Neoadjuvant treatment in pancreatic cance. Evidence-based medicine? A systematic review and meta-analysis

Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16-18.26 months); for resected patients OS was 22.78 months (95% CI 20.42-25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84-10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting

An overview of the clinical use of cabozantinib in the treatment of advanced non-clear-cell renal cell carcinoma (NCCRCC)

Patients diagnosed with non-clear renal cell carcinoma have often been excluded from clinical trials due to the shortage of treatments available, the low incidence of tumours with non-clear histology, and the corresponding diversity of intrinsic molecular features. This approach led to a knowledge gap in finding the optimal treatment for patients diagnosed with non-clear cell renal carcinoma. Cabozantinib, a potent multiple tyrosine kinase receptor inhibitor, has been recently investigated in patients with non-clear cell histologies of renal cell cancer. In this review, we have summarized available data on the use of cabozantinib in non-clear renal cell carcinoma.</p

Impact of sarcopenia on outcomes after pancreatectomy for malignancy

Background: Sarcopenia, which is a subclinical loss of skeletal muscle mass as measured by cross-sectional imaging, is commonly observed in patients with malignancy. Few studies have examined the association between the presence of sarcopenia and outcome following surgery. The aim of this study is to evaluate the prevalence of sarcopenia and to investigate its impact on short- and long-term outcomes in patients who underwent pancreatectomy for malignancy. Materials and Methods: A retrospective review of a pancreatectomy database was performed. Skeletal muscle index (SMI) was measured on preoperative cross-sectional imaging in 144 patients undergoing pancreatectomy for cancer between 2007 and 2014. Sarcopenia was defined, according to the international consensus, as an SMI <52.4 cm2 /m2 and <38.9 cm2 /m2 for men and women respectively. The prevalence and impact of sarcopenia on morbidity, mortality, disease-free and overall survivals was assessed relative to other clinicopathological factors. Results: Mean age was 67.15 years and 51% was female. Pancreatic adenocarcinoma represents 66.7% of all cases. Pancreaticoduodenectomy was performed in 114 cases (79.2%). Margin status was R0 in 76.9%. Mean BMI was 24.85 Kg/m2 and mean SMI was 35,43 cm2 /m2 . One hundred and eight (74.5%) were sarcopenic, 37 (43.5%) were overweight/ obese and 43 (29.7%) were both (p = 0.041). Sarcopenia was significantly related to histology, sex, BMI and albumin. Overall morbidity and 90-days mortality were 50.7% and 9.1% respectively. The median follow up was 21 months. Overall and disease-free survival rate were 25,44 months and 11,84 months respectively. Sarcopenia was associated to a not statistically significant increased risk of overall morbidity, mortality and shorter disease- free and overall survivals after pancreatic surgery for cancer. Conclusions: Sarcopenia was found in 74.5% of cancer patients underwent pancreatectomy. It is an occult condition in overweight/obese patients but can be identified using CT scans. This condition, as defined by international consensus, is not associated with worse short-term and long-term outcomes after surgery

Caesarean section in preventing stillbirths in pregnancy complicated with COVID-19. A narrative review

Introduction: COVID-19 is a complex syndrome caused by SARS-Cov-2. It mainly affects the respiratory system, but it could cause serious harm during pregnancy. An increase in stillbirths and preterm births has been highlighted by many authors. Although WHO and Royal College of Obstetrics and Gynecology don't recommend elective cesarean section in women with confirmed infection, cesarean sections were performed by many clinicians. This short narrative review aims to analyze pieces of evidence found in literature about the effectiveness of cesarean section in preventing stillbirths in COVID-19 positive mothers. Methods: Studies included in the present review were retrieved searching MEDLINE (last access August 5th, 2021) with the following keywords: "pregnant woman with covid-19", "Caesarean section", "Ab-dominal Delivery" and "Stillbirth". Studies regarding the mode of delive-ry in pregnant women infected with COVID-19 and neonatal outcomes were included. Studies about biology, anesthesiology and necroscopy were excluded. Filters for "human" and "English" were applied. Results: Searching MEDLINE, 24 references were found. Other 103 articles were found searching bibliography. Two references were excluded after duplicate removal, 77 references after the title screen and 27 after the abstract screen. The final number of references included was 23. Most of the included studies were case reports. Most of them were from China. Discussion: Many authors highlighted the increased risk of fetal death in pregnancies complicated with SARS-Cov-2 infection, but it is not clear if Caesarean Section could reduce this risk. Pieces of evidence show that most clinicians choose to perform an elective cesarean section mostly because of maternal conditions or the fear of possible vertical transmission. Data show that mode of delivery doesn't affect the neonatal outcome and Caesarean Section doesn't reduce the positivity rate among neonates. Different opinions were found about the possible infection of amniotic fluid, cord blood and placenta. The risk of vertical transmission is considered moderate or low by most of the authors. Positivity to SARS-Cov-2 isn't an indication of elective cesarean section by itself, but this mode of delivery should be optioned in patients with other obstetrical indications or with severe conditions due to COVID. The recent increase in stillbirths could be related to the overall deterioration of maternal conditions

The Role of Visfatin in Pregnancy, Complications and Procreation

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Water delivery in the inner solar nebula : Monte Carlo simulations of forsterite hydration

This work is part of the Dutch Astrochemistry program financed by the Netherlands Organisation for Scientific Research, NWO.Context:  Endogenous or exogenous, dry or wet, various scenarios have been so far depicted for the origin of water on our Solar Systems rocky bodies. Hydrated silicates found in meteorites and in interplanetary dust particles together with observations of abundant water reservoirs in the habitable zone of protoplanetary disks are evidences that support aqueous alteration of silicate dust grains by water vapor condensation in a nebular setting. Aims:  We investigate the thermodynamics (temperature and pressure dependencies) and kinetics (adsorption rates and energies, surface diffusion and cluster formation) of water adsorption on surfaces of forsterite grains, constraining the location in the solar nebula where aqueous alteration of silicates by water vapor adsorption could occur efficiently and lead to the formation of phyllosilicates. We analyze the astrophysical conditions favorable for such hydration mechanism and the implications for water on solid bodies. Methods:  The protoplanetary disk model (ProDiMo) code is tuned to simulate the thermochemical disk structure of the early solar nebula at three evolutionary stages. Pressure, temperature and water vapor abundance within 1 au from the protosun were extracted and used as input for a Monte Carlo code to model water associative adsorption using adsorption energies that resemble the forsterite [100] crystal lattice. Results:  Hydration of forsterite surfaces by water vapor adsorption could have occurred within the nebula lifetime already at a density of 108 cm3, with increasing surface coverage for higher water vapor densities. Full surface coverage is attained for temperatures lower than 500 K, while for hotter grain surfaces water cluster formation plays a crucial role. Between 0.5 and 10 number of Earth’s oceans can arise from the agglomeration of hydrated 0.1 μm grains into an Earth-sized planet. However, if grain growth occurs dry and water vapor processes the grains afterwards, this value can decrease by two orders of magnitude. Conclusions: This work shows that water cluster formation enhances the water surface coverage and enables a stable water layer to form at high temperature and low water vapor density conditions. Finally, surface diffusion of physisorbed water molecules shortens the timescale for reaching steady state, enabling phyllosilicate formation within the solar nebula timescale.PostprintPeer reviewe

Exploring the Interplay between Complex Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder Severity: Implications for Clinical Practice

Background and Objectives: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our study explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to OCD and anxiety disorders. Materials and Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p = 0.083), psychiatric familial history (p = 0.023), HAM-A, and Y-BOCS (p &lt; 0.0001). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p &lt; 0.0001). Conclusions: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms

Clinical outcomes and safety of patients treated with NAb-Paclitaxel plus Gemcitabine in metastatic pancreatic cancer:the NAPA study

BACKGROUND: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice.METHODS: From January 2015 to December 2018, patients with metastatic PDAC receiving first-line treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed.RESULTS: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95 % CI; 9-13) and the median progression free survival (PFS) was 6 months (95 % CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 haematological toxicity frequency was 22.61% for neutropenia, 5.22% for anaemia and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 nonhaematological events were reported. Dose reduction was necessary in 51.3 % of the patients.CONCLUSIONS: Our results confirm the efficacy and safety of a first line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.</p

COVID-19 and Youth Psychopathological Distress in Umbria, Central Italy: A 2-Year Observational Study in a Real-World Setting

IntroductionAdolescents and young adults represent a vulnerable population in the context of the Coronavirus disease 2019 (COVID-19) pandemic. The present retrospective study aims to investigate the pandemic's psychological impact on adolescents and young adults by analyzing data from an outpatient mental health service dedicated to youths in Umbria, central Italy. Materials and MethodsThe clinical charts of subjects aged 14-24 who first accessed the service in the timeframe between March 1st, 2019, and February 28th, 2021, were reviewed. Subjects were divided into two subgroups according to the period of time when they accessed the service (pre-COVID-19 vs. during- COVID-19 outbreak). Bivariate analyses were performed using the Chi-square test and the Welch's t-test. A secondary analysis was performed considering only subjects suffering from psychiatric disorders. Furthermore, data concerning individuals who were already followed by the service before the pandemic were analyzed by the McNemar's test and the t-paired test to assess changes in treatment features. ResultsThe number of new accesses during the pandemic period remained stable. After the emergency onset, youths accessing the service showed a higher prevalence of anxiety disorders (p = 0.022). During the COVID-19 period, services were more frequently delivered by using a digital mental health approach (p = 0.001). Psychopharmacological treatment was more frequently prescribed among subjects that were referred to the service after the pandemic onset (p = 0.033). As for substance use, a highly significant reduction in opioid use was observed (p = 0.003). Family therapy was delivered less frequently in the during-COVID-19 subgroup, especially in the subpopulation of subjects suffering from psychiatric disorders (p = 0.013). When considering subjects referred to the service in the pre-COVID-19 period, the number of interventions provided to this population increased after the pandemic outbreak (p = 0.038). ConclusionIn the context of the COVID-19-related public health crisis, youths represent an at-risk population for which pathways to care should be reinforced, and targeted interventions, including psychosocial treatments, should be implemented

Early-life exposure to environmentally relevant concentrations of triclocarban impairs ocular development in zebrafish larvae

Triclocarban (TCC), is an antimicrobial component in personal care products and it is one of the emerging contaminants since it has been detected in various environmental matrices. Its presence in human cord blood, breast milk, and maternal urine raised issues about its possible impact on development and increased concerns about the safety of daily exposure.This study aims to provide additional information about the effects of zebrafish early-life exposure to TCC on eye development and visual function. Zebrafish embryos were exposed to two concentrations of TCC (5 and 50 mu g/L) for 4 days. TCC-mediated toxicity was assessed in larvae at the end of exposure and in the long term (20 days post fertilization; dpf), through different biological end-points. The experiments showed that TCC exposure influences the retinal architecture. In 4 dpf treated larvae, we found a less organized ciliary marginal zone, a decrease in the inner nuclear and inner plexiform layers, and a decrease in the retinal ganglion cell layer. Photoreceptor and inner plexiform layers showed an increase in 20 dpf larvae at lower and both concentrations, respectively. The expression levels of two genes involved in eye development (mitfb and pax6a) were both decreased at the concentration of 5 mu g/L in 4 dpf larvae, and an increase in mitfb was observed in 5 mu g/L-exposed 20 dpf larvae. Interestingly, 20 dpf larvae failed to discriminate between visual stimuli, demonstrating notable visual perception impairments due to compound. The results prompt us to hypothesize that early-life exposure to TCC may have severe and potentially long-term effect on zebrafish visual function