Purpose
Preoxygenation with high-flow therapy by nasal cannulae (HFNC) is now widespread in the intensive care unit (ICU). However, no large randomized study has assessed its relevance in ...non-severely hypoxemic patients. In a randomized controlled trial (PROTRACH study), we aimed to evaluate preoxygenation with HFNC vs. standard bag-valve mask oxygenation (SMO) in non-severely hypoxemic patients during rapid sequence intubation (RSI) in the ICU.
Methods
Randomized controlled trial including non-severely hypoxemic patients requiring intubation in the ICU. Patients received preoxygenation by HFNC or SMO during RSI. HFNC was maintained throughout the intubation procedure whereas SMO was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry (SpO
2
) throughout the intubation procedure. Secondary outcomes included drop in SpO
2
, adverse events related to intubation, and outcome in the ICU.
Results
A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC
n
= 95; SMO
n
= 89), the median IQR lowest SpO
2
was 100% 97; 100 for HFNC and 99% 95; 100 for the SMO group (
P
= 0.30). Mild desaturation below 95% was more frequent with SMO (23%) than with HFNC (12%) (RR 0.51, 95% CI 0.26–0.99,
P
= 0.045). There were fewer adverse events in the HFNC group (6%) than in the SMO group (19%) (RR 0.31, 95% CI 0.13–0.76,
P
= 0.007), including fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and SMO (RR 0.38, 95% CI 0.15–0.95,
P
= 0.03).
Conclusions
Compared with SMO, preoxygenation with HFNC in the ICU did not improve the lowest SpO
2
during intubation in the non-severely hypoxemic patients but led to a reduction in intubation-related adverse events.
Trial registration
Clinical trial Submission: 7 March 2016. Registry name: Benefits of high-flow nasal cannulae oxygen for preoxygenation during intubation in non-severely hypoxemic patients: the PROTRACH study. Clinicaltrials.gov identifier: NCT02700321. Eudra CT: 2015-A00145-44. CPP: 15/13-975 (Comité de protection des personnes de Rennes). URL registry:
https://clinicaltrials.gov/ct2/show/record/NCT02700321
.
The use of physiotherapy (PT) in the hospital emergency department (ED) has shown positive results including improvements in patient waiting time, treatment initiation, discharge type, patient ...outcomes, safety and acceptability of the intervention by medical staffs. These findings originate from studies that primarily focus on musculoskeletal and orthopaedic conditions. Despite a significant number of people visiting the ED, there is a shortage of literature evaluating PT in the ED for elderly populations. The objective of this study is the evaluate the effect of delivering PT in the ED (versus no delivery) in patients aged 75 and over with 'falls' complaints. The main objective is the evaluate the effect on the discharge disposition (discharge home, hospitalization). Secondarily, we will evaluate the effect delivering PT on patient-length of stay, the number of falls at 7 days after admission to the ED, changes between the initial and final medical decision regarding patient orientation, and medical staff satisfaction. This study will follow a prospective longitudinal design involving participants aged 75 years and over. We plan to recruit a total n = 336 patients admitted to the ED with a 'fall' chief complaint. After consent, participants will be randomized into either the 'PT-group' (receiving a prescription and execution of PT within the ED), or to the 'no-PT group' (no delivery of PT within the ED). The PT intervention will involve a standardized assessment of motor capacities using validated clinical examinations, and the delivery of rehabilitative exercises based on individual needs. Outcomes will be recorded from the patient's medical record, and a phone call at 7 days. A questionnaire will be sent to medical staff. The results of this study will help to determine whether PT might be beneficial for the management of this increasing proportion of individuals who come to the ED. Trial registration: (Trial registration number: ClinicalTrials.gov NCT05753319). https://classic.clinicaltrials.gov/ct2/show/NCT05753319.
We previously demonstrated that HLA-E/β2m overexpression by tumor cells in colorectal cancers is associated with an unfavorable prognosis. However, the expression of its specific receptor CD94/NKG2 ...by intraepithelial tumor-infiltrating lymphocytes, their exact phenotype and function, as well as the relation with the molecular status of colorectal cancer and prognosis remain unknown. Based on a retrospective cohort of 234 colorectal cancer patients, we assessed the expression of HLA-E, β2m, CD94, CD8, and NKp46 by immunohistochemistry on tissue microarray. The expression profile of HLA-E/β2m on tumor cells and the density of tumor-infiltrating lymphocytes were correlated to the clinicopathological and molecular features (Microsatellite status, BRAF and RAS mutations). Then, from the primary tumors of 27 prospective colorectal cancers, we characterized by multiparameter flow cytometry the nature (T and/or NK cells) and the co-expression of the inhibitory NKG2A or activating NKG2C chain of ex vivo isolated CD94
tumor-infiltrating lymphocytes. Their biological function was determined using an in vitro redirected cytolytic activity assay. Our results showed that HLA-E/β2m was preferentially overexpressed in microsatellite instable tumors compared with microsatellite stable ones (45% vs. 19%, respectively, p = 0.0001), irrespective of the RAS or BRAF mutational status. However, HLA-E/β2m
colorectal cancers were significantly enriched in CD94
intraepithelial tumor-infiltrating lymphocytes in microsatellite instable as well as in microsatellite stable tumors. Those CD94
tumor-infiltrating lymphocytes mostly corresponded to CD8
αβ T cells, and to a lesser extent to NK cells, and mainly co-expressed a functional inhibitory NKG2A chain. Finally, a high number of CD94
intraepithelial tumor-infiltrating lymphocytes in close contact with tumor cells was independently associated with a worse overall survival. In conclusion, these findings strongly suggest that HLA-E/β2m-CD94/NKG2A represents a new druggable inhibitory immune checkpoint, preferentially expressed in microsatellite instable tumors, but also in a subgroup of microsatellite stable tumors, leading to a new opportunity in colorectal cancer immunotherapies.
In this study, we evaluated the efficacy of a micro-immunotherapy medicine (MIM), 2LALERG, in a preclinical model of allergic respiratory disease sensitized with birch pollen extract (BPE). BALB/c ...mice were immunized with BPE, or saline solution, and were then challenged. Micro-immunotherapy medicine pillules were diluted in water, and 3 doses (0.75; 1.5; 3 mg/mouse) were tested and compared to vehicle control (3 mg/mouse). Treatments and vehicle were orally administered by gavage for 10 days. Micro-immunotherapy medicine (0.75 mg/mouse) reduced the number of total cells as well as the levels of interleukin (IL)-13 in bronchoalveolar lavage fluid (BALF) compared to vehicle control. Eosinophils in BALF tended to be lower compared to vehicle group, and the difference is close to significance. Histological analysis in the lungs confirms a moderate effect of MIM (0.75 mg/mice) on inflammatory infiltration and mucus production. Serum levels of IL-5 in MIM (0.75 mg/mouse)-treated mice were lower compared to vehicle; IL-4 levels tended to be lower too. Total immunoglobulin E (IgE) decreased in serum of MIM (1.5 and 0.75 mg/mouse) groups compared to vehicle control. Micro-immunotherapy medicine exerted the highest effect at the lowest dose tested. Micro-immunotherapy medicine resolved the local and systemic inflammation, even if partially, in a model of pollen-induced, IgE-mediated inflammation.
Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and ...efficacy of a short course of intravenous ATO in patients with active SLE.
This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS).
Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P < 0.01). In the long term, 6 patients attained LLDAS at W52, which continued at last follow-up (median LLDAS duration 3 years, range 2-4).
A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy.
ClinicalTrials.gov, NCT01738360 registered 30 November 2012.
ObjectivesToday, the involvement of patients in their care is essential. As the population ages increases, the number of patients with chronic diseases is increasing. In the vascular medicine and ...surgery departments, patients are polymedicated and mostly suffer from several chronic diseases. Approximately 50% of patients with a chronic disease are not adherent. Among the factors that can influence therapeutic adherence are the beliefs and representations of patients.To evaluate the beliefs and representations of chronic treatments in patients with multiple medications and hospitalised in a vascular medicine and surgery department, and to evaluate the medication adherence, the knowledge and the importance patients attach to their treatments.DesignObservational, prospective and a single-centre study.SettingThe study was conducted in a French tertiary hospital centre of around 3000 beds in 9 institutions.ParticipantsAdult polymedicated (ie, minimum of five chronic treatments) patients hospitalised in a vascular medicine and surgery department were included after application of the exclusion criteria.MethodsPatient interviews were carried out in the department and were based on three interviewer-administered questionnaires (a global questionnaire, the Belief Medical Questionnaire and the GIRERD questionnaire).ResultsOur study showed that patients perceived their treatments as beneficial rather than worrying. A correlation between medication adherence and beliefs was observed. ‘Non-adherent’patients had a more negative overall view of medication than ‘adherent’ patients. The level of compliance and knowledge of our patients was low. Only 11% of the patients were ‘good adherent’, 16% of the patients could perfectly name their treatment and 36% knew all the indications.ConclusionKnowledge of treatment representation and beliefs are central to understanding patient behaviour. Considering patients’ representations will allow the identification of levers, and the development of actions and educational tools adapted to improve their adherence, their knowledge and therefore their drug management.
Abstract
Objectives
This study aimed to examine the sensitivity of muscle biopsy (MB) in ANCA-associated vasculitis (AAV), identify factors predicting MB positivity and assess the prognostic value of ...a positive MB.
Methods
We conducted a single-centre retrospective study of AAV with an MB performed at diagnosis. AAV classification granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA) followed the European Medicines Agency algorithm. A logistic regression model was used to identify the factors associated with MB positivity. Survival curves were generated using the Kaplan–Meier method.
Results
Among 276 AAV patients (1995–2018), 101 had an MB. Seventy-eight patients were included: 33 with GPA, 25 with MPA and 20 with EGPA. MB samples were positive in 45 cases (58%): 17 GPA, 16 MPA and 12 EGPA. Univariate analysis focussed on GPA and MPA, revealed that the MB yield was higher in females 22/31 (71%) vs 11/27 (41%); P = 0.02 and in anti-MPO patients 25/37 (68%) vs 6/19 (32%) for anti-PR3; P = 0.01. By multivariate analysis, three factors predicted MB positivity: anti-MPO ANCA odds ratio (OR) 10.67 (CI 2.09, 81.68), female sex OR 5.3 (CI 1.16, 32.35) and neutrophil count OR 1.33 (CI 1.07, 1.8). MB positivity had no impact on relapse, death or end-stage renal disease–free survival.
Conclusions
MB is a safe and efficient diagnostic tool for AAV. Predictors of MB yield include ANCA type, sex and neutrophil count. MB cannot substitute for kidney biopsy when indicated, but should be considered in other cases.
Dysautonomic symptoms are frequent non-motor complaints in patients with Parkinson’s disease. Numerous neuropathological studies have shown that Lewy bodies and neurites, the pathological hallmarks ...of Parkinson’s disease, are widely distributed throughout the peripheral autonomic nervous systems and across end organs. However, few investigations integrally explored the symptoms and physiology of dysautonomia in Parkinson’s disease. We, therefore, performed a comprehensive evaluation of the autonomic function in a prospective group of 45 patients with idiopathic Parkinson’s disease. Autonomic components (pupillomotor, tear, salivary, cardiovascular, digestive, urinary, sexual, sudomotor functions and skin sensitivity) were evaluated using questionnaires and functional tests. Skin biopsy was performed for intraepidermal nerve fibre density quantification. In addition, all patients underwent polysomnography and a complete neuropsychological and neurological assessment. The analysis association of autonomic components showed that dysautonomic signs and symptoms were heterogeneously distributed among patients. Skin denervation as assessed by intraepidermal nerve fibre density quantification was only associated with quantitative thermal sensory testing (OR = 12.0,
p
= 0.02), constipation (OR = 5.5,
p
= 0.01) and ocular dryness symptoms (OR = 8.29,
p
= 0.04). Cognitive alteration was associated with cardiovascular symptoms (OR = 4.33,
p
= 0.03) and dysfunction (OR = 5.83,
p
= 0.02) as well as with constipation (OR = 5.38,
p
= 0.02). Axial motor impairment and rapid eye movement (REM) sleep behaviour disorder were not related to any of the autonomic complaint or dysfunction. Our results show that autonomic functions are affected in a heterogeneous pattern in Parkinson’s disease, thereby suggesting that the progression of autonomic dysfunction follows an erratic rather than a stepwise progression.
Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients.
As early ...mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome.
This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score 0-2 at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure.
One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin 0-2 score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms.
Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke outcome with a realized 37% power. However, enrollment was sufficient to rule out effect sizes greater than 25% with 80% power, indicating that early sitting is unlikely to have an extreme effect in either direction on stroke outcome. Additionally, we were not able to provide a blinded assessment of the primary outcome. Taking these limitations into account, our results may help guide the development of more effective acute stroke rehabilitation strategies, and the design of future acute stroke trials involving out of bed activities and other mobilization regimens.
ClinicalTrials.gov NCT01573299.
Aggressive T-cell lymphomas (ATCLs) represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults. ATCLs show a worse prognosis than B-cell lymphomas.
On behalf of the Société Française de Greffe ...de Moëlle et de Thérapie Cellulaire, we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation (alloSCT).
The different diagnosis included anaplastic large-cell lymphoma (ALCL; n = 27), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n = 27), angioimmunoblastic T-cell lymphoma (AITL; n = 11), hepatosplenic gamma/delta lymphoma (HSL; n = 3), T-cell granular lymphocytic leukemia (T-GLL; n = 1), nasal natural killer (NK)/T-cell lymphoma (nasal-NK/L; n = 3) or non-nasal NK/T-cell lymphoma (non-nasal-NK/L; n = 2), enteropathy-type T-cell (n = 1), and human T-lymphotropic virus (HTLV)-1 lymphoma (n = 2). Fifty-seven patients received a myeloablative conditioning regimen. Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases. Thirty-one patients were in complete remission (CR) at the time of alloSCT, whereas 26 were in partial response (PR). Five-year toxicity-related mortality (TRM) incidence was 33% (95% CI, 24% to 46%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57% (95% CI, 45% to 68%) and 53% (95% CI, 41% to 64%), respectively. In multivariate analysis, chemoresistant disease (stable, refractory, or progressing disease) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease (aGVHD) were the strongest adverse prognostic factors for OS (P = .03 and .03, respectively). Disease status at transplantation significantly influenced the 5-year EFS (P = .003), and an HLA-mismatched donor increased TRM (P = .04).
We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospective clinical trials.
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