PD-1 blockade and allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma, a matter of time: a national study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

Not available.

Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19.

Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.

Use and reporting of inverse-probability-of-treatment weighting for multicategory treatments in medical research: a systematic review.

OBJECTIVES: Causal inference methods for observational data represent an alternative to randomised controlled trials when they are not feasible or when real-world evidence is sought. Inverse-probability-of-treatment weighting (IPTW) is one of the most popular approaches to account for confounding in observational studies. In medical research, IPTW is mainly applied to estimate the causal effect of a binary treatment, even when the treatment has in fact multiple categories, despite the availability of IPTW estimators for multiple treatment categories. This raises questions about the appropriateness of the use of IPTW in this context. Therefore, we conducted a systematic review of medical publications reporting the use of IPTW in the presence of a multi-category treatment. Our objectives were to investigate the frequency of use and the implementation of these methods in practice, and to assess the quality of their reporting. STUDY DESIGN AND SETTING: Using Pubmed, Embase and Web of Science, we screened 5660 articles and retained 106 articles in the final analysis that were from 17 different medical areas. This systematic review is registered on PROSPERO (CRD42022352669). RESULTS: The number of treatment groups varied between 3 and 9, with a large majority of articles (90 [84.9%]) including 3 or 4 groups. The most commonly used method for estimating the weights was multinomial regression (51 [48.1%]) and generalized boosted models (48 [45.3%]). The covariates of the weight model were reported in 91 articles (85.9 %). Twenty-six articles (24.5 %) did not discuss the balance of covariates after weighting, and only 16 articles (15.1 %) referred to the assumptions needed to obtain correct inferences. CONCLUSION: The results of this systematic review illustrate that medical publications scarcely use IPTW methods for more than two treatment categories. Among the publications that did, the quality of reporting was suboptimal, in particular in regard to the assumptions and model building. IPTW for multi-category treatments could be applied more broadly in medical research, and the application of the proposed guidelines in this context will help researchers to report their results and to ensure reproducibility of their research.

Easy-to-use imaging-cytometry assay to analyze chitin patterns in yeasts.

BACKGROUND & AIM: Pathogenic fungi are a major threat to public health, and fungal infections are becoming increasingly common and treatment resistant. Chitin, a component of the fungal cell wall, modifies host immunity and contributes to antifungal resistance. Moreover, chitin content is regulated by chitin synthases and chitinases. However, the specific roles and mechanisms remain unclear. In this study, we developed a cytometric imaging assay to quantify chitin content and identify the distribution of chitin in the yeast cell wall. METHODS: The Candida albicans SC5314 and Nakaseomyces glabratus (ex. C. glabrata) ATCC2001 reference strains, as well as 106 clinical isolates, were used. Chitin content, distribution, and morphological parameters were analysed in 12 yeast species. Moreover, machine learning statistical software was used to evaluate the ability of the cytometric imaging assay to predict yeast species using the values obtained for these parameters. RESULTS: Our imaging-cytometry assay was repeatable, reproducible, and sensitive to variations in chitin content in C. albicans mutants or after antifungal stimulation. The evaluated parameters classified the yeast species into the correct clade with an accuracy of 85 %. CONCLUSION: Our findings demonstrate that this easy-to-use assay is an effective tool for the exploration of chitin content in yeast species.

The individual and societal prices of non-adherence to continuous positive airway pressure, contributors, and strategies for improvement.

INTRODUCTION: Continuous positive airway pressure (CPAP) is the first-line therapy for obstructive sleep apnea (OSA). CPAP is highly effective for improving symptoms and quality of life, but the major issue is adherence, with up to 50% of OSA discontinuing CPAP in the first 3 years after CPAP initiation. AREAS COVERED: We present the individual and societal costs of non-adherence to CPAP, factors associated with non-adherence to CPAP, as well as current strategies for improving adherence including telehealth, couple-based interventions, and behavioral interventions. We also report on challenges and pitfalls for the visualization and analysis of CPAP remote monitoring platforms. EXPERT OPINION: CPAP termination rates and adherence to therapy remain major issues despite technical improvements in CPAP devices. The individual and societal price of non-adherence to CPAP for OSA patients goes beyond excessive sleepiness and includes cardiovascular events, all-cause mortality, and increased health costs. Strategies for improving CPAP adherence should be individually tailored and aim to also improve lifestyle habits including physical activity and diet. Access to these strategies should be supported by refining visualization dashboards of CPAP remote monitoring platforms, and by disseminating telehealth and innovative analytics, including artificial intelligence.

Safety profile of immune checkpoint inhibitors according to cancer type.

INTRODUCTION: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment in recent years, but have led to the emergence of new so-called immune-related adverse events (irAE). The objective of this study was to determine whether cancer type is a potential predictive factor of irAEs. METHODS: This retrospective study included patients who had started an ICI treatment between 2019 and 2020 at the Grenoble Alpes University Hospital. A logistic regression model and a Fine and Gray survival model with death as a competing risk were used to identify variables associated with grade≥2 irAEs and grade≥2 irAEs-free survival. RESULTS: Of the 512 patients included, 160 (31.2%) had a grade≥2 irAE. Grade≥2 irAEs were less frequent in head and neck cancer compared to other cancers. Ipilimumab (odds ratio [OR]: 6.05; 95% confidence interval [CI]: 2.81-13.7), treatment duration (OR: 1.01; 95% CI: 1.01-1.02), and history of autoimmune disease (OR: 6.04; 95% CI: 2.45-16.5) were independently associated with grade≥2 irAEs. With death as a competing risk, grade≥2 irAEs-free survival was independently improved with treatment duration (subdistribution hazard ratio [sdHR]: 0.93; 95% CI: 0.92-0.94), ipilimumab (sdHR: 0.24; 95% CI: 0.1-0.59) and history of autoimmune disease (sdHR: 0.23; 95% CI: 0.08-0.69) whereas it was poorer for patients with performance status≥2 (sdHR: 2.04; 95% CI: 1.5-2.76) and an older age (sdHR: 1.02; 95% CI: 1.00-1.03). CONCLUSION: Ipilimumab and history of autoimmune disease were both associated with the presence of grade≥2 irAEs and grade≥2 irAEs-free survival. The different cancer groups were not.

Impact of extended interval dosing of immune checkpoint inhibitors in lung cancer patients during the COVID-19 pandemic.

BACKGROUND: The COVID 19-pandemic has led physicians to change their approach to treating non-small cell lung cancer (NSCLC) to reduce hospital stays for patients. OBJECTIVES: We aimed to assess the toxicity and efficacy of extended interval (EI) dosing of immune checkpoint inhibitors (ICIs) compared to standard dosing (SD). METHODS: In this retrospective two-center study, we included patients with stage III/IV NSCLC who were treated with ICIs with or without maintenance pemetrexed during the month before March 2020. Adverse events and efficacy were collected until June 2021. Toxicity and survival were assessed using multivariate Cox models. RESULTS: Among the 134 patients identified (8 stage III and 126 stage IV; 66 first line and 60 second or subsequent lines), 70.9% received EI dosing. In the EI group, 12.6% of patients developed grade 3 or 4 immune-related adverse events versus 15.4% in the SD group (P- value = 0.8). Treatment was definitively discontinued due to toxicity in 9 patients in the EI group and in 5 in the SD group (P-value =0.5). Overall survival was not associated with dosage regimen or toxicity analyzed as a time-dependent variable. CONCLUSIONS: Our study suggests that EI dosing of ICIs did not affect toxicity and overall survival in lung cancer patients.

Quality of life of patients with solid malignancies at 3 months after unplanned admission in the intensive care unit: A prospective case-control study.

BACKGROUND: Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. METHODS: A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 1:2 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. RESULTS: In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients: median of 54 (interquartile range: 42-57) vs. 47 (37-52), respectively (p = 0.01). The physical component score of the SF-36 did not differ between groups: 35 (31-47) vs. 42 (34-47) (p = 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. CONCLUSION: In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients.

Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

Late relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity.

Application of Inverse-Probability-of-Treatment Weighting to Estimate the Effect of Daytime Sleepiness in Patients with Obstructive Sleep Apnea.

Rationale: Continuous positive airway pressure (CPAP), the first line therapy for obstructive sleep apnea (OSA), is considered effective in reducing daytime sleepiness. Its efficacy relies on adequate adherence, often defined as >4 hours per night. However, this binary threshold may limit our understanding of the causal effect of CPAP adherence and daytime sleepiness, and a multilevel approach for CPAP adherence can be more appropriate. Objectives: In this study, we show how two causal inference methods can be applied on observational data for the estimation of the effect of different ranges of CPAP adherence on daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS). Methods: Data were collected from a large prospective observational French cohort for patients with OSA. Four groups of CPAP adherence were considered (0-4, 4-6, 6-7, and 7-10 h per night). Multivariable regression, inverse-probability-of-treatment weighting (IPTW), and inverse propensity weighting with regression adjustment (IPW-RA) were used to assess the impact of CPAP adherence level on daytime sleepiness. Results: In this study, 9,244 patients with OSA treated by CPAP were included. The mean initial ESS score was 11 (±5.2), with a mean reduction of 4 points (±5.1). Overall, there was evidence of the causal effect of CPAP adherence on daytime sleepiness which was mainly observed between the lower CPAP adherence group (0-4 h) compared with the higher CPAP adherence group (7-10 h). There are no differences by considering higher level of CPAP adherence (>4 h). Conclusions: We showed that IPTW and IPW-RA can be easily implemented to answer questions regarding causal effects using observational data when randomized trials cannot be conducted. Both methods give a direct causal interpretation at the population level and allow the assessment of the appropriate consideration of measured confounders.