OBJECTIVE While the relationship between smoking and subarachnoid hemorrhage is well established, data regarding the probability of detecting unruptured intracranial aneurysms (UIAs) in smokers remain sparse. The aim of this systematic review and meta-analysis is to provide a comprehensive understanding of the relationship between smoking and the likelihood of identifying UIAs in healthy asymptomatic patients who underwent brain imaging for indications unrelated to UIAs. METHODS A systematic review was conducted following the PRISMA guidelines. The PubMed and Scopus databases were searched for studies published before March 2024 that reported on the presence of UIAs in healthy asymptomatic patients who had undergone brain imaging for indications unrelated to UIAs. Three independent reviewers assessed the eligibility of all retrieved studies. Risk of bias for the included observational studies was assessed using the methodological index for non-randomized studies. Data on UIA prevalence, smoking status, and patient and aneurysm characteristics were extracted. The association between smoking and the presence of UIA was studied. A prevalence proportional meta-analysis was conducted across the included studies. A meta-analysis was performed with a random-effects model by using summary statistics from the included studies. RESULTS Six studies involving 47,788 patients who had undergone brain imaging were identified for quantitative analysis. The pooled UIA prevalence in the sample was 3.07% (95% CI 2.27%–4.16%). Patients who smoked had higher rates of aneurysm detection than the patients who did not smoke (pooled prevalence of 2.96%, 95% CI 2.68%–3.27% vs 2.23%, 95% CI 2.08%–2.39%). Although the relation between the two was not statistically significant (p = 0.06), smoking was associated with higher odds for UIA detection, yielding an OR of 1.34 (95% CI 1.07–1.67) with an I 2 value of 53%. CONCLUSIONS This study suggests a potentially higher risk of UIAs in patients who smoked than in those who never smoked. However, the results of this meta-analysis revealed that smoking was not statistically associated with higher UIA detection. This result could be explained by the limited number of studies published on this topic. If these findings reach statistical significance in future larger studies, it could justify revising guidelines to include cigarette smokers in intracranial aneurysm screening.
The Global Prevalence of Iron Deficiency in Collegiate Athletes: A Systematic Review and Meta‐Analysis
ABSTRACTAthletes are at high risk of iron deficiency even without anemia. In this systematic review and meta‐analysis that included 17,519 athletes in 122 references from 23 countries, participating in 62 unique sports over a 41‐year timeframe, approximately 53.9% of student‐athletes were found to be hypoferritinemic (ferritin concentration below 50 mcg/L) with 23.0% percent showing absolute iron deficiency based on current definitions (ferritin concentration below 20 mcg/L). These findings strongly suggest that changes in clinical practice guidelines are warranted to enable routine screening for iron deficiency among adolescent and collegiate athletes.
Iron Deficiency in Collegiate Athletes Obtaining Preparticipation Hemoglobinopathy Screening in the Upper Midwest
ABSTRACTObjectiveIron and other biologically important metals are essential to mitochondrial function but are not routinely evaluated. Their equilibrium is critical to the optimal performance of cells with high metabolic activity such as neurons, cardiomyocytes, and skeletal myocytes. Teenagers are at a high risk of iron deficiency even without anemia. Metal ion imbalances can cause cognitive impairments, muscle weakness, and sudden cardiac death. We aim to assess the current prevalence of iron deficiency among collegiate athletes in the Upper Midwest.MethodsOur study is a multicenter, retrospective chart review of outpatient clinics in a regional healthcare system between January 2012 and December 2023, and a national public database between 2017 and March 2020. We reviewed the ferritin concentrations of regional collegiate athletes having preparticipation sport evaluations and nationally in the NHANES database.ResultsWe identified 643 unique individuals aged 16–21 years with 253 having ferritin screening. Iron deficiency (ferritin <20 mcg/L) was present in 24.5% and hypoferritinemia (ferritin <50 mcg/L) was present in 66.7% of collegiate athletes. From the NHANES database, 12.7% of active sampled participants aged 16–21 years were iron deficient.ConclusionOur study findings suggest the need for universal screening for iron deficiency among collegiate athletes given the high prevalence of iron deficiency in both the retrospective chart review and NHANES database analysis. Given the critical role of metal ion homeostasis to optimal mitochondrial function, these findings may warrant the inclusion of ferritin testing in cardiac, neurological, and skeletal muscle evaluations.
Cigarette Smoking and Observed Growth of Unruptured Intracranial Aneurysms: A Systematic Literature Review and Meta-Analysis
BACKGROUND: Smoking and observed growth of intracranial aneurysms are known risk factors for rupture. The mechanism by which smoking increases this risk is not completely elucidated. Furthermore, an association between smoking and aneurysm growth has not been clearly defined in the literature. We hypothesize that smoking is associated with aneurysm growth, which, in turn, may serve as one of the mechanisms by which smoking drives rupture risk. METHODS: We report a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Using the R software, we performed a meta-analysis to investigate the association between smoking and the growth of unruptured intracranial aneurysms. Studies on familial aneurysms and genetic syndromes known to increase the risk of aneurysms were excluded. RESULTS: Eighteen observational studies were included with a total of 3535 patients and 4289 aneurysms with a mean follow-up period ranging from 17 to 226 months. The mean age among the studies ranged from 38.4 to 73.9 years; 74% of patients were female. Ever-smoking status (odds ratio, 1.10 [95% CI, 0.87–1.38]) and current smoking status (odds ratio, 1.43 [95% CI, 0.84–2.43]) did not show a statistically significant association with growth of intracranial aneurysms. Patients currently smoking did not have a statistically significant association with the growth of intracranial aneurysms (odds ratio, 1.18 [95% CI, 0.72–1.93]) compared with patients without a smoking history. No significant association was found in patients who previously smoked compared with patients who never smoked (odds ratio, 1.46 [95% CI, 0.88–2.43]). CONCLUSIONS: Smoking is not clearly associated with the growth of unruptured intracranial aneurysms, despite trends being observed, there is no statistical association. The mechanism by which smoking increases rupture risk might not be growth. In patients for whom observation is recommended, the absence of growth over time in the setting of smoking history does not, therefore, imply protection from rupture.
CellKine clinical trial: first report from a phase 1 trial of allogeneic bone marrow–derived mesenchymal stem cells in subjects with painful lumbar facet joint arthropathy
Abstract Background: Lumbar facet joint arthropathy (LFJA) is a major cause of low back pain (LBP), with current treatments offering limited long-term benefits. Bone marrow–derived mesenchymal stem cells (BM-MSCs) show promise due to their immunomodulatory and trophic effects, potentially addressing underlying degenerative processes in LFJA. Objectives: This initial report describes the outcomes of the first treated patient in an ongoing mutidisciplinary phase 1 clinical trial evaluating the safety and feasibility of intra-articular allogeneic BM-MSCs for painful LFJA. Methods: Following enrollment in our IRB-approved protocol, symptomatic LFJA was confirmed through double blocks on L4 and L5 medial branches. Two 1-mL syringes, each containing 10 million BM-MSCs, were prepared in the cGMP facility and administered bilaterally to the patient’s L4-L5 lumbar facet joints. The patient underwent standardized follow-ups, including clinical examinations and functional and imaging assessments for 2 years, utilizing patient-reported outcomes measurement information system—computer adaptive tests (PROMIS CATs), visual analogue scale, Oswestry disability index, work functional status and opioid pain medication use, and MR imaging Fenton–Czervionke score. Results: The patient tolerated the procedure well, with no drug-related adverse events during the study period. Pain, spine function, and work functional status improved at multiple follow-ups. This patient also reported improvements in mental and social health, along with a notable improvement in the grade of facet synovitis observed at the one-year follow-up MRI evaluation. Conclusions: This case report suggests the safety and feasibility of administering intra-articular allogeneic BM-MSCs, offering therapeutic benefits for pain management and functional activities.
Trends in Transcatheter Aortic Valve Implantation Utilization, Outcomes, and Healthcare Resource Use in Patients With Liver Cirrhosis: A Decade of Insights (2011–2020)
It is well known that individuals with liver cirrhosis are considered at high risk for cardiac surgery, with an increased risk for morbidity and mortality as the liver disease progresses. In the last decade, there have been considerable advances in transcatheter aortic valve implantation (TAVI) as an alternative to surgical aortic valve replacement (SAVR) in individuals deemed to be at high risk for surgery. However, research surrounding TAVI in the setting of liver cirrhosis has not been as widely studied. In this national population-based cohort study, we evaluated the trends of mortality, complications, and healthcare utilization in liver cirrhotic patients undergoing TAVI, as well as analyzed the basic demographics of these individuals. We found that from 2011 to 2020, the amount of TAVI procedures conducted in cirrhotic patients was increasing annually, while mortality, procedural complications, and healthcare utilization trends in these cirrhotic patients undergoing TAVI decreased. Overall, TAVI does seem to be reasonable management for aortic stenosis patients with liver cirrhosis who need aortic valve replacement.
Clinical Outcomes of Cardiogenic Shock Due to Spontaneous Coronary Artery Dissection Versus Cardiogenic Shock Due to Coronary Artery Disease
Spontaneous coronary artery dissection (SCAD) can be treated conservatively. However, some SCAD patients can develop cardiogenic shock (CS). We evaluated the outcomes of SCAD-related CS using data from a national population-based cohort study from January 1, 2016, to December 30, 2019. In our study of 32,640 patients with SCAD, about 10.6% of patients presented with CS. We found that SCAD patients with CS had higher mortality and greater complications including use of mechanical circulatory devices, arrhythmias, respiratory support, and acute heart failure compared to those without CS. When comparing CS due to SCAD with that due to coronary artery disease, we found that although mortality rates were similar, those with CS due to SCAD were associated with higher risk of use of mechanical circulatory support, major bleeding, blood transfusion, and respiratory failure.
Real‐world evaluation of interconsensus agreement of risk of bias tools: A case study using risk of bias in nonrandomized studies‐of interventions (ROBINS‐I)
Abstract Background Risk of bias (RoB) tools are critical in systematic reviews and affect subsequent decision‐making. RoB tools should have adequate interrater reliability and interconsensus agreement. We present an approach of post hoc evaluation of RoB tools using duplicated studies that overlap systematic reviews. Methods Using a back‐citation approach, we identified systematic reviews that used the Risk Of Bias In Nonrandomized Studies‐of Interventions (ROBINS‐I) tool and retrieved all the included primary studies. We selected studies that were appraised by more than one systematic review and calculated observed agreement and unweighted kappa comparing the different systematic reviews' assessments. Results We identified 903 systematic reviews that used the tool with 51,676 cited references, from which we eventually analyzed 171 duplicated studies assessed using ROBINS‐I by different systematic reviewers. The observed agreement on ROBINS‐I domains ranged from 54.9% (missing data domain) to 70.3% (deviations from intended interventions domain), and was 63.0% for overall RoB assessment of the study. Kappa coefficient ranged from 0.131 (measurement of outcome domain) to 0.396 (domains of confounding and deviations from intended interventions), and was 0.404 for overall RoB assessment of the study. Conclusion A post hoc evaluation of RoB tools is feasible by focusing on duplicated studies that overlap systematic review. ROBINS‐I assessments demonstrated considerable variation in interconsensus agreement among various systematic reviewes that assessed the same study and outcome, suggesting the need for more intensive upfront work to calibrate systematic reviewers on how to identify context‐specific information and agree on how to judge it.
Anticoagulation during extracorporeal membrane oxygenation
Abstract Context Low vitamin D status is common and is associated with various common medical conditions. Objective To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. Methods We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. Results Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. Conclusion The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals’ and providers’ values and preferences and other important decisional and contextual factors to develop clinical recommendations.