Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients.

CD103-positive tissue resident memory-like CD8+ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.

[Alcohol withdrawal delirium: What's new for an old disease?] / Delirium tremens : quoi de neuf pour une vieille maladie ?

The management of alcohol withdrawal syndrome is a frequent work in both community medicine and hospital wards. One of the most severe complications of alcohol withdrawal is Delirium Tremens (DT). The purpose of this development is to update knowledge on this complication in terms of diagnosis, evaluation and therapeutic approaches. It also proposes a reflection on the trajectory of care during and after DT.

Reduced wound leakage in arthroplasty with modified wound closure: a retrospective cohort study.

INTRODUCTION: Wound leakage has been shown to increase the risk of prosthetic joint infections (PJIs) in primary total hip (THA) and knee arthroplasty (unicondylar and total knee arthroplasty; KA). The aim of this study is to determine whether the addition of a continuous subcuticular bonding stitch to a conventional three-layer closure method reduces the incidence of prolonged wound leakage and PJIs after THA and KA. MATERIALS AND METHODS: This retrospective cohort study included all patients receiving a THA or KA. Patients in the control group with a three-layer closure method had surgery between November 1st 2015 and October 31st 2016, and were compared to the study group with a four-layer closure method that had surgery between January 1st 2017 and December 31st 2018. The primary outcome was incidence of prolonged wound leakage longer than 72 h. Differences were evaluated using logistic regression. Incidence of PJIs was the secondary outcome. RESULTS: A total of 439 THA and 339 KA in the control group and 460 THA and 350 KA in the study group were included. In the control group, 11.7% of the patients had a prolonged leaking wound compared to 1.9% in the study group (p < 0.001). The modified wound closure method showed a protective effect for obtaining prolonged wound leakage; odds ratios were 0.09 (95% CI 0.04-0.22; p < 0.001) for THA and 0.21 (95% CI 0.10-0.43; p < 0.001) for KA. PJIs decreased from 1.54 to 0.37% (p = 0.019). CONCLUSIONS: The addition of a continuous subcuticular bonding stitch reduces the incidence of prolonged wound leakage and PJIs after THA and KA compared to a conventional three-layer wound closure method. The large reduction of incidence in wound leakage and PJIs in this study, combined with relatively negligible cost and effort of the modified wound closure method, would advocate for implementing this wound closure method in arthroplasty.

Impact of bedside diagnosis of influenza in the paediatric emergency ward.

OBJECTIVES: This prospective study performed in the paediatric emergency department of the University Hospital of Saint-Etienne aimed to measure the impact of the 24/7 bedside use of the Veritor™ System (Becton Dickinson) on the reduction of supplementary investigations, hospital stay and antimicrobial use. METHODS: Influenza virus A and B antigens were detected with a rapid influenza digital immunoassay (DIA) on nasopharyngeal aspirates (NPAs) sampled from the children consulting at the paediatric emergency department between January and March 2016 for influenza-like illness. The same NPA was tested by immunofluorescence and/or molecular routine assays. Before performing the DIA, the clinician filled in a questionnaire listing the tests that he/she would have prescribed in the absence of the rapid testing. The prescription of complementary investigations, antimicrobial treatments and hospital stay were also compared to those of the 3 previous years. RESULTS: A total of 514 children with flu-like symptoms were included. The use of the DIA at bedside decreased the prescription of blood puncture by 47.9% (21.2% to 6.6%), of chest X-rays by 69.0% (33.3% to 10.3%), of lumbar puncture by 77.8% (7.0% to 1.6%), of urine culture by 79.2% (23.3% to 4.9%), of antibiotic treatments by 70.1% (16.9% to 5.1%), and of hospital stay by 25.0% (27.2% to 20.4%), resulting in a reduction of medical costs estimated to more than €69 000 in a season. CONCLUSIONS: In addition to delivering a rapid aetiological diagnosis, this strategy saves medical costs and favours an antimicrobial stewardship strategy. However, further prospective studies are needed to confirm our findings.

L1CAM expression in uterine carcinosarcoma is limited to the epithelial component and may be involved in epithelial-mesenchymal transition.

Uterine carcinosarcoma (UCS) has been proposed as a model for epithelial-mesenchymal transition (EMT), a process characterized by a functional change facilitating migration and metastasis in many types of cancer. L1CAM is an adhesion molecule that has been involved in EMT as a marker for mesenchymal phenotype. We examined expression of L1CAM in UCS in a cohort of 90 cases from four different centers. Slides were immunohistochemically stained for L1CAM and scored in four categories (0%, < 10%, 10-50%, and > 50%). A score of more than 10% was considered positive for L1CAM. The median age at presentation was 68.6 years, and half of the patients (53.3%) presented with FIGO stage 1 disease. Membranous L1CAM expression was positive in the epithelial component in 65.4% of cases. Remarkably, expression was negative in the mesenchymal component. In cases where both components were intermingled, expression limited to the epithelial component was confirmed by a double stain for L1CAM and keratin. Expression of L1CAM did not relate to overall or disease-free survival. Our findings suggest L1CAM is either not a marker for the mesenchymal phenotype in EMT, or UCS is not a good model for EMT.

The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment.

BACKGROUND: Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). METHODS: Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses. RESULTS: Upregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37-0.89; HR 0.42 95% CI 0.25-0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09-0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70-106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression. CONCLUSIONS: Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations.

Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters.

BACKGROUND: Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort. METHODS: We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype. RESULTS: Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort. CONCLUSIONS: In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful.

[Agranulocytosis and vasculitis in a cocaine addict: levamisole, the hidden culprit]. / Agranulocytose et vascularite chez un patient cocaïnomane: lévamisole ou l'autre poison caché

INTRODUCTION: Adulterants are compounds added to street drugs to increase profits for the seller. Levamisole, a veterinary antihelminthic agent, has become the most common adulterant of cocaine. The prevalence of levamisole in samples of cocaine is increasing. Levamisole can lead to neutropenia and to a dramatic vasculopathy and even vasculitis of small and medium-size blood vessels. CASE REPORT: We here reported the first French case of levamisole related toxicity, due to cocaine use in a 50-year-old man, revealed by fever and agranulocytosis, high titters of antineutrophil cytoplasmic antibodies (ANCA), anticoagulant and positive Coombs tests. Outcome was slowly favorable with exposition withdrawal. CONCLUSION: Clinicians should be aware that agranulocytosis or vasculitis or vasculopathy could be related to levamisole toxicity in individuals who use cocaine.

[Alcohol withdrawal delirium: a retrospective case series of 39 patients]. / Delirium tremens : étude rétrospective de 39 observations.

INTRODUCTION: Alcohol withdrawal delirium (AWD) is one of the most serious complications of alcohol withdrawal. The daily practice of linking activity in addiction shows that this condition is not uncommon. PATIENTS AND METHODS: We extracted from the hospital database patients' admissions for which a diagnosis of AWD (F104) was registered between 2004 and 2009. The review of discharge reports allowed to select the patients for which the medical records were analyzed. RESULTS: Thirty-nine patients admitted for DT were selected. Mean age was 48 years (male 89.7%). A majority of patients (89.7%) were admitted through the emergency department. In about a half of cases (51.3%), blood alcohol concentration was null at admission. The main reasons for the admission were alcohol withdrawal syndrome (17.9%), fall/malaise (15.4%), and generalized seizures (12.8%). Approximately one-third of the patients had a medical history of seizures and 23.1% of AWD. No patient had severe liver failure. Six patients (15.4%) were transferred to intensive care. Two patients developed AWD after surgery. No deaths have been observed. CONCLUSION: Improving medical knowledge of AWD is a way to make this complication even more uncommon.

[Risk factors for delirium tremens: a literature review]. / Facteurs de risque du delirium tremens : revue de la littérature.

Delirium tremens (DT) is the most severe complication from alcohol withdrawal. Risk factors for DT (before the withdrawal begins) and early predictive factors for the development of the withdrawal syndrome towards DT (once withdrawal has started) are not clearly established. We reviewed the literature from PubMed/Medline database to identify risk factors for DT. Twenty-one studies were been selected. Three only were prospective. The most commonly identified risk factors included personal history of DT, seizures, presence of acute somatic comorbidity especially infectious, presence of early withdrawal symptoms, and genetic predisposition. Most of these risk factors are still debated and prospective studies might appear useful considering the DT prevalence and the absence of consensual both diagnostic and therapeutic protocols.

The contribution of six polymorphisms to cardiovascular risk in a Dutch high-risk primary care population: the HIPPOCRATES project.

This study was designed to examine the contribution of six polymorphisms to the occurrence of cardiovascular disease (CVD) in a Dutch primary care population with a high prevalence of cardiovascular risk factors. In this cross-sectional case-control study, 232 patients with CVD and 571 event-free controls were studied. Patients were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656rpt), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Univariate and multivariate odds ratios (ORs) were calculated to assess the relationship between genotypes and CVD. Receiver operating characteristic (ROC) analysis was used to quantify the contribution of the polymorphisms to the prediction of CVD. No differences in either genotype or allele frequencies were found between CVD cases and controls. Multivariate analyses, corrected for multiple testing according to Bonferroni, showed significant protective associations for the T-allele of AGT (OR=0.55 (0.34-0.84)) and for the T-allele of ADD1 (OR=0.52 (0.31-0.82)). ROC analysis showed only a very small improvement of CVD risk prediction by adding the six polymorphisms to a model with traditional risk factors. Our data suggest that a major attribution of the six polymorphisms to the cardiovascular risk prediction in a primary care population such as HIPPOCRATES is unlikely.

Regional differences in cardiovascular risk factor profile cannot fully explain differences in cardiovascular morbidity in the Netherlands: a comparison of two urban areas.

BACKGROUND: Our objective was to investigate whether a region in the south of the Netherlands (Heerlen/Kerkrade) had a high burden of cardiovascular disease in comparison with a nearby region (Maastricht) and the average Dutch population, respectively. We also wanted to determine if there are interregional differences in cardiovascular risk factor profile. DESIGN: Cross-sectional study. METHODS: Data from a nationwide registry (CBS) were used to analyse cardiovascular mortality in the two regions and the average in the Netherlands. Data from a primary care morbidity registration network (RNH) were used to compare cardiovascular morbidity and cardiovascular risk factors in both regions. A standardisation procedure was carried out for age and sex. Data were analysed using logistic regression analyses. RESULTS: The overall cardiovascular mortality rate was higher in the Heerlen/Kerkrade region (7.8 per thousand) compared with Maastricht (6.1 per thousand, OR=1.3, 95% CI 1.2-1.5) and the average in the Netherlands (5.7 per thousand). Similarly, most cardiovascular morbidity rates for Heerlen/Kerkrade were more elevated compared with the RNH overall and with Maastricht. Prevalence rates of risk factors such as diabetes mellitus (7.2%, OR=1.5, 95% CI 1.3-1.7) and overweight (10.8%, OR= 2.0, 95% CI 1.8-2.2) were significantly higher in the Heerlen/Kerkrade region compared with Maastricht. There were no differences with regard to hypertension (15.2%, OR=1.0, 95% CI 0.9-1.1). CONCLUSION: Heerlen/Kerkrade is indeed a region with a high burden of cardiovascular disease. Differences in morbidity between Heerlen/Kerkrade and Maastricht cannot be fully explained by differences in cardiovascular risk factor profile.