Urothelial carcinoma at the uretero-enteric junction: Multi-center evaluation of oncologic outcomes after radical nephroureterectomy

ObjectiveThe natural history of urothelial carcinoma arising at the uretero-enteric junction (UEJ) is poorly defined, and the data guiding clinical management of these patients is limited. Therefore, we evaluated oncologic outcomes of patients treated for urothelial carcinoma at the UEJ.MethodsUtilizing a multi-institutional database of patients treated with radical nephroureterectomy (RNU), we assessed the clinicopathologic parameters and oncologic outcomes of UEJ tumors compared with other upper tract urothelial carcinomas (UTUC). Survival analyses were performed to determine independent predictors of disease recurrence and cancer-specific mortality after RNU.ResultsThe study included 1,363 patients, 921 men and 442 women with 36 months median follow-up after RNU. Compared with UTUC in the kidney or ureter, UEJ tumors (n = 22) were more likely to demonstrate features of advanced disease, which were proved to be independent predictors of disease recurrence and cancer-specific mortality after RNU. The 5 year disease-free survival (DFS) and cancer-specific survival (CSS) rates were 25% and 39% in those with UEJ tumors vs. 69% and 73% in those with UTUC in the kidney or ureter (P = 0.001 and P = 0.008, respectively).ConclusionsUEJ tumors harbor features of locally advanced disease associated with high risk of systemic recurrence and death from cancer after RNU. Our findings suggest the need for integration of systemic therapy into the management paradigm of these patients.     

Long-term skeletal stability after maxillary advancement with distraction osteogenesis in cleft lip and palate patients: A systematic review

Objective:To systematically review the long-term skeletal stability after maxillary advancement with distraction osteogenesis (DO) in cleft lip and palate (CLP) patients.Materials and Methods:Electronic databases, grey literature, and reference list searches were conducted. The inclusion criteria were stability of maxillary advancement with distraction osteogenesis assessed at the posttreatment follow-up ≥ 1 year in CLP patients. Full articles were retrieved from abstracts or titles that appear to meet the inclusion criteria or lacked sufficient detail for immediate exclusion. Once full articles were collected, they were again reviewed considering more detailed inclusion criteria for a final selection decision. A methodologic quality assessment tool was utilized.Results:Thirty abstracts/titles met the initial search criteria, and 13 articles were finally selected. Overall, methodologic quality scores were high in only one randomized clinical trial. After maxillary advancement with DO in CLP patients, the long-term horizontal relapse in A-point was less than 15% in eight studies and between 20% and 25% in four studies. The study that was judged as a high-quality study reported 8.2% horizontal relapse in A-point. The relapse rate was higher in DO with external distracter device than DO with internal distracter device.Conclusions:Current evidence suggests maxillary advancement with DO has good stability in CLP patients with moderate and severe maxillary hypoplasia.     

Experimental and theoretical investigations of benzoic acid derivatives as corrosion inhibitors for AISI 316 stainless steel in hydrochloric acid medium: DFT and Monte Carlo simulations on the Fe (110) surface

The inhibition efficiency of benzoic acid (C1), para-hydroxybenzoic acid (C2), and 3,4-dihydroxybenzoic acid (C3) towards enhancing the corrosion resistance of austenitic AISI 316 stainless steel (SS) has been evaluated in 0.5 M HCl using weight loss (WL), open circuit potential (OCP), potentiodynamic polarization method, electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) analysis. The results obtained from the different experimental techniques were consistent and showed that the inhibition efficiency of these inhibitors increased with the increase in concentration in this order C3 > C2 > C1. In addition, the results of the weight loss measurements showed that these inhibitors followed the Villamil isotherm. Quantum chemical calculations and Monte Carlo simulations have also been used for further insight into the adsorption mechanism of the inhibitor molecules on Fe (110). The quantum chemical parameters have been calculated by density functional theory (DFT) at the B3LYP level of theory with 6-31G+(2d,p) and 6-31G++(2d,p) basis sets in gas and aqueous phase. Parameters such as the lowest unoccupied (E_LUMO) and highest occupied (E_HOMO) molecular orbital energies, energy gap (ΔE), chemical hardness (η), softness (σ), electronegativity (χ), electrophilicity (ω), and nucleophilicity (ε) were calculated and showed the anti-corrosive properties of C1, C2 and C3. Moreover, theoretical vibrational spectra were calculated to exhibit the functional hydroxyl groups (OH) in the studied compounds. In agreement with the experimental data, the theoretical results showed that the order of inhibition efficiency was C3 > C2 > C1.

The corrosion inhibition efficiencies of benzoic acid (C1), para-hydroxybenzoic acid (C2), and 3,4-dihydroxybenzoic acid (C3) have been evaluated in 0.5 M HCl toward protecting AISI 316 stainless steel (SS).     

Survey of the temporal changes in HIV-1 replicative fitness in the Amsterdam Cohort

Changes in virulence and fitness during an epidemic are common among pathogens. Several studies have shown that HIV fitness increases within a patient during disease progression, while bottlenecks, such as sexual transmission, immune pressure and drug treatment can reduce fitness. In this study, we analyzed how these opposing forces have shaped HIV-1 fitness over time. Therefore, we compared the replicative fitness of HIV-1 isolates from newly infected untreated individuals, diagnosed for HIV-1 infection early in the AIDS epidemic in Amsterdam, the Netherlands, with more recent isolates. Twenty-five early and late HIV-1 isolates, carefully matched for seroconversion time, were competed head-to-head in a dual infection/competition assay, employing peripheral blood mononuclear cells. In contrast with previous studies, we observed a trend of increasing fitness over time in the HIV epidemic of Amsterdam. Apparently, the bottleneck, occurring with each transmission event, does not completely reset the fitness increase acquired during disease progression.     

Prediction of drug‐drug interactions using physiologically‐based pharmacokinetic models of CYP450 modulators included in Simcyp software

In recent years, physiologically based PharmacoKinetic (PBPK) modeling has received growing interest as a useful tool for the assessment of drug pharmacokinetics. It has been demonstrated to be informative and helpful to quantify the modification in drug exposure due to specific physio‐pathological conditions, age, genetic polymorphisms, ethnicity and particularly drug–drug interactions (DDIs). In this paper, the prediction success of DDIs involving various cytochrome P450 isoenzyme (CYP) modulators namely ketoconazole (a competitive inhibitor of CYP3A), itraconazole (a competitive inhibitor of CYP3A), clarithromycin (a mechanism‐based inhibitor of CYP3A), quinidine (a competitive inhibitor of CYP2D6), paroxetine (a mechanism‐based inhibitor of CYP2D6), ciprofloxacin (a competitive inhibitor of CYP1A2), fluconazole (a competitive inhibitor of CYP2C9/2C19) and rifampicin (an inducer of CYP3A) were assessed using Simcyp^® software. The aim of this report was to establish confidence in each CYP‐specific modulator file so they can be used in the future for the prediction of DDIs involving new victim compounds. Our evaluation of these PBPK models suggested that they can be successfully used to evaluate DDIs in untested scenarios. The only noticeable exception concerned a quinidine inhibitor model that requires further improvement. Additionally, other important aspects such as model validation criteria were discussed.