High Cyclin E Staining Index in Blastemal, Stromal or Epithelial Cells Is Correlated with Tumor Aggressiveness in Patients with Nephroblastoma

PURPOSE: Identifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as a regulator of progression through the cell cycle and Ki-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies. METHODOLOGY/PRINCIPAL FINDINGS: A staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotherapy nephroblastoma including 42 nephroblastoma without metastasis and 12 with metastases. Median cyclin E and Ki-67 SI were 46% and 33% in blastemal cells, 30% and 10% in stromal cells, 37% and 29.5% in epithelial cells. The highest values were found for anaplastic nephroblastoma. A correlation between cyclin E and Ki-67 SI was found for the blastemal component and for the epithelial component. Univariate analysis showed prognostic significance for metastases with cyclin E SI in stromal cells, epithelial cells and blastemal cells (p = 0.03, p = 0.01 and p = 0.002, respectively) as well as with Ki-67 SI in blastema (p<10(-4)). The most striking data were that both cyclin E SI and blastemal Ki-67 SI discriminated between patients with metastases and patients without metastasis among intermediate-risk nephroblastoma. CONCLUSIONS: Our findings show that a high cyclin E SI in all components of nephroblastoma is correlated with tumor aggressiveness and metastases, and that assessment of its expression may have prognostic value in the categorization of nephroblastoma

Crohn's Disease and Early Exposure to Domestic Refrigeration

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood

Variants of the Mannose-Binding Lectin Gene in the Benin Population: Heterozygosity for the p.G57E Allele May Confer a Selective Advantage

Human mannose-binding lectin (MBL) plays an important role in innate immunity.MBLdeficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred fortytwo healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p = 0.002). This enrichment was exclusively due to an elevated proportion of heterozygotes for the p.G57E allele (47.0% vs. 35.3%, respectively; p = 0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV-positive patients

Emergency medicine residents in Italy: Data from a national survey

CoSMEU group (Italian Society of Emergency Medicine Residents): Cascio Michela, Ceschi Ludovica, Di Cristoforo Monica, La Spina Letizia, Malacarne Cecilia, Pons Sofia, Silvestri Giulia.&#x0D;  &#x0D; Emergency Medicine (EM) is a novel specialty in Italy. It exists only since 2009, and CoSMEU (Coordinamento Specializzandi Medicina d’Emergenza-Urgenza) is the national association of EM residents. On behalf of CoSMEU, we conducted an electronic survey open to all the Italian EM residents, with the aim to assess their awareness about the acquisition of technical skills and clinical knowledge during the academic year 2019-2020. Out of 1666 EM residents, 434 (26%) responded to the survey, in representation of all the 33 medical school programs. For 63.6% of them EM was their first-choice program. A high percentage of EM residents have denounced a lack of education and hands-on opportunities to fully complete their training as planned, in the absence of simulation and certifications, and with not-standardized educational programs across the EM schools. Although the Italian EM and specialty are currently facing a crisis, all the EM residents are working hard to support EM system optimization.</jats:p

Intranasal Dexmedetomidine for Pain Management in Older Patients: A Cross-Over, Randomized, Double-Blinded, Active-Controlled Trial

Background: Daily care procedures provoke breakthrough pain and anxiety in palliative situations. Dexmedetomidine may be an alternative to opioids during nursing procedures for older patients. Objective: We aimed to compare the efficacy of intranasal dexmedetomidine with subcutaneous opioids on the intensity of pain and anxiety during comfort management procedures. Methods: We conducted a randomized, active-controlled, double-blind, crossover trial (NCT03151863). Patients aged ≥ 65 years were randomized to receive, 45 min before nursing care, either intranasal dexmedetomidine together with subcutaneous placebo or intranasal placebo together with a subcutaneous opioid. Each of these two interventions were administered in a cross-over design and spaced out over a 24- or 48-h period. The primary outcome was the number of patients with an Elderly Caring Pain Assessment score &gt; 5. Secondary outcomes included pain, sedation score, and vital signs. Results: Because of difficult recruitment, the trial was interrupted after the inclusion of 24 patients. Three patients withdrew after randomization, leaving 21 patients undergoing 42 complete sessions for descriptive analyses. Of the 21 patients, 12 (57.1%) were women, and their median age was 84 years, interquartile range (75-87 years). Nine (42.9%) patients presented an Elderly Caring Pain Assessment score &gt; 5 when receiving subcutaneous opioids, and seven (33.3%) with intranasal dexmedetomidine. Hypoxemia occurred in a single patient receiving subcutaneous opioids. No episode of bradycardia was observed. Conclusions: Intranasal dexmedetomidine is feasible in elderly patients and may be an alternative to opioids to ensure comfort during nursing care. Future studies are needed to confirm the efficacy and safety of this procedure.</p

Variants of the Mannose-Binding Lectin Gene in the Benin Population: Heterozygosity for the p.G57E Allele May Confer a Selective Advantage

Human mannose-binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred forty-two healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p = 0.002). This enrichment was exclusively due to an elevated proportion of heterozy-gotes for the p.G57E allele (47.0% vs. 35.3%, respectively; p = 0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV-positive patients

Changes of health-related quality of life 6 months after high-risk oncological upper gastrointestinal and hepatobiliary surgery: a single-centre prospective observational study (ChangeQol Study)

Introduction Postoperative health-related quality of life (HRQoL) is an essential outcome in oncological surgery, particularly for elderly patients undergoing high-risk surgery. Previous studies have suggested that, on average, HRQoL returns to premorbid normal levels in the months following major surgery. However, the averaging of effect over a studied cohort may hide the variation of individual HRQoL changes. The proportions of patients who have a varied HRQoL response (stable, improvement, or a deterioration) after major oncological surgery is poorly understood. The study aims to describe the patterns of these HRQoL changes at 6 months after surgery, and to assess the patients and next-of-kin regret regarding the decision to undergo surgery.Methods and analysis This prospective observational cohort study is carried out at the University Hospitals of Geneva, Switzerland. We include patients over 18 years old undergoing gastrectomy, esophagectomy, pancreas resection or hepatectomy. The primary outcome is the proportion of patients in each group with changes in HRQoL (improvement, stability or deterioration) 6 months after surgery, using a validated minimal clinically important difference of 10 points in HRQoL. The secondary outcome is to assess whether patients and their next-of-kin may regret their decision to undergo surgery at 6 months. We measure the HRQoL using the EORTC QLQ-C30 questionnaire before and 6 months after surgery. We assess regret with the Decision Regret Scale (DRS) at 6 months after surgery. Key other perioperative data include preoperative and postoperative place of residence, preoperative anxiety and depression (HADS scale), preoperative disability (WHODAS V.2.0), preoperative frailty (Clinical Frailty Scale), preoperative cognitive function (Mini-Mental State Examination) and preoperative comorbidities. A follow-up at 12 months is planned.Ethics and dissemination The study was first approved by the Geneva Ethical Committee for Research (ID 2020-00536) on 28 April 2020. The results of this study will be presented at national and international scientific meetings, and publications will be submitted to an open-access peer-reviewed journal.Trial registration number NCT04444544

Distinction between arterial and venous occlusion with tissue oxygen pressure in a porcine fascio‐cutaneous flap model

International audienceBackground In recent years, many devices have been developed to monitor free flaps. The Licox probe, which measures tissue oxygen pressure (PtO 2 ), is one of the available devices. Our aim was to demonstrate that PtO 2 could distinguish arterial from venous occlusion in a porcine fascio‐cutaneous flap model. Materials and methods Twenty pigs ( Sus scrofa domestica , Youna strain, males) were included in this study. The median weight was 87.6 kg (84.6–90.8). Bilateral fascio‐cutaneous flaps based on the superficial inferior epigastric pedicle were harvested from each pig. Thirty‐eight flaps were analyzed in this study and were monitored by a Licox system during vascular occlusion. The flaps were randomized into two groups according to the clamped vessel: the arterial group ( n = 19) and the venous group ( n = 19). After a stabilization period of almost 40 min, vascular clamping (arterial or venous) was performed using a microvascular clamp for almost 20 min. The curve profiles were compared between arterial and venous occlusion. Results The inflection point was reached significantly faster in the arterial group: 11 min (9–16) for arterial clamping and 17 min (13–23) for venous clamping ( p = .001). A total of 18/19 (95%) pigs in the arterial group and 13/19 (68%) in the venous group ( p = .09) reached a level lower than 10 mmHg. The median duration for pressure to drop below 10 mmHg was 9 min (6–12) for arterial clamping and 10 min (9–16) for venous clamping ( p = .06). Conclusion We showed that PtO 2 decreased faster in cases of arterial occlusion than in cases of venous occlusion in a pig model. Based on this observation, it may be possible to distinguish arterial from venous occlusion