Large Meta-analysis Research Articles

Investigating the causal relationship between ankylosing spondylitis and osteoporosis in the European population: a bidirectional Mendelian randomization study.

Ankylosing Spondylitis (AS) is an inflammatory condition affecting the spine, which may lead to complications such as osteoporosis (OP). Many observational studies have demonstrated a close relationship with strong evidence between OP and AS. The combination of AS and OP is already an indisputable fact, but the exact mechanism of AS complicated with OP is unclear. To better prevent and treat OP in patients with AS, it is necessary to understand the specific mechanism of OP in these patients. In addition, there is a study showing that OP is a risk factor for AS, but the causal relationship between them is not yet clear. Therefore, we conducted a bidirectional Mendelian randomization (MR) analysis to determine whether there is a direct causal effect between AS and OP and to investigate the co-inherited genetic information between the two. Bone mineral density (BMD) was used as a phenotype for OP. The AS dataset was taken from the IGAS consortium and included people of European ancestry (9,069 cases and 13,578 controls). BMD datasets were obtained from the GEFOS consortium, a large GWAS meta-analysis study, and the UK Biobank and were categorized based on site (total body (TB): 56,284 cases; lumbar spine (LS): 28,498 cases; femoral neck (FN): 32,735 cases; forearm (FA): 8,143 cases; and heel: 265,627 cases) and age (0-15: 11,807 cases; 15-30: 4,180 cases; 30-45: 10,062 cases; 45-60: 18,062 cases; and over 60: 22,504 cases).To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used due to its good statistical power and robustness. The presence of heterogeneity was evaluated using Cochran's Q test. Pleiotropy was assessed utilizing MR-Egger regression and MR-pleiotropy residual sum and outlier (MR-PRESSO). Generally, there were no significant causal associations between genetically predicted AS and decreased BMD levels. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. However, there was a sign of a connection between genetically elevated BMD levels and a decreased risk of AS (Heel-BMD: OR = 0.879, 95% CI: 0.795-0.971, P = 0.012; Total-BMD: OR = 0.948, 95% CI: 0.907-0.990, P = 0.017; LS-BMD: OR = 0.919, 95% CI: 0.861-0.980, P = 0.010). The results were confirmed to be reliable by sensitivity analysis. This MR study found that the causal association between genetic liability to AS and the risk of OP or lower BMD in the European population was not evident, which highlights the second effect (e.g., mechanical reasons such as limited movement) of AS on OP. However, genetically predicted decreased BMD/OP is a risk factor for AS with a causal relationship, implying that patients with OP should be aware of the potential risk of developing AS. Moreover, OP and AS share similar pathogenesis and pathways.

Practice change: No benefit of extended lymphadenectomy at radical cystectomy in patients with muscle invasive bladder cancer

For many decades, extended pelvic lymph node dissection has been an integral part during radical cystectomy for patients with muscle invasive bladder cancer. This practice was based on large retrospective meta-analyses suggesting an oncologic benefit to an extended dissection. This mini review and meta-analysis includes the two available randomized trials in the current literature. Therefore, it can be considered as the strongest level of evidence regarding the prognostic benefit of an extended pelvic lymphadenectomy. Based on current randomized data, standard pelvic lymph node dissection up to the level of iliac bifurcation is sufficient, and extension of the dissection above this level does not provide any additional oncologic benefit.

Biomarkers for Response to Anti-PD-1/Anti-PD-L1 Immune Checkpoint Inhibitors: A Large Meta-Analysis.

Immune checkpoint inhibitors (ICIs) that block PD-1/PD-L1 have consistently demonstrated durable clinical activity across multiple histologies but have low overall response rates for many cancers-indicating that too few patients benefit from ICIs. Many studies have explored potential predictive biomarkers (eg, PD-1/PD-L1 expression, tumor mutational burden [TMB]), no consensus biomarker has been identified. This meta-analysis combined predictive accuracy metrics for various biomarkers, across multiple cancer types, to determine which biomarkers are most accurate for predicting ICI response. Data from 18,792 patients from 100 peer-reviewed studies that evaluated putative biomarkers for response to anti-PD-1/anti- PD-L1 treatment were meta-analyzed using bivariate linear mixed models. Biomarker performance was assessed based on the global area under the receiver operating characteristic curve (AUC) and 95% bootstrap confidence intervals. PD-L1 immunohistochemistry, TMB, and multimodal biomarkers discriminated responders and nonresponders better than random assignment (AUCs >.50). Excluding multimodal biomarkers, these biomarkers correctly classified at least 50% of the responders (sensitivity 95% CIs, >.50). Notably, variation in biomarker performance was observed across cancer types. Although some biomarkers consistently performed better, heterogeneity in performance was observed across cancer types, and additional research is needed to identify highly accurate and precise biomarkers for widespread clinical use.

Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis

ObjectiveTo investigate potential moderating effects of resistance exercise dose components including intensity, volume and frequency, for the management of common tendinopathies.DesignSystematic review with meta-analysis and meta-regressions.Data sourcesIncluding but not limited...

Effect of CD274 (PD-L1) overexpression on survival outcomes in 10 specific cancers: a systematic review and meta-analysis

AimThe prognostic role of CD274 (programmed cell death ligand 1 (PD-L1)) overexpression has been examined in many studies. However, the results are controversial and conflicting. The present study aims to...

Tickle Me ECMO…Differences and Outcomes Unearthed for Kids Requiring Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Syndrome Coronavirus 2-Associated Disease.

Tickle Me ECMO…Differences and Outcomes Unearthed for Kids Requiring Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Syndrome Coronavirus 2-Associated Disease.

Abstract 720: Integration Of Population Genetic And Human Knockout Studies With Smooth Muscle Cell Lineage Tracing In Mouse Models Identifies Novel Targets For Atherosclerosis And Cardiovascular Risk.

Despite lipid-lowering therapies, residual cardiovascular disease risk remains a major unmet clinical need. Large-scale genetic analyses have identified >250 loci for coronary artery disease (CAD) risk. Genes that function in vascular smooth muscle cells (SMC) are causal at several loci, yet the causal genes at most loci remain unknown. Using single cell profiling and SMC lineage tracing in mouse models, we and others have shown that SMC transition through an intermediate state to SMC-derived cells (SDC) with protective or harmful phenotypes for plaque stability. In this study, we integrated SMC lineage tracing in mouse models with ongoing analyses in > 1 million human participants with whole-genome (WGS) and whole-exome sequencing (WES) data, as well as rare variant analysis of human “knockouts” (homozygous for predicted loss-of-function variants) for a novel gene discovery pipeline (Figure 1). Through WES in 76,000 highly consanguineous participants in the Pakistan Genomic Resource (PGR), we assembled the largest global cohort of human KOs. At non-lipid CAD loci from a recent large multi-ethnic meta-analysis (~1.1 million participants), we prioritized genes as potentially causal in SMC/SDC as those that are expressed and regulated in human or mouse arteries and SMC in atherosclerosis progression. Through gene burden testing and analyses of rare predicted loss-of-function (pLoF) and damaging (pDMs) variants in the largest CAD WES/WGS meta-analyses we enriched for causal genes. We restricted to genes with at least 5 pLoF carriers in PGR to facilitate recall studies in Pakistan. Final prioritization incorporated state-of-the-art fine mapping and co-localization analyses as well as biological plausibility. From an initial pool of 1696 genes, our gene discovery pipeline prioritized 15 SMC/SDC genes, and initial recall in PGR identified multiple large pedigrees for mutations in candidate causal genes PDE3A, SERPINH1, HHIPL1, and ZEB2.

Abstract 371: Functional Characterization Of A Ccm2 Mutation Associated With Coronary Artery Disease

Introduction: Coronary Artery Disease (CAD) remains the leading cause of death despite effective therapies to lower serum cholesterol. To identify new mechanisms of disease for prevention and therapy, several recent genome-wide association studies (GWAS) have identified hundreds of loci with statistically significant association with CAD (5x10^-8). In a recent large meta-analysis of 181,522 cases and over 1 million controls subjects, the CARDIOGRAM consortium identified a locus with genome-wide significant association with CAD in the chromosome 7p14. Methods and Results: We functionally interrogated the chromosome 7p14 GWAS association with a combination of population genetics and in vitro experimental methods. Statistical fine-mapping identified a lead variant in the locus, rs2107732, with a posterior probability of association 63.5%. This variant has a significant association with CAD of P = 1.53 x 10^-8). The minor allele is present in 9.2% of subjects, reduced risk of CAD (OR=0.92), and encodes a valine to isoleucine substitution in CCM2 at amino acid position 74 (V74I). To understand the importance of CCM2 and the coding mutation V74I in CAD, we first knocked-down CCM2 in immortalized human aortic endothelial cells (teloHAECs). KLF2, a critical athero-protective gene, was upregulated upon CCM2 knockdown. However, overexpressing wildtype CCM2 decreased the level of KLF2, and overexpressing CCM2 with the V74I mutation downregulated KLF2 to a comparable level. To circumvent the potential interference from the endogenous wildtype CCM2, we used CRISPR-Cas9-mediated homology-directed repair in teloHAECs and generated multiple clones carrying homozygous CCM2 V74I mutation. These clones will serve as useful tools to understand the mechanism by which CCM2 V74I mutation decreases the risk of CAD. Conclusions: We identified a missense mutation in CCM2 which is associated with a decreased risk of coronary artery disease. Functional analysis of CCM2 in arterial endothelial cells suggests that the protective effect is through upregulation of KLF2 expression.

Digital Clock Drawing as an Alzheimer’s Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults

BackgroundAlzheimer’s disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.ObjectiveWe examined the validity of DCTclock™ (a digitized clock drawing task) as an AD susceptibility biomarker.DesignWe used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclock™ composite scores as dependent measures.SettingWe used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date.ParticipantsThe sample consisted of 2,398 older adults ages 60–94 with DCTclock™ data (mean age of 72.3, 55% female and 92% White).MeasurementsPRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD).ResultsResults showed that DCTclock™ performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclock™ Total Score as well as lower composite scores for Information Processing Speed (both command & copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women.ConclusionsOur results indicate that higher AD genetic risk is associated with poorer DCTclock™ performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS.

Association of Laparoscopic Surgery with Improved Perioperative and Survival Outcomes in Patients with Resectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis from Propensity-Score Matched Studies

BackgroundRecent studies have associated laparoscopic surgery with better overall survival (OS) in patients with hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). The potential benefits of laparoscopic liver resection (LLR) over open liver resection (OLR) have not been demonstrated in patients with intrahepatic cholangiocarcinoma (iCC).MethodsA systematic review of the PubMed, EMBASE, and Web of Science databases was performed to search studies comparing OS and perioperative outcome for patients with resectable iCC. Propensity-score matched (PSM) studies published from database inception to May 1, 2022 were eligible. A frequentist, patient-level, one-stage meta-analysis was performed to analyze the differences in OS between LLR and OLR. Second, intraoperative, postoperative, and oncological outcomes were compared between the two approaches by using a random-effects DerSimonian-Laird model.ResultsSix PSM studies involving data from 1.042 patients (530 OLR vs. 512 LLR) were included. LLR in patients with resectable iCC was found to significantly decrease the hazard of death (stratified hazard ratio [HR]: 0.795 [95% confidence interval [CI]: 0.638–0.992]) compared with OLR. Moreover, LLR appears to be significantly associated with a decrease in intraoperative bleeding (− 161.47 ml [95% CI − 237.26 to − 85.69 ml]) and transfusion (OR = 0.41 [95% CI 0.26–0.69]), as well as with a shorter hospital stay (− 3.16 days [95% CI − 4.98 to − 1.34]) and a lower rate of major (Clavien-Dindo ≥III) complications (OR = 0.60 [95% CI 0.39–0.93]).ConclusionsThis large meta-analysis of PSM studies shows that LLR in patients with resectable iCC is associated with improved perioperative outcomes and, being conservative, yields similar OS outcomes compared with OLR.

Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses. Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis. Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified. This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

The Three Most Discussed Questions in Carotid Artery Surgery. Review of Russian and Foreign Studies in the Last Five Years

This literature review analyzes Russian and foreign publications over the past five years on the three most discussed issues related to carotid artery surgery: 1.Which is more effective: eversion carotid endarterectomy or conventional carotid endarterectomy with patch closure? 2. Which is better: carotid endarterectomy (CEE) or carotid angioplasty and stenting (CAS)? 3. How soon after the development of ischemic stroke should cerebral revascularization be performed? The authors of the article came to the following conclusions: 1. According to the majority of large studies and meta-analyses, conventional CEE with patch closure is associated with a higher risk of internal carotid artery restenosis compared to eversion carotid endarterectomy. Single-center trials with small samples of patients do not find statistical differences between the outcomes of applying both surgical techniques. 2. Large multicenter randomized trials are required to address the effectiveness of CEA and CAS in symptomatic and asymptomatic patients. To date, there has been no consensus on this matter. 3. CEE and CAS can be equally effective and safe in the most acute and acute periods of ischemic stroke when performed in the presence of a mild neurological deficit and the ischemic brain lesion not exceeding 2.5 cm in diameter. Nevertheless, the choice of treatment strategy should be made strictly personalized by a multidisciplinary council based on the experience of the institution and current recommendations.

Genetic contribution of caspase-8 variants and haplotypes to breast cancer risk and prognosis: a case-control study in Iran

PurposeMultiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population.MethodsIn a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR.Resultsrs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32–2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23–0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14–0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02–0.43)].ConclusionThe present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.

Associations between diet and incidence risk of lung cancer: A Mendelian randomization study.

Observational studies have revealed associations between diet and lung cancer. However, it is unclear whether the association is disturbed by confounding factors. We used a two-sample Mendelian randomization (MR) method to characterize the associations between diet and the lung cancer risk (including 3 subtypes: lung adenocarcinoma (LA), squamous cell lung carcinoma (SqCLC), and small cell lung cancer (SCLC)). Data on 20 diets were screened from the UK Biobank. Lung cancer data came from a large meta-analysis of 85,716 individuals. The inverse-variance weighted method was used as the main analysis. Sensitivity analysis was also used to explain the different multiplicity patterns of the final model. Our results showed significant evidence that 3 diets were associated with lung cancer [odds ratio (OR): 0.271, 95% confidence interval (CI): 0.150-0.488, p = 1.46 × 10-4, dried fruit; OR: 3.010, 95% CI: 1.608-5.632, p = 5.70 × 10-4, beer] and SqCLC (OR: 0.135, 95% CI: 0.062-0.293, p = 2.33 × 10-5, dried fruit; OR: 0.485, 95% CI: 0.328-0.717, p = 2.9 × 10-4, cheese). There were also suggestive correlations between 5 dietary intakes and lung cancer (OR: 0.441, 95% CI: 0.250-0.778, p = 0.008, cereal; OR: 2.267, 95% CI: 1.126-4.564, p = 0.022, beef), LA (OR: 0.494, 95% CI: 0.285-0.858, p = 0.012, dried fruit; OR: 3.536, 95% CI: 1.546-8.085, p = 0.003, beer) and SCLC (OR: 0.006, 95% CI: 0.000-0.222, p = 0.039, non-oily fish; OR: 0.239, 95% CI: 0.086-0.664, p = 0.006, dried fruit). No other association between diet and lung cancer was observed. Our study preliminary found that cheese, dried fruit, and beer intake were significantly associated with the risk of lung cancer or its subtypes, while cereal, beef, and non-oily fish intake were suggestively associated with the risk of lung cancer or its subtypes. Well-designed prospective studies are still needed to confirm our findings in the future.

Etiology and risk factors for non-suicidal self-injurious behavior

The article presents a review of the literature on the subject of non-suicidal self-injurious behavior (NSSI), the study of which attracts the attention of authors, both in the Russian Federation and around the world. Large meta-analyses of NSSP studies, proposed models, probable causes and mechanisms of occurrence, neurobiological factors, social factors, as well as the influence of modern means of communication and social networks are considered. Objective is to study, summarize and present data on the causes and risk factors of non-suicidal self-injurious behavior. Research method — articles in the “MEDLINE/PubMed”, “Scopus” databases in international medical journals were selected and analyzed. Articles were searched by keywords: “Self-Injurious Behavior”, “Non-Suicidal Self Injury”, “Deliberate Self-Harm”, “Self-Harm”, “Risk Factors”. Inclusion criteria: publication date from 2017 to 2022, clinical studies, meta-analyses and systematic reviews, randomized controlled trials, availability of the full text in the public domain or abstract. Exclusion criteria: abstracts; monographs, study guides; publication date until 2017, inconsistency with the research topic. A total of 94 publications were found. The review included 61 publications from 2017 to 2022 that corresponded to the topic and purpose of the study, and also added 19 sources older than 2017 that are significant for disclosing the subject of the study from references in the reference lists of the analyzed sources.

Ancestral, Pregnancy, and Negative Early-Life Risks Shape Children’s Brain (Dis)similarity to Schizophrenia

BackgroundFamilial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development, leading to the formation of characteristic brain deficit patterns prior to onset of symptoms. We hypothesized that the insidious effects of these risks may increase brain similarity to adult SSD deficit patterns in prepubescent children. MethodsWe used data collected by the Adolescent Brain Cognitive Development (ABCD) Study (N = 8940, age = 9.9 ± 0.1 years, 4307/4633 female/male), including 727 (age = 9.9 ± 0.1 years, 351/376 female/male) children with family history of SSD, to evaluate unfavorable cerebral effects of ancestral SSD history, pre/perinatal environment, and negative early-life environment. We used a regional vulnerability index to measure the alignment of a child’s cerebral patterns with the adult SSD pattern derived from a large meta-analysis of case-control differences. ResultsIn children with a family history of SSD, the regional vulnerability index captured significantly more variance in ancestral history than traditional whole-brain and regional brain measurements. In children with and without family history of SSD, the regional vulnerability index also captured more variance associated with negative pre/perinatal environment and early-life experiences than traditional brain measurements. ConclusionsIn summary, in a cohort in which most children will not develop SSD, familial, pre/perinatal, and early developmental risks can alter brain patterns in the direction observed in adult patients with SSD. Individual similarity to adult SSD patterns may provide an early biomarker of the effects of genetic and developmental risks on the brain prior to psychotic or prodromal symptom onset.

Clarifying the clinical landscape of pediatric spinal arteriovenous shunts: an institutional experience and individual patient-data meta-analysis

BackgroundPediatric spinal arteriovenous shunts (SAVS) are rare lesions with heterogeneous pathogenesis and clinical manifestations.ObjectiveTo evaluate the clinical characteristics, angioarchitecture, and technical/clinical outcomes in SAVS through a large single-center cohort analysis...

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs.

The relationship between dietary patterns and ophthalmic disease.

There is a rising interest in the impact of diet on the pathogenesis of common ophthalmic conditions. The purpose of this review is to summarize the potential preventive and therapeutic power of dietary interventions described in recent basic science and epidemiological literature. Basic science investigations have elucidated a variety of mechanisms by which diet may impact ophthalmic disease, particularly through its action on chronic oxidative stress, inflammation and macular pigmentation. Epidemiologic investigations have shown the real-world influence of diet on the incidence and progression of a number of ophthalmic diseases, particularly cataract, age-related macular degeneration (AMD) and diabetic retinopathy. A large observational cohort study found a 20% reduction in the incidence of cataract among vegetarians compared with nonvegetarians. Two recent systematic reviews found that higher adherence to Mediterranean dietary patterns was associated with a decreased risk of progression of AMD to later stages. Finally, large meta-analyses found that patients following plant-based and Mediterranean diets had significant reductions of mean haemoglobin A1c scores and incidence of diabetic retinopathy as compared with controls. There is a significant and growing body of evidence that Mediterranean diet and plant-based diets - those that maximize fruits, vegetables, legumes, whole grains and nuts; and that minimize animal products and processed foods - help prevent vision loss from cataract, AMD and diabetic retinopathy. These diets may hold benefits for other ophthalmic conditions, as well. Nevertheless, there is a need for further randomized, controlled and longitudinal studies in this area.

SRS for Cavernous Malformations: Myths and Realities.

The optimal management of cavernous malformations (CMs) remains controversial. Over the past decade, stereotactic radiosurgery (SRS) has gained wider acceptance in the management of CMs, especially in those with deep location, eloquence, and where surgery is of high risk. Unlike arteriovenous malformations (AVMs), there is no imaging surrogate endpoint to confirm CM obliteration. Clinical response to SRS can only be gauged by a reduction in long-term CM hemorrhage rates. There is concern that the long-term benefits of SRS and the reduced rehemorrhage rate after a latency period of 2 years may only be a reflection of natural history. Of further concern is the development of adverse radiation effects (AREs), which were significant in the early experimental studies. The lessons learnt from that era have led to the progressive development of well-defined, lower marginal dose treatment protocols that have reported less toxicity (5%-7%) and consequently reduced morbidity. Currently, there is at least Class II, Level B evidence for use of SRS in solitary CMs with previous symptomatic hemorrhage in eloquent areas with high surgical risk. Recent prospective cohort studies observing untreated brainstem and thalamic CMs report significantly higher hemorrhage rates and neurological sequelae than the rates reported from contemporary pooled large natural history meta-analyses. Furthermore, this strengthens our recommendation for early proactive SRS in symptomatic deep-seated CMs due to the higher morbidity associated with observation and microsurgery. The key to successful outcomes for any surgical intervention is patient selection. We hope that our precis on contemporary SRS techniques in the management of CMs will assist this process.