Tandem versus single haematopoietic stem cell transplant and BV maintenance in relapsed/refractory Hodgkin lymphoma: A matched cohort analysis from the LYSA.

Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high-risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV-naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV-exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

Mechanisms of reinforcement in polymer nanocomposites.

Coarse-grained molecular dynamics simulations are used to elucidate molecular mechanisms responsible for different mechanical behaviours of elastomers containing spherical particles with different volume fractions. We observe that different filler volume fractions result in qualitatively different responses of the polymer nanocomposite to tensile strain. At relatively low filler volume fraction a yield drop appears in the stress-strain curve. As the filler volume fraction increases there is a reduction in the rate of plastic hardening, becoming plastic softening at sufficiently high filler volume fraction. We demonstrate that these behaviours are a result of the network formed by the polymer chains and filler particles. We identify three distinct molecular structural motifs between polymer and filler particles whose relative prevalence varies with the filler volume fraction and as the system is dynamically strained. We show how this evolution in molecular structure is directly linked to the observed mechanical response.

Distinctive cutaneous and systemic features associated with specific antimyositis antibodies in adults with dermatomyositis: a prospective multicentric study of 117 patients.

BACKGROUND: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype. OBJECTIVE: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA. METHODS: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis. RESULTS: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1). CONCLUSION: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis.

Comparison of anti-interleukin-5 therapies in patients with severe asthma: global and indirect meta-analyses of randomized placebo-controlled trials.

Inconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCTs with anti-IL5 treatments for patients with asthma over the 1990-September 2015 period. RCTs were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV1 changes, ACQ-5 improvement, adverse events and serious adverse events. A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. Further eosinophilic subgroup analysis and sensitivity analysis were also conducted in case of heterogeneity. Ten trials involving 3421 patients were eligible for meta-analysis. IL-5 blockade significantly reduced annual exacerbation rates vs. placebo by 40% [29-50] (P < 0.01, I2 = 0.61). ACQ-5 was significantly improved vs. placebo but below the recognized MCID level (-0.31 [-0.41, -0.21], P < 0.01, I2 = 0.11). FEV1 changes from baseline were improved vs. placebo by 0.09 L [0.05-0.12] (P < 0.01, I2 = 0.28). The subgroup analysis identified a slight additional improvement in mean treatment effects in eosinophilic (> 300 mm3 /L) patients with severe asthma. Similar patterns and rates of adverse events and severe adverse events were reported with the three drugs. The data interpretations were not affected by the sensitivity analysis. IL-5 blockade appears to be a relevant treatment strategy to improve severe asthma management, particularly for eosinophilic patients. No clear superiority appeared between the drugs when appropriate doses were compared.

Optimal step doses for drug provocation tests to prove beta-lactam hypersensitivity.

BACKGROUND: Drug provocation tests (DPT) are commonly performed as part of ß-lactam (BL) allergy workup, in case of negative skin tests (ST) and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e. empirical dosing, driven by both safety concerns and practical aspects). METHODS: The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during BL DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-min incremental 1-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to BLs, with negative ST and positive DPT. RESULTS: During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds, and we suggest the following steps for DPT to BLs: 5-15-30-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of 1-day protocol for immediate and mild nonimmediate reactors, for both children and adults, with a surveillance period of 2 h after the last administered dose, and a prolonged surveillance after discharge of 48 h. CONCLUSION: This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, BL antibiotics.

Field-testing the new anaphylaxis' classification for the WHO International Classification of Diseases-11 revision.

BACKGROUND: To consolidate the new classification model addressed to the allergic and hypersensitivity conditions according to the International Classification of Diseases (ICD)-11 revision timeline, we here propose real-life application of quality assurance methodology to evaluate sensitivity and accuracy of the 'Anaphylaxis' subsection. METHODS: We applied field-testing methodology by analysing all the consecutive inpatients' files documented as allergies from the University Hospital of Montpellier electronic database for the period of 1 year. The files clinically validated as being anaphylaxis were manually blind-coded under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the impressions regarding sensibility were evaluated. RESULTS: From all 2318 files related to allergic or hypersensitivity conditions, 673 had some of the anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and allergic or hypersensitivity comorbidities description. The correspondence between the two coders was perfect for 162 codes from all 309 entities (52.4%) (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa value 0.77) with the ICD-11. There was a high agreement regarding sensibility of the ICD-11 usability (Cohen-kappa value 0.75). CONCLUSION: We here propose the first attempt of real-life application to validate the new ICD-11 'Anaphylaxis' subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement when ICD-11 was used. By allowing all the relevant diagnostic terms for anaphylaxis to be included into the ICD-11 framework, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, healthcare planners and other stakeholders.

Analgesia nociception index for the assessment of pain in critically ill patients: a diagnostic accuracy study.

BACKGROUND: Behavioural pain tools are used in Intensive Care Unit (ICU) patients unable to self-report their pain-intensity but need sustained efforts to educate and train the ICU team because of the subjective nature of these clinical tools. This study measured the validity and performance of an electrophysiological monitoring tool based on the spectral analysis of heart rate variability, the Analgesia Nociception Index (ANI) which varies from 0 (minimal parasympathetic tone, maximal stress-response and pain) to 100 (maximal parasympathetic tone, minimal stress-response and pain). METHODS: Mean-ANI (ANIm) and Instant-ANI (ANIi) were continuously recorded then compared with the Behavioral Pain Scale (BPS) before, during and after routine care procedures in critically-ill non-comatose patients. RESULTS: 969 assessments were performed in 110 patients. ANIi was the most discriminative pain tool. It was significantly correlated with BPS (r=-0.30; 95%CI -0.37 to -0.25; P<0.001). For an ANIi threshold of 42.5, the sensitivity, specificity, positive and negative predictive values were respectively 61.4%, 77.4%, 37.0%, and 90.4%. Compared with the BPS, ANIi had no significantly different ability to change during turning and tracheal-suctioning but changed significantly more during dressing change. ANIi increased independently with age, obesity and severity of illness, and controlled mechanical-ventilation, vasopressors use and analgesia. ANIi decreased independently when vigilance status and respiratory rate increased. ANIm demonstrated poor psychometric properties to detect pain. CONCLUSIONS: Despite low sensitivity/specificity, ANIi≥43 had a Negative-Predictive-Value of 90%. Hence ANIi may be of highest benefit for excluding significant pain. A randomized controlled trial should compare sedation-analgesia protocols based on ANIi to presently recommended behavioural-pain-tools.

Comparison of different techniques of central venous pressure measurement in mechanically ventilated critically ill patients.

BACKGROUND: Several techniques exist for measuring central venous pressure (CVP) but little information is available about the accuracy of each method. The aim of this study was to compare different methods of CVP measurements in mechanically ventilated patients. METHODS: CVP was measured in mechanically ventilated patients without spontaneous breathing using four different techniques: 1) end expiratory CVP measurement at the base of the" c" wave (CVPMEASURED), chosen as the reference method; 2) CVP measurement from the monitor averaging CVP over the cardiac and respiratory cycles (CVPMONITOR); 3) CVP measurement after a transient withdrawing of mechanical ventilation (CVPNADIR); 4) CVP measurement corrected for the transmitted respiratory pressure induced by intrinsic PEEP (calculated CVP: CVPCALCULATED). Bias, precision, limits of agreement, and proportions of outliers (difference > 2 mm Hg) were determined. RESULTS: Among 61 included patients, 103 CVP assessments were performed. CVPMONITOR bias [-0.87 (1.06) mm Hg] was significantly different from those of CVPCALCULATED [1.42 (1.07), P < 0.001 and CVPNADIR (1.04 (1.29), P < 0.001]. The limits of agreement of CVPMONITOR [-2.96 to 1.21 mm Hg] were not significantly different to those of CVPNADIR (-1.49 to 3.57 mm Hg, P = 0.39) and CVPCALCULATED (-0.68 to 3.53 mm Hg, P = 0.31). The proportion of outliers was not significantly different between CVPMONITOR (n = 5, 5%) and CVPNADIR (n = 9, 9%, P = 0.27) but was greater with CVPCALCULATED (n = 16, 15%, P = 0.01). CONCLUSIONS: In mechanically ventilated patients, CVPMONITOR is a reliable method for assessing CVPMEASURED Taking into account transmitted respiratory pressures, CVPCALCULATED had a higher proportion of outliers and precision than CVPNADIR.

Cerebrospinal fluid volume in neonates undergoing spinal anaesthesia: a descriptive magnetic resonance imaging study.

BACKGROUND: Spinal anaesthesia (SA) reduces the risk of postoperative apnoea after general anaesthesia in neonates. In 30% of patients, however, the duration of anaesthesia provided does not allow completion of surgery. When compared with term infants, formerly preterm neonates experience a shorter duration of anaesthesia after SA. A difference in the cerebrospinal fluid (CSF) volume between those two populations could explain this difference, but this has never been investigated. The study was designed to evaluate the relationship between the spinal CSF volume and patient characteristics in neonates. METHODS: Sixty-seven neonates, aged 30-60 weeks postconception, were included in this study. Their spinal CSF volumes were calculated using magnetic resonance imaging, and these volumes were plotted individually against sex, term at birth, birth weight, current gestational age, civil age, and weight. Correlations between CSF volume and these variables were investigated. RESULTS: Fifty-four neonates completed the study. The CSF volume was found to be closely and linearly correlated with weight and postconceptional age. The relationship between spinal CSF volume and weight can be described as follows: CSF volume (ml)=1.94 weight (kg)+0.13. The CSF volume was not correlated with sex, weight, or term at birth, nor with civil age. CONCLUSIONS: The amount of spinal CSF in neonates can be estimated as 2 ml kg(-1) in both term and formerly preterm neonates. A difference in the CSF volume between them does not provide an explanation for a shorter duration of SA in the latter. Our findings reinforce weight-adjusted dosage of SA in neonates.

Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units.

BACKGROUND: Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT. METHODS: We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse). RESULTS: In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01). CONCLUSIONS: In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU. CLINICAL TRIAL REGISTRATION: Current controlled trials. Identifier: NCT01532063.

Cell-free DNA in human follicular fluid as a biomarker of embryo quality.

STUDY QUESTION: Could cell-free DNA (cfDNA) quantification in individual human follicular fluid (FF) samples become a new non-invasive predictive biomarker for in vitro fertilization (IVF) outcomes? SUMMARY ANSWER: CfDNA level in human follicular fluid samples was significantly correlated with embryo quality and could be used as an innovative non-invasive biomarker to improve IVF outcomes. WHAT IS KNOWN ALREADY: CfDNA fragments, resulting from apoptotic or necrotic events, are present in the bloodstream and their quantification is already used as a biomarker for gynaecological and pregnancy disorders. Follicular fluid is important for oocyte development and contains plasma components and factors secreted by granulosa cells during folliculogenesis. CfDNA presence in follicular fluid and its potential use as an IVF outcome biomarker have never been investigated. STUDY DESIGN, SIZE, DURATION: One hundred individual follicular fluid samples were collected from 43 female patients undergoing conventional IVF (n = 26) or ICSI (n = 17). CfDNA level was quantified in each individual follicular fluid sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: At oocyte collection day, follicles were aspirated individually. Only blood-free follicular fluid samples were included in the study. Follicle size was calculated based on the follicular fluid volume. Each corresponding cumulus-oocyte complex was isolated for IVF or ICSI procedures. Follicular fluid cfDNA was measured by quantitative PCR with ALU-specific primers. MAIN RESULTS AND THE ROLE OF CHANCE: Human follicular fluid samples from individual follicles contain measurable amounts of cfDNA (mean ± SD, 1.62 ± 2.08 ng/µl). CfDNA level was significantly higher in small follicles (8-12 mm in diameter) than in large ones (>18 mm) (mean ± SD, 2.54 ± 0.78 ng/µl versus 0.71 ± 0.44 ng/µl, respectively, P = 0.007). Moreover, cfDNA concentration was significantly and negatively correlated with follicle size (r = -0.34; P = 0.003). A weak significant negative correlation between DNA integrity and 17ß-estradiol level in follicular fluid samples at oocyte collection day was observed (r = -0.26; P = 0.008). CfDNA level in follicular fluid samples corresponding to top quality embryos was significantly lower than in follicular fluid samples related to poor quality embryos (P = 0.022). Similarly, cfDNA level was also significantly lower in follicular fluid samples related to embryos with low fragmentation rate (≤25%) than with high fragmentation rate (>25%) (P = 0.02). LIMITATIONS, REASONS FOR CAUTION: A larger study should be conducted in order to establish the predictive value of cfDNA level for embryo quality and to investigate whether follicular fluid cfDNA levels are correlated with embryo implantation rates and pregnancy outcomes. Moreover, the role of follicular fluid cfDNA on embryo quality should be studied to determine whether high cfDNA concentration in follicular fluid is only a consequence or also a cause of follicular dysfunction. WIDER IMPLICATIONS OF THE FINDINGS: CfDNA evaluation in individual follicular fluid samples might represent an innovative biomarker of embryo quality to use as a supplemental tool to predict embryo quality during IVF. STUDY FUNDING/COMPETING INTERESTS: This study was partially supported by the University Hospital of Montpellier and Ferring Pharmaceuticals. The authors of the study have no competing interests to report.

Partial acute transverse myelitis is a predictor of multiple sclerosis in children.

BACKGROUND: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. OBJECTIVES: To determine the clinical course and prognostic factors after a first episode of ATM in children. METHODS: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. RESULTS: Median age at onset was 11 years (range 3-15 years). Follow-up data were available for a median of 4 years (range 0.5-16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3-11), with a 60% probability of having a relapse at five years (p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). CONCLUSION: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.

Does the type of fluid affect rapidity of shock reversal in an anaesthetized-piglet model of near-fatal controlled haemorrhage? A randomized study.

BACKGROUND: The optimal resuscitation fluid for the early treatment of severe bleeding patients remains highly debated. The objective of this experimental study was to compare the rapidity of shock reversal with lactated Ringer (LR) or hydroxyethyl starch (HES) 130/0.4 at the early phase of controlled haemorrhagic shock. To assess the influence of vascular permeability in this model, we measured plasma vascular endothelial growth factor (VEGF) levels during the experiment. METHODS: Thirty-six anaesthetized and mechanically ventilated piglets were bled (<30 ml kg(-1)) to hold mean arterial pressure (MAP) at 40 mm Hg for more than 30 min and were resuscitated in two randomized groups: LR (n=14) or HES (n=14) at 1 ml kg(-1) min(-1) until MAP reached its baseline value of ±10%. MAP was maintained at its baseline value for 1 h. The time and fluid volume necessary to restore the baseline MAP value were measured. RESULTS: The time to restore the baseline MAP value of ±10% was significantly lower in the HES group (P<0.001). During the initial resuscitation phase, the infused volume was 279 (119) ml in the HES group and 1011 (561) ml in the LR group (P<0.0001). During the stabilization phase, the infused volume was 119 (124) ml in the HES group and 541 (506) ml in the LR group. Biological data and plasma VEGF levels were similar between the groups. CONCLUSIONS: Restoration of MAP was four times faster with HES than with LR in the early phase of controlled haemorrhagic shock. However, there was no evidence of increased vascular permeability.

Role of comorbid conditions in asthma hospitalizations in the south of France.

BACKGROUND: Reasons for asthma hospitalizations are dynamic and complex. Comorbid conditions are important contributors to most chronic diseases today. We aim to characterize and describe risk factors associated with hospitalizations due to asthma in the Languedoc-Roussillon region (France) in 2009. METHODS: Programme de Médicalisation des Systèmes d'Information (PMSI) data records from 2009 were sorted using selected International Classification of Diseases (ICD10) codes eliciting three groups of asthma hospitalizations according to acute severity. All available data including demographics, comorbid conditions, past hospitalizations either related or unrelated to asthma, seasonality and distance to medical facilities were used to compare the subjects within the three groups. RESULTS: One thousand two hundred and eighty-nine hospitalizations due to asthma exacerbation were found, concerning 1122 patients. We observed significant differences within the groups, using univariate analysis, concerning duration of hospitalizations (mean ± SD, 4.9 ± 5.9 days vs 6.4 ± 6.8 vs 15.8 ± 16.8, P < 0.001), deaths (percentage, 0.03% vs 1.50% vs 9.20%, P < 0.001) and numbers of comorbid conditions (0.80 ± 0.95 vs 0.75 ± 0.97 vs 1.74 ± 1.36, P < 0.001). Recurrent admissions for asthma during the period 2006-2008 were significantly more frequent in the more severe group (1.93 ± 3.91 vs 2.56 ± 4.47 vs 2.81 ± 3.97, P = 0.006). In the multivariate model, age and number of comorbid conditions were independently associated with severe hospitalizations and deaths. CONCLUSIONS: Asthma hospitalizations can be appropriately assessed using PMSI coding databases. In this study, age and the presence of comorbid conditions are the major risk factors for asthma hospitalizations and deaths.

Feasibility of a nasal breathing training during pulmonary rehabilitation. A pilot randomized controlled study.

Hyperventilation syndrome (HVS) is a common source of dyspnea and disability. While pulmonary rehabilitation (PR) including breathing exercises is indicated, randomized controlled trial are warranted to recommend one type of breathing exercise than another. We aimed to compare during PR, the effect of 5 sessions of nasal ventilation exercise (NV+PR) versus voluntary hypoventilation (vHV+PR) on exercise dyspnea (primary outcome) and capacity and health-related quality of life in patients. In this open label randomized controlled trial, 19 HVS patients (age=48.3 ± 15.2 y.o, female/male=18/1, Nijmegen score=33 ± 7.7) were randomized in a NV+PR (n = 9) or vHV+PR (n = 10) group. Modified Medical Research Council (mMRC) dyspnea, 6-minute walking distance (6MWD) with nasal/oral ventilation were assessed before and after 3 months of PR, and questionnaires (Nijmegen, VQ-11). There was a significant effect of PR of but no significant difference between groups in the improvements of dyspnea@max exercise (time effect (T): p < 0.01; group (G): p = 0.63; group*time interaction (G*T): p = 0.49), mMRC dyspnea (T: p < 0.01; G: p = 0.45; G*T: p = 0.62), 6MWD (T: p < 0.05; G: p = 0.36; G*T: p = 0.31), VQ-11 (T: p < 0.001; G: p = 0.16; G*T: p = 0.09) and plasma HCO3- (T: p < 0.05; G: p = 0.93; G*T; p = 0.36), Yet, Nijmegen score (T: p < 0.01; G: p = 0.32; G*T: p < 0.05) improvement was larger in NV+PR group. The exercise oronasal breathing shift during the 6MWT was significantly delayed in all patients (T: p < 0.05; G: p = 0.30; G*T: p = 0.32) and positively correlated with plasma HCO3-(r = 0.42; p < 0.05). Nasal exercise was not superior versus voluntary hypoventilation during PR in HVS patients. Yet, nasal exercise appeared feasible, leading to acquisition of a nasal breathing pattern during walking, improvement of PR outcomes and ventilatory alkalosis. The link between nasal breathing and hyperventilation is discussed in the light of the nasal ventilation rhythm in the limbic system and its role on the limbic emotional and ventilatory functions.

Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study.

Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.

Retrospective case-control study to predict a potential underlying appendiceal tumor in an acute appendicitis context based on a CT-scoring system.

OBJECTIVES: To assess CT signs to discriminate an appendiceal tumor versus a non-tumoral appendix in an acute appendicitis context. METHODS: A 10-year bicentric retrospective case-control study was performed in adults. Patients with a histopathological appendiceal tumor and appendicitis were paired for age and sex with patients with non-tumorous appendicitis (1/3 ratio, respectively). Two senior radiologists blindly analyzed numerous CT findings with final consensus to perform univariate and multivariate statistical analyses. A diagnostic CT scan score was calculated with a bootstrap internal validation. Reproducibility was assessed based on the kappa statistic. RESULTS: A total of 208 patients (51 +/- 21 years; 114 males) were included (52 patients in the tumor group and 156 in the non-tumor group). In the multivariate analysis, an appendicolith and fat stranding were protective factors with OR = 0.2 (p = 0.01) and OR = 0.3 (p = 0.02), respectively, while mural calcifications (OR = 47, p = 0.0001), an appendix mass (OR = 7.1, p = 0.008), a focal asymmetric wall abnormality (OR = 4.9, p = 0, 001), or a ≥ 15 mm diameter (OR = 3.5, p = 0.009) were positive predictive factors of an underlying tumor. Using a ≥1 cut-off, our diagnostic score had an AUC = 0.87 (95 % CI, 0.82-0.93) and a positive likelihood ratio = 13.5 (95 % CI, 6.7-27.1). CONCLUSION: We developed a reliable scoring system based on CT findings, which is highly predictive of an underlying appendiceal neoplasm in an appendicitis context using a ≥1 cut-off.

Prevalence of carotid web in a French cohort of cryptogenic stroke.

BACKGROUND AND PURPOSE: Carotid webs (CaW) may be an under-recognized cause of anterior circulation cryptogenic ischemic stroke (ACIS). Prevalence is still unknown in European patients with ACIS. OBJECTIVE: To evaluate the prevalence of CaW in ACIS and describe patients with CaW phenotype in a cohort of patients from a French stroke center. METHODS: We conducted a retrospective monocentric cohort study from 01/01/2015 to 31/12/2019 (Montpellier University Hospital, France), in consecutive anterior ischemic stroke (AIS) patients ≤65 years old from a prospective stroke database. Using ASCOD phenotyping, ACIS patients were selected and cervical CTA were reviewed to find CaW. RESULTS: Among 1053 consecutive AIS patients, 266 ACIS patients with CTA were included. Among patients included (mean age 50, women 58%), CaW was in the ipsilateral carotid (iCaW) in 21 patients: 7.9% (95%CI [4.6-11.1]), (mean age 51, 11 women, 16 Caucasian). iCaW were uncovered during study review of CTA in 6/21 (29%) patients. Comparison between patients with iCaW and those without iCaW showed no differences except that of a higher rate of intracranial large vessel occlusion (LVO) (62.4 vs 37.6%; p = 0.03). Patients with iCaW under conservative medical therapy had an annualized stroke recurrence rate (SRR) of 11.4% (95%CI [8.4-15.1]. CONCLUSIONS: iCaW was identified as a source of stroke in about 8% of a French population ≤65 years with ACIS. iCaW was associated with a higher rate of LVO and a high SRR under conservative medical therapy.