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Abstract Background Changes in the epidemiology of traumatic brain injury (TBI) in older patients have received attention, but limited data are available on the outcome of these patients after admission to intensive care units (ICUs). The aim of this study was to evaluate the outcomes of patients over 65 years of age who were admitted to an ICU for TBI. Methods This was a multicentre, retrospective, observational study conducted from January 2013 to February 2019 in the surgical ICUs of 5 level 1 trauma centres in France. Patients aged ≥ 65 years who were hospitalized in the ICU for TBI with or without extracranial injuries were included. The main objective was to determine the risk factors for unfavourable neurological outcome at 3 months defined as an Extended Glasgow Outcome Scale (GOSE) score

Objective: Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria., Methods: In this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated., Results: Among the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design., Conclusion: A majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up., (© 2024. The Author(s).)

Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection., Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician's decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log 10 IU/ml from baseline., Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log 10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30-65) copies/ml and 566 ± 307/mm 3 , respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level)., Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response., Impact and Implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported., (© 2024 The Author(s).)

Background: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients., Methods: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6)., Results: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected., Conclusion: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo., Trial Registration: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The objective was to assess the accuracy and optimal threshold of the Walking Impairment Questionnaire (WIQ) and the Walking Estimated-Limitation Calculated by History (WELCH) questionnaire in identifying patients with a maximal walking distance (MWD) below or equal to 250 m., Methods: This retrospective study screened 388 consecutive patients with suspected symptomatic lower extremity arterial disease (LEAD). Collected data included the patient's history, resting ankle-brachial index, WIQ, and WELCH. MWD was assessed with a treadmill test at 2 mph (3.2 km/h) with a 10% grade. An optimized threshold for detection of MWD ≤ 250 m was determined for each questionnaire via receiver operating characteristic (ROC) curves. Subsequently, multivariate analysis was performed to build a new simple score to detect MWD ≤ 250 m., Results: The study included 297 patients (63 ± 10 years old). With a threshold of ≤ 64%, the WIQ predicted MWD ≤ 250 m with an accuracy of 71.4% (66.2, 76.5%). With a threshold of ≤ 22, the WELCH predicted a treadmill walking distance of ≤ 250 m with an accuracy of 68.7% (63.4, 74.0%). A new score with only four "yes or no" questions had an accuracy of 71.4% (66.3, 76.6%). Items on this new score consisted of the level of difficulty of walking 1 block, declared maximum walking distance, usual walking speed, and maximum duration of slow walking., Conclusion: A WIQ score ≤ 64% and a WELCH score ≤ 22 help to predict a walking distance of ≤ 250 m in a treadmill test at 2 mph (3.2 km/h) with a 10% grade. A 4-item score could be used for rapid evaluation of walking distance among patients with LEAD, but the validity of this 4-item score requires further confirmation studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tollenaere, Métairie, Le Pabic, Le Faucheur and Mahé.)

Background: Scoliosis develops in a proportion of children with myelomeningocele; however, little is known about scoliosis in adulthood and in other forms of spina bifida (SB)., Objectives: The aims of this study were to describe the prevalence of scoliosis and identify risk factors for its development in a large cohort of adults with open and closed SB., Methods: This was a cross-sectional study of data from 580 adults with SB attending their first consultation at a French multidisciplinary referral centre for SB. Sex, anatomical location and type of SB (open or closed), neurological level, back pain and ambulatory status (new Functional Ambulation Classification [new FAC]) were compared in adults with and without scoliosis. These characteristics were used to determine scoliosis risk factors., Results: In total, 331 adults fulfilled the inclusion criteria: 221 had open and 110 had closed SB. Of these, 176 (53%) had scoliosis: 57% open and 45% closed SB. As compared with individuals without scoliosis, those with scoliosis more frequently had open SB (p=0.03), more cranially located SB (p<0.0001), more severe neurological deficits (p≤0.02) and poorer walking ability (mean new FAC score 3.5 [SD 3.3] vs 6.1 [2.6], [p<0.0001]). In total, 69% had chronic back pain, with no difference in frequency between those with and without scoliosis. The odds of scoliosis was associated with asymmetrical motor level and a new FAC score <4 (odds ratio 0.46, p<0.006, and 0.75, p<0.0001, respectively)., Conclusion: About half of adults with open and closed SB had scoliosis. Back pain was frequent in those both with and without scoliosis. Individuals with low walking ability and an asymmetrical motor level should be monitored early and continuously to limit the consequences of scoliosis during their lifetime. A major issue is to determine how scoliosis evolves and to determine appropriate monitoring and treatment strategies for individuals at risk., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Changes in the epidemiology of traumatic brain injury (TBI) in older patients have received attention, but limited data are available on the outcome of these patients after admission to intensive care units (ICUs). The aim of this study was to evaluate the outcomes of patients over 65 years of age who were admitted to an ICU for TBI., Methods: This was a multicentre, retrospective, observational study conducted from January 2013 to February 2019 in the surgical ICUs of 5 level 1 trauma centres in France. Patients aged ≥ 65 years who were hospitalized in the ICU for TBI with or without extracranial injuries were included. The main objective was to determine the risk factors for unfavourable neurological outcome at 3 months defined as an Extended Glasgow Outcome Scale (GOSE) score < 5., Results: Among the 349 intensive care patients analysed, the GOSE score at 3 months was ≤ 4 and ≥ 5 in 233 (67%) and 116 (33%) patients, respectively. The mortality rate at 3 months was 157/233 (67%), and only 7 patients (2%) fully recovered or had minor symptoms. Withdrawal or withholding of life-sustaining therapies in the ICU was identified in 140 patients (40.1%). Multivariate analysis showed that age (OR 1.09, CI 95% 1.04-1.14), male sex (OR 2.94, CI95% 1.70-5.11), baseline Glasgow Coma Scale score (OR 1.20, CI95% 1.13-1.29), injury severity score (ISS; OR 1.04, CI95% 1.02-1.06) and use of osmotherapy (OR 2.42, CI95% 1.26-4.65) were associated with unfavourable outcomes (AUC = 0.79, CI 95% [0.74-0.84]). According to multivariate analysis, the variables providing the best sensitivity and specificity were age ≥ 77 years, Glasgow Coma Scale score ≤ 9 and ISS ≥ 25 (AUC = 0.79, CI 95% [0.74-0.84])., Conclusions: Among intensive care patients aged ≥ 65 years suffering from TBI, age (≥ 77 years), male sex, baseline Glasgow coma scale score (≤ 9), ISS (≥ 25) and use of osmotherapy were predictors of unfavourable neurological outcome., Trial Registration: ClinicalTrials.gov Identifier: NCT04651803. Registered 03/12/2020. Retrospectively registered., (© 2022. The Author(s).)

Objectives: Ankle-brachial index (ABI) is commonly used for screening lower extremity peripheral artery disease (PAD) according to the international guidelines. Arterial Doppler waveform recordings is a tool to diagnose and assess PAD severity. We hypothesized that ABI measurement could be simplified by measuring only the pressure where the best arterial flow is recorded. The aim of this study was to evaluate the concordance between ABI performed according to the American Heart Association guidelines (AHA-ABI) and ABI measured according to best arterial waveform (FLOW-ABI)., Design: This was a monocentric cross-sectional study., Methods: We included patients with exertional limb symptoms suspected of PAD. Arterial Doppler waveforms and ABI were acquired on both lower extremities at the pedis and tibial posterior arteries. Each arterial waveform was classified using the Saint-Bonnet classification. Concordances were analyzed with the kappa coefficient (confidence interval 95%). Exercise PAD study was registered n° NCT03186391., Results: In total, one hundred and eighty-eight patients (62+/-12 years and 26.8+/-4.5 kg/m 2 ) with exertional limb symptoms were included from May 2016 to June 2019. On each extremity, FLOW-ABI had excellent concordance for the diagnosis of PAD with the AHA-ABI with a kappa of 0.95 (95% CI: 0.90, 0.99) in the right extremity and 0.91 (95% CI: 0.86, 0.97) in the left extremity., Conclusion: There is almost perfect concordance between AHA-ABI and FLOW-ABI. Thus, ABI can be simplified into five pressure measurements instead of seven in patient suspected of PAD with exertional limb symptoms. The question remains in patients with chronic limb ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Métairie, Tollenaere, Lanéelle, Le Faucheur, Le Pabic, Omarjee and Mahé.)

Objectives: Nothing is known about the interest of the combination of exercise tests to diagnose Lower-extremity Peripheral Artery Disease (LEPAD). The aim of this study was to assess if combining exercise testing criteria [post-exercise Ankle-Brachial Index (ABI) + exercise-oximetry (exercise-TcPO2)] improves the detection of lower limbs arterial stenoses as compared with post-exercise ABI using American Heart Association (AHA) criteria, or exercise-TcPO2 alone. Material and Methods: In a prospective monocentric study, consecutive patients with exertional-limb pain and normal resting-ABI referred to our vascular center (Rennes, France) were assessed from May 2016 to February 2018. All included patients had a computed tomography angiography (CTA), a resting-ABI, a post-exercise ABI and an exercise-TcPO2. AHA post-exercise criteria, new validated post-exercise criteria (post-exercise ABI decrease ≥18.5%, post-exercise ABI decrease <0.90), and Delta from Rest of Oxygen Pressure (Total-DROP) ≤-15mmHg (criterion for exercise-TcPO2) were used to diagnose arterial stenoses ≥50%. For the different combinations of exercise testing criteria, sensitivity or specificity or accuracies were compared with McNemar's test. Results: Fifty-six patients (mean age 62 ± 11 years old and 84% men) were included. The sensitivity of the combination of exercise testing criteria (post-exercise ABI decrease ≥18.5%, or post-exercise ABI decrease <0.90 or a Total-DROP ≤-15mmHg) was significantly higher (sensitivity = 81% [95% CI, 71-92]) than using only one exercise test (post-exercise AHA criteria (sensitivity = 57% [43-70]) or exercise-TcPO2 alone (sensitivity = 59% [45-72]). Conclusions: Combination of post-exercise ABI with Exercise-TcPO2 criteria shows better sensitivity to diagnose arterial stenoses compared with the AHA post-exercise criteria alone or Exercise-TcPO2 criteria used alone. A trend of a better accuracy of this combined strategy was observed but an external validation should be performed to confirm this diagnostic strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stivalet, Paisant, Belabbas, Le Faucheur, Landreau, Le Pabic, Omarjee and Mahé.)

Background: Anticoagulants are the recommended treatment for venous thromboembolic disease (VTE). The mode of anticoagulant administration may influence compliance, and therefore the effectiveness of the treatment. Unlike in atrial fibrillation or cancer-associated thrombosis, there is only limited data on patient preferences regarding the choice of anticoagulation in VTE. This study aims to evaluate patient preferences regarding anticoagulants in terms of administration: types (oral or injectable treatment) and number of doses or injections per day. Patients and Methods: This is a national survey through a questionnaire sent by e-mail to 1936 French vascular physicians between February and April 2019. They recorded the responses for each patient admitted for VTE. Results: Three hundred and eleven (response rate of 16%) of the 1936 contacted physicians responded for 364 patients. Among these, there were 167 fully completed questionnaires. Most patients (63%) express concerns about VTE and prefer oral treatment (81.5%), justified by the ease of administration (74%) and a fear of the injections (22%). When patients were taking more than three oral treatments they statistically chose injectable treatment more often (54%) than oral treatment (25%, p = 0.002). Patients who chose injectable treatment were also older (70 ± 16 vs. 58 ± 17 years old, p = 0.001). There was no statistically difference in anticoagulation preference according to gender or to the expected duration of treatment (6 weeks, 3 months, 6 months or unlimited). When oral treatment was preferred (81%), most chose oral treatment without dose adjustment and biomonitoring (74.3%). Among them, very few (5.8%) preferred a twice-daily intake. Conclusion: Patient preference in terms of anticoagulant treatment in VTE disease is in favor of oral treatment without adjustment or biomonitoring and with once-daily intake. When an injectable treatment is chosen, a prolonged duration of treatment does not seem to be a constraint for the patient. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03889457]., Competing Interests: GM has received fees as speaker from Bristol-Myers-Squibb, Leo Pharma, GSK, and Bayer. DL has received fees as speaker from Bristol-Myers-Squibb, Leo Pharma, and Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lanéelle, Le Brun, Mauger, Guillaumat, Le Pabic, Omarjee, Mahé and SFMV VTE Study Group.)

Objective: Arterial Doppler waveform recordings are commonly used to assess lower extremity arterial disease (LEAD) severity. However, little is known about the relationship between arterial Doppler waveform profiles and patients' walking capacity. The purpose of this study was to assess whether arterial Doppler waveforms are independently associated with maximal walking distance (MWD) in patients experiencing exertional limb symptoms. Materials and Methods: This cross-sectional study included suspected LEAD patients experiencing exertional limb symptoms. In both lower extremities, arterial Doppler waveforms and ankle-brachial index (ABI) values were obtained from the pedis and tibial posterior arteries. Each arterial flow measurement was ranked using the Saint-Bonnet classification system. Treadmill stress testing (3.2 km/h, 10% slope) coupled with exercise oximetry (Exercise-TcPO2) were used to determine MWD. Delta from rest oxygen pressure (DROP) was calculated. Following treadmill stress testing, post-exercise ABI values were recorded. Univariate and multivariate analyses were used to determine the clinical variables associated with MWD. Results: 186 patients experiencing exertional limb symptoms (62 ± 12 years and 26.8 ± 4.5 kg/m 2 ) were included between May 2016 and June 2019. Median [25th; 75th] treadmill MWD was 235 [125;500]m. Better arterial Doppler waveforms were associated with better walking distance ( p = 0.0012). Whereas, median MWD was 524 [185;525]m in the group that yielded the best Doppler waveforms, it was 182 [125,305]m in the group with the poorest Doppler waveforms ( p = 0.0012). MWD was significantly better ( p = 0.006) in the patients with the best ABIs. However, arterial Doppler waveforms alone were significantly associated with MWD ( p = 0.0009) in the multivariate model. When exercise variables (post-exercise ABI or DROP) were incorporated into the multivariate model, these were the only variables to be associated with MWD. Conclusion: Of the various clinical parameters at rest, Doppler flow waveform profiles were associated with MWD in suspected LEAD patients. A stronger link was however found between exercise variables and MWD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miossec, Tollenaere, Lanéelle, Guilcher, Métairie, Le Pabic, Carel, Le Faucheur and Mahé.)

Objective: We aimed to assess the effects of remote ischemic pre-conditioning (RIPC) on the incidence of contrast-induced nephropathy (CIN) after an intravenous (IV) or intra-arterial injection of contrast medium (CM) in patient and control groups., Materials and Methods: This prospective, randomized, single-blinded, controlled trial included 26 patients who were hospitalized for the evaluation of the feasibility of transcatheter aortic valve implantation and underwent investigations including contrast-enhanced computed tomography (CT), with Mehran risk scores greater than or equal to six. All the patients underwent four cycles of five minute-blood pressure cuff inflation followed by five minutes of total deflation. In the RIPC group (n = 13), the cuff was inflated to 50 mm Hg above the patient's systolic blood pressure (SBP); in the control group (n = 13), it was inflated to 10 mm Hg below the patient's SBP. The primary endpoint was the occurrence of CIN. Additionally, variation in the serum levels of cystatin C was assessed., Results: One case of CIN was observed in the control group, whereas no cases were detected in the RIPC group ( p = 0.48, analysis of 25 patients). Mean creatinine values at the baseline, 24 hours after injection of CM, and 48 hours after injection of CM were 88 ± 32 μmol/L, 91 ± 28 μmol/L and 82 ± 29 μmol/L, respectively ( p = 0.73) in the RIPC group, whereas in the control group, they were 100 ± 36 μmol/L, 110 ± 36 μmol/L, and 105 ± 34 μmol/L, respectively ( p = 0.78). Cystatin C values (median [Q1, Q3]) at the baseline, 24 hours after injection of CM, and 48 hours after injection of CM were 1.10 [1.08, 1.18] mg/L, 1.17 [0.97, 1.35] mg/L, and 1.12 [0.99, 1.24] mg/L, respectively ( p = 0.88) in the RIPC group, whereas they were 1.11 [0.97, 1.28] mg/L, 1.13 [1.08, 1.25] mg/L, and 1.16 [1.03, 1.31] mg/L, respectively ( p = 0.93), in the control group., Conclusion: The risk of CIN after an IV injection of CM is very low in patients with Mehran risk score greater than or equal to six and even in the patients who are unable to receive preventive hyperhydration. Hence, the Mehran risk score may not be an appropriate method for the estimation of the risk of CIN after IV CM injection., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 The Korean Society of Radiology.)

In patients with exertional limb symptoms and normal ankle-brachial index (ABI) at rest, exercise testing can be used to diagnose lower extremity arterial disease (LEAD). Post-exercise ABI decrease or Exercise transcutaneous oxygen pressure measurement (Exercise-TcPO2) can be used to diagnose LEAD. Objectives were (i) to assess the agreement between both methods (ii) to define the variables associated with the discordance, and (iii) to present results of healthy subjects. In this prospective cross-sectional study, patients with exertional limb symptoms and normal rest ABI were consecutively included. ABI was measured at rest and after standardized exercise protocol as well as Exercise-TcPO2. A kappa coefficient with a 95% confidence interval was used to assess the agreement between the two methods. Logistic regression analysis was performed to outline variables potentially responsible for discordance. Ninety-six patients were included. The agreement between the tests was weak with a k value of 0.23 [0.04-0.41]. Logistic regression analysis found that a medical history of lower extremity arterial stenting (odds ratio 5.85[1.68-20.44]) and age (odds ratio 1.06[1.01-1.11]) were the main cause of discordance. This study suggests that post-exercise ABI and Exercise-TcPO2 cannot be used interchangeably for the diagnosis of LEAD in patients with exertional symptoms and normal rest ABI.

Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels ≥516 pg/mL showed increased infiltration by CD3 + T cells ( P = 0.001), comprising both cytotoxic CD8 + ( P = 0.01) and CD4 + ( P = 0.0062) cells including FoxP3 + regulatory T cells ( P = 0.0044). Also, the number of tumor-infiltrating CD20 + B cells ( P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [<516 pg/mL, HR, 3.54; 95% confidence interval (CI), 1.13-11.11), and <1,200 activated CD8 + (Granzyme B + ) cells (HR, 2.63; 95% CI, 1.16-5.95) were independent poor prognostic factors for recurrence, whereas >6,000 CD3 + cells (HR, 0.34; 95% CI, 0.15-0.79) was a good prognostic factor. Thus, low levels of s-CD95L (<516 pg/mL) are correlated with lower numbers of tumor-infiltrating lymphocytes (CD3 + and CD8 + , and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker. IMPLICATIONS: Serum s-CD95L is correlated with a number of tumor-infiltrating immune cells in HGSOC and could be used as a noninvasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment., (©2019 American Association for Cancer Research.)

Background: Seasonal variation of relapses in multiple sclerosis (MS) suggests that season-dependent factors, such as ambient air pollution, may trigger them. However, only few studies have considered possible role of air pollutants as relapse's risk factor., Objective: We investigated the effect of particulate matter of aerodynamic diameter smaller than 10µm (PM 10 ) on MS relapses., Methods: In total, 536 relapsing MS patients from Strasbourg city (France) were included, accounting for 2052 relapses over 2000-2009 period. A case-crossover design was used with cases defined as the days of relapse and controls being selected in the same patient at plus and minus 35 days. Different lags from 0 to 30 days were considered. Conditional logistic regressions, adjusted on meteorological parameters, school and public holidays, were used and exposure was considered first as a quantitative variable and second, as a binary variable., Results: The natural logarithm of the average PM 10 concentration lagged from 1 to 3 days before relapse onset was significantly associated with relapse risk (OR =1.40 [95% confidence interval 1.08-1.81]) in cold season. Consistent results were observed when considering PM 10 as a binary variable, even if not significant., Conclusion: With an appropriate study design and robust ascertainment of neurological events and exposure, the present study highlights the effect of PM 10 on the risk of relapse in MS patients, probably through oxidative stress mechanisms., (Copyright © 2017 Elsevier Inc. All rights reserved.)