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Sarcopenia is the aging‐related loss of force‐generating capacity and atrophy of skeletal muscles and is a major contributor to morbidity and mortality in the elderly. The molecular mechanisms underlying sarcopenia remain to be elucidated. Skeletal muscles exhibit different rates of sarcopenia, generally reflecting their specific muscle fiber type composition. Muscles primarily composed of type IIx and/or IIb muscle fibers (i.e., extensor digitorum longus; EDLm) develop sarcopenia at a faster rate than other muscles. In the diaphragm, muscle fiber cross‐sectional area (CSA) is reduced in old age, predominantly in type IIx and/or IIb fibers. Autophagy is a multistep, catabolic process that targets dysfunctional cytoplasmatic structures including proteins and organelles for degradation and recycling. Autophagy is impaired in old age across several tissues, including motor neurons and skeletal muscle. Expression of core autophagy proteins can indicate changes in autophagy, e.g., LC3 reflects initiation/elongation steps and p62 clearance reflects degradation. We hypothesize that impaired autophagy is associated with the development of sarcopenia in type‐identified muscle fibers of the EDLm. Indeed, at 24‐months of age, the CSA of type I and IIa fibers was not reduced, whereas the CSA of type IIx and/or IIb fibers was ~25% smaller (p<0.01 in both cases), compared to 6‐month‐old mice. These findings are consistent with fiber type selective sarcopenia in the EDLm. Expression of LC3 and p62 in the EDLm of mice at 6‐ and 24‐ months of age was evaluated via immunofluorescence by quantification of the number of LC3 and p62 puncta per muscle fiber type. In type I and IIa fibers, the number of LC3 puncta increased by ~30% and of p62 increased three‐fold in 24‐ compared to 6‐month‐old mice (p<0.01 in both cases). In type IIx and/or IIb fibers, the number of LC3 puncta decreased by ~60% and p62 puncta increased by ~50% in 24‐ compared to 6‐month‐old mice (p<0.01 in both cases). Accordingly, compared to 6 month‐old mice, autophagic degradation is impaired across muscle fiber types in 24‐month old mice, but likely to a greater extent in type I and IIa fibers of old mice given the increase in both LC3 and p62. Autophagic initiation is primarily reduced in type IIx and/or IIb fibers in the EDL as indicated by the reduced LC3 expression. Taken together these findings indicate that fiber type selective sarcopenia may reflect differences in autophagy across muscle fiber types.

OBJECTIVE The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Abstract OBJECTIVE: The present study aimed to investigate postoperative swallowing disorders in patients diagnosed with CM I after decompression neurosurgery.METHODS: We selected 54 patients after decompression neurosurgery procedure for CM I from January 2017 to December 2019. We evaluated the speech-language assessment (CSLSA) 24-hours after post-surgical extubation. CSLSA observed aspects of posture, sensitivity, tone, and extra- and intraoral mobility of the FAO and visualizing the functions of breathing, phonation, articulation, chewing, and swallowing. We correlated the severity of the dysphagia and the presence of associated malformations in the CM I patients.RESULTS: In our study, 39 patients were female (mean age 41.3±47.1 years). Thirty-seven patients had associated malformations (p=0.0243): 21 patients syringomyelia, 11 basilar invagination and 5 syringomyelia and basilar invagination. Dysphagia was present in 37 of the cases (68.5%;p=0.0016). Dysphonia in 13 (24.1%;p=0.4785) and dysarthria in 3 (5.6%;p=0.0042). We observed in the CSLSA: orofacial hypomobility (29-patients–53.7%;p=0.0204), orofacial hyposensitivity (26-patients–48.1%; p=0.3023), reduced GAG reflex (24 patients–44.5%;p=0.1041), ineffective cough (19 patients–35.2%;p=0.0022), ineffective saliva swallowing (18-patients–33.3%;p=0.0396), dyspnea (13-patients–24.1%;p=0.4785), orofacial hypotonia (11-patients–20.4%;p=0.0004), altered cervical auscultation (10-patients–18.5%;p=0.0003), and dysarthria (3-patients–9.3%;p=0.0042). The presence of associated malformations significantly influenced the appearance of swallowing disorders, the severity of oropharyngeal dysphagia, the post-surgical complications (17-patients–31.5%;p<0.001), and the clinical outcomes (p=0.0029) of patients with CM type I. CONCLUSION: Decompressive neurosurgery for CM I had low rates of post-surgical complications overall. However, there was a high incidence of dysphagia. The presence of associated malformations is related with poorer prognosis and greater severity of oropharyngeal dysphagia in patients with CM I.

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program ( n = 63,302) and UK Biobank ( n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Background: An increased posterior tibial slope (PTS) results in greater force on the anterior cruciate ligament (ACL) and is a risk factor for ACL injuries. Biomechanical studies have suggested that a reduction in the PTS angle may lower the risk of ACL injuries. However, the majority of these investigations have been in the adult population. Purpose: To assess the mean medial and lateral PTS on pediatric cadaveric specimens without known knee injuries. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 39 pediatric knee specimens with computed tomography scans were analyzed. Specimens analyzed were between the ages of 2 and 12 years. The PTS of each specimen was measured on sagittal computed tomography slices at 2 locations for the medial and lateral angles. The measurements were plotted graphically by age to account for the variability in development within age groups. The anterior medial and lateral tibial plateau widths were measured. The distance between the top of the tibial plateau and the physis was measured. The independent-samples t test and analysis of variance were used to analyze the measurements. Results: The mean PTS angle for the medial and lateral tibial plateaus was 5.53° ± 4.17° and 5.95° ± 3.96°, respectively. The difference between the PTS angles of the medial and lateral tibial plateaus was not statistically significant ( P > .05). When plotted graphically by age, no trend between age and PTS was identified. Conclusion: This data set offers values for the PTS in skeletally immature specimens without a history of ACL injury and suggests that age may not be an accurate predictive factor for PTS.

Abstract Introduction Lumbar spinal stenosis affects more than 200,000 adults in the United States, resulting in approximately 38,000 operations among the Medicare population and greater than $1.5 billion in hospital bills alone. Fortunately, Minimally Invasive Lumbar Decompression (MILD) and the Superion Indirect Decompression System have shown lasting benefit and cost savings compared to more aggressive surgical options. Objective Our primary objective was to retrospectively determine the rate of lumbar decompression surgery following the MILD and Superion procedures. Materials and Methods This was a pooled retrospective review of LSS patients who received MILD and/or Superion procedures between January 2011 and July 2019. Adult patients with CPT codes for MILD and Superion procedures were identified. Patients were included if they had a follow‐up visit at least 2 years from the procedure date, preprocedural MRI results, and surgical notes. Results A total of 199 patients were included in the final analysis, of which 57 patients (28.6%) underwent MILD procedure only, 124 patients (62.3%) underwent Superion only, and 18 patients (9.0%) underwent an MILD procedure initially followed by a Superion procedure. Two patients had an MILD procedure performed twice at the same level at separate encounters. A total of four patients in the entire cohort (2.0%; MILD 5.3%, Superion 0.8%) underwent subsequent lumbar spine surgery when followed for at least 2 years. It is notable that some of these patients may not have been surgical candidates and this may have skewed the results. Conclusions Patients undergoing minimally invasive decompression treatment of lumbar spinal stenosis have low rates of subsequent open surgery which potentially results in cost savings and a reduction in severe adverse events. The reason for low surgical rate may reflect improvement in their symptoms, a preference to avoid surgery, or being deemed not a surgical candidate.