Pooled Analysis Research Articles

Marginal zone lymphoma international prognostic index: a unifying prognostic index for marginal zone lymphomas requiring systemic treatment

Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy. Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnosis or after observation were used to train a prognostic model. The primary endpoint was progression-free survival (PFS) from start of treatment. The model was externally validated in a pooled analysis of two independent cohorts from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource and the University of Miami. We identified 501 eligible patients. After multivariable modeling, lactate dehydrogenase (LDH) above upper normal limit, hemoglobin <12g/dL, absolute lymphocyte count <1×109/L, platelets <100×109/L, and MZL subtype (nodal or disseminated) were independently associated with inferior PFS. The proposed MZL International Prognostic index (MZL-IPI) combined these 5 factors, and we defined low (LRG, 0 factors, 27%), intermediate (IRG, 1-2 factors, 57%) and high (HRG, 3+ factors, 16%) risk groups with 5-y PFS of 85%, 66%, and 37%, respectively (c-Harrell=0.64). Compared to the LRG, the IRG (Hazard Ratio [HR]=2.30, 95% CI 1.39-3.80) and HRG (HR=5.41, 95% CI 3.12-9.38) had inferior PFS. Applying the MZL-IPI to the pooled US cohort (N=353), 94 (27%), 192 (54%), and 67 (19%) patients were classified as LRG, IRG, and HRG, respectively, and the model was validated for PFS (log-rank test p=0.0018; c-Harrell=0.578, 95% CI 0.54-0.62). The MZL-IPI was also prognostic for OS in both the training and the external validation sets. MZL-IPI is a new prognostic score for use in all patients with MZL considered for systemic treatment. The MER was supported by P50 CA97274 and U01 CA195568.

Factors associated with poor adherence to medication in patients with diabetes and hypertension in Peru: findings from a pooled analysis of six years of population-based surveys

ObjectiveTo evaluate the factors associated with poor medication adherence in patients with DM and HTN in Peru. Study designA cross-sectional study. MethodsWe analyzed data from the Peruvian Demographic and Family Health Survey from 2014 to 2019. Adjusted prevalence ratios (aPR) and their respective 95% confidence intervals (CI) were estimated to determine the factors associated with poor medication adherence. ResultsWe included 15,184 participants with a known diagnosis of DM and HTN. The frequency of poor medication adherence was 37.1%, with 36.7% among individuals with HTN and 29.2% among individuals with DM. Those belonging to age groups above 30 years (aPR: 0.77; 95% CI: 0.74–0.80, for the group ≥ 60 years) had a lower frequency of poor medication adherence. Meanwhile, being male (aPR: 1.03; 95% CI: 1.01–1.05), lacking health insurance (aPR: 1.08; 95% CI: 1.05–1.10), belonging to lower wealth quintiles (aPR: 1.12; 95% CI: 1.08–1.17, for the first quintile), and living in the mountain region (aPR: 1.09; 95% CI: 1.06–1.12) were associated with a higher frequency of poor medication adherence. These findings were consistent when stratifying by the type of disease. ConclusionThis study showed that poor medication adherence is common in patients with HTN and DM in Peru and is associated with sociodemographic factors, highlighting the importance of public health approaches to improve adherence.

Impact of chemotherapy delay on long-term prognosis of laparoscopic radical surgery for locally advanced gastric cancer: a pooled analysis of four randomized controlled trials.

Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors. Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.

Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis.

International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

The effects of mindfulness-based interventions on alleviating academic burnout in medical students: a systematic review and meta-analysis

BackgroundMindfulness-based interventions have been tested to be the effective approach for preventing/reducing burnout in medical students. Therefore, this systematic review and meta-analysis aimed to synthesize the scientific evidence and quantify the pooled effect of MBIs on the burnout syndrome in medical students.MethodsA comprehensive literature search was conducted in the databases, including PubMed, Embase, ERIC, PsycINFO, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), China National knowledge Information Database (CNKI) and WanFang Database from database inception to February 2023 using the terms of “mindfulness”, “burnout” and “medical students”. Two reviewers independently reviewed the studies, and extracted the data of the eligible studies, as well as assessed the risk of bias. A random-effects model was employed to calculate the standardized mean differences (SMD) with 95% confidence intervals (CI) of overall burnout and its sub-domains of burnout (i.e., emotional exhaustion, cynicism, and academic efficacy).ResultsOf 316 records in total, nine studies (with 810 medical students) were ultimately included. The four RCT studies demonstrated an overall judgment of some concerns risk of bias, and the overall risk of biases of the five qRCT studies were judged as serious. In term of the SORT, the RCT and qRCT studies were evaluated as level 2 evidence, and the overall strength of recommendation was classified as B (limited-quality patient-oriented evidence). The pooled analysis showed that MBIs were associated with significant small to moderate improvements for medical students’ overall burnout (SMD=-0.64; 95% CI [-1.12, -0.16]; P = 0.009) in the included four RCTs, emotional exhaustion (SMD=-0.27; 95% CI [-0.50, -0.03]; P = 0.03) and academic efficacy (SMD = 0.43; 95% CI [0.20, 0.66]; P<0.001) in the four qRCTs.ConclusionsMBIs can serve as an effective approach for reducing burnout symptoms in medical students. Future high-quality studies with a larger sample size and robust randomized controlled trial methodologies should be obtained to reinforce the effectiveness of MBIs for reducing academic burnout in medical students.

Quantitative genomics-enabled selection for simultaneous improvement of lint yield and seed traits in cotton (Gossypium hirsutum L.)

Key messageA Bayesian linkage disequilibrium-based multiple-locus mixed model identified QTLs for fibre, seed and oil traits and predicted breeding worthiness of test lines, enabling their simultaneous improvement in cotton.Improving cotton seed and oil yields has become increasingly important while continuing to breed for higher lint yield. In this study, a novel Bayesian linkage disequilibrium-based multiple-locus mixed model was developed for QTL identification and genomic prediction (GP). A multi-parent population consisting of 256 recombinant inbred lines, derived from four elite cultivars with distinct combinations of traits, was used in the analysis of QTLs for lint percentage, seed index, lint index and seed oil content and their interrelations. All four traits were moderately heritable and correlated but with no large influence of genotype × environment interactions across multiple seasons. Seven to ten major QTLs were identified for each trait with many being adjacent or overlapping for different trait pairs. A fivefold cross-validation of the model indicated prediction accuracies of 0.46–0.62. GP results based on any two-season phenotypes were strongly correlated with phenotypic means of a pooled analysis of three-season experiments (r = 0.83–0.92). When used for selection of improvement in lint, seed and oil yields, GP captured 40–100% of individuals with comparable lint yields of those selected based on the three-season phenotypic results. Thus, this quantitative genomics-enabled approach can not only decipher the genomic variation underlying lint, seed and seed oil traits and their interrelations, but can provide predictions for their simultaneous improvement. We discuss future breeding strategies in cotton that will enhance the entire value of the crop, not just its fibre.

The Association Between Overall, Healthy, and Unhealthy Plant-Based Diet Index and Risk of Prediabetes and Type 2 Diabetes Mellitus: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

The global incidence of prediabetes and type 2 diabetes mellitus (T2DM) has increased substantially in recent years. Among the established, modifiable lifestyle factors associated with favorable prediabetes and T2DM risk, healthy dietary patterns have attracted considerable attention. The association between adherence to plant-based dietary pattern indices (PDIs), including the overall PDI (O-PDI), healthy PDI (H-PDI), and unhealthy PDI (U-PDI), and the risk of prediabetes and T2DM was investigated in this study. A literature search was conducted of the PubMed/Medline, Scopus, and Web of Sciences databases from their inception to February 2024. A systematic review and meta-analysis were conducted using random effects models and dose-response analyses. The Cochran Q test and the I2 statistic were used to evaluate heterogeneity between studies. A total of 16 publications, with data on a total of 721 012 participants, were identified for the meta-analysis. According to a pooled analysis, compared with the lowest category of O-PDI and H-PDI adherence, the highest category was associated with a 14% and 19% reduction in T2DM risk, respectively, for O-PDI (effect size [ES] = 0.86; 95%CI, 0.82-0.90; I2 = 57.7) and H-PDI (ES = 0.81; 95%CI, 0.75-0.88; I2 = 82.6). Greater adherence to U-PDI was significantly associated with an 10% increase in the risk of T2DM (ES = 1.10; 95%CI, 1.04-1.16). Consistent associations were found within the predetermined subgroups. As well, there was a nonlinear inverse association between O-PDI, H-PDI, and T2DM risk. No significant association was found between adherence to O-PDI (ES = 0.87; 95%CI, 0.75-1.01; I2 = 68%), H-PDI (ES = 0.99; 95%CI, 0.87-1.13; I2 = 0.0%), and U-PDI (ES = 1.09; 95%CI, 0.94-1.21; I2 = 22.9%) and risk of prediabetes. These findings underscore the importance of dietary selections within the framework of a plant-based dietary pattern, particularly when incorporating healthful, plant-based foods, which may have potential benefits in reducing the T2DM risk. PROSPERO registration no. CRD42023459851.

Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials.

Avenciguat is a novel, potent soluble guanylate cyclase activator in development for CKD. Two trials investigated avenciguat in diabetic (NCT04750577) and non-diabetic (NCT04736628) CKD. A prespecified pooled analysis of two randomized, double-blind, placebo-controlled trials of identical design. Adults with CKD (eGFR ≥20 and <90 mL/min/1.73 m2, urine albumin-to-creatinine ratio [UACR] ≥200 and <3500 mg/g) were randomized to 20 weeks of placebo or avenciguat 1, 2, or 3 mg three times daily (TID; adjunctive to angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker. Primary endpoint: change from baseline in UACR in 10-hour urine at week 20, analyzed per protocol. Secondary endpoint: UACR change from baseline in first morning void urine at week 20. Safety was monitored throughout. Overall 500 patients (mean age 62 years [SD 13]; mean eGFR 44 mL/min/1.73 m2 [SD 18] and median 10-hour UACR 719 [interquartile range 379-1285] mg/g ) received placebo (n=122) or avenciguat 1 mg (n=125), 2 mg (n=126), or 3 mg (n=127) TID. All 243 patients in study one and 27/261 patients in study two had diabetes. Avenciguat 1, 2, and 3 mg TID reduced UACR in 10-hour and first morning void urine versus placebo throughout the treatment period. At week 20, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UACR in 10-hour urine with avenciguat 1, 2, and 3 mg TID were -15.5% (-26.4, -3.0), -13.2% (-24.6, -0.1), and -21.5% (-31.7, -9.8), respectively, analyzed per protocol. Corresponding changes in first morning void urine were -19.4% (-30.0, -7.3), -15.5% (-26.9, -2.5), and -23.4% (-33.5, -11.8), respectively. Avenciguat was well tolerated, overall frequency of adverse events was low and similar to placebo. The number of patients who discontinued study drug due to adverse events with avenciguat 1, 2, and 3 mg TID were 5 (4%), 11 (9%), and 11 (9%), respectively, compared with 4 (3%) in the placebo group. Avenciguat lowered albuminuria, and was well tolerated in patients with CKD.

Systematic review and meta-analysis: proton pump inhibitors slightly decrease the severity of chronic cough

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI − 0.22; 0.88), 0.31 (CI − 1.74; 2.35), 0.32 (CI − 0.29; 0.93) and 0.34 (CI − 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI − 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.

Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials.

CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC). These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity. The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients. In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.

Pulsed field ablation for atrial fibrillation: efficacy, safety and lesion durability in patients with recurrences

Abstract Background Initial findings from feasibility studies regarding pulsed field ablation (PFA) for atrial fibrillation (AF) indicated substantial efficacy and safety of the procedure, including high rates of lesion durability upon systematic remapping. However, data regarding PFA for AF in real-life settings remains scarce. Objective This pooled analysis was conducted to provide insights into PFA’s practical performance and safety profile in real-life settings, as well as information regarding lesion durability in patients with arrhythmia recurrences. Methods MEDLINE/EMBASE databases were searched up to August 31, 2023 for studies including patients undergoing catheter ablation for AF using PFA. Independent searches were performed by 2 investigators (K.B. and K.V.). Feasibility studies, first-in-human studies, small studies with population overlap, and those with a follow-up duration shorter than one year were excluded from the analysis. Authors were contacted for missing information or to confirm the absence of population overlap. Two investigators (K.B. and K.V.) independently extracted data from studies meeting inclusion criteria. Any discrepancies were resolved by a third experienced reviewer. Results We assessed for relevance a total of 952 references. Five studies met the inclusion criteria (comprising of 1 randomized trial, 2 single arm prospective trials, and 2 post-market registries), with a combined cohort of 2,359 patients who underwent PFA for AF. The pooled rate of acute PVI was 99.6% (95%CI 99.2-99.8, I2:7%). The pooled one-year rates of freedom from atrial arrhythmia for individuals with paroxysmal or persistent AF were 79.5% (95%CI 75.7-83.1, I2:70%) and 67.5% (95%CI 60.9-73.7, I2:60%), respectively. Among patients who underwent repeat catheter ablation for AF recurrences (n=197), the pooled rate of durable PVI per patient was 48.9% (95%CI 30.4-67.7, I2:71%), while durable PVI per vein was 74.1% (95%CI 65.1-82.2, I2: 75%). Incidence of overall complications and serious procedure-related complications were 1.8% (95% CI: 0.2-4.8, I2: 92%) and 0.9% (95% CI: 0.3-1.7, I2:59%), respectively. The most prevalent complication types were access site complications (48.6%), pericardial effusions/tamponades (24.8%) and stroke/transient ischemic attack (9.5%). No esophageal damage or PV stenosis were reported . There was one case of persistent phrenic nerve palsy and two cases of reversible coronary spasm (during ablation along the posterior mitral isthmus, and during PVI, both resolving with intracoronary nitroglycerin). Conclusion This pooled analysis confirms that catheter ablation of atrial fibrillation using pulsed field ablation is associated with high rates of atrial arrhythmia-free survival at one year while maintaining low rates of procedure-related complications. Durable pulmonary vein isolation is observed in approximately half of the patients undergoing a repeat procedure for atrial fibrillation recurrence.

Meta-Analysis of Efficacy of Platelet-Rich Plasma Combined with Minoxidil for Androgenetic Alopecia.

Androgenetic alopecia (AGA) is a prevalent type of hair loss that impacts individuals of both genders. Platelet-rich plasma (PRP) and minoxidil have been employed as therapeutic interventions for AGA, yet the efficacy of their concurrent use remains ambiguous. To perform a comprehensive review and meta-analysis aimed at evaluating the effectiveness of platelet-rich plasma (PRP) in combination with minoxidil for the treatment of androgenetic alopecia (AGA). We conducted a comprehensive search of the databases PubMed, Embase, Web of Science, and Cochrane Library, encompassing their complete records up until December 2023. Eligible studies were randomized controlled trials that compared the combination of PRP and minoxidil with minoxidil or PRP alone in patients with AGA. The primary outcome measure was the change in hair growth as assessed by the hair density or hair thickness. Secondary outcome measures included patient satisfaction, and global photographic assessment. A total of 6 studies involving 343 participants were included in this meta-analysis. The results showed that PRP combined with minoxidil significantly improved hair growth compared to minoxidil or PRP alone. The pooled analysis demonstrated a significant increase in hair density (weighted mean difference [WMD] = 9.14; 95% confidence interval [CI]: 6.57-11.70) and hair diameter (WMD = 4.72; 95% CI 3.21-6.23) in the PRP combined with minoxidil group. Moreover, patients receiving PRP combined with minoxidil reported higher satisfaction rates compared to those using minoxidil or PRP alone. This meta-analysis suggests that PRP combined with minoxidil is an effective treatment for AGA, providing significant improvement in hair growth and patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Postoperative atrial fibrillation is associated with late mortality independently of patient comorbidities: a systematic review and reconstructed individual patient data meta-analysis

Abstract Background Early postoperative atrial fibrillation (POAF) is the most common complication within the first days after cardiac surgery. It is hypothesized to result from perioperative stressors such as inflammation, oxidative stress, and increased adrenergic tone, along with an advanced arrhythmogenic substrate resulting from advanced age and cardiovascular comorbidities including hypertension, heart failure, or chronic obstructive pulmonary disease (COPD).[1, 2] Although prior studies have demonstrated an association between in-hospital POAF and late mortality or stroke, it is questionable whether these long-term adverse events result from the occurrence of early-POAF or, rather, from the advanced cardiovascular risk profile that partly underlies the development of early-POAF.[3] Purpose To investigate the association of early-POAF with late mortality (primary outcome) and stroke (secondary outcome) in patients undergoing cardiac surgery after adjustment for age and the cardiovascular risk profile. Methods A systematic search, covering PubMed, EMBASE, and the Cochrane Library, was conducted to identify studies reporting on late mortality after cardiac surgery in patients with and without new-onset POAF during hospitalization. Articles meeting the criteria, which included Kaplan-Meier (KM) curves along with risk tables, were included for a pooled analysis of late mortality and stroke. Individual time-to-event data were reconstructed from the KM curves and incorporated into a multivariable frailty Cox model. The model included adjustments for age, sex, preoperative cardiovascular comorbidity profile (hypertension, diabetes mellitus [DM], peripheral artery disease [PAD], history of stroke, heart failure, and COPD), type of surgery, and a frailty term (study variable). Results In total, 28 studies were included in the analysis for late mortality (N=112931), and 9 studies in the analysis for late stroke (N=35004). Overall, 31039 patients had early-POAF with a pooled incidence of 29.7% (95% CI: 25.7-34.1%). Patients developing POAF were older (68.5 vs. 64.1 years old, p&amp;lt;0.001), had a more frequent history of PAD (9.5% vs. 7.8%, p=0.026), a history of stroke (9.3% vs. 7.6%, p&amp;lt;0.001), heart failure (17.2% vs. 15.1%, p&amp;lt;0.001), and COPD (12.5% vs. 9.7%, p&amp;lt;0.001). Unadjusted analysis showed that POAF was strongly associated with increased late mortality (Hazard Ratio [HR]=1.64, 95% CI: 1.59 to 1.69, p&amp;lt;0.001) and late stroke (HR=1.46, 95% CI: 1.36 to 1.58, p&amp;lt;0.001) (Figure 1). POAF was an independent predictor for late mortality (HR=1.46, 95% CI: 1.36 to 1.58, p&amp;lt;0.001) but not for late stroke (HR=1.10, 95% CI: 0.85 to 1.43, p=0.48) after adjustment for age, cardiovascular comorbidity profile, type of surgery, and frailty (study term). Conclusion Early-POAF after cardiac surgery is an independent predictor of mortality in the years following discharge after cardiac surgery, regardless of age, cardiovascular comorbidity profile, and type of surgery.Figure 1

#1595 Use of machine learning directed interventions to reduce fluid related hospital admissions in hemodialysis patients

Abstract Background and Aims Patients with end-stage kidney disease (ESKD) are hospitalized nearly two times per year on average; volume overload, infections and other cardiovascular complications are amongst the most common causes of hospitalization. We developed a machine learning (ML) model to predict haemodialysis (HD) patients at imminent risk of hospitalization due to fluid overload within the next 7 days. Patients identified as high risk by the model were assessed, intervened, and triaged on by group of telephonic nurses. The goal of this analysis is to evaluate the impact of the ML model-directed interventions on fluid related hospital admissions and all cause hospital admissions. Method We used data from a group of ESKD patients on HD modality who were identified as high risk by the ML model between baseline months April 2022 and June 2023. These high-risk patients were eligible to receive an assessment by telephonic nurses. The follow-up months were defined as the month immediately following the baseline month. Intervention group was identified as the high-risk patients where a clinical chart review was performed with needs identified, clinical chart review was performed and patients were managed by the clinic, some contact was made over phone/mail by the telephonic nurse, or some clinical recommendation was made. High-risk patients without any intervention or activity documented by the telephonic nurse served as the control population. We used linear regression analysis with repeated measures to account for within patient variability to produce estimated outcome rates with 95% confidence intervals adjusting for baseline factors such as average ML model risk score, average albumin, gender, race, age, vintage, comorbidities like chronic heart failure, diabetes, hypertension, ischemic heart disease, and primary insurance. Results There were 15,878 patients (36,932 patient months) in the group that received intervention; there were 51,800 patients (398,594 patient months) in the group that did not receive intervention. The pooled analysis (Table 1) showed a 38% reduction in all cause hospital admission rate between the baseline and follow-up months for the group that received intervention and there was a 34% reduction in all cause hospital admission rate for the group that did not receive any intervention. There was a 36% reduction in the fluid related hospital admission rate between the baseline and follow-up months for the group that received intervention and there was a 32% reduction in the fluid related hospital admission for the group that did not receive any intervention. Conclusion There is a larger magnitude reduction in fluid related hospital admissions and all cause hospital admissions between the baseline and follow-up months for the high-risk group as identified by the ML model that received intervention from the nurses compared to those that did not receive any intervention. Further studies are necessary to prove this association.

#2887 Interdialytic weight gain and low dialysate sodium concentration in patients on chronic hemodialysis: a systematic review and meta-analysis

Abstract Background and Aims In many patients on chronic hemodialysis, interdialytic weight gain (IDWG) is greater than 4.0%-4.5% of dry weight, the value recommended by the international guidelines. High IDWG is a condition associated with risk of all-cause mortality and hospitalization and it depends on elevate intake of fluids and/or foods. More specifically, high intake of water is secondary to the disturbing and constant presence of thirst in such patients, so the limitation of the IDWG is a challenge both for the patients and the physicians. Low dialysate sodium levels can significantly reduce thirst as well as the water intake in the interdialytic period because they can increase the removal of sodium during the dialytic session, and this leads to a reduced content of sodium in the body. The present systematic review and meta-analysis aims at evaluating the efficacy of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic hemodialysis patients. Method Studies were eligible for inclusion if they were English language papers published in a peer-reviewed journal and met the following inclusion criteria: 1) Primary research studies in adult patients (over 18 years of age), 2) Included patients with end-stage renal disease on chronic hemodialysis since at least 6 months; 3) Compared standard (138-140 mmol/l) or high (&amp;gt;140 mmol/l) dialysate sodium concentration with low (&amp;lt;138 mmol/l) dialysate sodium concentration; 4) Included one outcome of interest: interdialytic weight gain. We excluded studies on pediatric patients, pre-dialysis CKD patients, acute kidney injury patients, ESRD patients with other renal replacement therapy modalities such as peritoneal dialysis and transplant. Medline, PubMed, Web of Science, and the Cochrane Library were searched for studies comparing low or high dialysate sodium concentration. Outcome of interest was IDWG. The quality of reporting for each study was performed using the Quality Assessment Tool of Controlled Intervention Studies of the National Institutes of Health. The quality of reporting of each cross-over study was performed using the Revised Cochrane Risk of Bias (RoB) tool for cross-over trials as proposed by Ding et al. Results Nineteen studies (710 patients) were included in the analysis: 15 were cross-over and 4 parallel randomized controlled studies. In cross-over studies, pooled analysis revealed that dialysate sodium concentration reduced IDWG with a pooled MD of −0.40 kg (95% CI -0.50 to −0.30; P &amp;lt; 0.00001). The systematic review of four parallel, randomized, studies revealed that the use of a low dialysate sodium concentration was associated with a significant reduction of the IDWG in two studies, sustained and almost significant (P=0.05) reduction in one study, and not significant reduction in one study. In most studies, the frequency of intradialytic hypotensive events did not differ significantly between low and high sodium dialysate hemodialysis. The GRADE methodology was used to assess the quality of the body of retrieved evidence and studies risk of bias, inconsistency and imprecision were estimated as low. Conclusion Low dialysate sodium concentration reduces the IDWG in patients on chronic hemodialysis.

Safety and Efficacy of Resmetirom in the treatment of patients with NASH and Liver Fibrosis: A systematic review and meta-analysis

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-β agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom’s use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction (SMD -4.61, 95% CI -6.77 to -2.44, P &lt; 0.0001), NASH resolution without worsening fibrosis (RR 2.51, 95% CI 1.74 to 3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20 to 4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.

The role of plant-based dietary patterns in reducing COVID-19 risk and/or severity in adults: A systematic review and meta-analysis of observational studies

Background & AimsPlant-based dietary patterns (PBDs) might protect against COVID-19 risk and reduce severity of infection. This systematic review with meta-analysis aimed to examine the association between PBDs and risk of COVID-19 infection, hospitalization, intensive care unit (ICU) admission, and/or mortality, in adults. MethodsPubmed, Embase, CINAHL and Web of Science were searched for observational studies, published in English up to 3rd April 2023, comparing the highest with the lowest adherence to a specific PBD. Data were screened, extracted, and risk of bias assessed using the Newcastle-Ottawa Quality Assessment Scale, by independent reviewers. ResultsSeven studies (one cross-sectional, three case-control, and three prospective cohort), reporting on 649,315 participants, were eligible. Across them, there were 8,512 events of COVID-19 infection (six studies), and 206 events of COVID-19 hospitalization (four studies), in addition to one study reporting on a composite hospitalization outcome (740 events). The pooled analysis showed that PBDs are associated with a 59% (odds ratio (OR)=0.41, 95% confidence intervals (CI) 0.23-0.59; two studies) and 18% (OR=0.82, 95% CI 0.78-0.85; three studies) reduction in COVID-19 infection risk in case-control and cohort studies, respectively. The pooled analysis of one case-control and two cohort studies showed an inverse association between high adherence to a PBD and risk of COVID-19 hospitalization (OR=0.38, 95% CI 0.04-0.72). ConclusionFindings suggest a protective role of PBDs against the risk of COVID-19 infection and severity. More studies are needed to establish the association between PBDs and risk of ICU admission and mortality due to COVID-19.

Indications for oropharyngeal biopsy in head and neck squamous cell carcinoma of unknown primary: A systematic review (HNSCCUP).

Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary. The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP. Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative. High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.

Lag effect of ambient temperature on respiratory emergency department visits in Beijing: a time series and pooled analysis

BackgroundAlthough the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China.MethodsDaily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China.ResultsThe single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0–21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender.ConclusionsTemperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases.

Adherence to Healthy and Unhealthy Plant-Based Diets and the Risk of Gout

Plant-based diets are increasing in popularity due, in part, to their health benefits for selected cardiometabolic diseases as well as favorable environmental impact. Little is known about how such a diet is related to gout risk. To examine associations between adherence to a plant-based diet (including healthy and unhealthy versions of this diet), as well as its 18 individual food groups, and incident gout. This prospective cohort study used data from population-based cohorts of US men and women enrolled in the Health Professionals Follow-Up Study (1986-2012) and Nurses' Health Study (1984-2010). Participants were men and women free of gout at baseline. Statistical analyses were performed over March 2020 to August 2023. An overall plant-based diet index (PDI), as well as healthy (hPDI) and unhealthy (uPDI) versions of this index that emphasize healthy and less healthy plant-based foods, respectively. These diet indices were comprised of 18 food groups, assessed using a validated semiquantitative food frequency questionnaire. Incident cases of gout that were confirmed with a supplementary questionnaire to meet the preliminary American College of Rheumatology survey criteria for gout. Cox proportional hazards regression models were used to evaluate multivariable-adjusted associations of all 3 PDIs with incident gout using quintiles (Q) of adherence. Among a total of 122 679 participants (mean [SD] age, 53.8 [9.8] years among 43 703 men; mean [SD] age, 50.9 [7.2] years among 78 976 women) over 2 704 899 person-years of follow-up, 2709 participants experienced incident gout. The overall PDI was not significantly associated with gout in either cohort (Q5 vs Q1 pooled hazard ratio [HR], 1.02 [95% CI, 0.89-1.17]; P for trend = .63). In the pooled analysis, hPDI was significantly inversely associated with risk of gout (Q5 vs Q1 HR, 0.79 [95% CI, 0.69-0.91]; P for trend = .002), while the uPDI was positively associated with risk of gout (Q5 vs Q1 HR, 1.17 [95% CI, 1.03-1.33]; P for trend = .02), particularly in women (Q5 vs Q1 HR, 1.31 [95% CI, 1.05-1.62]; P for trend = .01). In analysis of individual food groups, higher intakes of certain healthy plant foods, such as whole grains (pooled HR per 1 serving/d, 0.93 [95% CI, 0.89-0.97]) and tea and coffee (pooled HR per 1 serving/d, 0.95 [95% CI, 0.92-0.97]), as well as dairy (pooled HR per 1 serving/d, 0.86 [95% CI, 0.82-0.90]), were independently associated with a lower risk of gout, while selected unhealthy plant foods, such as fruit juice (pooled HR per 1 serving/d, 1.06 [95% CI, 1.00-1.13]) and sugar-sweetened beverages (pooled HR per 1 serving/d, 1.16 [95% CI, 1.07-1.26]) were associated with increased risk of gout. The findings of this prospective cohort study of PDIs and gout support current dietary recommendations to increase consumption of healthy plant foods while lowering intake of unhealthy plant foods to mitigate gout risk.