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Kessler posted an update 8 months, 4 weeks ago
There are conflicting data regarding the relationship between pathologic complete response (pCR) and post-operative complications following rectal cancer resection. The objective of this study was to compare the rates of morbidity among pCR patients and non-pCR patients and to identify factors that predict pCR morbidity in a large national database.
This is a retrospective study using American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted proctectomy data (2016-18). Patients with neoadjuvant chemoradiation therapy followed by proctectomy were included, and divided into pCR and non-pCR groups according to final stage. The groups were compared with Student’s t-test, Chi-squared or Fisher’s exact test. Multivariate logistic regression models were constructed to estimate the association between pCR status and post-operative morbidity while adjusting for key covariates.
244 pCR and 1656 non-pCR patients were included. pCR patients had higher body mass index (28.1±6.2 hnical challenges resecting larger, non-responsive tumors.
Urological complications after renal transplantation (RT), including urine leaks, remain the most common type of surgical complications in the early post-transplant period. In this study we evaluated 324 consecutive RTs recipients in whom Haberal’s corner-saving anastomosis technique was used for ureteroneocystostomy.
Since January 2018, 461 RTs were performed at our center. Haberal’s corner-saving anastomosis technique was used in 324 of these 461 RTs and the effectiveness of the technique was analyzed retrospectively. P7C3 NAMPT activator There were 115 female patients and 209 male patients, with a mean age of 42.1 ± 13.9 years. The most common etiology resulting in RT was hypertension among the recipients.
We observed 8 (2.4%) ureteral complications in 7 recipients as follows ureteral stenosis in 2 recipients (0.6%), anastomotic leaks in 1 (0.3%), concomitant leak-stenosis in 1 (0.3%), and vesicoureteral reflux in 3 (0.9%). Six complications were treated with interventional radiological techniques and 2 were treated surgically. There was no graft and patient loss in the event of urological complications.
Because of the low complication rate, we believe that Haberal’s corner-saving ureteral anastomosis technique is a safe method for performing a ureteroneocystostomy.
Because of the low complication rate, we believe that Haberal’s corner-saving ureteral anastomosis technique is a safe method for performing a ureteroneocystostomy.Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The worldwide increase in the incidence of opportunistic fungal infections and the emerging resistance to available azole-based antifungal drugs, raise the need to develop structurally distinct and selective fungal CYP51 inhibitors. In this work we have, for the first time, investigated the binding of pyridylethanol(phenylethyl)amines to any fungal CYP51. The comparison of the binding to Candida albicans and human CYP51 studied by spectroscopic and modeling methods revealed moieties decisive for selectivity and potency and resulted in the development of highly selective derivatives with significantly increased inhibitory potency. The structure-based insight into the selectivity requirements of this new chemical class of fungal CYP51 inhibitors, their unique binding properties and the low molecular weight of lead derivatives offer novel directions for the targeted development of antifungal clinical candidates.In quest of promising anticancer agents, the pharmacophores of natural (β-carboline) and synthetic origin (benzothiazole) were adjoined by a carboxamide bridge and three-point diversification was accomplished. The in vitro cytotoxic ability of the compounds was established on adherent and suspension human cancer cell lines and compounds 8u and 8f advanced as pre-eminent molecules with IC50 values of 1.46 and 1.81 μM respectively in A549 cell line. The cytospecificity was entrenched for potent compounds 8u and 8f by evaluating against normal human lung epithelial cells and selectivity index was calculated. Furthermore, EtBr displacement, relative viscosity and gel-based topoisomerase II target assays unveiled the intercalative topo-II inhibitory capability and DNA binding studies (absorbance) revealed the dissociation constant (Kd) for compounds 8u and 8f as 98 and 103 μM respectively. Additionally, cell-based flow cytometric assays like Annexin-V/PI dual staining aids in the quantification of apoptosis induced and JC-1 staining disclosed the depolarization of mitochondrial membrane potential by compound 8u in A549 cells in a dose-dependent manner. Moreover, wound healing assay established the inhibition of in vitro cell migration by compound 8u on A549 cells. In addition, molecular docking studies proved the binding of compounds 8u and 8f in the active site of DNA complexed with topo IIα and stabilized by interactions with DNA base pairs and amino acid residues. Remarkably, the compounds 8u and 8f follow Lipinski’s rule of five and are in the recommended range for Jorgensen’s rule of three with a minimal violation and other pharmacokinetic parameters revealing druggability of the synthesized hybrids.The virus SARS CoV-2, which causes the respiratory infection COVID-19, continues its spread across the world and to date has caused more than a million deaths. Although COVID-19 vaccine development appears to be progressing rapidly, scientists continue the search for different therapeutic options to treat this new illness. In this work, we synthesized five new 1-aryl-5-(3-azidopropyl)indol-4-ones and showed them to be potential inhibitors of the SARS CoV-2 main protease (3CLpro). The compounds were obtained in good overall yields and molecular docking indicated favorable binding with 3CLpro. In silico ADME/Tox profile of the new compounds were calculated using the SwissADME and pkCSM-pharmacokinetics web tools, and indicated adequate values of absorption, distribution and excretion, features related to bioavailability. Moreover, low values of toxicity were indicated for these compounds. And drug-likeness levels of the compounds were also predicted according to the Lipinski and Veber rules.