Pooled Hazard Ratios Research Articles

#1704 GLP-1RA versus DPP-4 inhibitors and rates of hyperkalemia and discontinuation of renin-angiotensin system (RAS) blockade in Swedish routine care

Abstract Background and Aims Emerging evidence suggest that glucagon-like peptide-1 receptor agonists (GLP-1RA) influence tubular handling of electrolytes and increase potassium excretion, which may translate into reduced risk of hyperkalemia. Hyperkalemia is a common complication that limits persistence on guideline-recommended RAS inhibitors (RASi). Here, we quantified and compared rates of hyperkalemia and RASi discontinuation among users of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in a large healthcare system. Method We used data from the SCREAM project (Jan 2008-Dec 2021) to conduct a population-based active-comparator, new-user cohort study of adults with type-2 diabetes who started GLP-1RA or DPP-4i. The primary outcome was hyperkalemia occurrence, overall (plasma potassium>5.0 mmol/L) and by severity (mild -potassium >5-≤5.5 mmol/L- and moderate-severe -potassium >5.5 mmol/L- hyperkalemia). Among ongoing RASi users, we assessed time to RASi discontinuation through evaluation of subsequent RASi dispensations. Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate pooled hazard ratios (HRs) and rate differences. Major cardiovascular events (MACEs) served as positive control outcome to evaluate unmeasured confounding bias. Results During a median follow-up of 3.0 (Interquartile range [IQR] 1.2-5.6) years, we identified 33 280 eligible participants, of which 13 633 started GLP-1RA and 19 647 DPP-4i. Mean age was 64 years and 40% were women. Compared with DPP-4i, starting GLP-1RA was associated with a lower rate of hyperkalemia (Hazard ratio [HR] 0.91; 95% CI: 0.84-0.99, Fig. 1), with no suggestion of effect modification by baseline eGFR strata (HR 0.91 (0.78-1.07) for eGFR ≥60 and HR 0.92 (0.83-1.01) for eGFR <60 ml/min/1.73 m2, P for interaction >0.05). Similar findings were observed for mild (HR 0.90; 0.83-0.98) and moderate-severe (HR 0.92; 0.80-1.06) hyperkalemia. Out of 21 751 participants that were using RASi, 8 463 discontinued this therapy during median 2.0 (0.7, 4.1) years of follow-up. Initiation of GLP-1RA vs. DPP-4i was associated with lower rate of RASi discontinuation (HR: 0.93; 0.87-0.98), with no interaction across strata of baseline eGFR (HR 0.97 (0.83-1.12) for eGFR ≥60 and HR 0.93 (0.87-0.99) for <60 ml/min/1.73 m2, P for interaction >0.05). Consistent with trial evidence, we observed a lower rate of MACE for GLP-1RA vs DPP-4i (HR 0.87; 0.78-0.98). Conclusion In patients with diabetes managed in routine care, the use of GLP-1RA was associated with lower rates of hyperkalemia and discontinuation of RASi compared with DPP-4i, providing further observational evidence in support of the use of these medications.

Long- and Intermediate-Term Ambient Particulate Pollution Is Associated with Increased Osteoarthritis Risk: A Population-Based Prospective Analysis.

Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5 (23.32 μg/m3) and PM10 (23.92 μg/m3) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per μg/m3 for annual PM2.5 exposure at below 67.85 μg/m3. Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5 exposure and the three osteoarthritis-related outcomes.

Bayesian pairwise meta-analysis of time-to-event outcomes in the presence of non-proportional hazards: A simulation study of flexible parametric, piecewise exponential and fractional polynomial models.

Traditionally, meta-analysis of time-to-event outcomes reports a single pooled hazard ratio assuming proportional hazards (PH). For health technology assessment evaluations, hazard ratios are frequently extrapolated across a lifetime horizon. However, when treatment effects vary over time, an assumption of PH is not always valid. The Royston-Parmar (RP), piecewise exponential (PE), and fractional polynomial (FP) models can accommodate non-PH and provide plausible extrapolations of survival curves beyond observed data. Simulation study to assess and compare the performance of RP, PE, and FP models in a Bayesian framework estimating restricted mean survival time difference (RMSTD) at 50 years from a pairwise meta-analysis with evidence of non-PH. Individual patient data were generated from a mixture Weibull distribution. Twelve scenarios were considered varying the amount of follow-up data, number of trials in a meta-analysis, non-PH interaction coefficient, and prior distributions. Performance was assessed through bias and mean squared error. Models were applied to a metastatic breast cancer example. FP models performed best when the non-PH interaction coefficient was 0.2. RP models performed best in scenarios with complete follow-up data. PE models performed well on average across all scenarios. In the metastatic breast cancer example, RMSTD at 50-years ranged from -14.6 to 8.48 months. Synthesis of time-to-event outcomes and estimation of RMSTD in the presence of non-PH can be challenging and computationally intensive. Different approaches make different assumptions regarding extrapolation and sensitivity analyses varying key assumptions are essential to check the robustness of conclusions to different assumptions for the underlying survival function.

The Efficacy and Safety of Tandem Transplant Versus Single Stem Cell Transplant for Multiple Myeloma Patients: A Systematic Review and Meta-Analysis.

While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.

Value of the HOTAIR expression assay in predicting therapy target in hepatocellular carcinoma: A meta-analysis and bioinformatics analysis.

Several studies show that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in human cancer, which was associated with several clinical features and may have the potential to be prognostic markers. However, the significance of HOTAIR in hepatocellular carcinoma remains unclear. We performed a meta-analysis and bioanalysis to further investigate the association between HOTAIR and hepatocellular carcinoma. Eligible literature was systematically retrieved from PubMed, Embase, and Web of Science databases. The pooled hazard ratios with 95% confidence intervals were used to evaluate to the effect. Raw data on HOTAIR expression were obtained from The Cancer Genome Atlas data portals. All bioinformatics analyses were performed using R software (version 4.3.1). We identified eight studies in this meta-analysis with a total of 399 patients. High-level HOTAIR expression was found to be significantly related to advanced tumor node metastasis stage, distant metastasis, poor tumor differentiation, and patients with hepatitis. Correspondingly, HOTAIR was also associated with poor overall survival and relapse-free survival. Subsequently, in bioanalysis, HOTAIR expression was higher in hepatocellular carcinoma as well as poor overall survival. High HOTAIR expression was strongly correlated with tumor node metastasis stage. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes related to HOTAIR may be involved in the cancer-associated signaling pathway. HOTAIR may be a potential biomarker for HCC prediction and is expected to become a new choice for clinical HCC prediction..

Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.

Clinical evidence for the prognostic impact of metformin in cancer patients treated with immune checkpoint inhibitors

BackgroundPreclinical studies suggest that metformin might enhance the efficacy of immune checkpoint inhibitors (ICIs) and potentially influence the prognoses of cancer patients undergoing ICIs treatment. This study endeavors to assess the prognostic significance of metformin in cancer patients undergoing ICIs therapy, aiming to furnish evidence-based insights for clinical practice. MethodsA thorough literature search was conducted across electronic databases to encompass all potential records published before November 20th, 2023. A meta-analysis was executed utilizing Stata 17.0 to derive pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for both overall survival (OS) and progression-free survival (PFS). ResultsA total of 22 studies encompassing 9,011 patients met the inclusion criteria. Meta-analyses revealed a significant correlation between metformin use and poorer OS (HR, 1.13; 95 %CI, 1.04–1.23; P = 0.004) rather than PFS (HR, 1.04; 95 %CI, 0.96–1.14; P = 0.345) among cancer patients undergoing ICIs treatment. Subgroup analysis delineated that the concurrent administration of metformin and ICIs significantly associated with adverse prognoses in the European population (OS: HR, 1.23; 95 %CI, 1.10–1.39; P = 0.001; PFS: HR, 1.14; 95 %CI, 1.02–1.28; P = 0.024). ConclusionBased on current clinical evidence, concomitant metformin use does not appear to improve the prognostic outcomes for cancer patients undergoing ICIs therapy and may potentially correlate with inferior prognoses. Further studies are imperative to comprehensively elucidate the impact of metformin within the realm of ICIs therapy.

Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis

BackgroundThyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes.MethodsA systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected.ResultsSix articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71–1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible.ConclusionsThis systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years.Systematic review registrationPROSPERO CRD42022308006

Meta-Analysis and Systematic Review of the Role of Appendectomy in the Pathogenesis of Colorectal Cancer

Aim. Given the potential for physiological alterations in the gastrointestinal tract following appendix removal, which may influence carcinogenesis, we embarked on a systematic review and meta-analysis to explore the possible association between appendectomy and the subsequent risk of colorectal cancer (CRC).Methods. Our systematic investigation utilized sources including the Cochrane Library, Embase, PubMed, ClinicalTrials.gov, and Web of Science, covering research up to February 1, 2023. We assessed the impact of appendectomy on colorectal cancer, employing a random effects model to calculate the pooled hazard ratio (HR) for developing CRC post-appendectomy and its 95 % confidence interval (CI).Results. This review and meta-analysis incorporated a total of 10 studies, comprising 1,001,693 cases of appendectomy and 39,463 instances of CRC. The meta-analysis revealed a pooled HR of 1.04 (95 % CI: 1.0–1.08) for developing CRC following appendectomy. Notably, the HR for CRC development increased to 1.20 (95 % CI: 0.69–1.69) when considering only cases with more than 10 years of follow-up.Conclusion. The findings indicate a marginally increased risk of colorectal cancer in cases without a specified follow-up period. However, this elevated risk did not persist over the long term (exceeding 10 years). The heterogeneity of the included studies appears to have influenced our results. Nevertheless, it is advisable for physicians to weigh the potential benefits of alternative therapies and consider the future complications that may arise from an unnecessary appendectomy.

Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death

Age-standardized dementia mortality rates are on the rise. Whether long-term consumption of olive oil and diet quality are associated with dementia-related death is unknown. To examine the association of olive oil intake with the subsequent risk of dementia-related death and assess the joint association with diet quality and substitution for other fats. This prospective cohort study examined data from the Nurses' Health Study (NHS; 1990-2018) and Health Professionals Follow-Up Study (HPFS; 1990-2018). The population included women from the NHS and men from the HPFS who were free of cardiovascular disease and cancer at baseline. Data were analyzed from May 2022 to July 2023. Olive oil intake was assessed every 4 years using a food frequency questionnaire and categorized as (1) never or less than once per month, (2) greater than 0 to less than or equal to 4.5 g/d, (3) greater than 4.5 g/d to less than or equal to 7 g/d, and (4) greater than 7 g/d. Diet quality was based on the Alternative Healthy Eating Index and Mediterranean Diet score. Dementia death was ascertained from death records. Multivariable Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs adjusted for confounders including genetic, sociodemographic, and lifestyle factors. Of 92 383 participants, 60 582 (65.6%) were women and the mean (SD) age was 56.4 (8.0) years. During 28 years of follow-up (2 183 095 person-years), 4751 dementia-related deaths occurred. Individuals who were homozygous for the apolipoprotein ε4 (APOE ε4) allele were 5 to 9 times more likely to die with dementia. Consuming at least 7 g/d of olive oil was associated with a 28% lower risk of dementia-related death (adjusted pooled HR, 0.72 [95% CI, 0.64-0.81]) compared with never or rarely consuming olive oil (P for trend < .001); results were consistent after further adjustment for APOE ε4. No interaction by diet quality scores was found. In modeled substitution analyses, replacing 5 g/d of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8% (95% CI, 4%-12%) to 14% (95% CI, 7%-20%) lower risk of dementia mortality. Substitutions for other vegetable oils or butter were not significant. In US adults, higher olive oil intake was associated with a lower risk of dementia-related mortality, irrespective of diet quality. Beyond heart health, the findings extend the current dietary recommendations of choosing olive oil and other vegetable oils for cognitive-related health.

Use of melatonin supplements and risk of type 2 diabetes and cardiovascular diseases in the USA: insights from three prospective cohort studies

Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults. In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work. For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses. With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work. US National Institutes of Health.

Prognostic impact of CD68+ tumor-associated macrophages in hepatocellular carcinoma: A meta-analysis.

Evidence from clinical research suggests that the tumor-associated macrophages (TAMs) were associated with prognosis in hepatocellular carcinoma (HCC). The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of CD68 + TAMs in HCC. This study conducted a systematic search in Pubmed, Embase, the Cochrane Library and China National Knowledge Internet from inception of the databases to November 2023. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. The Newcastle-Ottawa Scale was used to evaluate the risk of prejudice. We analyzed 4362 HCC patients. The present research indicated that the expression levels Of CD68 + TAMs were significantly associated with overall survival (OS) (HR = 1.55, 95% CI: 1.30-1.84) and disease-free survival (DFS) (HR = 1.44, 95% CI: 1.17-1.78). Subgroup analysis based on cutoff values showed that the "Median" subgroup showed a pooled HR of 1.66 with a 95% CI ranging from 1.32 to 2.08, which was slightly higher than the "Others" subgroup that exhibited a pooled HR of 1.40 and a 95% CI of 1.07 to 1.84. The "PT" subgroup had the highest pooled HR of 1.68 (95% CI: 1.19-2.37), indicating a worse OS compared to the "IT" (pooled HR: 1.50, 95% CI: 1.13-2.01) and "Mix" (pooled HR: 1.52, 95% CI: 1.03-2.26) subgroups. Moreover, in the sample size-based analysis, studies with more than 100 samples (>100) exhibited a higher pooled HR of 1.57 (95% CI: 1.28 to 1.93) compared to studies with fewer than 100 samples (<100), which had a pooled HR of 1.45 (95% CI: 1.00-2.10). The analysis suggests that CD68 + TAMs were significantly associated with unfavorable OS and DFS in HCC patients, and may be served as a promising prognostic biomarker in HCC. However, more large-scale trials are needed to study the clinical value of TAMs in HCC.

Neoadjuvant Chemo-Immunotherapy for Early-Stage Non–Small Cell Lung Cancer

Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data. To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors. Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023. Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included. Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated. Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005). In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.

Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis

PurposeMinimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.MethodsWe searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).ResultsOur study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62–0.89), 0.74 (95% CI 0.64–0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02–52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73–91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17–0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11–1.07)].ConclusionIn AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.

Risk of Stroke Among HIV Patients: A Systematic Review and Meta-analysis of Global Studies and Associated Comorbidities.

Despite advancements in the management of HIV infection, the factors contributing to stroke development among HIV-positive individuals remain unclear. This systematic review and meta-analysis aim to identify and evaluate the relative risk factors associated with stroke susceptibility in the HIV population. A comprehensive search was conducted in PubMed, Scopus, and Web of Science databases to identify studies investigating the risk of stroke development in HIV patients and assessing the role of different risk factors, including hypertension, diabetes, dyslipidemia, smoking, sex, and race. The quality assessment of case-control studies was conducted using the Newcastle-Ottawa Scale, whereas cohort studies were assessed using the National Institute of Health tool. Meta-analyses were performed using a random-effects model to determine pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). A total of 18 observational studies involving 116,184 HIV-positive and 3,184,245 HIV-negative patients were included. HIV-positive patients exhibited a significantly higher risk of stroke compared with HIV-negative patients [OR (95% CI): 1.31 (1.20 to 1.44)]. Subgroup analyses revealed increased risks for both ischemic stroke [OR (95% CI): 1.32 (1.19 to 1.46)] and hemorrhagic stroke [OR (95% CI): 1.31 (1.09 to 1.56)]. Pooled adjusted HRs showed a significant association between stroke and HIV positivity (HR: 1.37, 95% CI: 1.22 to 1.54). Among HIV-positive patients with stroke, hypertension [OR (95% CI): 3.5 (1.42 to 8.65)], diabetes [OR (95% CI): 5 (2.12 to 11.95)], hyperlipidemia, smoking, male gender, and black race were associated with an increased risk. Our study revealed a significant increased risk of stroke development among people with HIV. A multitude of factors, encompassing sociodemographic characteristics, racial background, underlying health conditions, and personal behaviors, significantly elevate the risk of stroke in individuals living with HIV. The use of observational studies introduces inherent limitations, and further investigations are necessary to explore the underlying mechanisms of stroke in people with HIV for potential treatment strategies. HIV patients face a higher risk of stroke development, either ischemic and hemorrhagic strokes. Hypertension, diabetes, hyperlipidemia, smoking, male gender, and black race were identified as significant risk factors. Early identification and management of these risk factors are crucial in reducing stroke incidence among patients living with HIV.

Subcellular expression of MTA1, HIF1A and p53 in primary tumor predicts aggressive triple negative breast cancers: a meta-analysis based study.

The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with contradictory reports. Identification of a set of specific biomarkers from the very many number of proteins reported in the literature to predict prognosis of TNBC is an urgent clinical need. A systematic review of key molecular biomarkers in cohort studies that have been investigated for their role in breast cancer prognosis was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. A meta-analysis was used to evaluate their pooled hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) statistically. Immunohistochemical characterization of the meta-analyzed markers were performed in a cohort of 200 retrospective TNBC and 100 non TNBC patient tissues. Kaplan-Meier plot were used to evaluate disease free survival (DFS), and overall survival (OS). Cox regression models were used to evaluate predictors of DFS and OS. Using a meta-analytical approach, we consolidated the biomarker signatures associated with survival outcomes in breast cancers. The promising markers that emerged for the prediction of DFS and OS included E-Cadherin, Survivin, p53, MTA1, HIF1A, CD133, Vimentin and CK5/6. Evaluation of these markers in tumor tissue revealed that subcellular localization of p53, MTA1 and HIF1A had a significant association in predicting TNBC prognosis. Kaplan Meier plot revealed that p53 (OS p = 0.007, DFS p = 0.004), HIF 1A (OS p = 0.054, DFS p = 0.009) and MTA1 (OS p = 0.043, DFS = p = 0.001) expression in the primary tumor tissue were found to be significantly correlated with poor OS and DFS, whereas expression of Survivin (DFS p = 0.024) and E Cadherin (DFS p = 0.027) correlated with DFS alone in TNBC. Univariate analysis revealed that p53, HIF1A and MTA1 could be independent prognostic markers. Our study suggests cytoplasmic over expression of HIF1A, nuclear over expression of MTA1 and mutated p53 in the primary tumor tissue of TNBC have significance as markers predicting survival of TNBC patients.

The association between disability and all-cause mortality in low-income and middle-income countries: a systematic review and meta-analysis

There are 1·3 billion people with disabilities globally. On average, they have poorer health than their non-disabled peers, but the extent of increased risk of premature mortality is unknown. We aimed to systematically review the association between disability and mortality in low-income and middle-income countries (LMICs). We searched MEDLINE, Global Health, PsycINFO, and EMBASE from Jan 1, 1990 to Nov 14, 2022. Longitudinal epidemiological studies in any language with a comparator group that measured the association between disability and all-cause mortality in people of any age were eligible for inclusion. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to calculate the pooled hazard ratio (HR) for all-cause mortality by disability status. We then conducted meta-analyses separately for different impairment and age groups. We identified 6146 unique articles, of which 70 studies (81 cohorts) were included in the systematic review, from 22 countries. There was variability in the methods used to assess and report disability and mortality. The meta-analysis included 54 studies, representing 62 cohorts (comprising 270 571 people with disabilities). Pooled HRs for all-cause mortality were 2·02 (95% CI 1·77-2·30) for people with disabilities versus those without disabilities, with high heterogeneity between studies (τ2=0·23, I2=98%). This association varied by impairment type: from 1·36 (1·17-1·57) for visual impairment to 3·95 (1·60-9·74) for multiple impairments. The association was highest for children younger than 18 years (4·46, [3·01-6·59]) and lower in people aged 15-49 years (2·45 [1·21-4·97]) and people older than 60 years (1·97 [1·65-2·36]). People with disabilities had a two-fold higher mortality rate than people without disabilities in LMICs. Interventions are needed to improve the health of people with disabilities and reduce their higher mortality rate. UK National Institute for Health and Care Research; and UK Foreign, Commonwealth and Development Office.

Prognostic and clinicopathological value of systemic inflammation response index (SIRI) in patients with breast cancer: a meta-analysis

Background Many studies have explored the value of the systemic inflammation response index (SIRI) in predicting the prognosis of patients with breast cancer (BC); however, their findings remain controversial. Consequently, we performed the present meta-analysis to accurately identify the role of SIRI in predicting BC prognosis. Methods PubMed, Embase, Cochrane Library, and Web of Science databases were comprehensively searched between their inception and February 10, 2024. The significance of SIRI in predicting overall survival (OS) and disease-free survival (DFS) in BC patients was analyzed by calculating pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results Eight articles involving 2,997 patients with BC were enrolled in the present study. According to our combined analysis, a higher SIRI was markedly associated with dismal OS (HR = 2.43, 95%CI = 1.42–4.15, p < 0.001) but not poor DFS (HR = 2.59, 95%CI = 0.81–8.24, p = 0.107) in patients with BC. Moreover, based on the pooled results, a high SIRI was significantly related to T3–T4 stage (OR = 1.73, 95%CI = 1.40–2.14, p < 0.001), N1–N3 stage (OR = 1.61, 95%CI = 1.37–1.91, p < 0.001), TNM stage III (OR = 1.63, 95%CI = 1.34–1.98, p < 0.001), and poor differentiation (OR = 1.25, 95%CI = 1.02–1.52, p = 0.028). Conclusion According to our results, a high SIRI significantly predicted poor OS in patients with BC. Furthermore, elevated SIRI was also remarkably related to increased tumor size and later BC tumor stage. The SIRI can serve as a novel prognostic biomarker for patients with BC.

Association of herpes zoster with dementia: A systematic review and meta-analysis with GRADE assessment

Abstract Background: Herpes zoster (HZ) is the reactivation of varicella zoster virus predominantly affecting individuals aged over 50 years. Dementia is a prevalent age-related condition. The association between HZ and dementia was under dispute. Objectives: The objective of this study was to evaluate the evidence on the association of HZ with dementia. Methods: We conducted a systematic review and meta-analysis to evaluate the risk of dementia in individuals with a history of HZ compared to those without such a history. We searched PubMed, Embase, Medline, and Cochrane Library for studies published up to February 24, 2024. The risk of bias of studies was examined by the Newcastle–Ottawa Scale. A random effects model meta-analysis was performed to calculate the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI). Subgroup analyses on Alzheimer’s disease (AD), vascular dementia (VD), and cranial nerve involvement of HZ were executed. We used the GRADE methodology to assess the certainty of evidence. Results: We included seven cohorts and two case–control studies involving 3,550,251 subjects. The risk of bias of included studies was generally low. The meta-analysis found no association of HZ with dementia (pooled HR 1.00, 95% CI 0.94–1.07 for cohort studies; pooled OR 1.05, 95% CI 0.84–1.30 for case-control studies), with the certainty of evidence being very low. Subgroup analyses for AD, VD, and cranial never HZ also revealed no significant differences (pooled HR being 0.99, 95% CI 0.89–1.09; 1.04, 95% CI 0.85–1.27; and 1.36, 95% CI 0.76–2.43, respectively). Conclusion: The current evidence does not support an association of HZ with dementia.

Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients

Background: Scoring systems are a method of risk assessment used to stratify patients with metastatic renal cell carcinoma (mRCC) and guide systemic therapy. The variables are weighed equally when calculating total score. However, the difference of even 1 positive predictor can change one's risk category and therapy. Objective: To compare the relative strength of association between predictive variables and overall survival (OS) in mRCC. Methods: A search of Medical Literature Analysis and Retrieval System Online (MEDLINE) and Embase was conducted. Clinical studies, retrospective and prospective, were included if the association of at least 1 predictor and OS in patients with mRCC receiving first-line systemic therapy was evaluated. Meta-analysis was performed to generate pooled hazard ratios (HRs) and 95% CIs for OS for predictors with ≥ 5 included studies. Sensitivity analysis identified outlier heterogeneity and publication bias. Results: Sixty-six studies containing 29,366 patients were included. Meta-analysis indicated lung metastases, bone metastases, thrombocytosis, time to systemic therapy &lt; 1 year, liver metastases, hypercalcemia, anemia, elevated neutrophil-lymphocyte ratio, multiple metastatic sites, neutrophilia, poor Eastern Cooperative Oncology Group (ECOG) status, no previous nephrectomy, elevated lactate dehydrogenase, Fuhrman grade 3 or 4, central nervous system metastases, elevated C-reactive protein, and Karnofsky Performance Status &lt; 80% were associated with significantly worse OS. The HRs varied from 1.34 to 2.76, representing heterogeneity in predictive strength. The effects of study heterogeneity and publication bias were minimal to moderate across all predictors. Conclusions: Based on the differences in pooled HRs, prognostic strength between the variables is likely not equivalent. Restructuring scoring models, through inclusion of other variables and usage of relative weighting, should be considered to improve accuracy of risk stratification.