruction as >4 weeks after injury. There was no evidence of a difference between early and late ACLR regarding the incidence of meniscal [relative risk (RR), 0.98; 95% confidence interval (CI), 0.74-1.29] or chondral lesions (RR, 0.88; 95% CI, 0.59-1.29), postoperative infection, graft rupture, functional outcomes, or range of motion. CONCLUSIONS: We found no evidence of benefit of early ACLR. Further studies may consider delaying surgery even further (eg, >3 months) to determine whether there are any real benefits to earlier reconstruction.

Seasonal influenza vaccination among cancer patients: A systematic review and meta-analysis of the determinants.

Cancer patients are among high-risk individuals for whom seasonal influenza vaccine (SIV) is recommended, but rates of vaccination in this subpopulation remain suboptimal; even in jurisdictions with universal influenza vaccination programs. We sought to summarize the evidence to better understand the determinants of SIV uptake (vaccine receipt) among cancer patients. We searched MEDLINE, Embase, and CINAHL from 2000 to February 12, 2020, focusing on articles on the determinants of seasonal influenza vaccination among cancer patients, published in English. Study selection was conducted independently by 2 reviewers. One reviewer extracted data from the included studies and another reviewer checked the extracted data for errors. Outcomes were sociodemographic and health-related factors. We pooled adjusted results from studies using the inverse variance, random-effects method, and reported the odds ratios (OR) and their 95% confidence intervals (CI). Out of 2664 citations, 10 studies (mostly from USA and South Korea) met our eligibility criteria. Overall, being older (OR 2.23, 95% CI 1.46-3.38; I2 92.3%, [6 studies]), a nonsmoker (1.43, 1.32-1.51; I2 0%, [4 studies]), having a chronic illness (1.18, 1.07-1.29; I2 15.7%, [5 studies]), having had a medical check-up in the past year (1.75, 1.65-1.86; I2 0%, [2 studies]), and having health insurance (1.39, 1.13-1.72; I2 21.8%, [3 studies]) were associated with increased SIV uptake. Compared with being African-American, being Caucasian was also associated with increased SIV uptake (1.79, 1.47-2.13; I2 10.7%, [3 studies]). Limited evidence suggests seasonal influenza vaccination among cancer patients may be determined by some sociodemographic and health-related factors.

Association of Mindfulness-Based Interventions With Anxiety Severity in Adults With Cancer: A Systematic Review and Meta-analysis.

Importance: Mindfulness-based interventions (MBIs), grounded in mindfulness, focus on purposely paying attention to experiences occurring at the present moment without judgment. MBIs are increasingly used by patients with cancer for the reduction of anxiety, but it remains unclear if MBIs reduce anxiety in patients with cancer. Objective: To evaluate the association of MBIs with reductions in the severity of anxiety in patients with cancer. Data Sources: Systematic searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and SCOPUS were conducted from database inception to May 2019 to identify relevant citations. Study Selection: Randomized clinical trials (RCTs) that compared MBI with usual care, waitlist controls, or no intervention for the management of anxiety in cancer patients were included. Two reviewers conducted a blinded screening. Of 101 initially identified studies, 28 met the inclusion criteria. Data Extraction and Synthesis: Two reviewers independently extracted the data. The Cochrane Collaboration risk-of-bias tool was used to assess the quality of RCTs, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Summary effect measures were reported as standardized mean differences (SMDs) and calculated using a random-effects model. Main Outcomes and Measures: Our primary outcome was the measure of severity of short-term anxiety (up to 1-month postintervention); secondary outcomes were the severity of medium-term (1 to ≤6 months postintervention) and long-term (>6 to 12 months postintervention) anxiety, depression, and health-related quality of life of patients and caregivers. Results: This meta-analysis included 28 RCTs enrolling 3053 adults with cancer. None of the trials were conducted in children. Mindfulness was associated with significant reductions in the severity of short-term anxiety (23 trials; 2339 participants; SMD, -0.51; 95% CI, -0.70 to -0.33; I2 = 76%). The association of mindfulness with short-term anxiety did not vary by evaluated patient, intervention, or study characteristics. Mindfulness was also associated with the reduction of medium-term anxiety (9 trials; 965 participants; SMD, -0.43; 95% CI, -0.68 to -0.18; I2 = 66%). No reduction in long-term anxiety was observed (2 trials; 403 participants; SMD, -0.02; 95% CI, -0.38 to 0.34; I2 = 68%). MBIs were associated with a reduction in the severity of depression in the short term (19 trials; 1874 participants; SMD, -0.73; 95% CI; -1.00 to -0.46; I2 = 86%) and the medium term (8 trials; 891 participants; SMD, -0.85; 95% CI, -1.35 to -0.35; I2 = 91%) and improved health-related quality of life in patients in the short term (9 trials; 1108 participants; SMD, 0.51; 95% CI, 0.20 to 0.82; I2 = 82%) and the medium term (5 trials; 771 participants; SMD, 0.29; 95% CI, 0.06 to 0.52; I2 = 57%). Conclusions and Relevance: In this study, MBIs were associated with reductions in anxiety and depression up to 6 months postintervention in adults with cancer. Future trials should explore the long-term association of mindfulness with anxiety and depression in adults with cancer and determine its efficacy in more diverse cancer populations using active controls.

Ipilimumab-Induced Enterocolitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Checkpoint inhibitor drugs including ipilimumab have been reported to induce intestinal injury. OBJECTIVE: We aimed to evaluate the risk of chronic (> 6 weeks) enterocolitis following ipilimumab administration, and the likelihood that an enteritis vs colitis or enterocolitis is seen. PATIENTS AND METHODS: We searched MEDLINE, EMBASE, CENTRAL, the World Health Organization International Clinical Trials Registry, and conference proceedings. We included: (1) randomized controlled trials comparing ipilimumab administration with placebo/standard care/other active chemotherapy regimens and (2) prospective observational studies. Separate meta-analyses were performed for randomized controlled trials and observational studies. RESULTS: Of 4760 records, we included ten unique randomized controlled trials (n = 5814 subjects) and 34 unique prospective observational studies (n = 3699 subjects). In randomized controlled trials, the pooled relative risk of ≥ grade 3 enterocolitis or ≥ grade 3 diarrhea associated with ipilimumab was 13.31 (95% confidence interval 6.01-29.48, I2 = 0%, ten trials) and 6.72 (95% confidence interval 3.30-13.65, I2 = 63%, ten trials), respectively. In observational studies, the 3-monthly risk of developing grade 3 or higher enteritis, colitis, or enterocolitis was 4% (95% confidence interval 3-7, I2 = 77.40%, 25 studies). Randomized controlled trials and observational studies did not distinguish between acute and chronic enterocolitis. Of the included observational studies, the pooled risk of incurring small bowel involvement associated with ipilimumab was 1% (95% CI 0-4, I2 = 0%, four studies) per every 3-month time period. CONCLUSIONS: Insufficient data exist to quantify or distinguish the risk of acute vs chronic enterocolitis following ipilmumab use. Because of the serious impact of chronic enterocolitis on quality of life and further cancer treatment, future trials evaluating the safety of immunotherapy should report gastrointestinal events in greater detail.

The effect of restrictive versus liberal transfusion strategies on longer-term outcomes after cardiac surgery: a systematic review and meta-analysis with trial sequential analysis.

PURPOSE: Blood transfusions are frequently administered in cardiac surgery. Despite a large number of published studies comparing a "restrictive" strategy with a "liberal" strategy, no clear consensus has emerged to guide blood transfusion practice in cardiac surgery patients. The purpose of this study was to identify, critically appraise, and summarize the evidence on the overall effect of restrictive transfusion strategies compared with liberal transfusion strategies on mortality, other clinical outcomes, and transfusion-related outcomes in adult patients undergoing cardiac surgery. SOURCE: We searched MEDLINE (OvidSP), EMBASE (OvidSP) and Cochrane CENTRAL (Wiley) from inception to 1 December 2017 and queried clinical trial registries and conference proceedings for randomized-controlled trials of liberal vs restrictive transfusion strategies in cardiac surgery. PRINCIPAL FINDINGS: From 7,908 citations, we included ten trials (9,101 patients) and eight companion publications. Overall, we found no significant difference in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; 95% confidence interval [CI], 0.76 to 1.54; I2 = 33%; seven trials; 8,661 patients). The use of a restrictive transfusion strategy did not appear to adversely impact any of the secondary clinical outcomes. As expected, the proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; 95% CI, 0.64 to 0.73; I2 = 56%; 5 trials; 8,534 patients). Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy. CONCLUSIONS: In adult patients undergoing cardiac surgery, a restrictive transfusion strategy reduces RBC transfusion without impacting mortality rate or the incidence of other perioperative complications. Nevertheless, further large trials in subgroups of patients, potentially of differing age, are needed to establish firm evidence to guide transfusion in cardiac surgery. TRIAL REGISTRATION: PROSPERO (CRD42017071440); registered 20 April, 2018.

RéSUMé: OBJECTIF: Les transfusions sanguines sont fréquentes après une chirurgie cardiaque. Malgré le nombre important d'études publiées comparant une stratégie « restrictive ¼ à une stratégie « libérale ¼, aucun consensus clair n'est apparu pour guider la pratique de la transfusion sanguine chez les patients de chirurgie cardiaque. L'objectif de cette étude était d'identifier, d'évaluer de façon critique et de résumer les données probantes sur l'effet global des stratégies de transfusion restrictives comparativement aux stratégies libérales sur la mortalité, les autres devenirs cliniques, et les devenirs liés à la transfusion chez des patients adultes subissant une chirurgie cardiaque. SOURCE: Nous avons réalisé des recherches dans les bases de données MEDLINE (OvidSP), EMBASE (OvidSP) et Cochrane CENTRAL (Wiley) de leur création jusqu'au 1er décembre 2017 et avons exploré les registres d'études cliniques et les actes de conférence pour en tirer les études randomisées contrôlées évaluant des stratégies transfusionnelles restrictives vs libérales en chirurgie cardiaque. CONSTATATIONS PRINCIPALES: Sur 7908 citations, nous avons inclus dix études (9101 patients) et huit publications connexes. Globalement, nous n'avons observé aucune différence significative en matière de mortalité entre les stratégies transfusionnelles restrictives et libérales (risque relatif [RR], 1,08; intervalle de confiance [IC] 95 %, 0,76 à 1,54; I2 = 33 %; sept études; 8661 patients). Le recours à une stratégie de transfusion restrictive n'a semblé avoir aucun impact négatif sur quelque résultat clinique secondaire que ce soit. Comme anticipé, la proportion de patients ayant reçu des érythrocytes dans le groupe restrictif était significativement plus basse que dans le groupe libéral (RR, 0,68; IC 95 %, 0,64 à 0,73; I2 = 56 %; 7 études; 8534 patients). Parmi les patients transfusés, une stratégie de transfusion restrictive a été associée à un nombre moindre d'unités d'érythrocytes transfusées par patient que dans une stratégie transfusionnelle libérale. CONCLUSION: Dans une population de patients adultes subissant une chirurgie cardiaque, une stratégie transfusionnelle restrictive réduit la transfusion d'érythrocytes sans avoir d'impact sur le taux de mortalité ou sur l'incidence d'autres complications périopératoires. D'autres grandes études sur différents sous-groupes de patients, peut-être d'âges différents, sont toutefois nécessaires afin d'établir des données probantes concluantes pour guider les transfusions en chirurgie cardiaque. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42017071440); enregistrée le 20 avril 2018.

Resveratrol for adults with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic disorder that is characterised by insulin resistance and hyperglycaemia, which over time may give rise to vascular complications. Resveratrol is a plant-derived nutritional supplement shown to have anti-diabetic properties in many animal models. Less evidence is available on its safety and efficacy in the management of T2DM in humans. OBJECTIVES: To assess the efficacy and safety of resveratrol formulations for adults with type 2 diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and International Pharmaceutical Abstracts, as well as the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. The date of the last search was December 2018 for all databases. No language restrictions were applied. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing effects of oral resveratrol (any dose or formulation, duration, or frequency of administration) with placebo, no treatment, other anti-diabetic medications, or diet or exercise, in adults with a diagnosis of T2DM. DATA COLLECTION AND ANALYSIS: Two review authors independently identified and included RCTs, assessed risk of bias, and extracted study-level data. Study authors were contacted for any missing information or for clarification of reported data. We assessed studies for certainty of the evidence using the GRADE instrument. MAIN RESULTS: We identified three RCTs with a total of 50 participants. Oral resveratrol not combined with other plant polyphenols was administered at 10 mg, 150 mg, or 1000 mg daily for a period ranging from four weeks to five weeks. The comparator intervention was placebo. Overall, all three included studies had low risk of bias. None of the three included studies reported long-term, patient-relevant outcomes such as all-cause mortality, diabetes-related complications, diabetes-related mortality, health-related quality of life, or socioeconomic effects. All three included studies reported that no adverse events were observed, indicating that no deaths occurred (very low-quality evidence for adverse events, all-cause mortality, and diabetes-related mortality). Resveratrol versus placebo showed neutral effects for glycosylated haemoglobin A1c (HbA1c) levels (mean difference (MD) 0.1%, 95% confidence interval (CI) -0.02 to 0.2; P = 0.09; 2 studies; 31 participants; very low-certainty evidence). Due to the short follow-up period, HbA1c results have to be interpreted cautiously. Similarly, resveratrol versus placebo showed neutral effects for fasting blood glucose levels (MD 2 mg/dL, 95% CI -2 to 7; P = 0.29; 2 studies; 31 participants), and resveratrol versus placebo showed neutral effects for insulin resistance (MD -0.35, 95% CI -0.99 to 0.28; P = 0.27; 2 studies; 36 participants). We found eight ongoing RCTs with approximately 800 participants and two studies awaiting assessment, which, when published, could contribute to the findings of this review. AUTHORS' CONCLUSIONS: Currently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM. The limited available research does not provide sufficient evidence to support any effect, beneficial or adverse, of four to five weeks of 10 mg to 1000 mg of resveratrol in adults with T2DM. Adequately powered RCTs reporting patient-relevant outcomes with long-term follow-up periods are needed to further evaluate the efficacy and safety of resveratrol supplementation in the treatment of T2DM.

Efficacy and Safety of Tranexamic Acid in Major Non-Cardiac Surgeries at High Risk for Transfusion: A Systematic Review and Meta-Analysis.

Tranexamic acid (TXA) reduces transfusion requirements in cardiac surgery and total hip and knee arthroplasty, where it has become standard of care. Our objective is to determine the efficacy and safety of TXA in other surgeries associated with a high risk for red blood cell (RBC) transfusion. We identified randomized controlled trials in Medline, Embase, CENTRAL, and CAB abstracts from inception to June 2019. We included trials evaluating intraoperative IV TXA in adult patients undergoing a non-cardiac and non-hip and knee arthroplasty surgeries at high-risk for RBC transfusion, defined as a baseline transfusion rate ≥5% in comparator arm. We assessed risk of bias using the Cochrane Risk of Bias tool. We used GRADE methodology to assess certainty of evidence. From 8565 citations identified, we included 69 unique trials, enrolling 6157 patients. TXA reduces both the proportion of patients transfused RBCs (relative risk (RR) 0.59; 95% confidence interval (CI) 0.48 to 0.72; low certainty evidence) and the volume of RBC transfused (MD -0.51 RBC units; 95%CI -0.13 to -0.9 units; low certainty evidence) when compared to placebo or usual care. TXA was not associated with differences in deep vein thrombosis, pulmonary embolism, all-cause mortality, hospital length of stay, need for re-operation due to hemorrhage, myocardial infarction, stroke or seizure. In patients undergoing a broad range of non-cardiac and non-hip and knee arthroplasty surgeries at high risk for RBC transfusion, perioperative TXA reduced exposure to RBC transfusion. No differences in thrombotic outcomes were identified; however, summary effect estimates were limited by lack of systemic screening and short duration of follow-up.

Advancement in the quality of operative documentation: A systematic review and meta-analysis of synoptic versus narrative operative reporting.

BACKGROUND: The operative report is vital for patients and central to surgical quality assessment. Narrative operative reports are often poor quality. Synoptic reporting can improve documentation. The objective was to identify and appraise studies comparing synoptic and narrative operative reporting. DATA SOURCES: A systematic review of the literature was performed. The primary outcome was completion of critical elements for an operative report. Additional secondary outcomes were measured. Meta-analysis was performed where possible. Quality analysis was performed using Newcastle-Ottawa Scale (NOS). RESULTS: 1471 citations were identified; 16 studies included. Mean NOS was 7.09 out of 9 (+/-- SD 1.73). Meta-analysis demonstrated that synoptic reporting was significantly more complete (SMD 1.70, 95% CI 1.13 to 2.26; I2 98%). Completion time was shorter with synoptic reporting (mean difference -0.86, 95% CI -1.17 to -0.55). Secondary outcomes favoured synoptic reporting. CONCLUSIONS: Synoptic reporting platforms outperform narrative reporting and should be incorporated into surgical practice.