Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is ...still frequent. The programmed cell death protein 1 (PD-1) pathway-blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT. However, PD-1 blocking strategy can increase the risk of graft-versus-host disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in 6 patients (30%) after nivolumab initiation. All 6 patients had prior history of acute GVHD. The patients with nivolumab-induced GVHD were managed by standard treatment for acute GVHD. Two patients died as a result of GVHD, 1 of progressive disease and 1 of complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, the 1-year progression-free survival rate was 58.2% (95% CI, 33.1%-76.7%) and the overall survival rate was 78.7% (95% CI, 52.4%-91.5%). Among 13 patients still in response, 6 received a single dose of nivolumab and 7 remain on nivolumab. Compared with standard options for this indication, our results show that nivolumab is effective with an acceptable safety profile.
•PD-1 blockade with nivolumab provides durable disease control after allo-HCT.•PD-1 blockade with nivolumab after allo-HCT is associated with 30% acute GVHD.
The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a subject of debate, even more since the ARUBA trial. Here, we report the obliteration rate, the risk of hemorrhage and ...the functional outcomes after Gamma Knife radiosurgery (GKRS) as first-line treatment for non-hemorrhagic AVMs treated before the ARUBA publication, in a reference university center with multimodal AVM treatments available. We retrospectively analyzed data from a continuous series of 172 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our Lille University Hospital, France, between April 2004 and December 2013. The primary outcome was obliteration rate. Secondary outcomes were the hemorrhage rate, the modified Rankin Scale (mRS), morbidity and epilepsy control at last follow-up. The minimal follow-up period was of 3 years. Median age at presentation was 40 years (IQR 28; 51). Median follow-up was 8.8 years (IQR 6.8; 11.3). Median target volume was 1.9 cm
(IQR 0.8-3.3 cm
), median Spetzler-Martin grade: 2 (IQR 1-2), median Pollock-Flickinger score: 1.07 (IQR 0.82-2.94), median Virginia score: 1 (IQR 1-2). Median treatment dose was 24 Gy at 50% isodose line. Twenty-three patients underwent a second GKRS after a median time of 58 months after first GKRS. The overall obliteration rate was of 76%, based primarily on cerebral angiography and/or rarely only upon MRI. Hemorrhage during the post-treatment follow-up was reported in 18 (10%) patients (annual risk of 1.1%). Transient post-GKRS morbidity was reported in 14 cases (8%) and persistent neurological deficit in 8 (4.6%) of patients. At last follow-up, 86% of patients had a mRS ≤ 1. Concerning patients with pretherapeutic epilepsy, 84.6% of them were seizure-free at last follow-up. GKRS as first-line therapeutic option for unruptured cerebral AVMs achieves high obliteration rates (76%) while maintaining a high-level patient's autonomy. All hemorrhagic events occurred during the first 4 years after the initial GKRS. In cases with epilepsy, there was 84.6% seizure free at last follow-up. Permanent morbidity was reported in only 4.6%.
Relapse is a major cause of treatment failure after allogeneic hematopoietic cell transplantation (allo-HCT) in myeloid malignancies. Additional strategies have been devised to further maximize the ...immunologic effect of allo-HCT, notably through maintenance therapy with hypomethylating agents such as 5-azacytidine (AZA). We conducted a single-center retrospective study to investigate the efficacy of AZA after allo-HCT for high-risk myeloid malignancies. All patients transplanted between Jan 2014 and Sept 2019 for high-risk acute myeloid leukemia (
n
= 123), myelodysplastic syndrome (
n
= 51), or chronic myelomonocytic leukemia (
n
= 11) were included. Patients who died, relapsed, or developed grade ≥ 2 acute graft-versus-host disease before day + 60 were excluded, as well as those who were eligible for anti-FMS-like tyrosine kinase 3 maintenance. Of the 185 included patients, 65 received AZA while 120 did not. Median age at transplant was 59 years; 51.9% of patients were males. The median follow-up was 24 months for both groups. Regarding main patient characteristics and transplantation modalities, the two groups were comparable. In multivariate analyses, there were no significant differences between the two groups in terms of 2-year cumulative incidence of relapse (HR = 1.19; 95% confidence interval (CI) 0.67–2.12;
p
= 0.55), overall survival (HR = 0.62; 95%CI 0.35–1.12;
p
= 0.12) and event-free survival (HR = 0.97; 95%CI 0.60–1.58;
p
= 0.91) rates. In conclusion, single-agent AZA does not appear to be an optimal drug for preventing post-transplant relapse in patients with high-risk myeloid malignancies. This study highlights the need for prospective studies of alternative therapies or combination approaches in the post-transplant setting.
Background
The collapsibility index of the inferior vena cava (cIVC) has potential for predicting fluid responsiveness in spontaneously breathing patients, but a standardized approach for measuring ...the inferior vena cava diameter has yet to be established.
The aim was to test the accuracy of different measurement sites of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with sepsis-related circulatory failure and examine the influence of a standardized breathing manoeuvre.
Results
Among the 81 patients included in the study, the median Simplified Acute Physiologic Score II was 34 (24; 42). Sepsis was of pulmonary origin in 49 patients (60%). Median volume expansion during the 24 h prior to study inclusion was 1000 mL (0; 2000). Patients were not severely ill: none were intubated, only 20% were on vasopressors, and all were apparently able to perform a standardized breathing exercise. Forty-one (51%) patients were responders to volume expansion (i.e.
a
≥ 10% stroke volume index increase). The cIVC was calculated during non-standardized (cIVC-ns) and standardized breathing (cIVC-st) conditions. The accuracy with which both cIVC-ns and cIVC-st predicted fluid responsiveness differed significantly by measurement site (interaction
p
< 0.001 and < 0.0001, respectively). Measuring inferior vena cava diameters 4 cm caudal to the right atrium predicted fluid responsiveness with the best accuracy. At this site, a standardized breathing manoeuvre also significantly improved predictive power: areas under ROC curves mean and (95% CI) for cIVC-ns = 0.85 0.78–0.94 versus cIVC-st = 0.98 0.97–1.0,
p
< 0.001. When cIVC-ns is superior or equal to 33%, fluid responsiveness is predicted with a sensitivity of 66% and a specificity of 92%. When cIVC-st is superior or equal to 44%, fluid responsiveness is predicted with a sensitivity of 93% and a specificity of 98%.
Conclusion
The accuracy with which cIVC measurements predict fluid responsiveness in spontaneously breathing patients depends on both the measurement site of inferior vena cava diameters and the breathing regime. Measuring inferior vena cava diameters during a standardized inhalation manoeuvre at 4 cm caudal to the right atrium seems to be the method by which to obtain cIVC measurements best-able to predict patients’ response to volume expansion.
Background
High-field intraoperative MRI (IoMRI) is part of the neurosurgical armamentarium to improve the extent of glioma resection (EOR).
Objective
To report our oncological and functional ...outcomes using IoMRI for neuronavigated glioma surgery.
Methods
In this prospective monocentric study, we reported 100 consecutive adult patients operated on for glioma using IoMRI with neuronavigation, under general anesthesia without intraoperative stimulation, from July 2014 to April 2017. The volumetric evaluation was based on the FLAIR hypersignal for non-enhancing tumors after Gadolinium infusion and on the T1 hypersignal after Gadolinium infusion for enhancing tumors. We evaluated the surgical workflow, the EOR and the clinical outcomes (using Karnofsky performance score (KPS)).
Results
Sixty-nine patients underwent one IoMRI, and 31 from two IoMRI controls. At first IoMRI, the median tumor residue was higher in the FLAIR group than in the T1G+ group whereas no more difference was reported after the second IoMRI between the 2 groups (
p
= 0.56). Additional resection was performed 6 times more frequently in the FLAIR group (OR = 5.7, CI (1.9–17)). The median EOR was 100% (IQR, 93.6–100) whatever the tumor type (first surgery or recurrence) and location. Higher residues were reported only in the insula area (
p
= 0.004). The median KPS was 90 (IQR, 80–100) at discharge, 3, 6 and 12 months after surgery, with no statistical difference between low- and high-grade gliomas (
p
= 0.34).
Conclusion
IoMRI neuronavigated surgery provided maximal EOR whatever the type of glioma and location. IoMRI was all the more useful for non- or minimally enhancing tumors. The step by step surgical resection, introducing the concept of “staged volume” surgery, ensured a high security for the surgeon and low permanent morbidity for the patients.
Objectives
Although dyslipidemia is a strong risk factor for thrombosis in antiphospholipid syndrome (APS), it has been poorly studied. This study aimed to assess lipids profile and risk factors for ...unachieved cholesterol levels in a real-life APS population.
Methods
Inclusion criteria were: APS diagnosis according to international classification criteria, referring to the out-patients clinic of our tertiary care center for their follow-up, and having a blood sample collection for lipids levels determination. Cholesterol level targets for each patient were defined according to 2019 ESC/EAS guidelines for the management of dyslipidemia.
Results
Between January 2020 and April 2021, 114 APS patients were included (male 37 (32.5%); mean age 49 ± 14 years). Among them, 40 (35.1%) had a history of dyslipidemia, 48 (42.1%) were under lipid-lowering therapies, and 59 (51.8%) had a history of cardiovascular disease (CVD). Mean levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride were, respectively, 110 ± 40 mg/dL, 60±20 mg/dL, and 120 (80–190) mg/dL. Unachieved LDL-C levels were found in 77 (67.5%) patients of whom 53 had history of CVD. Overall, 90 (78.9%) had protective HDL-C and 31 (27.2%) had hypertriglyceridemia. In the multivariate analysis, independent risk factors for unachieved LDL-C levels were older age and history of CVD; triple aPL negativity, defined as complete disappearance of aPL over time in APS patients who were previously positive in accordance to international criteria, was an independent protective factor for unachieved LDL-C.
Conclusion
Our finding suggested that dyslipidemia is frequent in APS patients and mainly insufficiently treated, especially in patients with history of CVD, who are at highest risk of future CV events.
BackgroundIt has been shown that meteorological conditions and season affect physical activity (PA) during adolescence. Today, meteorological conditions have never been combined to study their ...influence on PA level in a single sample of a large adolescent multicountries population. The aim of this study was to explore the influence of meteorological conditions on PA in adolescents from several European countries.MethodsThe study included 2024 healthy adolescents aged 12.5–17.4 years who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study. Participants wore a uniaxial accelerometer for 7 consecutive days to measure total PA and moderate to vigorous physical activity (MVPA) in a one-off measurement manner. Comparison of PA according to meteorological conditions was done using linear mixed models.ResultsThe highest difference of MVPA was observed in boys on free days when comparing the best meteorological conditions versus the worse (ie, +39% with highest temperature, +29% without rainfall, +39% with highest sunlight duration and +21% with highest length of day) and in girls on free days (ie, +26% with highest sunlight duration). This increase in MVPA contributed to a simultaneous increase in total PA when considering the same meteorological condition parameters.ConclusionsMeteorological conditions act as a determinant of PA differentially between boys and girls. PA and MVPA in boys are mainly modified by meteorological conditions on free days whereas PA and MVPA in girls are modified by sunlight duration.
Accelerometers are widely used to measure sedentary time and daily physical activity (PA). However, data collection and processing criteria, such as non-wear time rules might affect the assessment of ...total PA and sedentary time and the associations with health variables. The study aimed to investigate whether the choice of different non-wear time definitions would affect the outcomes of PA levels in youth.
Seventy-seven healthy youngsters (44 boys), aged 10-17 years, wore an accelerometer and kept a non-wear log diary during 4 consecutives days. We compared 7 published algorithms (10, 15, 20, 30, 60 min of continuous zeros, Choi, and Troiano algorithms). Agreements of each algorithm with the log diary method were assessed using Bland-Altmans plots and by calculating the concordance correlation coefficient for repeated measures.
Variations in time spent in sedentary and moderate to vigorous PA (MVPA) were 30 and 3.7%. Compared with the log diary method, greater discrepancies were found for the algorithm 10 min (p < 0.001). For the time assessed in sedentary, the agreement with diary was excellent for the 4 algorithms (Choi, r = 0.79; Troiano, r = 0.81; 30 min, r = 0.79; 60 min, r = 0.81). Concordance for each method was excellent for the assessment of time spent in MVPA (> 0.86). The agreement for the wear time assessment was excellent for 5 algorithms (Choi r = 0.79; Troiano r = 0.79; 20 min r = 0.77; 30 min r = 0.80; 60 min r = 0.80).
The choice of non-wear time rules may considerably affect the sedentary time assessment in youth. Using of appropriate data reduction decision in youth is needed to limit differences in associations between health outcomes and sedentary behaviors and may improve comparability for future studies. Based on our results, we recommend the use of the algorithm of 30 min of continuous zeros for defining non-wear time to improve the accuracy in assessing PA levels in youth.
NCT02844101 (retrospectively registered at July 13th 2016).
Background
The protective cardiovascular effect of high-density lipoproteins (HDLs) is considered to chiefly rely on reverse cholesterol transport from peripheral tissues back to the liver. However, ...HDL particles display pleiotropic properties, including anti-inflammatory, anti-apoptotic or antioxidant functions. Some studies suggest that HDL concentration decreases during sepsis, and an association was reported between low HDL levels and a poor outcome. Like sepsis, trauma is also associated with a systemic inflammatory response syndrome. However, no study has yet explored changes in lipid profiles during trauma. We sought to compare lipid profiles between sepsis and trauma patients in intensive care unit (ICU). In septic patients, we analyzed the association between lipid profile, severity and prognosis.
Methods
A prospective, observational, single-centered study was conducted in a surgical ICU. For each patient, total cholesterol, HDL, triglyceride and low-density lipoprotein cholesterol levels were assessed at admission. Short-term prognosis outcome was prospectively assessed.
Results
Seventy-five consecutive patients were admitted (50 sepsis and 25 trauma). There was no difference in SOFA and SAPSII scores between the two groups. Patients with sepsis had lower total cholesterol levels than patients with trauma. Regarding the lipoprotein profile, only HDLs differed significantly between the two groups (median IQR = 0.33 mmol/l 0.17–0.78 in sepsis patients versus median IQR = 0.99 mmol/l 0.74–1.28 in trauma patients;
P
< 0.0001). Whereas ICU mortality was not associated with lipid levels in the sepsis group, a significant negative correlation was found between HDL concentration and the length of ICU stay (
r
= −0.35;
P
= 0.03) in the group of survivor septic patients at ICU discharge. In addition, poor outcome defined as death or a SOFA score >6 at day 3 was associated with lower HDL levels (median IQR = 0.20 mmol/l 0.11–0.41 vs. 0.35 mmol/l 0.19–0.86 in patients with poor outcome versus others;
P
= 0.03).
Conclusions
Lipid profile was totally different between sepsis and trauma in ICU patients: HDL levels were low in septic patients, whereas their concentration was not altered in trauma patients. This major difference reinforces the necessity to explore the therapeutic potential of HDL in sepsis.
This study aimed to investigate whether awareness of being monitored by an accelerometer has an effect on physical activity in young people.
Eighty healthy participants aged 10-18 years were ...randomized between blinded and nonblinded groups. The blinded participants were informed that we were testing the reliability of a new device for body posture assessment and these participants did not receive any information about physical activity. In contrast, the nonblinded participants were informed that the device was an accelerometer that assessed physical activity levels and patterns. The participants were instructed to wear the accelerometer for 4 consecutive days (2 school days and 2 school-free days).
Missing data led to the exclusion of 2 participants assigned to the blinded group. When data from the blinded group were compared with these from the nonblinded group, no differences were found in the duration of any of the following items: (i) wearing the accelerometer, (ii) total physical activity, (iii) sedentary activity, and (iv) moderate-to-vigorous activity.
Our study shows that the awareness of wearing an accelerometer has no influence on physical activity patterns in young people. This study improves the understanding of physical activity assessment and underlines the objectivity of this method.
NCT02844101 (retrospectively registered at July 13th 2016).
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