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Miscell: A competent self-supervised learning method for dissecting single-cell transcriptome.
Meningioma is the most common radiation-induced brain neoplasm, usually occurring after a latency of 20 - 35 years, with multiplicity in 10% of cases. Radiation-induced meningiomas (RIMs) have not previously been reported in patients with tuberous sclerosis complex (TSC), unlike their well-known occurrence in other familial tumor predisposition syndrome patients. We report a TSC patient who developed numerous intracranial meningiomas twenty five year after radiation therapy for subependymal giant cell astrocytoma (SEGA). Autopsy examination showed innumerable, coalescent, benign, meningothelial meningiomas, WHO grade 1, ranging in size from 0.2 cm to 3.3 cm. Autopsy also showed small residual SEGA, radiation-induced cerebral vasculopathy, and classic TSC features including several small subependymal nodules ("candle gutterings"), white matter radial heterotopia, facial angiofibromas, dental enamel pitting, one ash leaf spot, and multiple hepatic and renal angiomyolipomas. Next-generation sequencing analysis utilizing a 500+ gene cancer panel demonstrated chromosomal loss involving the majority of chromosome 22, including the NF2 gene locus, as well as a truncating nonsense mutation in TSC1 p. R509*. While TSC patients rarely require radiation therapy, this striking case suggests that patients with TSC should be monitored closely if cranial therapeutic radiation is administered.Pulmonary hypertension (PH) is a serious disease with pulmonary arterial fibrotic remodeling and limited responsiveness to vasodilators. Our data suggest that mild acidosis induced by carbonic anhydrase inhibition could ameliorate PH, but the vascular mechanisms are unclear. We tested the hypothesis that carbonic anhydrase inhibition ameliorates PH by improving pulmonary vascular reactivity and relaxation mechanisms. Male Sprague-Dawley rats were either control normoxic (Nx), or injected with Sugen 5416 (20 mg/kg, sc) and subjected to hypoxia (9% O2) (Su + Hx), or Su + Hx treated with acetazolamide (ACTZ, 100 mg/kg/day, in drinking water). SR1 antagonist clinical trial After measuring the hemodynamics, right ventricular hypertrophy was assessed by Fulton's Index; vascular function was measured in pulmonary artery, aorta, and mesenteric arteries; and pulmonary arteriolar remodeling was assessed in lung sections. Right ventricular systolic pressure and Fulton's Index were increased in Su + Hx and reduced in Su + Hx + ACTZ rats. Pulmonary artery contraction to KCl and phenylephrine were reduced in Su + Hx and improved in Su + Hx + ACTZ. Acetylcholine (ACh)-induced relaxation and nitrate/nitrite production were reduced in pulmonary artery of Su + Hx and improved in Su + Hx + ACTZ. ACh relaxation was blocked by nitric oxide (NO) synthase and guanylate cyclase inhibitors, supporting a role of NO-cGMP. Sodium nitroprusside (SNP)-induced relaxation was reduced in pulmonary artery of Su + Hx, and ACTZ enhanced relaxation to SNP. Contraction/relaxation were not different in aorta or mesenteric arteries of all groups. Pulmonary arterioles showed wall thickening in Su + Hx that was ameliorated in Su + Hx + ACTZ. Thus, amelioration of pulmonary hemodynamics during carbonic anhydrase inhibition involves improved pulmonary artery reactivity and NO-mediated relaxation and may enhance responsiveness to vasodilator therapies in PH.Background The key to high-quality care at the end of life is goal-concordant care, defined as care that is consistent with patient wishes. Objectives To characterize decedent wishes for care at the end of life and to examine next of kin narratives of their loved ones' perceptions of whether wishes were honored. Design Mortality follow-back survey and in-depth interviews. Setting/Subjects Survey responses (n = 601) were from next of kin of decedents who died in the San Francisco Bay area of the United States. Interviews were conducted with 51 next of kin, of whom 14 indicated that the decedent received care that was inconsistent with their wishes. Measurements The survey asked if the decedent had wishes or plans for care and if care provided ever went against those wishes. In-depth interviews focused on aspects of care at the end of life that were not consistent with the decedent's wishes. Results Approximately 10% of next of kin who reported on the survey that the decedent had specific wishes for medical care at the end of life also reported that the decedent received care that went against their wishes in the last month of life. The main theme of the in-depth interviews with next of kin who reported care that went against wishes was that discordant care was inconsistent with wishes for comfort-focused care and a lack of symptom palliation. Conclusions Despite decades of work to improve quality of end-of-life care, poor pain and symptom management that result in lack of comfort remain the main reason that next of kin state wishes were not honored.Background Lymphocele is a common complication after kidney transplantation, which does not require treatment unless it is symptomatic. In this study, we aimed to evaluate the incidence, clinical symptoms, treatment choices, and success of different treatment methods of symptomatic lymphocele. Materials and Methods We evaluated 168 patients who had kidney transplantation between January 2012 and January 2020. Patients with decreased kidney functions due to lymphocele formation during the clinical follow-up were included in the study. External drainage catheter was placed in all patients, except one. In case of treatment failure with external drainage, laparoscopic fenestration guided by intraperitoneal ultrasonography was performed. Clinical symptoms and success rates of treatments were evaluated. Results Symptomatic lymphocele requiring interventional treatment was detected in 15 (8.9%) of 168 renal transplant patients. All of the symptomatic lymphocele cases had increased serum creatinine levels, whereas 10 had decreased urine volume, 4 had abdominal discomfort, and 2 had ipsilateral lower extremity edema. External drainage catheter was placed as the first-line treatment in 13 patients. In 6 cases, due to treatment failure with external drainage and in 2 patients as a first-choice treatment, laparoscopic fenestration was performed. No lymphocele recurrence was observed during follow-up. Conclusion Among various methods defined in the treatment of lymphocele, use of laparoscopic fenestration is increasing because of its high success rate and advantages over other methods. Intraperitoneal ultrasound-guided laparoscopic fenestration is a useful and safe method that can be performed as a first-choice treatment since it eliminates the risk of organ injury or bleeding.
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