Positive margins prediction in breast cancer conservative surgery: Assessment of a preoperative web-based nomogram

Margin status of the surgical specimen has been shown to be a prognostic and risk factor for local recurrence in breast cancer surgery. It has been studied as a topic of intervention to diminish reoperation rates and reduce the probability of local recurrence in breast conservative surgery (BCS).This study aims to validate the Dutch BreastConservation! nomogram, created by Pleijhus et al., which predicts preoperative probability of positive margins in BCS.Patients with diagnosis of breast cancer stages cT1-2, who underwent BCS at the Breast Center of São João University Hospital (BC-CHSJ) in 2013–2014, were included. Association and correlation were evaluated for clinical, radiological, pathological and surgical variables. Multivariable logistic regression and ROC curves were used to assess nomogram parameters and discrimination.In our series of 253 patients, no associations were found between margin status and other studied variables (such as age or family history of breast cancer), except for weight (p-value = 0.045) and volume (p-value = 0.012) of the surgical specimen.Regarding the nomogram, a statistically significant association was shown between cN1 status and positive margins (p-value = 0.014). No differences were registered between the scores of patients with positive versus negative margins. Discrimination analysis showed an AUC of 0.474 for the basic and 0.508 for the expanded models.We cannot assume its external validation or its applicability to our cohort. Further studies are needed to determine the validity of this nomogram and achieve a broader view of currently available tools.     

Design,synthesis, and evaluation of novel 2-substituted 1,4-benzenediol library as antimicrobial agents against clinically relevant pathogens

Development of new antimicrobial agents, capable of combating resistant and multidrug-resistant fungal and bacterial clinical strains, is necessary. This study presents the synthesis and antimicrobial screening of 42 2-substituted-1,4-benzenediols, being 10 novel compounds. In total, 23 compounds showed activity against fungi and/or bacteria. Benzenediol compounds 2, 5, 6, 8, 11, and 12 demonstrated broad spectrum antimicrobial actions, including resistant and multidrug-resistant species of dermatophytes (Trichophyton mentagrophytes), Candida spp. and the ESKAPE panel of bacteria. Minimum inhibitory concentrations of these compounds for fungi and bacterial strains ranged from 25 to 50 µg/ml and 8–128 µg/ml, respectively. The antifungal mechanism of action is related to the fungal cell wall of dermatophytes and membrane disruption to dermatophytes and yeasts, in the presence of compound 8. Specific structural changes, such as widespread thinning along the hyphae and yeast lysis, were observed by scanning electron microscopy. The effects of compound 8 on cell viability are dose-dependent; however they did not cause genotoxicity and mutagenicity in human leukocyte cells nor haemolysis. Moreover, the compounds were identified as nonirritant by the ex-vivo Hen’s egg test-chorioallantoic membrane (HET-CAM). The furan-1,4-benzenediol compound 5 showed in vivo efficacy to combat S. aureus infection using embryonated chicken eggs. Therefore, the compounds 8, and 5 are promising as hits for the development of new antimicrobial drugs with reduced toxicity.     

Prognostic Effect of Renal Function in Ambulatory Patients With Heart Failure and Reduced Ejection Fraction: The Kidney Is a Marker of Cardiac Function

Background

Chronic kidney disease is a frequent comorbidity in heart failure (HF), associated with increased mortality. The impact of temporal evolution of kidney function in HF prognosis is largely unknown. We evaluated the effect of renal function over time in all-cause mortality among ambulatory patients with HF.

Short and extended provocation tests have similar negative predictive value in non-immediate hypersensitivity to beta-lactams in children

Introduction and objectivesDrug provocation tests (DPTs) are the gold-standard method to diagnose non-immediate hypersensitivity reactions (NIHSR) to beta-lactam antibiotics (BL) in children. Our aim was to compare the negative predictive value (NPV) of one-day (short) DPT versus 3–7 days (extended) DPT for the diagnosis of NIHSR to BL in paediatric age. A secondary aim was to compare confidence on drug re-exposure after short and extended negative DPTs.MethodsThe occurrence of HSR on drug re-exposure and drug refusal after negative diagnostic DPTs were evaluated in children/adolescents with a history of NIHSR to BL using a questionnaire performed six months to ten years after DPT. Patients were divided into two groups according to the protocol performed: short DPT vs. extended DPT.ResultsWe enrolled 212 children and adolescents (86 females, 126 males, mean age at DPT 5.52 years, p25 = 3 years, p75 = 7.25 years): 69 tested with short DPT, and 143 with extended DPT. The NPV of both types of DPT together was 95.2%. The NPV of short DPT was 97.5% and the NPV of extended DPT was 93.8% (p = 0.419). After negative DPT, beta-lactams were refused by carers in 14.75% of the children requiring subsequent treatment, 6.98% in the short DPT group and 18.99% in the extended DPT group (p = 0.074).ConclusionsIn our paediatric sample, prolonging drug administration did not increase the NPV of diagnostic DPT for NIHSR to BL or reduce drug refusal. Altogether, the data here reported suggest that, however intuitive, prolonging DPT is not beneficial in the parameters analysed.     

Longitudinal association of adiposity and high-sensitivity C-reactive protein from adolescence into early adulthood

Background and aimsLongitudinal studies relating adiposity with low-grade inflammation are scarce. We aimed to examine the longitudinal association between the cumulative exposure to adiposity and low–grade inflammation from adolescence into early adulthood.Methods and resultsData from a population-based cohort (EPITeen) (n = 1147) was analyzed. Body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-height ratio (WHtR) and high-sensitivity C-reactive protein (hsCRP) were ascertained at 13, 17 and 21 years of age and standardized for each wave. Generalized least squares models with a compound symmetry correlation structure were fitted to estimate the longitudinal effect of adiposity on hsCRP and results were presented as linear regression coefficients and 95% confidence intervals [β (95%CI)].The final model estimated the association between the difference in adiposity between two consecutive evaluations (13–17 and 17 to 21-years-old), adjusted for previous adiposity and hsCRP levels, sex, parental education, leisure-time physical activity and fruits and vegetables intake. A positive association between the cumulative exposure to adiposity and final hsCRP was observed, in which the difference between adiposity indicators of two consecutive study waves was independently associated with hsCRP: 0.382 (0.299; 0.465) for BMI, 0.234 (0.164; 0.304) for WC, 0.395 (0.314; 0.477) for BF% and 0.195 (0.133; 0.258) for WHtR.ConclusionA significant longitudinal effect of the accumulation of adiposity on low-grade inflammation was observed. The change in adiposity from consecutive study waves was shown to have a stronger effect on final hsCRP concentrations than both previous adiposity and hsCRP levels.     

Daclatasvir and Sofosbuvir With or Without Ribavirin in Liver Transplant Recipients: A Single-Center Real-World Study

Background

Treatment with direct-acting antiviral drugs in interferon-free regimens is currently recommended for viral hepatitis C recurrence after liver transplantation. There are limited data regarding its results in this population, and no optimal treatment scheme has yet been singled out.

Neuromuscular electrical stimulation to improve gross motor function in children with cerebral palsy: a meta-analysis

ObjectiveTo systematically review the effectiveness of neuromuscular electrical stimulation (NMES) as an adjuvant therapy to improve gross motor function in children with spastic cerebral palsy.MethodsMEDLINE, EMBASE, Cochrane CENTRAL, PEDro and Scopus were searched. We included randomized controlled trials examining the effects of NMES combined with other therapies on gross motor function as assessed by the Gross Motor Function Measure (GMFM) and its functional dimensions. Two reviewers independently screened, extracted data, assessed the risk of bias (PEDro) and quality of the evidence (GRADE).ResultsSix randomized controlled trials (pooled n = 174) were included in the meta-analysis. NMES combined with other therapies presented medium effect size to improve gross motor function in children with cerebral palsy in comparison with conventional physical therapy or neurodevelopmental therapy. Our sensitivity analysis showed that NMES combined with other therapies was effective to improve GMFM-sitting and standing dimensions but not GMFM-walking dimension.ConclusionLow-quality evidence suggests that NMES may be used as adjuvant therapy to improve sitting and standing dimensions of GMFM in children with spastic cerebral palsy.     

Relevance of Chimerism Analysis After Allogeneic Stem Cell Transplantation

Hematopoietic stem cell transplantation is a potentially curative therapy for a range of malignant and non-malignant hematological diseases. Analysis of chimerism following allogeneic stem cell transplantation has been a routine method for the assessment of engraftment and early detection of graft failure. Lineage-specific chimerism monitoring is progressively used to specifically detect chimerism in one or more cell subsets, which may be undetected in assessment of the whole leukocyte population. The chimerism study in different leukocyte subpopulations increases sensitivity and specificity in the monitoring after transplantation, especially the analysis of T lymphocytes. All peripheral blood samples were separated into mononuclear cells and granulocytes by Ficoll density gradient centrifugation and T, B, and CD34+ was separated by immunomagnetic automatic cell separator. After DNA extraction, chimerism monitoring was performed using short tandem repeat by multiplex polymerase chain reaction followed by capillary electrophoresis. Quantification of chimerism was performed by determining the ratio of peak areas from donor and recipient informative short tandem repeat. Donor-recipient chimerism analysis in patients after allogeneic stem cell transplantation is a practical, feasible, and useful tool that predicts clinical outcomes and provides a guide for suitable therapeutic interventions.