Citations

AbstractObjectiveThe radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS.MethodsPatients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age‐matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility‐based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions.Results180 participants (45 RIS, 45 MS, 90 non‐MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non‐MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non‐MS than MS from non‐MS (p = 0.837). When a 6‐lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis.InterpretationThis study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non‐MS, with similar performances to those in MS.

AbstractNew‐onset atrial fibrillation (NOAF) in COVID‐19 raises significant clinical and public health issues. This systematic review and meta‐analysis aims to compile and analyze the current literature on NOAF in COVID‐19 and give a more comprehensive understanding of the prevalence and outcomes of NOAF in COVID‐19. A comprehensive literature search was carried out using several databases. The random effect model using inverse variance method and DerSimonian and Laird estimator of Tua2 was used to calculate the pooled prevalence and associated 95% confidence interval (CI). Results for outcome analysis were presented as odds ratios (ORs) with 95% CI and pooled using the Mantel‐Haenszel random‐effects model. The pooled prevalence of NOAF in COVID‐19 was 7.8% (95% CI: 6.54%–9.32%),a pooled estimate from 30 articles (81 929 COVID‐19 patients). Furthermore, our analysis reported that COVID‐19 patients with NOAF had a higher risk of developing severe disease compared with COVID‐19 patients without a history of atrial fibrillation (OR = 4.78, 95% CI: 3.75–6.09) and COVID‐19 patients with a history of pre‐existing atrial fibrillation (OR = 2.75, 95% CI: 2.10–3.59). Similarly, our analysis also indicated that COVID‐19 patients with NOAF had a higher risk of all‐cause mortality compared with, COVID‐19 patients without a history of atrial fibrillation (OR = 3.83, 95% CI: 2.99–4.92) and COVID‐19 patients with a history of pre‐existing atrial fibrillation (OR = 2.32, 95% CI: 1.35–3.96). The meta‐analysis did not reveal any significant publication bias. The results indicate a strong correlation between NOAF and a higher risk of severe illness and mortality. These results emphasize the importance of careful surveillance, early detection, and customized NOAF management strategies to improve clinical outcomes for COVID‐19 patients.

Background: Pedicle subtraction osteotomy (PSO) is a powerful tool for sagittal plane correction in patients with rigid adult spinal deformity (ASD); however, it is associated with high intraoperative blood loss and the increased risk of durotomy. The objective of the present study was to identify intraoperative techniques and baseline patient factors capable of predicting intraoperative durotomy. Methods: A tri-institutional database was retrospectively queried for all patients who underwent PSO for ASD. Data on baseline comorbidities, surgical history, surgeon characteristics and intraoperative maneuvers were gathered. PSO aggressiveness was defined as conventional (Schwab 3 PSO) or an extended PSO (Schwab type 4). The primary outcome of the study was the occurrence of durotomy intraoperatively. Univariable analyses were performed with Mann–Whitney U tests, Chi-squared analyses, and Fisher’s exact tests. Statistical significance was defined by p < 0.05. Results: One hundred and sixteen patients were identified (mean age 61.9 ± 12.6 yr; 44.8% male), of whom 51 (44.0%) experienced intraoperative durotomy. There were no significant differences in baseline comorbidities between those who did and did not experience durotomy, with the exception that baseline weight and body mass index were higher in patients who did not suffer durotomy. Prior surgery (OR 2.73; 95% CI [1.13, 6.58]; p = 0.03) and, more specifically, prior decompression at the PSO level (OR 4.23; 95% CI [1.92, 9.34]; p < 0.001) was predictive of durotomy. A comparison of surgeon training showed no statistically significant difference in durotomy rate between fellowship and non-fellowship trained surgeons, or between orthopedic surgeons and neurosurgeons. The PSO level, PSO aggressiveness, the presence of stenosis at the PSO level, nor the surgical instrument used predicted the odds of durotomy occurrence. Those experiencing durotomy had similar hospitalization durations, rates of reoperation and rates of nonroutine discharge. Conclusions: In this large multisite series, a history of prior decompression at the PSO level was associated with a four-fold increase in intraoperative durotomy risk. Notably the use of extended (versus) standard PSO, surgical technique, nor baseline patient characteristics predicted durotomy. Durotomies occurred in 44% of patients and may prolong operative times. Additional prospective investigations are merited.

Adaptive therapy, an ecologically inspired approach to cancer treatment, aims to overcome resistance and reduce toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life instead of killing the maximum number of cancer cells. In preparation for a clinical trial, we used endocrine-resistant MCF7 breast cancer to stimulate second-line therapy and tested adaptive therapy using capecitabine, gemcitabine, or their combination in a mouse xenograft model. Dose modulation adaptive therapy with capecitabine alone increased survival time relative to MTD but not statistically significantly (HR = 0.22, 95% CI = 0.043–1.1, p = 0.065). However, when we alternated the drugs in both dose modulation (HR = 0.11, 95% CI = 0.024–0.55, p = 0.007) and intermittent adaptive therapies, the survival time was significantly increased compared to high-dose combination therapy (HR = 0.07, 95% CI = 0.013–0.42, p = 0.003). Overall, the survival time increased with reduced dose for both single drugs (p < 0.01) and combined drugs (p < 0.001), resulting in tumors with fewer proliferation cells (p = 0.0026) and more apoptotic cells (p = 0.045) compared to high-dose therapy. Adaptive therapy favors slower-growing tumors and shows promise in two-drug alternating regimens instead of being combined.

Background: The medial patellofemoral ligament (MPFL) is the primary soft tissue restraint to lateral patellar translation and is often disrupted by lateral patellar dislocation. Surgical management for recurrent patellar instability focuses on restoring the MPFL function with repair or reconstruction techniques. Recent studies have favored reconstruction over repair; however, long-term comparative studies are limited. Purpose: To compare long-term clinical outcomes, complications, and recurrence rates of isolated MPFL reconstruction and MPFL repair for recurrent lateral patellar instability. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 55 patients (n = 58 knees) with recurrent lateral patellar instability were treated between 2005 and 2012 with either MPFL repair or MPFL reconstruction. The exclusion criteria were previous or concomitant tibial tubercle osteotomy or trochleoplasty and follow-up of <8 years. Pre- and postoperative descriptive, surgical, imaging, and clinical data were recorded for each patient. Results: MPFL repair was performed on 26 patients (n = 29 knees; 14 women, 15 men), with a mean age of 18.4 years. MPFL reconstruction was performed on 29 patients (n = 29 knees; 18 women, 11 men), with a mean age of 18.2 years. At a mean follow-up of 12 years (range, 8.3-18.9 years), the reconstruction group had a significantly lower rate of recurrent dislocation compared with the repair group (14% vs 41%; P = .019). There were no differences in the number of preoperative dislocations or tibial tubercle–trochlear groove distance. The reconstruction group had significantly more time from initial injury to surgery compared with the repair group (median, 1460 days vs 627 days; P = .007). There were no differences in postoperative Tegner, Lysholm, or Kujala scores at the final follow-up. In addition, no statistically significant differences were detected in return to sport (RTS) rates (repair [81%] vs reconstruction [75%]; P = .610) or reoperation rates for recurrent instability (repair [21%] vs reconstruction [7%]; P = .13). Conclusion: MPFL repair resulted in a nearly 3-fold higher rate of recurrent patellar dislocation (41% vs 14%) at the long-term follow-up compared with MPFL reconstruction. Given this disparate rate, the authors recommend MPFL reconstruction over repair because of the lower failure rate and similar, if not superior, clinical outcomes and RTS.

AbstractBackground and PurposeThe Alberta Stroke Program Early CT Score (ASPECTS) is a widely used scoring system for evaluating ischemic stroke to determine therapeutic strategy. However, there is variation in the interobserver agreement of ASPECTS. This systematic review and meta‐analysis aimed to investigate the interobserver agreement of total and regional ASPECTS.MethodsA comprehensive search was conducted in the Web of Sciences, PubMed, and Scopus databases to identify relevant studies. Inclusion criteria were studies of noncontrast CT performed within 24 hours of ischemic stroke in the middle cerebral artery territory.ResultsA total of 20 studies, with 3482 patients, reporting interobserver agreement of total and regional ASPECTS were included in the meta‐analysis. The interobserver agreement for total ASPECTS in studies using Kappa coefficient (κ) analysis was substantial (κ = .67, 95% confidence interval [CI]: .57‐.78). In studies using intraclass correlation coefficient (ICC) analysis, agreement was excellent (ICC = .84, 95% CI: .77‐.90). Interobserver agreement was higher in studies in which the observer was unblinded to clinical scenario in both groups (κ = .74, 95% CI: .59‐.89, and ICC = .82, 95% CI: .79‐.85). Per‐region analysis showed that the caudate nucleus had the highest agreement (κ = .68, 95% CI: .60‐.76, and ICC = .84, 95% CI: .74‐.93), while M2 and internal capsule in Kappa studies (κ = .45, 95% CI: .34‐.55 and κ = .47, 95% CI: .28‐.66), and M4 and internal capsule in ICC studies (ICC = .54, 95% CI: .43‐.64 and ICC = .55, 95% CI: .18‐.91) had the lowest agreement.ConclusionThis meta‐analysis demonstrates substantial to excellent interobserver agreement for total ASPECTS, which supports using this method for stroke treatment. However, findings emphasize the need to consider interobserver agreement in specific regions of ASPECTS for treatment decisions.

Dental caries is a significant oral and public health problem worldwide, especially in low-income populations. The risk of dental caries increases with frequent intake of dietary carbohydrates, including sugars, leading to increased acidity and disruption of the symbiotic diverse and complex microbial community of health. Excess acid production leads to a dysbiotic shift in the bacterial biofilm composition, demineralization of tooth structure, and cavities. Highly acidic and acid-tolerant species associated with caries include Streptococcus mutans, Lactobacillus, Actinomyces, Bifidobacterium, and Scardovia species. The differences in microbiotas depend on tooth site, extent of carious lesions, and rate of disease progression. Metagenomics and metatranscriptomics not only reveal the structure and genetic potential of the caries-associated microbiome, but, more importantly, capture the genetic makeup of the metabolically active microbiome in lesion sites. Due to its multifactorial nature, caries has been difficult to prevent. The use of topical fluoride has had a significant impact on reducing caries in clinical settings, but the approach is costly; the results are less sustainable for high-caries-risk individuals, especially children. Developing treatment regimens that specifically target S. mutans and other acidogenic bacteria, such as using nanoparticles, show promise in altering the cariogenic microbiome, thereby combatting the disease.

Muscle atrophy and weakness are prevalent and debilitating conditions in dogs that cannot be reliably prevented or treated by current approaches. In non-canine species, the natural dietary compound ursolic acid inhibits molecular mechanisms of muscle atrophy, leading to improvements in muscle health. To begin to translate ursolic acid to canine health, we developed a novel ursolic acid dietary supplement for dogs and confirmed its safety and tolerability in dogs. We then conducted a randomized, placebo-controlled, proof-of-concept efficacy study in older beagles with age-related muscle atrophy, also known as sarcopenia. Animals received placebo or ursolic acid dietary supplements once a day for 60 days. To assess the study’s primary outcome, we biopsied the quadriceps muscle and quantified atrophy-associated mRNA expression. Additionally, to determine whether the molecular effects of ursolic acid might have functional correlates consistent with improvements in muscle health, we assessed secondary outcomes of exercise participation and T-maze performance. Importantly, in canine skeletal muscle, ursolic acid inhibited numerous mRNA expression changes that are known to promote muscle atrophy and weakness. Furthermore, ursolic acid significantly improved exercise participation and T-maze performance. These findings identify ursolic acid as a natural dietary compound that inhibits molecular mechanisms of muscle atrophy and improves functional performance in dogs.

Septal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy with outflow tract obstruction (oHCM). However, outcomes data in this population is predominantly from specialized centers. The National Inpatient Database was queried from 2011 to 2019 for relevant international classification of diseases (ICD)-9 and -10 diagnostic and procedural codes. We compared baseline characteristics and in-hospital outcomes of patients with oHCM who underwent SM vs ASA. A p-value < 0.001 was considered statistically significant. We identified 15,119 patients with oHCM who underwent septal reduction therapies, of whom 57.4% underwent SM, and 42.6% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR: 1.8 (1.3–2.5)), post-procedure ischemic stroke (OR: 2.3 (1.7–3.2)), acute kidney injury (OR: 1.4 (1.2–1.7)), vascular complications (OR: 3.6 (2.3–5.3)), ventricular septal defect (OR: 4.4 (3.2–6.1)), cardiogenic shock (OR: 1.7 (1.3–2.3)), sepsis (OR: 3.2 (1.9–5.4)), and left bundle branch block (OR: 3.5 (3–4)), compared to ASA. Patients who underwent ASA had higher post-procedure complete heart block (OR: 1.3 (1.1–1.4)), right bundle branch block (OR: 6.3 (5–7.7)), ventricular tachycardia (OR: 2.2 (1.9–2.6)), supraventricular tachycardia (OR: 1.6 (1.4–2)), and more commonly required pacemaker insertion (OR: 1.4 (1.3–1.7)) (p < 0.001 for all) compared to SM. This nationwide analysis evidenced that patients undergoing SM had higher in-hospital mortality and periprocedural complications than ASA; however, those undergoing ASA had more post-procedure conduction abnormalities and pacemaker implantation. The implications of these findings warrant further investigation regarding patient selection strategies for these therapies.