Comparative assessment of angiotensin receptor blockers in different clinical settings

Cardiovascular and renal disease can be regarded as progressing along a sort of continuum which starts with cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, etc), evolves with progression of atherosclerotic lesions and organ damage, and then becomes clinically manifest with the major clinical syndromes (myocardial infarction, stroke, heart failure, end-stage renal disease). The blood pressure control remains a fundamental mechanism for prevention of cardiovascular disease. The renin–angiotensin system is believed to play an important role along different steps of the cardiovascular disease continuum. Convincing evidence accumulated over the last decade that therapeutic intervention with angiotensin receptor blockers (ARBs) is effective to slow down or block the progression of cardiovascular disease at different steps of the continuum, with measurable clinical benefits. However, despite the shared mechanism of action, each ARB is characterized by specific pharmacological properties that may influence its clinical efficacy. Indeed, important differences among available ARBs emerged from clinical studies. Therefore, generalization of results obtained with a specific ARB to all available ARBs may be misleading. The present review provides a comparative assessment of the different ARBs in their efficacy on major clinical endpoints along the different steps of the cardiovascular disease continuum

Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems

Purpose Automated treatment planning systems are available for linear accelerator (linac)-based single-isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) of brain metastases. In this study, we compared plan quality between Brainlab Elements Multiple Brain Metastases (Elements MBM) software which utilizes dynamic conformal arc therapy (DCAT) and Varian HyperArc (HA) software using a volumetric modulated arc therapy (VMAT) technique. Patients and methods Between July 2018 and April 2021, 36 consecutive patients >= 18 years old with 367 metastases who received SIMT SRS at UPMC Hillman Cancer San Pietro Hospital, Rome, were retrospectively evaluated. SRS plans were created using the commercial software Elements MBM SRS (Version 1.5 and 2.0). Median cumulative gross tumor volume (GTV) and planning tumor volume (PTV) were 1.33 cm(3) and 3.42 cm(3), respectively. All patients were replanned using HA automated software. Extracted dosimetric parameters included mean dose (D-mean) to the healthy brain, volumes of the healthy brain receiving more than 5, 8,10, and 12 Gy (V-5Gy, V-8Gy, V-10Gy and V-12Gy), and doses to hippocampi. Results Both techniques resulted in high-quality treatment plans, although Element MBM DCAT plans performed significantly better than HA VMAT plans, especially in cases of more than 10 lesions). Median V-12Gy was 13.6 (range, 1.87-45.9) cm(3) for DCAT plans and 18.5 (2.2-62,3) cm(3) for VMAT plans (p < 0.0001), respectively. Similarly, V-10Gy, V-8Gy, V-5Gy (p < 0.0001) and median dose to the normal brain (p = 0.0001) were favorable for DCAT plans. Conclusions Both Elements MBM and HA systems were able to generate high-quality plans in patients with up to 25 brain metastases. DCAT plans performed better in terms of normal brain sparing, especially in patients with more than ten lesions and limited total tumor volume

Is there a place for nutritional supplements in the treatment of idiopathic male infertility?

Objective: Infertility affects 15% of couples in fertile age. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT). The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility. Material and methods: A Pub Med and Medline review of the published studies utilizing nutritional supplements for the treatment of male infertility has been performed. Results: Clinical trials on Vitamin E, Vitamin A, Vitamin C. Arginine, Carnitine, N-Acetyl-Carnitine, Glutathione, Coenzyme Q10, Selenium and Zinc were reviewed. Although there is a wide variability in selected population, dose regimen and final outcomes, nutritional supplements both alone and in combination seems to be able to improve semen parameters (sperm count, sperm motility and morphology) and pregnancy rate in infertile men. Conclusions: There are rising evidences from published randomized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT. This improvement, however, is not consistent and there is a wide variation in the treatment regimens used. Well designed and adequately powered RCTs are needed to better clarify the role of nutritional supplements as treatment for male infertility

25-Hydroxyvitamin D Plasma Levels in Natural Populations of Pigmented and Partially Pigmented Land Iguanas from Galápagos (Conolophus spp.)

: We report the first data on 25-hydroxyvitamin D plasma levels in natural populations of three species of land iguana endemic to the Galápagos Islands (Conolophus marthae, C. subcristatus, and C. pallidus). The pigment is present throughout the whole body in the skin of C. subcristatus and C. pallidus. On the contrary, pigment is not present in the skin of an extended part of the body in C. marthae. The only existing population of C. marthae is syntopic with a population of C. subcristatus, and the two species are closely related. These circumstances would suggest that, under the assumption that the species show a similar basking behavior and in the absence of compensatory mechanisms, lighter pigmentation should favor higher vitamin D levels. Thus, C. marthae, compared with C. subcristatus in Wolf Volcano, could show higher levels of 25(OH)D plasma levels, or equal, if compensatory mechanisms exist. The three species showed levels in the range of average values for healthy iguanas. However, contrary to the expectation, C. marthae consistently exhibited the lowest 25(OH)D plasma levels. We discuss possible factors affecting vitamin concentration and hypothesize that C. marthae may use the habitat to limit exposure to the high UVB irradiation at Wolf Volcano

Of detectability and camouflage: evaluating Pollard Walk rules using a common, cryptic butterfly

Abstract Estimating distribution and abundance of species depends on the probability at which individuals are detected. Butterflies are of conservation interest worldwide, but data collected with Pollard walks—the standard for national monitoring schemes—are often analyzed assuming that changes in detectability are negligible within recommended sampling criteria. The implications of this practice remain poorly understood. Here, we evaluated the effects of sampling conditions on butterfly counts from Pollard walks using the Arctic fritillary, a common but cryptic butterfly in boreal forests of Alberta, Canada. We used an open population binomial N‐mixture model to disentangle the effects of habitat suitability and phenology on abundance of Arctic fritillaries, and its detectability by sampling different conditions of temperature, wind, cloud cover, and hour of the day. Detectability varied by one order of magnitude within the criteria recommended for Pollard walks (P varying between 0.04 and 0.45), and simulations show how sampling in suboptimal conditions increases substantially the risk of false‐absence records (e.g., false‐absences are twice as likely than true‐presences when sampling 10 Arctic fritillaries at P = 0.04). Our results suggest that the risk of false‐absences is highest for species that are poorly detectable, low in abundance, and with short flight periods. Analysis with open population binomial N‐mixture models could improve estimates of abundance and distribution for rare species of conservation interest, while providing a powerful method for assessing butterfly phenology, abundance, and behavior using counts from Pollard walks, but require more intensive sampling than conventional monitoring schemes

Survival of dental implants in patients with oral cancer treated by surgery and radiotherapy: a retrospective study

BACKGROUND: The aim of this retrospective study was to evaluate the survival of dental implants placed after ablative surgery, in patients affected by oral cancer treated with or without radiotherapy. METHODS: We collected data for 34 subjects (22 females, 12 males; mean age: 51 ± 19) with malignant oral tumors who had been treated with ablative surgery and received dental implant rehabilitation between 2007 and 2012. Postoperative radiation therapy (less than 50 Gy) was delivered before implant placement in 12 patients. A total of 144 titanium implants were placed, at a minimum interval of 12 months, in irradiated and non-irradiated residual bone. RESULTS: Implant loss was dependent on the position and location of the implants (P = 0.05-0.1). Moreover, implant survival was dependent on whether the patient had received radiotherapy. This result was highly statistically significant (P < 0.01). Whether the implant was loaded is another highly significant (P < 0.01) factor determinin

Survival and divergence in a small group: The extraordinary genomic history of the endangered Apennine brown bear stragglers

About 100 km east of Rome, in the central Apennine Mountains, a critically endangered population of ∼50 brown bears live in complete isolation. Mating outside this population is prevented by several 100 km of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. We found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show nonrandom peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles (i) can be an important driver of divergence in isolation, (ii) can be tolerated when balancing selection prevents random loss of variation at important genes, and (iii) is followed by or results directly in favorable behavioral changes

Testis Sparing Surgery of Small Testicular Masses: Retrospective Analysis of a Multicenter Cohort

PURPOSE: We evaluated possible factors predicting testicular cancer in patients undergoing testis sparing surgery. MATERIALS AND METHODS: We retrospectively analyzed the records of all patients who underwent testis sparing surgery for a small testicular mass at a total of 5 centers. All patients with 1 solitary lesion 2 cm or less on preoperative ultrasound were enrolled in the study. Testis sparing surgery consisted of tumor enucleation for frozen section examination. Immediate radical orchiectomy was performed in all cases of malignancy at frozen section examination but otherwise the testes were spared. Univariate and multivariate analysis were performed and ROC curves were produced to evaluate preoperative factors predicting testicular cancer. RESULTS: Overall 147 patients were included in the study. No patient had elevated serum tumor markers. Overall 21 of the 147 men (14%) presented with testicular cancer. On multivariate analysis the preoperative ultrasound diameter of the lesion was a predictor of malignancy (OR 6.62, 95% CI 2.26-19.39, p=0.01). On ROC analysis lesion diameter had an AUC of 0.75 (95% CI 0.63-0.86, p=0.01) to predict testicular cancer. At the best cutoff of 0.85 the diameter of the lesion had 81% sensitivity, 58% specificity, 24% positive predictive value and 95% negative predictive value. CONCLUSIONS: Our study confirms that small testicular masses are often benign and do not always require radical orchiectomy. Preoperative ultrasound can assess lesion size and the smaller the nodule, the less likely that it is malignant. Therefore, we suggest a stepwise approach to small testicular masses, including tumorectomy, frozen section examination and radical orchiectomy or testis sparing surgery according to frozen section examination results

MRI index lesion radiomics and machine learning for detection of extraprostatic extension of disease: a multicenter study

Objectives: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions. Methods: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction. Data from one institution was used for training, feature selection (using reproducibility, variance and pairwise correlation analyses, and a correlation-based subset evaluator), and tuning of a support vector machine (SVM) algorithm, with stratified 10-fold cross-validation. The model was tested on the two remaining institutions' data and compared with a baseline reference and expert radiologist assessment of EPE. Results: In total, 193 patients were included. From an initial dataset of 2436 features, 2287 were excluded due to either poor stability, low variance, or high collinearity. Among the remaining, 14 features were used to train the ML model, which reached an overall accuracy of 83% in the training set. In the two external test sets, the SVM achieved an accuracy of 79% and 74% respectively, not statistically different from that of the radiologist (81-83%, p = 0.39-1) and outperforming the baseline reference (p = 0.001-0.02). Conclusions: A ML model solely based on radiomics features demonstrated high accuracy for EPE detection and good generalizability in a multicenter setting. Paired to qualitative EPE assessment, this approach could aid radiologists in this challenging task