42 research outputs found

    Unexpected thymoma in a challenging case of hyperparathyroidism

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    We report the case of a woman with primary hyperparathyroidism suspected of mediastinal ectopic parathyroid adenoma revealed to be a thymoma. Our aim was to focus on some possible criticisms in distinguishing between ectopic parathyroid and thymus

    Development of the first in vivo GPR17 ligand through an iterative drug discovery pipeline: A novel disease-modifying strategy for multiple sclerosis

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    The GPR17 receptor, expressed on oligodendroglial precursors (OPCs, the myelin producing cells), has emerged as an attractive target for a pro-myelinating strategy in multiple sclerosis (MS). However, the proof-of-concept that selective GPR17 ligands actually exert protective activity in vivo is still missing. Here, we exploited an iterative drug discovery pipeline to prioritize novel and selective GPR17 pro-myelinating agents out of more than 1,000,000 compounds. We first performed an in silico high-throughput screening on GPR17 structural model to identify three chemically-diverse ligand families that were then combinatorially exploded and refined. Top-scoring compounds were sequentially tested on reference pharmacological in vitro assays with increasing complexity, ending with myelinating OPC-neuron co-cultures. Successful ligands were filtered through in silico simulations of metabolism and pharmacokinetics, to select the most promising hits, whose dose and ability to target the central nervous system were then determined in vivo. Finally, we show that, when administered according to a preventive protocol, one of them (named by us as galinex) is able to significantly delay the onset of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. This outcome validates the predictivity of our pipeline to identify novel MS-modifying agents

    Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

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    Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202

    Microwave-Assisted Paal−Knorr Reaction. A Rapid Approach to Substituted Pyrroles and Furans

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    An array of tetrasubstituted pyrroles (and trisubstituted furans) was obtained using a simple three-step procedure. Functional homologation of a ��-ketoester with an aldehyde followed by oxidation gave a series of differently substituted 1,4-dicarbonyl compounds that can be rapidly cyclized with the Paal−Knorr procedure carried out under microwave irradiation

    Solution Phase Synthesis of a Library of Tetrasubstituted Pyrrole Amides.

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    An efficient strategy for the solution-phase parallel synthesis of a library of pyrrole-amides is described. Key reactions include functional homologation of beta-ketoesters with a set of aldehydes followed by oxidation to produce a series of differently substituted 1,4-dicarbonyl compounds. Rapid cyclization using a microwave-assisted Paal-Knorr reaction provided a set of 24 pyrrole esters that were further functionalized through a trimethylaluminum-mediated aminolysis to obtain a larger library of 288 diverse pyrrole-3-amides. The tetrasubstitution allows a good exploration of the chemical space around the central pyrrole core. The last step was entirely automated with a Bohdan Myriad personal synthesizer

    Personal experience in surgical management of pulmonary pleomorphic carcinoma

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    Background Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary pleomorphic carcinoma was introduced by the 1999 World Health Organization classification as a new peculiar type of lung carcinoma showing concurrent malignant epithelial and sarcomatoid spindle cell elements. Few reports describe its clinical behavior. My colleagues and I report a series of patients surgically treated for pulmonary pleomorphic carcinoma to describe our experience with this malignant neoplasm. Methods Twenty cases of pleomorphic pulmonary carcinoma were collected and studied clinicopathologically. All patients underwent surgical resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA. Histologic diagnosis was established by using light microscopic examination and immunohistochemistry. Survival rates were calculated with the Kaplan-Meier method. Results We postoperatively diagnosed 20 cases of pleomorphic carcinoma: 14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0. The remaining 16 patients died from early distant metastases. The median duration of disease-free survival was 5 months. The median duration of overall survival was 8 months. Conclusions The prognosis of patients with pleomorphic carcinoma was poor, despite surgery and adjuvant chemotherapy, because of early relapse of disease. Nodal involvement was a determinant prognostic variable, because advanced stages were related to worse prognosis. In case of preoperatively proven pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients. (copyright) 2004 by The Society of Thoracic Surgeons

    Indocyanine Green as a Beacon Light in Laparoscopy: A New Application in Transplant Surgery: A Case Report

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    Introduction: Indocyanine green (ICG) fluorescence imaging system is a now a consolidated complementary technique for several surgical fields. The development of post-transplant lymphocele following lymph spread could affect kidney function; between therapeutic options, the literature reports a 12% overall conversion rate from laparoscopic to open surgery with a major risk of damaging the urinary tract. Objective: The goal of the present study was to demonstrate that intraoperative ICG fluorescent imaging is a safe technique that can be used in laparoscopy establishing the exact location of the lymphocele and reducing intraoperative risks. Method: Fifty milligrams of ICG dissolved in 20 mL of saline solution was injected via percutaneous drainage placed into the lymphocele to decompress transplanted kidneys 2 weeks before a laparoscopic lymphocele marsupialization procedure. Results: During the first exploratory laparoscopy, in the flank and right iliac fossa, near the 2 renal grafts, fluorescence was identified in 3 raised areas that were the internal side of the lymphocele lobes. The lymphocele wall was dissected and 300 mL of serous fluid was aspirated after puncturing. A 5 cm breach was then made in the cyst wall using the Ultracision harmonic scalpel (Ethicon US). Afterwards, a pedicle of the omentum in the lymphocele core was interfered with and fixed by 2 stitches. Conclusions: Laparoscopic surgery seems to be the preferred surgical option for the treatment of primary symptomatic lymphocele after kidney transplantation. Intraoperative ICG fluorescent imaging is a safe technique to establish the exact location of the lymphocele and reduces the risk of damaging urinary structures during surgery
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