Improved survival over time with immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinomas.

PURPOSE: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in white-skinned populations. There is little information on the epidemiology of cSCC, and even less on advanced cases (acSCC). Therefore, we analyzed acSCC patients to describe their characteristics, management, and outcomes over time. METHODS: A single-center retrospective study was conducted over a period of 5 years, including all patients who started systemic therapy for acSCC. The patient characteristics, cSCC management, response to therapy, and survival were recorded. Patients were stratified into equal chronological periods (periods 1 and 2). A subgroup analysis was performed to compare patients who received immunotherapy (group 1) with those who did not (group 2). RESULTS: The study included 127 patients, and patient numbers increased by an average of 19.7% per year. Most patients were male (88/127), elderly (mean 81.6 years), with comorbidities, and 27.6% were immunocompromised. The median overall survival (OS) was higher in period 2 (20 months) than in period 1 (10 months) (hazard ratio [95% confidence interval] = 0.62 [0.39; 0.98], p = 0.04). The risk of progression increased with age and immunosuppression. Of the 64 patients who received second-line therapy, 38 had immunotherapy (group 1) and 26 received other therapies (group 2). Immunotherapy reduced mortality and progression by 71% (p = 0.004) and 67% (p = 0.002), respectively. CONCLUSIONS: Patients with acSCC are usually very frail and elderly. OS increased over time, with a twofold improvement between periods 1 and 2, whereas progression-free survival (PFS) did not increase. Access to immunotherapy reduced mortality in a majority of patients in period 2. Immunosuppression and advanced age were associated with lower PFS.

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Proliferative Tumor-Infiltrating Lymphocytes' Abundance within the Microenvironment Impacts Clinical Outcome in Cutaneous B-Cell Lymphomas.

Primary cutaneous large B-cell lymphoma, leg-type (PCLBCL-LT) is the most aggressive primary cutaneous B-cell lymphoma (PCBCL). Tumor microenvironment has a crucial role in tumor development, and tumor-infiltrating lymphocytes (TILs) can be targeted by immunotherapies. We characterized TILs in 20 PCBCLs to identify the tumor microenvironment features associated with clinical outcomes. We developed a seven‒multiplex immunofluorescence panel using Opal staining and image analysis using HALO software. In PCLBCL-LT, TILs were sparsely intermingled within tumor infiltrate in contrast to those in indolent PCBCL where TILs were scattered around tumor nodule edges with variable tumor infiltration. In PCLBCL-LT, TILs were composed of CD8 and CD4, whereas CD4 was predominant in indolent PCBCL. Proliferative TILs (CD3+Ki-67+ cells) were more abundant in PCLBCL-LT (P = 0.0036) than in indolent PCBCL. In PCLBCL-LT, proliferative TILs' abundance tended to be associated with better progression-free survival. These data were confirmed in a second independent cohort of 23 cases showing that proliferative TILs were more abundant in PCLBCL-LT (P = 0.0205) and that in PCLBCL-LT, high CD3+Ki-67+ cell density was associated with better progression-free survival (P = 0.002). These distinct TILs composition and distribution among PCBCL suggest that proliferative T lymphocytes represent a good prognostic factor in PCLBCL-LT and that stimulating their functions may represent a therapeutic approach.

The benefit of augmenting open data with clinical data-warehouse EHR for forecasting SARS-CoV-2 hospitalizations in Bordeaux area, France.

Objective: The aim of this study was to develop an accurate regional forecast algorithm to predict the number of hospitalized patients and to assess the benefit of the Electronic Health Records (EHR) information to perform those predictions. Materials and Methods: Aggregated data from SARS-CoV-2 and weather public database and data warehouse of the Bordeaux hospital were extracted from May 16, 2020 to January 17, 2022. The outcomes were the number of hospitalized patients in the Bordeaux Hospital at 7 and 14 days. We compared the performance of different data sources, feature engineering, and machine learning models. Results: During the period of 88 weeks, 2561 hospitalizations due to COVID-19 were recorded at the Bordeaux Hospital. The model achieving the best performance was an elastic-net penalized linear regression using all available data with a median relative error at 7 and 14 days of 0.136 [0.063; 0.223] and 0.198 [0.105; 0.302] hospitalizations, respectively. Electronic health records (EHRs) from the hospital data warehouse improved median relative error at 7 and 14 days by 10.9% and 19.8%, respectively. Graphical evaluation showed remaining forecast error was mainly due to delay in slope shift detection. Discussion: Forecast model showed overall good performance both at 7 and 14 days which were improved by the addition of the data from Bordeaux Hospital data warehouse. Conclusions: The development of hospital data warehouse might help to get more specific and faster information than traditional surveillance system, which in turn will help to improve epidemic forecasting at a larger and finer scale.

A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma.

Erythroderma is challenging to diagnose. The aim of this single-centre retrospective study was to identify factors that can be used to improve the diagnosis of erythroderma. Among 91 patients with erythroderma, 21 were diagnosed with eczema, 17 with psoriasis, 20 with drug-induced erythroderma, 13 with erythrodermic mycosis fungoides and 20 with Sézary syndrome. Nail alterations, ear involvement, and severe scaling were significantly associated with psoriasis (p = 0.044). Fever and hypereosinophilia were associated with drug-induced erythroderma. Expression of programmed cell death protein 1 was observed in all skin biopsies. However, with Sézary syndrome, programmed cell death protein 1 expression was significantly higher than with other aetiologies. A programmed cell death protein 1 hormone receptor score (H-score) >50 was associated with Sézary syndrome (p < 0.001, sensitivity 75%, specificity 92%) as well as CXCL13 expression (p < 0.044). CD7 loss was more frequent with erythrodermic mycosis fungoides and Sézary syndrome (p = 0.022). This study reports the importance of programmed cell death protein 1 expression for the differential diagnosis of Sézary syndrome and other aetiologies, including erythrodermic mycosis fungoides.

Risk Factors of Midterm Mortality After Aortic Valve Replacement for Severe Calcified Tricuspid Aortic Valve Stenosis: A retrospective analysis of Perioperative Events Assessment in Adult Cardiac surgery (PESSAC) Registry.

OBJECTIVE: The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) initially developed for predicting early postoperative mortality of all types of cardiac surgery, is less able to predict, more specifically, long-term outcomes after aortic valve replacement (AVR). The study authors here evaluated the risk factors for three-year mortality after isolated aortic valve replacement (AVR) for severe calcified tricuspid aortic valve stenosis and compared them with EuroSCORE II to predict long-term outcomes. DESIGN: A retrospective study. SETTING: A university teaching hospital. PARTICIPANTS: This study included 1,101 adults who underwent isolated AVR for severe calcified tricuspid aortic valve stenosis between September 2010 to June 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was that of three-year all-cause mortality after AVR. By three years, 168 patients (15.3%) had died. Risk factors for all-cause mortality were: male gender (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.21-2.62; p < 0.01), peripheral arterial disease (OR = 1.77; 95% CI = 1.08-2.92; p = 0.03), age (OR = 1.06 per year increase; 95% CI =1.04-1.09; p < 0.01), pulmonary artery systolic pressure (OR = 1.02 per mmHg increase; 95% CI = 1.01-1.03; p < 0.01), platelet count (OR = 1.003 per G/L increase; 95% CI = 1.000-1.005; p = 0.04), and valve area (OR = 0.97 per cm²/m² increase; 95% CI= 0.95-0.99; p < 0.01). The area under the receiver operating characteristic curves were 0.67 (95% CI = 0.60-0.75) and 0.60 (95% CI = 0.56-0.65) for the authors' logistic regression model and EuroSCORE II, respectively (p = 0.11). CONCLUSIONS: The study authors identified six independent risk factors for three-year mortality after isolated AVR. The logistic regression model had relatively modest predictive performance for three-year mortality.

Accuracy of COVID-19 rapid antigenic tests compared to RT-PCR in a student population: The StudyCov study.

OBJECTIVE: There is a lack of data evaluating performance of antigenic test (AT) for SARS-CoV-2 diagnosis (Ag-RDT) in clinical practice, especially in asymptomatic subjects. The main objective of this study was to evaluate the diagnostic performance of AT compared to Reverse Transcription Polymerase Chain Reaction (RT-PCR) for SARS-CoV-2 diagnosis. METHODS: StudyCov is a monocentric cross-sectional study. A SARS-CoV-2 screening facility was set up in the Bordeaux University health campus from October 28th to November 20th 2020. Students willing to have a RT-PCR test (ARGENE SARS-CoV-2 R-GENE, BioMérieux, France) for SARS-CoV-2 diagnosis were also offered the Abbott Panbio™ SARS-CoV-2 antigenic rapid test. All participants attending the screening facility with an AT in addition to RT-PCR and having signed an informed consent were included in the study. The main objective was to assess performance of AT as compared with RT-PCR in the recruited population. Secondary objectives dealt with the analysis of the main objective stratified by current symptoms and risk exposure. A sensitivity analysis with different RT-PCR cycle thresholds was included. RESULTS: RT-PCR and AT results were available for 692 subjects. Overall sensitivity and specificity of AT tests were respectively 63.5% (95% confidence interval (CI): 49.0 - 76.4) and 100% (95% CI: 99.4 - 100). In the asymptomatic sub-group, they were respectively 35.0% (95% CI: 15.4% - 59.2%) and 100% (95% CI: 99.3 - 100). CONCLUSIONS: This study shows the poor sensitivity of AT in asymptomatic subjects, specificity being however excellent. The performance results fall below the World Health Organization recommendation of 80% sensitivity and question using AT in general population, especially when asymptomatic.

Real-World Survival in Patients with Metastatic Melanoma after Discontinuation of Anti-PD-1 Immunotherapy for Objective Response or Adverse Effects: A Retrospective Study.

OBJECTIVE: Anti-PD-1 has dramatically improved the survival of patients with advanced melanoma. However, there is a lack of data on maintenance of the response after treatment discontinuation. We aimed to evaluate the progression-free survival (PFS) of patients with metastatic melanoma after anti-PD-1 interruption for objective response (OR) or limiting toxicity during clinical trials. METHODS: All patients with advanced melanoma who stopped single-agent anti-PD-1 antibodies for objective response or toxicity were included between April 2014 and January 2019 in our institution (data cut-off, September 10th, 2019). Clinical and biological factors associated with relapse were studied. RESULTS: The median follow-up after introduction of treatment was 36.5 months [4.6-62.4], and the median follow-up after discontinuation of treatment was 15.7 months (2.5-45.1). Out of 65 patients, 28 patients stopped immunotherapy for limiting adverse effects (AEs) (43.1%), 25 for complete response (CR) (38.4%), and 12 for partial response (PR) or long-term stable disease (SD) (18.5%). Twelve patients relapsed (18.5%) after a median time of 9 months [1.9-40.9 months]. Seven relapsed after discontinuation for AEs, 3 after discontinuation for CR, and 2 after discontinuation for PR/SD. The median PFS after therapy discontinuation was not reached. No statistical association was found between recurrence and age, sex, increased LDH, BRAF status, presence of brain metastases, previous treatments, radiotherapy, or time on anti-PD-1 treatment. CONCLUSION: This cohort shows a global recurrence rate of 18.5% and confirms a long-lasting response after anti-PD-1 cessation regardless of the cause of discontinuation.

Real world safety outcomes using cemiplimab for cutaneous squamous cell carcinoma.

INTRODUCTION: Locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) mostly affects older and frail patients. Cemiplimab is an anti-PD1 antibody used in this indication since its approval by the FDA and the EMA in 2019 after encouraging results from phase II trials. We aimed to evaluate cemiplimab safety in patients from daily practice. METHODS: Retrospective and monocentric study including all patients who received at least one infusion of cemiplimab between August 2018 and September 2019. Adverse effects (AEs), treatment interruption, and efficacy were recorded (data cut-off, November 1st 2020). RESULTS: Twenty-two patients were included, median age was 83 [55-93], 73% were Eastern Cooperative Oncology Group (ECOG) 0 or 1, 36% were immune compromised. After a median time on treatment of six months [0.7-22], seventeen patients (77%) experienced 24 AEs, comprising 45% serious AEs (SAEs) grade ≥ 3 and one SAE grade 5 (myositis). Patients who presented SAEs were all >65 years old. Nine patients (41%) definitively discontinued treatment due to AEs. Seventeen patients were evaluable, after a median follow-up of eleven months [1-22], 32% had an objective response (2 complete and 5 partial responses), 47% had controlled disease and 35% experienced progression. CONCLUSIONS: In our cohort, safety seemed to be worse than in phase II trial with more treatment discontinuations due to cemiplimab toxicity, probably reflecting the distinct demographic and medical characteristics of patients in daily care.

Automatic phenotyping of electronical health record: PheVis algorithm.

Electronic Health Records (EHRs) often lack reliable annotation of patient medical conditions. Phenorm, an automated unsupervised algorithm to identify patient medical conditions from EHR data, has been developed. PheVis extends PheNorm at the visit resolution. PheVis combines diagnosis codes together with medical concepts extracted from medical notes, incorporating past history in a machine learning approach to provide an interpretable parametric predictor of the occurrence probability for a given medical condition at each visit. PheVis is applied to two real-world use-cases using the datawarehouse of the University Hospital of Bordeaux: i) rheumatoid arthritis, a chronic condition; ii) tuberculosis, an acute condition. Cross-validated AUROC were respectively 0.943 [0.940; 0.945] and 0.987 [0.983; 0.990]. Cross-validated AUPRC were respectively 0.754 [0.744; 0.763] and 0.299 [0.198; 0.403]. PheVis performs well for chronic conditions, though absence of exclusion of past medical history by natural language processing tools limits its performance in French for acute conditions. It achieves significantly better performance than state-of-the-art unsupervised methods especially for chronic diseases.