French Centers Research Articles

Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study).

Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy. We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study. At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow-up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P= .015). A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin.

Medico-economic impact of thoracoscopy versus thoracotomy in lung cancer: multicentre randomised controlled trial (Lungsco01)

BackgroundLungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context.MethodsTwo hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method.ResultsThe average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months).ConclusionsGiven our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds.Trial registrationNCT02502318.

Negative Survival Impact of Occult Lymph Node Involvement in Small HER2-Positive Early Breast Cancer Treated by Up-Front Surgery.

(1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5-64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04-5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03-6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients.

Cerebral Vasospasm After Subarachnoid Hemorrhage: Respective Short-Term Effects of Induced Arterial Hypertension and its Combination With IV Milrinone: A Proof-of-Concept Study Using Transcranial Doppler Ultrasound.

It is unclear whether IV milrinone relaxes spasmed cerebral arteries and therefore reduces cerebral blood mean velocity (Vmean). In patients treated for cerebral vasospasm, we aimed to assess and delineate the respective impacts of induced hypertension and its combination with IV milrinone on cerebral hemodynamics as assessed with transcranial Doppler. Observational proof-of-concept prospective study. ICU in a French tertiary care center. Patients with aneurysmal subarachnoid hemorrhage who received induced hypertension (mean arterial blood pressure [MBP] of 100-120 mm Hg) and IV milrinone (0.5 µg/kg/min) for moderate-to-severe cerebral vasospasm. We excluded patients who underwent invasive angioplasty or milrinone discontinuation within 12 hours after the diagnosis of vasospasm. None. Vmean was measured at vasospasm diagnosis (TDIAGNOSIS), after the induction of hypertension (THTN), and 1 (THTN+MILRINONE_H1) and 12 hours after the adjunction of IV milrinone (THTN+MILRINONE_H12). Thirteen patients were included. Median Vmean was significantly lower (p < 0.01) at THTN+MILRINONE_H1 (99 [interquartile range (IQR) 89; 134] cm.s-1) and THTN+MILRINONE_H12 (85 [IQR 73-127] cm/s) than at TDIAGNOSIS (136 [IQR 115-164] cm/s) and THTN (148 [IQR 115-183] cm/s), whereas TDIAGNOSIS and THTN did not significantly differ. In all patients but one, Vmean at THTN+MILRINONE_H1 was lower than its value at TDIAGNOSIS (p = 0.0005). Vmean-to-MBP and Vmean-to-cardiac output (CO) ratios (an assessment of Vmean regardless of the level of MBP [n = 13] or CO [n = 7], respectively) were, respectively, similar at TDIAGNOSIS and THTN but were significantly lower after the adjunction of milrinone (p < 0.01). The induction of arterial hypertension was not associated with a significant decrease in Vmean, whereas the adjunction of IV milrinone was, regardless of the level of MBP or CO. This suggests that IV milrinone may succeed in relaxing spasmed arteries.

Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry

AbstractCD19 chimeric antigen receptor (CAR) T cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory large B-cell lymphomas. However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the nonrelapse mortality (NRM) after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM and identified risk factors of NRM. We report on 957 patients who received standard-of-care axicabtagene ciloleucel (n = 598) or tisagenlecleucel (n = 359) between July 2018 and April 2022, in 27 French centers. With a median follow-up of 12.4 months, overall NRM occurred in 48 patients (5.0% of all patients): early (before day 28 after infusion) in 9 patients (0.9% of all patients and 19% of overall NRM), and late (on/after day 28 after infusion) in 39 patients (4.1% of all patients and 81% of overall NRM). Causes of overall NRM were distributed as follows: 56% infections (29% with non–COVID-19 and 27% with COVID-19), 10% cytokine release syndromes, 6% stroke, 6% cerebral hemorrhage, 6% second malignancies, 4% immune effector cell associated neurotoxicities, and 10% deaths from other causes. We report risk factors of early NRM and overall NRM. In multivariate analysis, both diabetes and elevated ferritin level at lymphodepletion were associated with an increased risk of overall NRM. Our results may help physicians in patient selection and management in order to reduce the NRM after CAR T-cell therapy.

P13.14.A PREDICTION OF OVERALL SURVIVAL IN HIGH-GRADE GLIOMA USING MULTIPARAMETRIC MRI-BASED RADIOMICS. APPLICATION TO A MULTICENTER COHORT

Abstract BACKGROUND High-grade gliomas are the most common type of primary brain tumor in adult patients. Despite a multimodal treatment, the prognosis remains poor. Accurate stratification of survival is crucial for choosing the best course of therapy. The objective of this study was to use radiomics analysis based on multiparametric MRI combined with clinical data of high-grade gliomas patients with incomplete resection to identify a predictive signature for the stratification of patients according to their overall survival. MATERIAL AND METHODS In this multicentric retrospective study, we included a sub-cohort of 237 patients treated for high-grade gliomas, from 2009 to 2021, at three French medical centers. This data collection was carried out as part of a national funding to promote the integration of AI tools into clinical routine in oncology (AI.DReAM project). Clinical and pathological data, together with the MR images before treatment and at the time of relapse were collected.Patients with gross tumor resection were excluded to homogenize the automatic contouring. Three tumor subregions were generated by a deep learning framework based in the BraTS challenge on the MR images at the time of radiotherapy: label 1, corresponding to the necrosis part of the tumor; label 2, the hypersignal in the T2/FLAIR sequence; and label 3, corresponding to the enhancing part after the injection of gadolinium. The cohort was split into a training data set of 189 patients with cross-validation to ensure robustness and evaluated using a test set of 48 patients. The survival stratification of the two classes was based on the median in month of overall survival (OS) in our cohort with short survival defined as OS inferior to 17 months. The open-source software Pyradiomics and the ensemble classifiers XGBoost, in conjunction with grid search were used for calculating radiomic parameters. RESULTS In total, 976 patients were collected. For this analysis, 237 patients with high-grade gliomas were included, 82 % being IDH-wildtype glioblastoma. One-hundred and nineteen patients underwent subtotal tumor resection. A total of 936 radiomics were extracted from the three tumor subregions and 14 clinical data features were added to the algorithm. The areas under the ROC curve (ROC-AUC) for survival prediction based on radiomic and clinical parameters alone were 0.61 and 0.60 respectively on the test set. The combination of radiomic features with clinical features showed superior performance with ROC-AUC of 0.67 in the 5-fold cross-validation and 0.64 in the test set. CONCLUSION In this preliminary study, we achieved a reproducible estimation of patient survival using radiological and clinical features. In future analyses, we will seek to better account for the biological heterogeneity of high-grade glioma by increasing the number of labels and having them corrected by experts in the field.

P11.79.B MULTICENTRE MULTI-COMPONENT DATA COLLECTION TO DEFINE NEW PREDICTORS OF RELAPSE IN HIGH GRADE GLIOMA

Abstract BACKGROUND The aim of our multi-centric study is to evaluate the predictive relapse factors for high-grade glioma patients. MATERIAL AND METHODS We studied retrospectively multi-centric cohort of high-grade glioma patients, from 2009 to 2021 at three French medical centers. This data collection was carried out as part of national funding to promote the integration of AI tools into clinical oncology routine (AI.DReAM project). Clinical, pathological, genomic, and radiotherapy data, with MR images before treatment and at relapse, were collected and are being analyzed.Relapse patterns were separated into radiotherapy and radiological-related patterns. The latter were defined based on T1-gadolinium and FLAIR sequences. We distinguished local and disseminated disease. We then sub-categorized into residual growth, new local or distal lesion, multi-focal and multi-centric relapse.We underwent a uni-variate analysis with the Chi-squared test and a multivariate analysis with logistic regression to find multi-centric relapse-related factors. RESULTS Overall, 976 files were collected. In this preliminary analysis, we evaluated data from 203 patients. Out of the latter, 70% were male. 28% of the patients were aged more than 69 years. 43% of patients underwent Gross Tumor Resection, and 36% had only biopsy. Considering that of 20,7% of patients underwent Subtotal Tumor Resection, less than 10% had a resection of more than 90%.23% of patients had multi-focal disease and 16,7% had multi-centric disease. 54,6% had temporal disease making it the most frequent site, 26,6% of patients had a deep location. Ventricular contact was noted in 58% of the cases. MGMT methylation was noted in 34% of the patients.The median radiation dose received was 60Gy [33Gy-72Gy]. 98,5% of patients received Temozolomide with radiation and 80% continued it in the adjuvant setting.The median progression-free survival was 7 months, and the median overall survival was 17,6 months [3 to 92 months].The univariate analysis showed a correlation between multi-centric or bilateral initial disease and multicentric relapse pattern (p=0.015 and p=0.012 respectively). The multivariate analysis showed no correlation between our data and the multi-centric relapse. CONCLUSION The preliminary results of our study did not find an association between the analyzed data and the multi-centric relapse pattern.The challenge set is ambitious, as there are no studies yet that identify the factors associated with the multi-centric relapse pattern.Further analyses, currently in progress, are needed for the cohort of 976 patients, taking into account disease and radiotherapy volumes. The final results will be presented at the congress

Return to sport after surgery for osteochondral lesions of the talar dome. Results of a multicenter prospective study on 58 patients

IntroductionOsteochondral lesions of the talar dome (OLTD) are most often found in patients for whom the return to sports activities is the main issue. Two types of surgery have been distinguished at present, bone marrow stimulation techniques and mosaicplasty techniques. The size of the lesion indicating the need for bone marrow stimulation as the required surgical procedure has recently been decreased (<1cm). The main objective of this study was therefore to evaluate the return to sport after OLTD surgery. Our hypothesis is that surgery of osteochondral lesions of the talar dome allows the resumption of sports activities in the majority of cases. Material and methodsThis multicenter prospective study was conducted across 10 French centers specializing in foot and ankle surgery. All patients aged 18 to 65 with symptomatic OLTD resistant to thorough medical treatment for at least 6 months, justifying surgery, were included from June 2018 to September 2019. In addition to the usual demographic data, the practice of sport and level (professional, competitive, leisure) were systematically investigated preoperatively. A common protocol for surgical management and postoperative follow-up had previously been established according to the arthrographic stage of the lesion. The most recent recommendations based on size, but also depth, were taken into account. The primary endpoint was return to sport. ResultsA final functional evaluation with the AOFAS (American Orthopedic Foot & Ankle Society) score was performed at a minimum of 12 months. Of 58 sports patients, 70.6% returned to sport (41/58) with an average delay of 4.3 months. A high AOFAS functional score (p=0.02) and a stage 1 lesion (p=0.006) were the only preoperative criteria significantly associated with a return to sport. No other factor was predictive of a return to sport. ConclusionOur prospective study shows that 70.6% of sports patients returned to sport after OLTD surgery according to a surgical protocol and standardized follow-up. Level of evidenceII.

Endovascular ultrasound renal denervation to lower blood pressure in young hypertensive women planning pregnancy: study protocol for a multicentre randomised, blinded and sham controlled proof of concept study

IntroductionA major issue confronting clinicians treating hypertension in pregnancy is the limited number of pharmacological options. Endovascular catheter-based renal denervation (RDN) is a new method to lower blood pressure (BP)...

Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center.

Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p=0.05) and OS (74vs 44 months; p=0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.

Clinical Implications of CT-detected Hypoattenuation Thickening on Left Atrial Appendage Occlusion Devices.

Background At follow-up CT after left atrial appendage occlusion (LAAO), hypoattenuation thickening (HAT) on the atrial aspect of the device is a common finding but the clinical implications require further study. Purpose To assess the association of HAT grade at follow-up CT with clinical characteristics and outcomes in patients who underwent LAAO. Materials and Methods This prospective study included consecutive participants with atrial fibrillation and who were at high risk for stroke (CHA2DS2-VASc score ≥4) who underwent LAAO and were administered pacifier or nonpacifier devices at two French medical centers between January 2012 and November 2020. Postprocedure CT images were evaluated by two radiologists in consensus and device-specific interpretation algorithms were applied to classify HAT as low grade (low suspicion of thrombosis) or high grade (high suspicion of thrombosis). The association between HAT grade and clinical characteristics was assessed using multinomial logistic regression, and variables associated with risk of stroke were assessed using a Cox proportional hazard model. Results This study included 412 participants (mean age, 76 years ± 8 [SD]; 284 male participants) who underwent follow-up CT at a mean of 4.2 months ± 1.7 after LAAO. Low-grade and high-grade HAT were depicted in 98 of 412 (23.8%) and 21 of 412 (5.1%) participants, respectively. High-grade HAT was associated with higher odds of antithrombotic drug discontinuation during follow-up (odds ratio, 9.5; 95% CI: 3.1, 29.1; P < .001), whereas low-grade HAT was associated with lower odds of persisting left atrial appendage patency (odds ratio, 0.46; 95% CI: 0.27, 0.79; P = .005). During a median follow-up of 17 months (IQR, 11-41 months), stroke occurred in 24 of 412 (5.8%) participants. High-grade HAT was associated with stroke (hazard ratio, 4.6; 95% CI: 1.5, 14.0; P = .008) and low-grade HAT (P = .62) was not. Conclusion Low-grade HAT was a more common finding at CT performed after LAAO CT (24%) than was high-grade HAT (5%), but it was associated with more favorable outcomes than high-grade HAT, which was associated with higher stroke risk. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Choe in this issue.

A 16-year bicentric retrospective analysis of ovarian tissue cryopreservation in pediatric units: indications, results, and outcome.

Cancer treatments of the last decades improve the survival rate of children and adolescents. However, chemo- and radiotherapy result in gonadal damage, leading to acute ovarian failure and sterility. The preservation of fertility is now an integral part of care of children requiring gonadotoxic treatments. Ovarian tissue cryopreservation (OTC) is an effective fertility preservation option that allows long-term storage of primordial follicles, subsequent transplantation, and restoration of endocrine function and fertility. The efficacy of this technique is well-demonstrated in adults but the data are scarce for pediatric patients. Currently, OTC represents the only possibility of preserving the potential fertility in prepubertal girls. This is a retrospective study of OTC practice of two French centers from January 2004 to May 2020.A total of 72 patients from pediatric units underwent cryopreservation of ovarian tissue before gonadotoxic therapy for malignant or non-malignant diseases. The ovarian cortex was cut into fragments and the number of follicles per square millimeter was evaluated histologically. The long-term follow-up includes survival rate and hormonal and fertility status. The mean age of patients at OTC was 9.3 years [0.2-17] and 29.2% were postpubertal; 51 had malignant diseases and 21 had non-malignant diseases. The most frequent diagnoses included acute leukemia, hemoglobinopathies, and neuroblastoma. Indication for OTC was stem cell transplantation for 81.9% (n = 59) of the patients. A third of each ovary was collected for 62.5% (n = 45) of the patients, a whole ovary for 33.3% (n = 24) of the patients, and a third of one ovary for 4.2% (n = 3) of the patients. An average of 17 fragments [5-35] per patient was cryoconserved. A correlation was found between the age of the patients and the number of fragments (p < 0.001). More fragments were obtained from partial bilateral harvesting than from whole ovary harvesting (p < 0.05). Histological analysis of ovarian tissue showed a median of 6.0 primordial follicles/mm2 [0.0-106.5] and no malignant cells were identified. A negative correlation was found between age and follicular density (p < 0.001). Median post-harvest follow-up was 92 months [1-188]. A total of 15 girls had died, 11 were still under treatment for their pathology, and 46 were in complete remission. Of all patients, 29 (40.2%) were subjected to a hormonal status evaluation and 26 were diagnosed with premature ovarian insufficiency (POI) (p < 0.001). One patient had undergone thawed ovarian tissue transplantation. OTC should be proposed to all girls with high risk of developing POI following gonadotoxic therapies in order to give them the possibility of fertility and endocrine restoration.

Activities of Clinical Expertise and Research in a Rare Disease Referral Centre: A Place for Telemedicine beyond the COVID-19 Pandemic?

Rare disease referral centres are entrusted with missions of clinical expertise and research, two activities that have to contend with numerous obstacles. Providing specialist opinions is time-consuming, uncompensated and limited by difficulties in exchanging medical data. Clinical research is constrained by the need for frequent research protocol visits. Our objective was to determine whether telemedicine (TLM) can overcome these difficulties. To better characterise the activity of clinical expertise provided by our French centre, each opinion delivered by our team was reported on a standardised form. To investigate our clinical research activity, investigators and patients were asked to complete a questionnaire on the acceptability of research protocol teleconsultations. Regarding clinical expertise, our team delivered 120 opinions per week (representing a total of 21 h), of which 29% were delivered to patients and 69% to medical practitioners. If these were delivered using TLM, it would represent a potential weekly income of EUR 500 (tele-expertise) and EUR 775 (teleconsultations). Regarding the research activity, 70% of investigators considered the frequency of visits to be a limiting factor for patient inclusions; nearly half of the patients surveyed would be in favour of having teleconsultations in place of (40%) or in addition to (56%) in-person visits. Whereas TLM has become widely used as a back-up procedure to in-person consultations during the COVID-19 pandemic, the solutions it provides to the problems encountered in performing expertise and research activities have made it a new conventional follow-up modality for patients with rare diseases.

Prehospital extracorporeal cardiopulmonary resuscitation: a retrospective French regional centers experience.

Prehospital extracorporeal cardiopulmonary resuscitation: a retrospective French regional centers experience.

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics.

Patients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels. Patients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients. In total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas. The prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy.

Atezolizumab and paclitaxel as first line therapy in advanced triple-negative breast cancer patients included in the French early access program

Following the results of the IMpassion130 trial, an early access program (EAP) was opened in France, allowing patients with PD-L1-positive advanced triple negative breast cancer (aTNBC) to receive a combination of paclitaxel and atezolizumab as first line therapy. This EAP was later discontinued when the IMpassion131 trial read out with negative results. We performed a retrospective multicentric analysis in patients who were prospectively enrolled in the French EAP. Efficacy and toxicity data were obtained on 64 patients treated from August 2019 to August 2020 in 10 French cancer centers. Median progression-free survival (PFS) and overall survival (OS) were 4.1 months (95% CI [3.0–5.8]) and 17.9 months (95% CI [12.4–NR]), respectively. The 6-months PFS rate was 28% (95% CI [16–40%]) (N = 18/64), while N = 33/64 patients (52%, 95% CI [38–63%]) experienced a tumor response. Exploratory subgroup analyses retrieved that corticosteroid use at inclusion in the EAP, before treatment initiation, was the only independent unfavorable prognostic factor for PFS (HR 2.7, 95% CI [1.3–5.6]). No new safety signal was observed. This real-life study, unique by its setting (EAP granted by anticipation and later withdrawn), suggests atezolizumab and paclitaxel has a limited efficacy in PD-L1-positive aTNBC, especially in patients receiving corticosteroids as comedication before treatment start.

Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome)

PurposeTo describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome. MethodRetrospective analysis from two French tertiary centers. ResultsForty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1–15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1–44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%). ConclusionPatients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy.

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

Prevalence and impact of recreational drug use in patients with acute cardiovascular events

ObjectiveWhile recreational drug use is a risk factor for cardiovascular events, its exact prevalence and prognostic impact in patients admitted for these events are not established. We aimed to assess...

Pathologic complete response and survival in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy

BackgroundBreast cancers without HER2 amplification but still expressing this membrane protein constitute a new entity called HER2-low tumors. It is important to characterize them in terms of sensitivity to treatment and prognosis.Patients and methodsTo investigate chemosensitivity and long-term prognosis of HER2-low early breast cancer (eBC), compared to HER2-0 tumors, we retrospectively retrieved clinicopathological characteristics, response to treatment, and survival data from 511 patients treated for eBC with neoadjuvant chemotherapy (NAC) in a French cancer center between 2007 and 2018. Factors associated with the achievement of pathologic complete response (pCR) and survival were studied among hormone receptor positive (HR+) and negative (HR–) eBC.ResultsA total of 280 HR+ (61% HER2-low), and 231 HR– (28% HER2-low) eBC were included. We found classical clinicopathological factors usually associated with chemosensitivity and prognosis, in both HR+ and HR– eBC. By uni- and multivariable analysis, HER2 status (low vs 0) was not independently associated with pCR, either in HR+ or HR– eBC. Relapse free (RFS) and overall survival (OS) were not significantly different between HER2-low and HER2-0 among HR+ tumors. In contrast, among HR– negative tumors, RFS and OS were slightly better in HER2-0 eBC by univariable but not by multivariable analysis.ConclusionsIn eBC patients treated with NAC, taking into account HR expression subtype and other current clinicopathological features, HER2-low tumors did not appear to have different chemosensitivity or prognosis, compared to their HER2-0 counterparts.