Background Avoiding operative intervention during the active phase of vasculitis is a central tenant of management of this pathology. For unusual presentations of vascular disease, the early diagnosis of vasculitis is imperative to guide treatment. Methods We present the case of a 68-year-old female who presented with a spontaneous brachial artery pseudoaneurysm and was found to have granulomatosis with polyangiitis. Results and conclusion The management of arterial complications of vasculitis are particularly difficult in the active phase of disease. Our patient had successful resolution of her pseudoaneurysm with ultrasound compression, avoiding open or endovascular intervention during the active phase of disease.
Purpose Treatment of invasive rectal adenocarcinoma is stratified into upfront surgery versus neoadjuvant chemoradiotherapy, in part, based on tumor distance from the anal verge (AV). This study examines the correlation between tumor distance measurements (endoscopic and MRI) and relationship to the anterior peritoneal reflection (APR) on MRI. Methods A single-center retrospective study was performed at a tertiary center accredited by the National Accreditation Program for Rectal Cancer (NAPRC). 162 patients with invasive rectal cancer were seen between October of 2018 and April of 2022. Sensitivity and specificity were determined for MRI and endoscopic measurements in their ability to predict tumor location relative to the APR. Results 119 patients had tumors endoscopically and radiographically measured from the AV. Pelvic MRI characterized tumors as above (intraperitoneal) or at/straddles/below the APR (extraperitoneal). True positives were defined as extraperitoneal tumors < 10cm. True negatives were defined as intraperitoneal tumors > 10cm. Endoscopy was 81.9% sensitive and 64.3% specific in predicting tumor location with respect to the APR. MRI was 86.7% sensitive and 92.9% specific. Utilizing a 12cm cutoff, sensitivity of both modalities increased (94.3%, 91.4%) but specificity decreased (50%, 64.3%). Conclusion For locally invasive rectal cancers, tumor position relative to the APR is an important factor in determining the role of neoadjuvant therapy. These results suggest endoscopic tumor measurements do not accurately predict tumor location relative to the APR, and may lead to incorrect treatment stratification. When the APR is not identified, MRI-reported tumor distance may be a better predictor of this relationship.
Treatment of invasive rectal adenocarcinoma is strati ed into upfront surgery versus neoadjuvant chemoradiotherapy, in part, based on tumor distance from the anal verge (AV). This study examines the correlation between tumor distance measurements (endoscopic and MRI) and relationship to the anterior peritoneal re ection (APR) on MRI. MethodsA single-center retrospective study was performed at a tertiary center accredited by the National Accreditation Program for Rectal Cancer (NAPRC). 162 patients with invasive rectal cancer were seen between October of 2018 and April of 2022. Sensitivity and speci city were determined for MRI and endoscopic measurements in their ability to predict tumor location relative to the APR. Results119 patients had tumors endoscopically and radiographically measured from the AV. Pelvic MRI characterized tumors as above (intraperitoneal) or at/straddles/below the APR (extraperitoneal). True positives were de ned as extraperitoneal tumors < 10cm. True negatives were de ned as intraperitoneal tumors > 10cm. Endoscopy was 81.9% sensitive and 64.3% speci c in predicting tumor location with respect to the APR. MRI was 86.7% sensitive and 92.9% speci c. Utilizing a 12cm cutoff, sensitivity of both modalities increased (94.3%, 91.4%) but speci city decreased (50%, 64.3%). ConclusionFor locally invasive rectal cancers, tumor position relative to the APR is an important factor in determining the role of neoadjuvant therapy. These results suggest endoscopic tumor measurements do not accurately predict tumor location relative to the APR, and may lead to incorrect treatment strati cation.When the APR is not identi ed, MRI-reported tumor distance may be a better predictor of this relationship.
Aging severely limits myocardial regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesize that short telomeres induce autophagy and elicit the age-associated change in cardiac progenitor cell fate. We compared mouse strains with different telomere lengths (TL) for phenotypic characteristics of aging and also isolated CPCs from them. Naturally occurring wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres (TL:18Kb) exhibits early cardiac aging with diastolic dysfunction, hypertrophy, fibrosis and increase in senescence markers p53 and p16, as compared to common lab strains FVB (TL:75Kb) and C57 (TL:50Kb). CAST CPCs with short TLs have altered cell fate as characterized by slower proliferation (p<0.01); increased senescence identified by beta-galactosidase activity (p<0.05); increased basal commitment as determined by expression of lineage markers smooth muscle actin, Tie2, and sarcomeric actinin (16.6, 1.7 and 1.75, p<0.05); as well as loss of quiescence marker expression. Consistent findings of altered cell fate are also evident in old CPCs isolated from aged mice with significantly shorter TLs. Cell fate changes occurring downstream from short TL are at least partially p53 dependent, as p53 inhibition rescues the irreversible cell cycle arrest observed in CAST CPCs. Mechanistically, short TLs induce autophagy, a catabolic protein degradation process. Autophagy flux is increased in CAST CPCs as evidenced by increased LC3 (p<0.05), reduced p62 expression (-52%, p<0.05) and increased accumulation of autophagic puncta. Pharmacological inhibition of autophagosome formation, but not autolysosome formation reverses the cell fate to a more youthful phenotype. Overall the data suggests that short TLs activate autophagy to accommodate cell fate changes that tip the equilibrium away from quiescence and proliferation into differentiation and senescence, leading to age-associated exhaustion of CPCs. The study provides the mechanistic basis underlying age-associated cell fate changes that will enable identification of molecular strategies to enhance the therapeutic effects of aged CPCs.
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