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Patients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease-specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human-platelet-derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)-like module-containing mucin-like hormone receptor-like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll-like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL-1ß), transforming growth factor-beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7-9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T-cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.
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Cardiomiopatía Dilatada , Miocarditis , Humanos , Ratones , Masculino , Femenino , Animales , Miocardio/metabolismo , Cardiomiopatía Dilatada/metabolismo , Inmunidad Innata , Macrófagos/metabolismoRESUMEN
Introduction: The SARS-CoV-2 (COVID-19) pandemic continues to substantially alter previously established clinical practice patterns and has transformed patient care in American healthcare. However, studies to evaluate the impact of COVID-19 on neuroemergent patient care and associated clinical outcomes are limited. Herein, we describe the impact of COVID-19 on the Neuroemergency Transfer Program (NTP) - a novel, urban, high volume interhospital patient transfer program. Objective: To evaluate and describe the clinical impact of the COVID-19 pandemic on the NTP. Study Design: A single-center retrospective study of prospectively collected consecutive neuroemergent patient transfer data between 2018-2021 was analyzed. Adult patients were divided based upon transfer date into a Pre-COVID (PCOV) or COVID cohort. Patient demographics, transfer characteristics and clinical data and outcomes were analyzed. Results: 3,096 patients were included for analysis. Mean age at transfer in the PCOV and COVID cohorts were 62.4 ± 0.36 and 61.1 ± 0.6 years. A significant decrease in mean transfers per month was observed between cohorts (PCOV = 97.8 vs. COV = 68.2 transfers/month, p < 0.01). Total transfer time in the PCOV cohort was 155.1 ± 3.4â min which increased to 169.3 ± 12.8â min in the COVID cohort (p = 0.13). Overall mean transfer distance was significantly longer in the PCOV cohort at 22.0 ± 0.4 miles vs. 20.3 ± 0.67 miles in the COV cohort (p = 0.03). The relative frequency of transfer diagnoses was unchanged between cohorts. A significant increase in mean inpatient length of stay was noted, 7.9 ± 0.15 days to 9.6 ± 0.33 days in the PCOV vs. COVID cohorts (p < 0.01). Ultimately, no difference in the frequency of good vs. poor clinical outcome were noted between the PCOV (79.8% and 19.4%) vs. COV (78.8% and 20.4%) cohorts. Conclusion: The impact of COVID-19 on current healthcare dynamics are far reaching. Here, we show a significant decrease in interhospital patient transfers and increased length of stay between a Pre-COVID and COVID cohort. Further work to better elucidate the specific interplay of clinical contributors to account for these changes is indicated.
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BACKGROUND: Single-level lumbar degenerative disc disease (DDD) remains a significant cause of morbidity in adulthood. Anterior lumbar interbody fusion (ALIF) and Transforaminal lumbar interbody fusion (TLIF) are surgical techniques developed to treat this condition. With limited studies on intermediate term outcomes in a single cohort, we compare radiographic and clinical outcomes in patients undergoing ALIF and TLIF. METHODS: A retrospective chart review was performed on 164 patients (111 TLIF; 53 ALIF) over a 60-month period. X-ray radiographs obtained pre-operatively, prior to discharge, and at one year were utilized for radiographic assessment. Segmental lordosis, lumbar lordosis and HRQOL scores were measured preoperatively and at one-year timepoints. RESULTS: Changes in lumbar lordosis and segmental lordosis were significantly greater after ALIF (4.6° vs. -0.6°, P=0.05; 4.7° vs. -0.7°, P<0.05) at one year (mean time, 366±20 days). At one year or greater, there was a greater reduction in mean VAS-leg score in TLIF patients (3.4 vs. 0.6, P<0.05) and ODI score (16.2 vs. 5.4, P<0.05). Similar outcomes were seen for VAS-back, SF-12 Physical Health, and SRS-30 Function/Activity. SF-12 Mental Health scores were found to be lower in patients undergoing TLIF (-3.5 vs. 2.7, P<0.05). CONCLUSIONS: ALIF demonstrated a superior method of increasing lumbar and segmental lordosis. TLIF was utilized more in patients with higher pre-operative VAS-leg pain scores and therefore, showed a greater magnitude of VAS-leg pain improvement. TLIF also demonstrated a greater improvement in ODI scores despite similar baseline scores, suggesting a possible enhanced functional outcome.
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OBJECTIVE: The goal of this study was to evaluate the clinical and radiographic outcomes of a novel multidirectional in situ expandable minimally invasive surgery (MIS) transforaminal lumbar interbody fusion (TLIF) cage. METHODS: A retrospective analysis of 69 consecutive patients undergoing a 1- or 2-level MIS TLIF using an expandable cage was performed over a 2-year period. Standard MIS techniques with pedicle screw fixation were used in all cases. Upright lateral dynamic flexion/extension radiographs were reviewed prior to and at 1 year after surgery. Clinical metrics included numeric rating scale for back and leg pain, Oswestry Disability Index, and the SF-12 and VR-12 physical and mental health surveys. Radiographic parameters included anterior and posterior disc height, neuroforaminal height, spondylolisthesis, segmental lordosis, lumbar lordosis, and fusion rate. RESULTS: A total of 69 patients representing 75 operative levels met study inclusion criteria. The mean patient age at surgery was 63.4 ± 1.2 years, with a female predominance of 51%. The average radiographic and clinical follow-ups were 372 and 368 days, respectively. A total of 63 patients (91%) underwent 1-level surgery and 6 patients (9%) underwent 2-level surgery. Significant reductions of numeric rating scale scores for back and leg pain were observed-from 6.1 ± 0.7 to 2.5 ± 0.3 (p < 0.0001) and 4.9 ± 0.6 to 1.9 ± 0.2 (p < 0.0001), respectively. A similar reduction in Oswestry Disability Index from 38.0 ± 4.6 to 20.0 ± 2.3 (p < 0.0001) was noted. Likewise, SF-12 and VR-12 scores all showed statistically significant improvement from baseline (p < 0.001). The mean anterior and posterior disc heights improved from 8.7 ± 1.0 mm to 13.4 ± 1.5 mm (p = 0.0001) and 6.5 ± 0.8 mm to 9.6 ± 1.1 mm (p = 0.0001), respectively. Neuroforaminal height improved from 17.6 ± 2.0 mm to 21.9 ± 2.5 mm (p = 0.0001). When present, spondylolisthesis was, on average, reduced from 4.3 ± 0.5 mm to 1.9 ± 0.2 mm (p = 0.0001). Lumbar lordosis improved from 47.8° ± 5.5° to 58.5° ± 6.8° (p = 0.2687), and no significant change in segmental lordosis was observed. The overall rate of radiographic fusion was 93.3% at 1 year. No perioperative complications requiring operative revision were encountered. CONCLUSIONS: In this series of MIS TLIFs, use of this novel interbody cage was shown to be safe and effective. Significant improvements in pain and disability were observed. Effective and durable restoration of disc height and neuroforaminal height and reduction of spondylolisthesis were obtained, with concurrent gains in lumbar lordosis. Taken together, this device offers excellent clinical and radiographic outcomes via an MIS approach.