Meta-análisis: Intervalos de confianza e Intervalos de predicción / Meta-analysis: Confidence intervals and Prediction intervals

En los informes meta-analíticos se suelen reportar varios tipos de intervalos, hecho que ha generado cierta confusión a la hora de interpretarlos. Los intervalos de confianza reflejan la incertidumbre relacionada con un número, el tamaño del efecto medio paramétrico. Los intervalos de predicción reflejan el tamaño paramétrico probable en cualquier estudio de la misma clase que los incluidos en un meta-análisis. Su interpretación y aplicaciones son diferentes. En este artículo explicamos su diferente naturaleza y cómo se pueden utilizar para responder preguntas específicas. Se incluyen ejemplos numéricos, así como su cálculo con el paquete metafor en R.(AU)

Several types of intervals are usually employed in meta-analysis, a fact that has generated some confusion when interpreting them. Confidence intervals reflect the uncertainty related to a single number, the parametric mean effect size. Prediction intervals reflect the probable parametric effect size in any study of the same class as those included in a meta-analysis. Its interpretation and applications are different. In this article we explain in de-tail their different nature and how they can be used to answer specific ques-tions. Numerical examples are included, as well as their computation with the metafor Rpackage.(AU)

Effects of saturated fatty acid consumption on lipoprotein (a): a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: An inverse relationship between saturated fatty acid (SFA) intake and Lp(a) concentration has been observed; however, there has been no quantification of this effect. OBJECTIVES: The objective was to determine whether SFA consumption alters Lp(a) concentrations among adults without atherosclerotic cardiovascular disease (ASCVD). METHODS: A systematic review and meta-analysis of randomized controlled trials contrasting a lower SFA diet(s) with a higher SFA diet(s) among adults without ASCVD was conducted. PubMed, Cochrane Central Register of Clinical Trials, clinicaltrials.gov, and Web of Science databases and registers were searched through October 2023. The standardized mean difference (SMD) in Lp(a) between diets lower and higher in SFA [percentage of energy (%E)] was determined using random-effects meta-analysis. Analyses were also conducted to examine the effect of replacing SFA with carbohydrates (CHO), monounsaturated (MUFAs), polyunsaturated (PUFAs), or trans fatty acids (TFAs). RESULTS: In total, 6255 publications were identified in the systematic search. Twenty-six publications reporting 27 randomized controlled trials, including 1325 participants and 49 diet comparisons, were included. The mean difference in SFA between lower and higher SFA diets was 7.6%E (3.7%-17.8%E). After lower SFA diets, Lp(a) concentration was higher (SMD: 0.14; 95% confidence interval [CI]: 0.03, 0.24) than that after higher SFA diets. Subgroup analyses showed higher Lp(a) following diets where SFA was replaced by CHO (trials = 8; n = 539; SMD 0.21: 95% CI: 0.02, 0.40) or TFAs (trials = 8; n = 300; SMD: 0.32; 95% CI: 0.17, 0.48). No differences in Lp(a) were observed when MUFA (trials = 16; n = 641; SMD: 0.04; 95% CI: -0.08, 0.16) or PUFA (trials = 8; n = 415; SMD: 0.09; 95% CI: -0.04, 0.22) replaced SFA. CONCLUSIONS: Lower SFA diets modestly increase Lp(a) than higher SFA diets among individuals without ASCVD. This effect appeared to be driven by replacement of SFA with CHO or TFA. Research investigating the atherogenicity of diet-induced Lp(a) changes is needed to inform dietary management of lipid/lipoprotein disorders. This trial was registered with PROSPERO as CRD42020154169.

Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network meta-analysis.

BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Pulmonary artery catheter use and in-hospital outcomes in cardiac surgery: a systematic review and meta-analysis.

OBJECTIVES: To determine the association of intraoperative pulmonary artery catheter (PAC) use with in-hospital outcomes in cardiac surgical patients. METHODS: MEDLINE, Embase, and Cochrane Library (Wiley) databases were screened for studies that compared cardiac surgical patients receiving intraoperative PAC with controls and reporting in-hospital mortality. Secondary outcomes included intensive care unit length of stay, cost of hospitalization, fluid volume administered, intubation time, inotropes use, acute kidney injury (AKI), stroke, myocardial infarction (MI), and infections. RESULTS: Seven studies (25 853 patients, 88.6% undergoing coronary artery bypass graft surgery) were included. In-hospital mortality was significantly increased with PAC use [odds ratio (OR) 1.57; 95% confidence interval (CI) 1.12-2.20, P = 0.04]; PAC use was also associated with greater intraoperative inotrope use (OR 2.61; 95% CI 1.54-4.41) and costs [standardized mean difference (SMD) = 0.20; 95% CI 0.16-0.23], longer intensive care unit stay (SMD = 0.29; 95% CI 0.25-0.33), and longer intubation time (SMD = 0.44; 95% CI 0.12-0.76). CONCLUSIONS: PAC use is associated with significantly increased odds of in-hospital mortality, but the amount and quality of the available evidence is limited. Prospective randomized trials testing the effect of PAC on the outcomes of cardiac surgical patients are urgently needed.

Seropositivity of toxoplasmosis in pregnant women living with HIV/AIDS worldwide: A systematic review and meta-analysis.

BACKGROUND: Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii, a food- and water-borne zoonotic protozoan parasite that is able to infect almost all warm-blooded vertebrates. It has a major effect on public health, particularly in underdeveloped nations. Immune-competent individuals typically exhibit no symptoms or experience a mild influenza-like sickness, while there is a possibility of severe manifestation and fatal or high-risk for life-threatening diseases in immunocompromised people like pregnant women and HIV/AIDS patients and lead to severe pathological effects on the fetus. METHOD: We conducted a systematic search of databases (PubMed, Google Scholar, Science Direct, EMBASE, and Scopus) using the PRISMA criteria. We used specific keywords such as Toxoplasma gondii, Toxoplasmosis, pregnant women, prevalence, HIV/AIDS, and worldwide studies published from 2018 to 2022. We use Stata (version 14) software to estimate the pooled prevalence and heterogeneity of toxoplasmosis in pregnant women and HIV-infected people using a random-effects model and the Cochran's Q-test, respectively. The Joanna Briggs Institute Critical Appraisal Instrument and Egger's regression asymmetry test were used to assess study quality and publication bias, respectively, while the single study omission analysis was used to test the robustness of a pooled estimate. RESULTS: We included and analyzed a total of 12,887 individuals in this review. The pooled prevalence of T. gondii in this review was 40% (95% CI = 0.31-0.50). The sub-group analysis revealed that the evaluation included 11,967 pregnant women. In pregnant women, the pooled sero-prevalence was 40% (95% CI = 0.31-0.50). In pregnant women and HIV/AIDS patients, 920 individuals were evaluated, and the pooled sero-prevalence was 41% (95% CI = 0.20-0.61). CONCLUSION: This review identified an overall sero-prevalence of Toxoplasma infection of 40% among pregnant women and HIV/AIDS. The expansion of prevention and control strategies, with a primary focus on enhancing educational initiatives, is necessary to avoid reactivation and stop the spread of infection, so investigative sero-prevalence is important work among pregnant women and HIV patients. In order to achieve a comprehensive explanation of the disease condition and reach this goal, we conducted a systematic review and meta-analysis in Worldwide for future use.

Effect of different exit-site care dressings on preventing peritoneal dialysis related infection from nontropical area: a systematic review and network meta-analysis.

OBJECT: This study aims to conduct a systematic review and network meta-analysis to comprehensively evaluate the efficacy of various dressings in preventing exit-site infection (ESI) and peritonitis. METHODS: We searched PubMed, Embase, Web of Science, CINAHL Plus with Full Text (EBSCO), Sino Med, Wan Fang Data, China National Knowledge Infrastructure (CNKI) from 1 January 1999 to 10 July 2023. The language restrictions were Chinese and English. Randomized controlled trials, non-randomized controlled trials, and self-controlled trials were included in this study. We used ROB 2 tool to evaluate the quality of the included literature. Two authors independently extracted the data according to the Cochrane Handbook. A Frequentist network meta-analysis was performed using Stata17.0 according to PRISAMA with a random effects model. RESULTS: From 2092 potentially eligible studies, thirteen studies were selected for analysis, including nine randomized controlled studies, three quasi-experimental studies and one self-controlled trial. A total of 1229 patients were included to compare five types of exit site care dressings, named disinfection dressings, antibacterial dressings, non-antibacterial occlusive dressings, sterile gauze, and no-particular dressings. The outcome of prevention ESI is antibacterial dressings (SUCRA = 97.6) >non-antibacterial occlusive dressings (SUCRA = 68.3) >disinfection dressings (SUCRA = 50.6) >no-particular dressings (SUCRA = 23.9) >sterile gauze (SUCRA = 9.5). The antibacterial dressings were more effective than sterile gauze (OR = 0.13, 95%CI 0.04∼0.44), and no-particular dressing (OR = 0.18, 95%CI 0.07∼0.50) in preventing ESI; the non-antibacterial occlusive dressings were effective than sterile gauze (OR:0.30, 95%CI 0.16∼0.57). There is no statistical significance between no-particular dressings and other types of dressings in preventing the mature ESI. There is no statistical significance in the effectiveness of five types of dressings in preventing peritonitis. CONCLUSIONS: The no-particular dressings maybe more cost-effective for preventing mature ESI. None of the dressings was more effective than another in preventing peritonitis. Then, none of the different types of dressing is strongly recommended for preventing ESI or peritonitis.RegistrationCRD42022366756.

The Effectiveness of Auricular Acupressure on Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To assess the effectiveness of auricular acupressure (AA) in managing pain and disability in individuals with chronic musculoskeletal pain. Materials and Methods: A systematic search on six electronic databases was performed from their inception to May 7, 2023, to identified relevant randomized controlled trials (RCTs). Two independent reviewers screened the abstracts and full texts, extracted data, and assessed risk of bias using RoB 2. The primary outcomes were pain intensity and disability. The secondary outcomes were pain pressure thresholds, pain catastrophizing level, and fear avoidance beliefs. A random-effects model was used for meta-analyses. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. Sensitivity analyses were conducted after removing low-quality papers. Results: Of 633 identified records, six studies involving 496 participants were included. All included studies compared the effectiveness of AA with sham controls in treating various chronic musculoskeletal pain. Four meta-analyses were conducted to compare the effectiveness of AA with sham controls. Low-quality evidence supported that AA had a large effect size on postintervention subjective pain reduction (standardized mean difference [SMD] = -0.95; 95% confidence interval [CI]: -1.36 to -0.54; p = 0.00; I2 = 52.61%); moderate-quality evidence substantiated that AA had a large effect size on enhancing postintervention pressure pain threshold (SMD = -0.55; 95% CI: -0.88 to -0.23; p = 0.00; I2 = 0%). There was low-quality evidence that AA had a large effect on reducing postintervention disability (SMD = -0.68; 95% CI: -1.24 to -0.12; p = 0.02; I2 = 51.33%). Our sensitivity analysis reaffirmed the same conclusion regarding pain reduction immediately after the intervention. Fourteen participants reported minimal adverse events, including soreness, tenderness, irritation, and redness, which disappeared within 1-7 days. Discussion: Our systematic review revealed that AA significantly improved pain, pressure pain thresholds, and disability in individuals with various chronic musculoskeletal pain conditions immediately post-treatment compared with sham treatment. Given the paucity of studies and inconsistent protocols, future RCTs are warranted to evaluate the effectiveness of AA in people with chronic musculoskeletal pain at a longer follow-up with detailed protocols, which allows researchers and clinicians to optimize AA intervention. Conclusion: AA has immediate post-treatment benefits for chronic musculoskeletal pain, whereas its effects at the 1- or 6-month follow-up remain uncertain.

The association between emotional regulation dimensions and somatic symptom disorders: A systematic review and meta-analysis.

Clarifying the effect size of the association between somatic symptom disorders (SSDs) and defects in emotional regulation (ER) dimensions through a meta-analysis may improve ER-related treatment for SSD patients. SSDs exhibited a lower level of adaptive ER (overall Hedge's g = -0.618, 95 %CI [0.872, -0.365]; Hedge's g for ER dimensions of Awareness, Description, Clarity, Acceptance, Tolerance, Self-efficacy belief, and Cognitive Reappraisal ranged from -0.451 to -1.344). Maladaptive ER dimensions (catastrophizing and expressive inhibition) showed no significant associations with SSDs. Psychotherapy focusing on developing adaptive ER rather than reducing maladaptive ER may be a more promising approach for treating SSD patients.

Unravelling the impact of light, temperature and nutrient dynamics on duckweed growth: A meta-analysis study.

Nature-based solutions have been proven in recent decades as a reliable and cost-effective technology for the treatment of wastewaters. Different plant species have been studied for this purpose, but particular attention has been given to duckweeds, the smallest flowering plant in the world. Duckweed-based systems for simultaneous wastewater treatment and nutrient recovery have the potential to provide sustainable and cost-effective solutions to reduce water pollution and increase nutrient efficiency at catchment level. However, despite being considered a seemingly simple technology, the performance of wastewater treatment systems using duckweed depends on environmental and operational conditions not very well understood. For that reason, careful consideration must be given to such environmental factors controlling duckweed biomass growth but the evidence in published literature is scare and dispersed. This study employs a systematic review approach to conduct a meta-analysis of the effect of environmental conditions on duckweed growth by means of standardised IQ-scores. The results suggest that duckweed biomass growth rates reach a maximum within specific ranges for temperature (11.4-32.3 °C), daily light integral (DLI) (5-20 mol m-2), and nitrogen (>5 mg N L-1) and phosphorus (>1 mg P L-1) concentrations; DLI was found to be a better parameter to assess the overall effect of light (photoperiod and intensity) on duckweed growth and that the effect of nitrogen and phosphorus supply should consider the nitrogen species available for plant growth and its ratio to phosphorus concentrations (recommended N:P ratio = 15:1). By establishing the optimal range of culture conditions for duckweed, this study provides important insights for optimizing engineered wastewater treatment systems that rely on duckweed for nutrient control and recovery, which is primarily mediated by duckweed growth.

Priority interventions for the prevention of falls or fractures in patients with osteoporosis: A network meta-analysis.

BACKGROUND: The fractures of patients with osteoporosis represent a major health care burden that requires efficient prevention. OBJECTIVE: To analyze the efficacy and significance of diverse interventions for preventing falls or fractures in patients with osteoporosis, and to establish a foundation for clinical interventions. METHODS: Ten databases were searched for studies published before January 30, 2024. Screening, data extraction, and risk of bias assessment were independently conducted by two researchers using Stata 14.0 software. A network meta-analysis using the frequentist framework was then performed to determine the effectiveness of various interventions for preventing and managing falls and fractures in patients with osteoporosis. The findings were used as basis for the prioritization of interventions. RESULTS: The initial search yielded 3894 studies. After 3878 studies were excluded, 16 studies were finally included. For the prevention of falls in patients with osteoporosis, effective interventions include exercise and exercise plus medication. A combination of exercise, assessment and modifications, quality improvement strategies, social engagement, basic falls risk assessment, and assistive technology may be the preferred recommended intervention. For the prevention of fractures in patients with osteoporosis, no statistically significant disparities were observed among the compared interventions, exercise may be the preferred recommended intervention. CONCLUSION: Exercise and exercise plus medication are effective in reducing the number of falls in patients with osteoporosis. Although exercise may be the optimal intervention for fracture prevention, the quality of current evidence remains inadequate. Large-scale high-quality randomized controlled trials are necessary to substantiate these findings. TRIAL REGISTRATION: PROSPERO CRD42024507487.

Recurrence of atypical and anaplastic intracranial Meningiomas: A meta-analysis of risk factors.

BACKGROUND: The predictive role of multiple risk factors for intracranial atypical and anaplastic meningioma recurrence is convoluted. This meta-analysis assessed the predictive value of selected factors for recurrence in these Meningiomas. METHODS: Studies encompassing risk factor data including gross total resection (GTR), subtotal resection (STR), post-op radiotherapy, Ki-67 % index >3 %, and location were searched for in PubMed, Embase, and Web of Science, and thereafter analyzed using robust Bayesian meta-analysis. RESULTS: Eighteen observational studies involving 1589 patients met inclusion criteria for analysis. GTR was identified as a good prognostic factor for recurrence (OR = 0.212; 95 % CI (-1.972, -1.002); heterogeneity BF=0.702), and STR had a significantly higher risk of recurrence (OR = 4.43; 95 % CI 0.658-2.011; heterogeneity BF=0.724). Post-operative radiotherapy did not statistically significantly affect the recurrence process (OR = 1.02; 95 % CI (-1.848, 0.626); heterogeneity (BF=1.034)). Ki67 % index >3 % had an augmented chance of recurrence (OR = 2.38; 95 % CI (-0.220, 2.355); heterogeneity (BF=1.162)). A meta-regression analysis showed that WHO grade III Meningiomas had a higher chance of recurring than grade II Meningiomas. CONCLUSION: Among the selected factors, STR and Ki67 % index > 3 % were associated with a higher risk of recurrence, with post-operative radiotherapy making no difference. GTR appeared to inversely impact recurrence. Compared to grade II, grade III Meningiomas had higher odds of recurring.

Recombinant Human Hepatocyte Growth Factor Plasmids for Treating Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-analysis.

OBJECTIVE: Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data were conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI. DATA SOURCES: Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using Medline, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases. REVIEW METHODS: Meta-analyses of the reported relative risks (RR) or mean differences (MD) were conducted. Subgroup analyses determined the efficacy of HGF plasmids in cohorts excluding Buerger's disease. Certainty of evidence for each outcome was assessed. RESULTS: Seven studies (n = 655) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% CI 1.30 - 3.04; p = .015) than patients treated with placebo. The HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at the 3 month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence), or all-cause mortality (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle-brachial index at 6 months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved 3 month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence). CONCLUSION: Hepatocyte growth factor treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI.

Universal irradiation of platelets: Does irradiation affect the quality, effectiveness, and safety of platelets for transfusion?

We aimed to identify any detrimental effects on platelet quality and clinical effectiveness, of irradiated platelets compared to non-irradiated platelets for transfusion. The review was conducted in accordance with PRISMA guidelines. The protocol was prospectively registered on PROSPERO [CRD42023441930]. Our search identified 3002 references, of which we included 44 studies. Forty-one were in vitro only studies, two studies were in healthy volunteers, and one study reported clinical outcomes in thrombocytopenic patients. X-ray was used exclusively in three studies, and alongside gamma irradiation in one study. Two studies did not report the source of irradiation. The remaining 38 studies used gamma irradiation only. We assessed risk of bias (ROB) for studies reporting clinical and in vivo outcomes using ROB 2.0 (3 studies). We adapted a ROB tool designed for animal studies to assess ROB for the studies reporting in vitro outcomes (43 studies). We assessed the certainty of the evidence for the eight outcomes deemed most important to assess platelet quality and clinical effectiveness (where day 0 is the day of the blood draw). Overall, gamma irradiation has little to no effect on most markers of platelet quality and effectiveness. Where there is evidence of detriment from irradiation, differences are small in vitro, and are unlikely to affect clinical outcomes following transfusion. However, the evidence base is limited. Only half the studies could be included in any analysis. There is very limited evidence for x-ray as a source of irradiation and, given the potential benefits of using x-ray over gamma irradiation (ease of use and safety requirements), we would welcome further research comparing x-ray to gamma, and x-ray to a non-irradiated control.

Benefits and risks of using laparoscopic ultrasonography versus intraoperative cholangiography during laparoscopic cholecystectomy for gallstone disease: a systematic review and meta-analysis.

BACKGROUND: Intraoperative laparoscopic ultrasonography (LUS) or intraoperative cholangiography (IOC) can be used for visualisation of the biliary tract during laparoscopic cholecystectomy. The aim of this systematic review was to compare use of LUS with IOC. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched (last update: April 2024). PICO: P = patients undergoing intraoperative imaging of the biliary tree during laparoscopic cholecystectomy for gallstone disease; I = intervention: LUS; C = comparison: IOC; O = outcomes: mortality, bile duct injury, retained gallstone, conversion to open cholecystectomy, procedural failure, operation time including imaging time. Included articles were critically appraised using checklists. Conclusions were based on studies without major risk of bias. Meta-analyses were performed using random effects models. Certainty of evidence was assessed according to GRADE. RESULTS: Sixteen non-randomised studies met the PICO. Two before/after studies (594 versus 807 patients) contributed to conclusions regarding mortality (no events; very low certainty evidence), bile duct injury (1 versus 0 events; very low certainty evidence), retained gallstone (2 versus 2 events; very low certainty evidence), and conversion to open cholecystectomy (6 versus 21 events; risk ratio: 0.38 (95% confidence interval: 0.15-0.95); I2 = 0%; low certainty evidence). Seven additional studies, using intra-individual comparisons, contributed to conclusions regarding procedural failure; risk ratio: 1.12 (95% confidence interval: 0.70-1.78; I2 = 83%; very low certainty evidence). No studies reported operation time. Mean imaging time for LUS and IOC, reported in 12 studies, was 4.8‒10.2 versus 10.9‒17.9 min (mean difference: - 7.8 min (95% confidence interval: - 9.3 to - 6.3); I2 = 95%; moderate certainty evidence). CONCLUSION: It is uncertain whether there is any difference in mortality/bile duct injury/retained gallstone using LUS compared with IOC, but LUS may be associated with fewer conversions to open cholecystectomy and is probably associated with shorter imaging time.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. METHODS: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. RESULTS: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). CONCLUSIONS: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Pan-cancer mapping of single CD8+ T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.

CD8+ T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8+ T cells from 132 patients with seven human cancers. Our meta-single-cell analyses uncover a pan-cancer T cell dysfunction program that predicts clinical non-response to checkpoint blockade in melanoma and highlights CXCR6 as a pan-cancer marker of chronically activated T cells. Cxcr6 is trans-activated by AP-1 and repressed by TCF1. Using mouse models, we show that Cxcr6 deletion in CD8+ T cells increases apoptosis of PD1+TIM3+ cells, dampens CD28 signaling, and compromises tumor growth control. Our study uncovers a TCF1:CXCR6 axis that counterbalances PD1-mediated suppression of CD8+ cell responses and is essential for effective anti-tumor immunity.

Effects of flaxseed supplementation on inflammatory biomarkers: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Several studies reported the benefits of flaxseed on inflammatory biomarkers, while others reported conflicting findings. Thus, the aim of this meta-analysis was to assess the impacts of flaxseed on inflammatory biomarkers in adults. Databases including Embase, PubMed, Scopus, and Web of Sciences were searched till February 2024. The 54 RCTs were included in the final analysis, which involved 3000 individuals from 12 countries. Overall, the flaxseed supplementation had a significant reduction in C-reactive protein (CRP) (SMD = -0.46; 95 % CI: -0.70, -0.23, P < 0.001; I2 = 82.9 %, P < 0.001), and interleukin 6 (IL-6) (SMD = -0.64, 95 % CI: -1.13, -0.16, P = 0.010; I2 = 92.7, P < 0.001). Furthermore, flaxseed did not significantly change the concentration of tumor necrosis factor α (TNF-α) (SMD = -0.17; 95 % CI: -0.63, 0.29, P = 0.467; I2 = 92, P < 0.001). Flaxseed supplementation significantly decreased serum concentrations of CRP and IL-6, but not TNF-a. Thus, this meta-analysis suggests that the current evidence supports the potential benefits of flaxseed in managing inflammatory conditions.

Culprit-Only Revascularization, Single-Setting Complete Revascularization, and Staged Complete Revascularization in Acute Myocardial Infarction: Insights From a Mixed Treatment Comparison Meta-Analysis of Randomized Trials.

BACKGROUND: Complete revascularization improves cardiovascular outcomes compared with culprit-only revascularization in patients with acute myocardial infarction ([MI]; ST-segment-elevation MI or non-ST-segment-elevation MI) and multivessel coronary artery disease. However, the timing of complete revascularization (single-setting versus staged revascularization) is uncertain. The aim was to compare the outcomes of single-setting complete, staged complete, and culprit vessel-only revascularization in patients with acute MI and multivessel disease. METHODS: PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized controlled trials that compared 3 revascularization strategies. RESULTS: From 16 randomized controlled trials that randomized 11 876 patients with acute MI and multivessel disease, both single-setting complete and staged complete revascularization reduced primary outcome (cardiovascular mortality/MI; odds ratio [OR], 0.52 [95% CI, 0.41-0.65]; OR, 0.74 [95% CI, 0.62-0.88]), composite of all-cause mortality/MI (OR, 0.52 [95% CI, 0.40-0.67]; OR, 0.78 [95% CI, 0.67-0.91]), major adverse cardiovascular event (OR, 0.42 [95% CI, 0.32-0.56]; OR, 0.62 [95% CI, 0.47-0.82]), MI (OR, 0.39 [95% CI, 0.26-0.57]; OR, 0.73 [95% CI, 0.59-0.90]), and repeat revascularization (OR, 0.30 [95% CI, 0.18-0.47]; OR, 0.46 [95% CI, 0.30-0.71]) compared with culprit-only revascularization. Single-setting complete revascularization reduced cardiovascular mortality/MI (OR, 0.70 [95% CI, 0.55-0.91]), major adverse cardiovascular event (OR, 0.67 [95% CI, 0.50-0.91]), and all-cause mortality/MI driven by a lower risk of MI (OR, 0.53 [95% CI, 0.36-0.77]) compared with staged complete revascularization. Single-setting complete revascularization ranked number 1, followed by staged complete revascularization (number 2) and culprit-only revascularization (number 3) for all outcomes. The results were largely consistent in subgroup analysis comparing ST-segment-elevation MI versus non-ST-segment-elevation MI cohorts. CONCLUSIONS: Single-setting complete revascularization may offer the greatest reductions in cardiovascular events in patients with acute MI and multivessel disease. A large-scale randomized trial of single-setting complete versus staged complete revascularization is warranted to evaluate the optimal timing of complete revascularization.

Unmet needs in relapsed/refractory mantle cell lymphoma (r/r MCL) post-covalent Bruton tyrosine kinase inhibitor (BTKi): a systematic literature review and meta-analysis.

To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9-14.6) and 9.1 months (95% CI: 7.3-11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34-57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5-21.0) and 32.1 months (95% CI: 25.2-41.2), with a pooled ORR of 89% (95% CI: 86-91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi.

The effects of flaxseed (Linum usitatissimum) supplementation on anthropometric indices: An updated systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: Flaxseed (Linum usitatissimum) supplementation has shown promise as an anti-obesity agent in various clinical trials, although results have been inconsistent. To provide a more accurate assessment of the impact of flaxseed supplementation on anthropometric indices, a systematic review and meta-analysis was performed. METHODS: We searched several international databases until August 2023, including Scopus, PubMed, Web of Science, Embase, and Cochrane Library. Weighted mean differences (WMDs) were analyzed using a random-effects model. RESULTS: Sixty-four trials comprising 72 treatment arms were included. All studies reported the intervention types (Lignans, Whole flaxseed, and Flaxseed oil) and dosage. However, three studies did testing for purity, and 40 studies reported potency. Also, the risk of contamination with heavy metals was not mentioned in studies. Another limitation was the lack of blind evaluation in the studies. According to three trials included in the systematic review, flaxseed did not affect anthropometric indices. Our meta-analysis revealed significant reductions in body weight (WMD = -0.63 kg; 95 % CI: -1.00, -0.27, P < 0.001; I2 = 76.7 %, P < 0.001), body mass index (BMI) (WMD: -0.24 kg/m2, 95 % CI: -0.36, -0.11, P < 0.001; I2 = 78.5 %, P < 0.001) and waist circumference (WC) (WMD: -1.43 cm, 95 % CI: -2.06, -0.80, P < 0.001; I2 = 81.1 %, P < 0.001) following flaxseed supplementation. Subgroup analyses indicated that interventions lasting 10-20 weeks, and studies involving subjects with higher BMI (>30 kg/m2) showed more significant anti-obesity effects. Based on the GRADE evaluation, body weight, BMI, and WC results were considered as moderate-certainty evidence. CONCLUSION: Our systematic review and meta-analysis suggests that supplementation with flaxseed (Linum usitatissimum) leads to meaningful improvements in body weight, BMI, and WC. Therefore, flaxseed can be considered as an adjunctive therapeutic approach in improving obesity.