NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome has recently become an intriguing target of several chronic and viral diseases. Here, we argue that targeting NLRP3 inflammasome ...could be a strategy to prevent cardiovascular outcomes fulminant myocarditis, heart failure, venous thromboembolism (VTE) and acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 infection. We discuss the rationale for NLRP3 targeting in clinical trials as an effective therapeutic strategy aimed to improve prognosis of COVID-19, analyzing the potential of two therapeutic options (tranilast and OLT1177) currently available in clinical practice.
Background Sporadic, nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) are diagnosed with increasing frequency. We compared the risk of tumor growth, metastasis, and mortality between ...patients treated versus those treated expectantly. Method A retrospective study of patients seen at our institution with sporadic NF-PNETs, with ≥12 months of follow-up. Kaplan-Meier analysis was performed. Results Between 1999 and 2014, 35 patients with an incidentally discovered nonfunctional PNET were identified. Twenty underwent resection and 15 were followed with imaging. In the operative group, 8 had NF-PNETs < 2 cm, while 12 had NF-PNETs ≥ 2 cm. In the nonoperative expectant management by serial imaging group, 10 had NF-PNETs < 2 cm while 5 had NF-PNETs ≥ 2 cm. Small NF-PNETs (<2 cm) in either the operative or nonoperative groups demonstrated no evidence of progression or metastasis (median follow-up of 27.8 months). Morbidity in the operative group was 35% with pancreatic pseudocyst the most common. Conclusion Incidentally discovered NF-PNETs < 2 cm in size can be observed safely with serial imaging.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objectives Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum. Morbidity and mortality are almost invariably owing to ...locoregional progression. Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome. Methods Between January 1992 and 2010, 211 patients with MPM treated at 3 major referral centers with operative CRS and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were analyzed. Results The median, actuarial overall survival was 38.4 months; the actuarial 5- and 10-year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were younger age <60 years ( P < .01), complete or near complete (R0–1 ) versus incomplete (R2–3 ) resection ( P < .02), low versus high histologic grade ( P < .01), and the use of cisplatin versus mitomycin-C during HIPEC ( P < .01). There was a trend toward female sex and improved survival (male hazard ratio, 1.46; 95% confidence interval, 0.89–2.41; P = .13). Conclusion Operative CRS with HIPEC is associated with prolonged survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Primary hyperparathyroidism is a disease that is caused by excess parathyroid hormone (PTH) secretion from 1 or more of the parathyroid glands. Surgery is the only cure. Traditional surgical ...management consists of a 4-gland cervical exploration. Development of imaging specific to identification of parathyroid glands and application of the rapid PTH assay to operative management have made more minimal exploration possible. There are distinct advantages and disadvantages of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE). The advantages of MIP seem to outweigh those of BNE, and MIP has replaced BNE as the operation of choice by many surgeons.
A phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose ...(MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy.
Subjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m(2) and 60 mg/m(2) were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed.
DLT criteria were met at 60 mg/m(2), and the MTD was defined as 50 mg/m(2). RF ablation was performed during the peak of the plasma concentration-time curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia.
LTLD can be safely administered systemically at the MTD (50 mg/m(2)) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors.
Background In bicarbonate-based hemodialysis, dialysate total calcium (tCa) concentration may have effects on mineral metabolism. Study Design Randomized crossover trial of 3 dialysate tCa ...concentrations (2.5, 2.75, and 3.0 mEq/L). Setting & Participants 22 stable anuric uremic patients underwent three 4-hour bicarbonate hemodialysis sessions with the 3 different dialysate tCa concentrations using a single-pass batch dialysis system. Outcomes Hourly measurements of plasma water ionized calcium (iCa) and plasma parathyroid hormone (PTH) concentrations. tCa mass balances were measured from the dialysate side. Results Hourly plasma water iCa concentrations were higher with a dialysate tCa concentration of 3.0 compared with 2.75 and 2.5 mEq/L ( P < 0.05), as were iCa concentrations at the end of dialysis sessions (2.66 ± 0.1, 2.56 ± 0.12, and 2.4 ± 0.08 mEq/L, respectively; P < 0.001). Mean tCa mass balance values (diffusion gradient from the dialysate to the patient) were positive with all dialysate tCa concentrations and increased progressively with dialysate tCa concentration (75 ± 122, 182 ± 125, and 293 ± 228 mg, respectively; P < 0.001). Plasma PTH levels increased during dialysis using dialysate tCa concentration of 2.5 mEq/L (mean increase, 225 ± 312 pg/mL) and decreased with dialysate tCa concentrations of 2.75 and 3.0 mEq/L (mean decreases, 68 ± 325 and 99 ± 432 pg/mL, respectively). Limitations Small sample size and lack of measurement of total-body calcium mass balances. Conclusions A dialysate tCa concentration of 2.75 mEq/L might be preferable to 2.5 or 3.0 mEq/L because it is associated with mildly positive tCa mass balance values, plasma water iCa levels in the reference range, and stable PTH levels during dialysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
10.
Insulinoma Mathur, Aarti; Gorden, Philip; Libutti, Steven K
The Surgical clinics of North America,
10/2009, Volume:
89, Issue:
5
Journal Article
Peer reviewed
Open access
Insulinoma is a rare neuroendocrine tumor with an incidence of 4 per 1 million persons per year, which may occur as a unifocal sporadic event in patients without an inherited syndrome or as a part of ...multiple endocrine neoplasia type 1. Key neuroglycopenic and hypoglycemic symptoms in conjunction with biochemical proof establish the diagnosis. Once the diagnosis is established, the insulinoma is preoperatively localized within the pancreas with the goal of surgical excision for cure. This review discusses the historical background, diagnosis, and management of sporadic insulinoma.
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