Roachsejersen2702
Altogether, these findings indicate that DMD muscle stem cells are dysfunctional and have impaired regenerative potential. Although recent advances in adeno-associated vector and antisense oligonucleotide-mediated mechanisms for gene therapy have shown clinical promise, the current therapeutic strategies for muscular dystrophy do not effectively target muscle stem cells and do not address the deficiencies in muscle stem cell function. Here, we discuss the merits of restoring endogenous muscle stem cell function in degenerating muscle as a viable regenerative medicine strategy to mitigate DMD.
The continuous availability of open micropores is crucial for a successful microneedle (MN) drug delivery strategy. However, micropore lifetime depends on intrinsic skin functional and anatomical characteristics, which vary significantly at different anatomical sites.
This pilot study explored if differences exist in micropore closure timeframes at 3 anatomical sites - upper arm, volar forearm, and abdomen.
Healthy subjects (n = 35) self-identifying as Asian (n = 9), Bi-/multiracial (n = 2), Black (n = 9), Latino (n = 6), and White (n = 9) completed the study. The upper arm, volar forearm, and abdomen were treated with MNs; skin impedance and transepidermal water loss (TEWL) were measured at baseline and post-MN to confirm micropore formation. Impedance was measured for 3 days to evaluate micropore lifetime. Measurements of L*, which quantifies the skin lightness/darkness, were made using a tristimulus colorimeter. Micropore lifetime was determined by comparing baseline and post-MN impedance measurementthat need to be explicitly considered when developing drug products to support MN-assisted drug delivery strategies.
Our results suggest that anatomical site of application may not be a source of significant variability in micropore closure time. These findings may help reduce the number of physiological parameters that need to be explicitly considered when developing drug products to support MN-assisted drug delivery strategies.
For older patients with cancer, maintaining or regaining their ability to care of themselves is of major interest. Which tools are appropriate to measure this? Different tools to assess functional status (FS) are established in geriatric and oncological care, but they have been compared poorly in the past.
Within a prospective cohort trial, we included 483 patients 198 older patients with cancer, 156 younger patients with cancer, and 129 older patients with benign disease. read more FS was assessed as Eastern Cooperative Oncology Group performance status (ECOG-PS), activities of daily living (ADL), and instrumental activities of daily living (IADL). Results were compared for their differences in identifying patients as functionally compromised.
The relative frequency of cancer patients with limitations in ECOG-PS, ADL, and IADL, respectively, increased from 25.7, 13.5, and 17.9% in those <60 years of age to 50.0, 47.1, and 66.7% in those ≥80 years. Results in older patients with cancer were comparable to oldervely; of those without limitations in ADL and IADL, 34.7 and 26.0%, respectively, had a poor ECOG-PS. Treatment approach (curative vs. palliative) was found to be significantly associated with functional limitations. Key Messages Geriatric and oncological measure of FS report differences in functional impairment. Geriatric functional measures are more sensitive to age-related changes and should be included as patient-reported outcomes in clinical trials and care.
Necrotizing crescentic glomerulonephritis (GN) associated with anti-neutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase (MPO) is a devastating disease that quickly progresses to kidney failure. Current therapies are broadly immunosuppressive and associated with adverse effects. We wanted to set up a model that could be suitable for testing narrowly targeted therapies.
The model was constructed in male Wistar Kyoto rats through injections of human MPO (hMPO) and pertussis toxin, followed by a sub-nephritogenic dose of sheep anti-rat glomerular basement membrane (GBM) serum to boost the disease. Rats were monitored for 35 days. Rats given hMPO alone, saline, or human serum albumin with or without anti-GBM serum were also studied.
Rats receiving hMPO developed circulating anti-hMPO and anti-rat MPO antibodies. Challenging hMPO-immunized rats with the anti-GBM serum led to more glomerular neutrophil infiltration and MPO release, and severe haematuria, heavy proteinuria, and higher blood urea nitrogen than hMPO alone. Pauci-immune GN developed with crescents, affecting 25% of glomeruli. The majority of crescents were fibrocellular. Necrotizing lesions and Bowman capsule ruptures were detected. Cells double positive for claudin-1 (a marker of parietal epithelial cells [PECs]) and neural cell adhesion molecule (NCAM; progenitor PECs) were present in crescents. Double staining for NCAM and Ki-67 established proliferative status of progenitor PECs. Podocyte damage was associated with endothelial and GBM changes by electron microscopy. Monocyte/macrophages and CD4+ and CD8+ T cells accumulated in glomeruli and the surrounding area and in the tubulointerstitium. Lung haemorrhage also manifested.
This model reflects histological lesions of human ANCA-associated rapidly progressive GN and may be useful for investigating new therapies.
This model reflects histological lesions of human ANCA-associated rapidly progressive GN and may be useful for investigating new therapies.
After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy.
A total of 52 patients with SESCC who underwent complete but noncurative ESD from January 2008 to December 2016 at the Samsung Medical Center and Asan Medical Center in Korea were retrospectively analyzed. Clinicopathologic characteristics and oncologic outcomes were compared between the observation group (n = 23) and the additional surgery group (n = 29).
During a mean follow-up of 34.4 and 41.7 months, respectively, the rates of death (observation vs. surgery, 17.4 vs. 10.3%; p = 0.686), recurrence (observation vs. surgery, 13 vs. 17.2%; p = 1.000), and disease-specific death (observation vs. surgery, 4.3 vs. 6.9%; p = 1.000) did not significantly differ between the 2 groups. The 3-year overall survival was 86.3 and 96.4%, respectively (p = 0.776). The 3-year recurrence-free survival (observation vs. surgery, 85.0 vs. 88.7%; p = 0.960) and disease-specific survival (observation vs. surgery, 95.2 vs. 96.4%; p = 0.564) also did not significantly differ.
The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients.
The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients.
We aimed to compare the oncological outcomes of laparoscopy and open resection for patients with rectal cancer following neoadjuvant chemoradiotherapy (NCRT).
We searched the publications that compared the efficacy of laparoscopic surgery and open thoracotomy in treatment outcomes of rectal cancer after NCRT. All trials analyzed the summary hazard ratios of the endpoints of interest, including survival and individual postoperative complications.
Totally, 10 trials met our inclusion criteria. The pooled analysis of 3-year disease-free survival (OR 1.39, 95% CI 0.93-2.06; p = 0.11) and 3-year overall survival (OR 1.01, 95% CI 0.70-1.45; p = 0.97) showed that laparoscopic surgery did not achieve beneficial effects compared with open thoracotomy. The pooled result of duration of surgery indicated that laparoscopic surgery was associated with a trend for longer surgery time (SMD 27.53, 95% CI 1.34-53.72; p = 0.04), shorter hospital stay (SMD -1.64, 95% CI -2.70 to -0.58; p = 0.002), more postoperative complications (OR 0.77, 95% CI 0.60-0.99; p = 0.04), and decreased blood loss (SMD -49.87, 95% CI -80.61 to -19.14; p = 0.001). However, the number of removed lymph nodes, positive circumferential resection margin, as well as complications after surgery showed significant differences between the 2 groups.
We focused on current evidence and reviewed the studies indicating that similar oncological outcomes were associated with laparoscopic surgery following NCRT for patients with locally advanced lower rectal cancer in comparison with open surgery.
We focused on current evidence and reviewed the studies indicating that similar oncological outcomes were associated with laparoscopic surgery following NCRT for patients with locally advanced lower rectal cancer in comparison with open surgery.
The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood.
Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34).
Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to <15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO2] <90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO2, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = -0.39; p = 0.03) and end-systolic (r = -0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO2 but not with measures of OSA severity or daytime clinical variables.
OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.
OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.
