Pancreatic neuroendocrine tumors (pNETs) occur in 60–70% of multiple endocrine neoplasia (MEN1) patients; about 30% of pNETs undergo a malignant progression, manifesting local or distant metastases, ...which are one of the main causes of death in MEN1 patients.1,2 Their molecular characteristics are still undefined. ...despite the common genetic basis, their clinical phenotype is highly variable among patients, even in the presence of the same mutation, suggesting a possible role of other cofactors and/or epigenetic mechanisms in each individual tumorigenesis process.3–5 We analyzed, through next-generation sequencing (NGS), the specific miRNA expression signatures of normal pancreas, gastrinoma, and neuroendocrine pancreatic tumor in a MEN1 patient, whose histopathological examination (via duodenopancreatectomy biopsies) revealed diffuse microadenomatosis with eight macrotumors (>0.5 cm) in the pancreas and four gastrin-secreting tumors (three in the duodenum and one in the gallbladder) (Figure S1). Importantly, the trend of the alteration in the expression was generally concordant (six out of seven) between the sequencing data and qRT-PCR (Figure 4A). ...for most of these miRNAs, qRT-PCR results showed a good agreement with the expression levels found in the BON1 cell line (pancreatic carcinoid tumor), commonly used as a reference model for NETs. Exerting their role as key determinants of gene expression, transcription factors and miRNAs are able to co-regulate the expression of targets in the form of feed-forward loops (FFLs) and feedback loops: feed-forward loop analysis evidenced interactions between hub miRNAs and the principal genes involved in the MEN1 gastro-entero-pancreatic neoplasia, as transcription factors (TF) and/or other mRNAs (Figure 4D and E).6 The analysis showed miRNAs “hubs” organized in FFLs with chromatin-remodeling genes (MEN1, ATRX, DAXX) involved in familial and sporadic cancer, as well as with classical oncogenes (RB, TP53) normally mutated in neuroendocrine carcinomas (NEC) (Figure 4D and E). ...it is tempting to suggest that these epigenetic bistable molecular regulatory circuits7,8 could influence the transition from normal neuroendocrine cells to either well-differentiated GEP-NET cancer or to a poorly differentiated NEC.
Aims
Primary outcome of this observational study was to compare weight changes in two groups of overweight and obese individuals: subjects who had a diet prescribed on the base of resting energy ...expenditure (REE) measured by indirect calorimetry and subjects whose REE was estimated by a predictive equation. In addition, we analyzed differences in weight and metabolic parameter variation in subjects with and without an adequate to predicted REE.
Methods
We retrospectively analyzed data of 355 overweight and obese patients: 215 on a diet based on REE measured by indirect calorimetry and 140 following a diet based on REE estimated by the Harris–Benedict equation. Anthropometric and metabolic parameters were evaluated for 18 months from baseline. Propensity score adjustment was used to adjust for known differences between the groups being compared.
Results
A significant greater decrease in body weight was observed in the group that underwent indirect calorimetry compared to the group that did not undergo it (
p
< 0.001). No significant differences were observed between patients with not adequate to predicted REE compared to patients with adequate to predicted REE.
Conclusions
A weight reduction program based on REE measurement appears more effective than a dietary program based on predictive formulas. This study suggests the routine use of indirect calorimetry in all weight reduction procedures.
COVID-19 outbreak had a major impact on the organization of care in Italy, and a survey to evaluate provision of for arrhythmia during COVID-19 outbreak (March–April 2020) was launched. A total of ...104 physicians from 84 Italian arrhythmia centres took part in the survey. The vast majority of participating centres (95.2%) reported a significant reduction in the number of elective pacemaker implantations during the outbreak period compared to the corresponding two months of year 2019 (50.0% of centres reported a reduction of > 50%). Similarly, 92.9% of participating centres reported a significant reduction in the number of implantable cardioverter-defibrillator (ICD) implantations for primary prevention, and 72.6% a significant reduction of ICD implantations for secondary prevention (> 50% in 65.5 and 44.0% of the centres, respectively). The majority of participating centres (77.4%) reported a significant reduction in the number of elective ablations (> 50% in 65.5% of the centres). Also the interventional procedures performed in an emergency setting, as well as acute management of atrial fibrillation had a marked reduction, thus leading to the conclusion that the impact of COVID-19 was disrupting the entire organization of health care, with a massive impact on the activities and procedures related to arrhythmia management in Italy.
Abstract
Fishery discard survival depends on multiple conditions; caution is essential when survival study outputs are employed to support management decisions. The study presents a stepwise ...procedure, devised to estimate discard survival, that accounts for the variability characterizing commercial fishing practices. The procedure was applied to the first survival study performed onboard rapido trawlers targeting Solea solea in the Mediterranean Sea. Undersized specimens collected during sorting were assessed for vitality; some were retained for captive observation. The main drivers affecting discard survival at the time of catch sorting (immediate survival) were identified and used to outline four different operational conditions set (scenarios). Immediate survival in each scenario was subsequently modified by applying a hazard coefficient of survival after 5 days of captive observation in relation to each vitality class, thus obtaining relative survival estimates following discarding. Temperature and air exposure duration were found to exert a major effect on survival, with catch weight and seabed type being additional important factors. The relative survival rate showed an aggregate value of 22.9% (10.5–33.4%). Scenario approach can enhance our understanding of the stressors influencing discard survival. The outcomes are discussed to explore the potential applications of the procedure to the identification of mitigation strategies.
Dialysis is a rare but serious complication after transcatheter aortic valve replacement. We analyzed the large multicenter TRITAVI (transfusion requirements in transcatheter aortic valve ...implantation) registry in order to develop and validate a clinical score assessing this risk.
A total of 10 071 consecutive patients were enrolled in 19 European centers. Patients were randomly assigned (2:1) to a derivation and validation cohort. Two scores were developed, 1 including only preprocedural variables (TRITAVIpre) and 1 also including procedural variables (TRITAVIpost). In the 6714 patients of the derivation cohort (age 82±6 years, 48% men), preprocedural factors independently associated with dialysis and included in the TRITAVIpre score were male sex, diabetes, prior coronary artery bypass graft, anemia, nonfemoral access, and creatinine clearance <30 mL/min per m
. Additional independent predictors among procedural features were volume of contrast, need for transfusion, and major vascular complications. Both scores showed a good discrimination power for identifying risk for dialysis with C-statistic 0.78 for TRITAVIpre and C-statistic 0.88 for TRITAVIpost score. Need for dialysis increased from the lowest to the highest of 3 risk score groups (from 0.3% to 3.9% for TRITAVIpre score and from 0.1% to 6.2% for TRITAVIpost score). Analysis of the 3357 patients of the validation cohort (age 82±7 years, 48% men) confirmed the good discrimination power of both scores (C-statistic 0.80 for TRITAVIpre and 0.81 for TRITAVIpost score). Need for dialysis was associated with a significant increase in 1-year mortality (from 6.9% to 54.4%;
=0.0001).
A simple preprocedural clinical score can help predict the risk of dialysis after transcatheter aortic valve replacement.
Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing ...evidence suggests that protein translation control may play a crucial role.
We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells.
We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.
Abstract Background/objectives Sedation with propofol should be administered by personnel trained in advanced airway management. To overcome this limitation, the use of short acting benzodiazepines ...by cardiologists spread widely, causing concerns about the safety of this procedure in the absence of anesthesiology assistance. The aim of the study was to compare feasibility of a cardiologist-only approach with an anesthesiologist-assisted sedation protocol during elective direct-current cardioversion (DCC) of persistent atrial fibrillation (AF). Methods This prospective, open-blinded, randomized study included 204 patients, which were admitted for scheduled cardioversion of persistent AF, and randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the propofol group underwent DCC with anesthesiologist assistance, while patients in the midazolam group saw the cardiologist as the only responsible for both sedation and DCC. Results Twenty-three adverse events occurred: 13 in the propofol group and 10 in the midazolam group (p = NS). Most of them were related to bradyarrhythmias and respiratory depressions. There was no need of intubation or other advanced resuscitation techniques in any of these patients. No differences were found regarding procedure tolerability and safety endpoints between the two groups. DCC procedures with anesthesiology support were burdened by higher delay from scheduled time and higher costs. Conclusions Sedation with midazolam administered by cardiologist-only appears to be as safe as sedation with propofol and anesthesiologist assistance. Adverse events were few in both groups and easily handled by the cardiologist alone. A cardiologist-only approach to sedation provides less procedural delay, thus being easier to schedule and correlated with fewer costs.
Bleeding is frequent during transcatheter aortic valve implantation (TAVI), especially when performed through a transapical approach (TA), and is associated with a worse prognosis. The present study ...aims to test the implication of red blood cell (RBC) transfusion and the optimal transfusion strategy in this context.
Among 11,265 participants in the multicenter TRITAVI (Transfusion Requirements in Transcatheter Aortic Valve Implantation) registry, 548 patients (4.9%) who received TA-TAVI at 19 European centers were included. One-to-one propensity score matching was performed to reduce treatment selection bias and potential confounding among transfused versus non-transfused patients. The primary endpoint of the study was the 30-day occurrence of all-cause mortality.
209 patients (38 %) received RBC transfusions. The primary endpoint occurred in 47 (8.6 %) patients. Propensity score matching identified 188 pairs of patients with and without RBC transfusion. In the propensity score-matched analysis, RBC transfusion was associated with increased 30-day mortality (HR 3.35, 95 % CI 1.51 – 7.39; p = 0.002). At multivariable cox regression analysis, RBC transfusion was an independent predictor of 30-day mortality (HR 3.07, 95 % CI 1.01–9.41, p = 0.048), as well as baseline ejection fraction (HR 0.96, 95 % CI 0.92–0.99, p = 0.043), and acute kidney injury (HR 3.95, 95 % CI 1.11–14.05, p = 0.034).
RBC transfusion is an independent predictor of short-term mortality in patients undergoing TA-TAVI, regardless of major bleeding.
Clinical trial registration: https://www.clinicaltrials.gov Unique identifier: NCT03740425.
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