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Cureus Jun 2024Psoriasis is a chronic immune-mediated disease affecting the skin, nails, and/or joints. It is associated with systemic inflammation and may also be linked to an... (Review)
Review
Psoriasis is a chronic immune-mediated disease affecting the skin, nails, and/or joints. It is associated with systemic inflammation and may also be linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). The objectives of this study were to determine the overall risk of ASCVD in patients with psoriasis and to evaluate the risk according to ASCVD type and the severity of psoriasis. This was a systematic review and meta-analysis of observational studies reporting the association between psoriasis and one or more of the clinical types of ASCVD. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Excerpta Medica Database (EMBASE), Scopus, Bielefeld Academic Search Engine (BASE), and Google Scholar for relevant studies in the English language from the beginning of their records to July 2023. Study selection and data extraction were conducted by four independent reviewers. A total of 21 observational studies (three cross-sectional, one case-control, and 17 cohort) were included in this review, representing a total of 778,049 patients with psoriasis and 16,881,765 control subjects without psoriasis. The included studies had varying degrees of covariate adjustment, and thus, their findings may have been subject to residual confounding. All the meta-analyses used the adjusted effect sizes and were based on the random-effects model. However, the cohort studies were analysed separately from the non-cohort studies (the case-control and cross-sectional studies). There was a significant association between psoriasis and ASCVD (cohort studies: hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.14 to 1.28; I = 63%; p < 0.001; non-cohort studies: odds ratio (OR), 1.60; 95% CI, 1.34 to 1.92; I = 31%; p = 0.23). Psoriasis was also significantly associated with myocardial infarction (cohort studies: HR, 1.20; 95% CI, 1.10 to 1.31; I = 60%; p < 0.001; non-cohort studies: OR, 1.57; 95% CI, 1.15 to 2.15; I = 74%; p = 0.05), coronary artery disease (cohort studies: HR, 1.20; 95% CI, 1.13 to 1.28; I = 67%; p < 0.001; non-cohort studies: OR, 1.60; 95% CI, 1.34 to 1.92; I = 31%; p = 0.23), aortic aneurysm (HR, 1.45; 95% CI, 1.04 to 2.02; I = 67%; p = 0.08) but not with ischaemic stroke (HR, 1.14; 95% CI, 0.96 to 1.36; I = 44%; p = 0.17). Pooled analysis in terms of the severity of psoriasis showed that both mild (cohort studies: HR, 1.17; 95% CI, 1.08 to 1.26; I = 74%; p < 0.001; non-cohort studies: OR, 1.54; 95% CI, 1.25 to 1.90; I = 0%; p = 0.50) and severe (cohort studies: HR, 1.43; 95% CI, 1.23 to 1.65; I = 65%; p < 0.001; non-cohort studies: OR, 1.65; 95% CI, 1.29 to 2.12; I = 25%; p = 0.26) psoriasis were significantly associated with ASCVD. Psoriasis (including mild and severe disease) is associated with an increased risk of ASCVD, including coronary artery disease (CAD) and aortic aneurysm (AA). ASCVD risk assessment and prevention should be prioritised in all adult psoriasis patients. Future observational studies investigating the association between psoriasis and ASCVD should conduct a more comprehensive adjustment of covariates.
PubMed: 38947134
DOI: 10.7759/cureus.63379 -
Endoscopic Ultrasound 2024The altered anatomy in Roux-en-Y gastric bypass (RYGB) makes conventional endoscopic retrograde cholangiopancreatography (ERCP) a technically challenging procedure.... (Review)
Review
The altered anatomy in Roux-en-Y gastric bypass (RYGB) makes conventional endoscopic retrograde cholangiopancreatography (ERCP) a technically challenging procedure. EUS-directed transgastric ERCP (EDGE) and laparoscopic-assisted ERCP (LA-ERCP) are alternative modalities used with comparable efficacy and adverse events in such patients. We conducted a meta-analysis comparing EDGE and LA-ERCP to assess the efficacy and safety in patients with RYGB. We conducted a comprehensive literature search from inception to July 7, 2022, on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases using the core concepts of EDGE and LA-ERCP. We excluded case reports, case series (<10 patients), and review articles. Relative risk (RR) was calculated when comparing dichotomous variables, whereas mean difference was calculated for continuous outcomes. A 95% confidence interval (CI) and values (<0.05 considered significant) were also generated. The search strategy yielded a total of 55 articles. We finalized 4 studies with total 192 patients (75 EDGE and 117 LA-ERCP). The rates of technical success were not significantly different for LA-ERCP and EDGE (RR, 0.994; 95% CI, 0.939-1.051; = 0.830, = 0%) Similarly, no difference in adverse events was noted between the 2 groups (RR, 1.216; 95% CI, 0.561-2.634; = 0.620, = 10.67%). Shorter procedure time was noted for EDGE compared with the LA-ERCP group (mean difference, 91.53 min; 95% CI, 69.911-113.157 min; < 0.001, = 8.32%). EDGE and LA-ERCP are comparable in terms of efficacy and safety. In addition, EDGE has overall lower procedural time. Our study suggests that EDGE should be considered as a first-line therapy if expertise available.
PubMed: 38947118
DOI: 10.1097/eus.0000000000000032 -
MedRxiv : the Preprint Server For... Jun 2024Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal...
UNLABELLED
Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal models and computational modelling has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first conduct a systematic review of human TUS studies for perturbing neural function and alleviating brain disorders. We then collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the human TUS study reported outcomes to date ( 32 studies, 37 experiments). We find that parameters such as the duty cycle show some predictability regarding whether the targeted area's function is likely to be enhanced or suppressed. Given that human TUS sample sizes are exponentially increasing, we recognize that results can stabilize or change as further studies are reported. Therefore, we conclude by establishing an Iowa-Newcastle (inTUS) resource for the systematic reporting of TUS parameters and outcomes to support further hypothesis testing for greater precision in brain stimulation and neuromodulation with TUS.
HIGHLIGHTS
Systematic review of human TUS studies for enhancing or suppressing neural functionCollated set of hypotheses on using TUS to bias towards enhancement or suppressionMeta-analysis results identify parameters that may bias the directionality of effectsTUS resource established for systematic reporting of TUS parameters and outcomes.
PubMed: 38947047
DOI: 10.1101/2024.06.14.24308829 -
MedRxiv : the Preprint Server For... Jun 2024Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We...
UNLABELLED
Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4 (median odds ratio 9.3 vs. median true odds ratio 1.7), while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6 (2.7 vs. 1.7). We conclude that Bayesian estimation of odds ratio attenuates the exaggeration of significant effect sizes in underpowered studies. This approach could help improve patient counseling about the chance of seizure freedom after epilepsy surgery.
SHORT SUMMARY
We estimated the statistical power of studies predicting seizure freedom after epilepsy surgery. We exacted data from a Cochrane meta-analysis. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4, while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6. We conclude that Bayesian estimation of odds ratios attenuates the exaggeration of significant effect sizes in underpowered studies. This result could improve patient counseling regarding epilepsy surgery.
PubMed: 38947027
DOI: 10.1101/2024.06.21.24309313 -
MedRxiv : the Preprint Server For... Jun 2024Network meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by...
UNLABELLED
Network meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of network meta-analysis within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This paper introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including a network meta-analysis comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.
HIGHLIGHTS
Network meta-analysis extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis.A significant challenge in network meta-analysis is the lack of reported within-study correlations among treatment comparisons in the published studies. We propose a new method for network meta-analysis that ensures vaild statistical inference without the need for knowledge of within-study correlations.The proposed method employs a composite likelihood and a sandwich-type robust variance estimator, offering a computationally efficient and scalable solution, particularly for network meta-analysis with a large number of treatments and studies. The proposed method can be easily applied to any univariate network meta-analysis project without requiring knowledge of within-study correlations among treatment comparisons.
PubMed: 38947001
DOI: 10.1101/2024.06.19.24309163 -
MedRxiv : the Preprint Server For... Jun 2024Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown...
BACKGROUND
Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than (non- CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.
METHODS
In this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulating -CHIP compared to controls transplanted wild-type bone marrow.
RESULTS
Across all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m , and 24% had CHIP. Upon meta-analysis, non- CHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non- CHIP carriers, relative to non-carriers (β -0.61 ± 0.31 ml/min/1.73m , p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD, -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis.
CONCLUSION
Non- CHIP is a potentially targetable novel risk factor for CKD progression.
PubMed: 38946975
DOI: 10.1101/2024.06.19.24309181 -
MedRxiv : the Preprint Server For... Jun 2024Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million...
Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million children under 5-years-old worldwide. Complete anthropometric recovery after standard inventions is rare with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). Here we conduct a randomized controlled trial (RCT), involving 12-18-month-old Bangladeshi children from urban and rural sites, who after hospital-based treatment for SAM received a 3-month intervention with a microbiota-directed complementary food (MDCF-2) or a ready-to-use supplementary food (RUSF) as they transitioned to MAM. The rate of WLZ improvement was significantly greater with MDCF-2 than the more calorically-dense RUSF, as we observed in a previous RCT of Bangladeshi children with MAM without antecedent SAM. A correlated meta-analysis of aptamer-based measurements of 4,520 plasma proteins in this and the prior RCT revealed 215 proteins positively-associated with WLZ (prominently those involved in musculoskeletal and CNS development) and 44 negatively-associated proteins (related to immune activation), with a significant enrichment in levels of the positively WLZ-associated proteins in the MDCF-2 arm. Characterizing changes in 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome, its transition as each child achieves a state of MAM, and how specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and the rescue of growth faltering. These results provide a rationale for further testing the generalizability of the efficacy of MDCF and identify biomarkers for defining treatment responses.
PubMed: 38946965
DOI: 10.1101/2024.06.11.24307076 -
MedRxiv : the Preprint Server For... Jun 2024Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.
BACKGROUND
Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.
AIM
To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension.
METHODS
We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data.
RESULTS
Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials.
CONCLUSIONS
RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication.
CLINICAL PERSPECTIVE
What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.
PubMed: 38946962
DOI: 10.1101/2024.06.12.24308869 -
MedRxiv : the Preprint Server For... Jun 2024Atopic dermatitis (AD) is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to AD genetic...
UNLABELLED
Atopic dermatitis (AD) is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to AD genetic association studies are poised to boost power to detect genetic signal and identify ancestry-specific loci contributing to AD risk. Here, we present a multi-ancestry GWAS meta-analysis of twelve AD cohorts from five ancestral populations totaling 56,146 cases and 602,280 controls. We report 101 genomic loci associated with AD, including 15 loci that have not been previously associated with AD or eczema. Fine-mapping, QTL colocalization, and cell-type enrichment analyses identified genes and cell types implicated in AD pathophysiology. Functional analyses in keratinocytes provide evidence for genes that could play a role in AD through epidermal barrier function. Our study provides new insights into the etiology of AD by harnessing multiple genetic and functional approaches to unveil the mechanisms by which AD-associated variants impact genes and cell types.
DISCLOSURE STATEMENT
BRG, MO, CH, KMS are employees of AbbVie. FT was an employee of AbbVie at the time of the study. JEG (University of Michigan) has received research support from AbbVie, Janssen, Almirall, Prometheus Biosciences/Merck, BMS/Celgene, Boehringer Ingelheim, Galderma, Eli Lilly, and advisor to Sanofi, Eli Lilly, Galderma, BMS, Boehringer Ingelheim. MKS, RU, MTP, QL, RW, JMK, LCT are employees of University of Michigan and have no funding to disclose. MEM, AHS, FDM, DW, JTG, HH are employees of the Children's Hospital of Philadelphia and no funding to disclose. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.
PubMed: 38946956
DOI: 10.1101/2024.06.17.24308897 -
Clinical and Translational Radiation... Jul 2024Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the... (Review)
Review
BACKGROUND
Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes.
METHODS
We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the -analysis.
RESULTS
A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes.
CONCLUSIONS
The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.
PubMed: 38946805
DOI: 10.1016/j.ctro.2024.100801