Are the results of intravenous thrombolysis trials reproduced in clinical practice? Comparison of observed and expected outcomes with the stroke-thrombolytic predictive instrument (STPI).

AIM: In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. METHOD: Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months. The observed outcomes were then compared with the probability of good (mRS 0-1) and of catastrophic (mRS 5-6) outcomes, as predicted by the stroke-thrombolytic predictive instrument (STPI). RESULTS: Of the 1000 consecutive patients (469 male, median age 74 years, median baseline National Institutes of Health Stroke Scale 11, median onset-to-needle time 143min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0-2 or similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%) developed symptomatic intracerebral hemorrhage according to ECASS-II (Second European-Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%) eligible for evaluation by the s-TPI, the observed rate of good outcomes was 41.3% (95% CI: 37.5-45.3%), while expected rates with and without rt-PA were 48.8% (95% CI: 44.8-52.7%) and 32.5% (95% CI: 28.8-36.2%), respectively; the observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0-19.9%), while the expected rate was 19.2% (95% CI: 16.1-22.4%) with or without rt-PA. CONCLUSION: In clinical practice, the rate of good outcomes is slightly lower than expected, according to the s-TPI, except for the most severe cases, whereas the rate of catastrophic outcomes is roughly similar. However, the rate of good outcomes is higher than predicted without treatment. This finding suggests that rt-PA is effective for improving outcomes in clinical practice.

Effects of small airway dysfunction on the clinical expression of asthma: a focus on asthma symptoms and bronchial hyper-responsiveness.

BACKGROUND: The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied. AIM: To investigate the association of small and large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness (BHR). METHODS: Fifty-eight patients with asthma were characterized with spirometry, body plethysmography, impulse oscillometry, alveolar and bronchial exhaled nitric oxide, and a methacholine provocation. Symptoms of nocturnal asthma, exercise-related symptoms, BHR symptoms, and respiratory symptoms were assessed with the Asthma Control Questionnaire and Bronchial Hyper-responsiveness Questionnaire. Perception of dyspnea was rated with the Borg score during the provocation test. RESULTS: Small and large airway dysfunction did not associate with higher scores for nocturnal, exercise-related, or BHR symptoms. Only higher scores on wheezing were significantly associated with higher values of difference between R5 and R20 (R5-R20) (r = 0.367, P < 0.01) and AX (r = 0.354, P < 0.01). Lower FEF25-75% (P = 0.024) and higher R5-R20 (P = 0.003) values were independently associated with more severe BHR to methacholine, but not FEV1 or R20 values. The increase in dyspnea during the methacholine provocation was strongly and independently correlated with the decrease in FEV1 and reactance of the respiratory system at 5 Hertz. CONCLUSION: Small and large airway dysfunction poorly associate with asthma symptoms in our patients. However, deteriorations in small airway dysfunction are strongly related to an increase in dyspnea during bronchial provocation with methacholine. Small airway dysfunction contributes also independently to the clinical expression of asthma, as reflected by the severity of BHR.

Treatment of the bronchial tree from beginning to end: targeting small airway inflammation in asthma.

Asthma is a chronic respiratory disease, characterized by airway obstruction and inflammation. Increasing evidence shows that the small airways contribute significantly to the clinical expression and severity of asthma. Traditionally, high levels of disease activity are thought to be necessary before symptoms occur in the small airways because of their large reserve capacity. However, this concept is being challenged and increasing evidence shows small airway disease to be associated with symptoms, disease severity, and bronchial hyper-responsiveness. Particle size and distribution are of key importance when developing inhaled treatments for small airway disease. The availability of small-particle aerosols such as HFA-ciclesonide and HFA-beclomethasone dipropionate (HFA-BDP) enables a higher drug deposition into the peripheral lung and potentially provides additional clinical benefits compared with large-particle treatment. However, improved methods are needed to monitor and assess small airway disease and its response to treatment because conventional spirometry mainly reflects large airway function. This remains a challenging area requiring further research. The aim of the current manuscript is to review the clinical relevance of small airway disease and the implications for the treatment of asthma.

Less small airway dysfunction in asymptomatic bronchial hyperresponsiveness than in asthma.

BACKGROUND: Bronchial hyperresponsiveness (BHR) can be present in subjects without any respiratory symptoms. Little is known about the role of the small airways in asymptomatic subjects with BHR. METHODS: We investigated small airway function assessed by spirometry and impulse oscillometry, as well as Borg dyspnea scores at baseline and during a methacholine provocation test in 15 subjects with asymptomatic BHR, 15 asthma patients, and 15 healthy controls. RESULTS: At baseline, small airway function (R5 -R20 and X5 ) was comparable between subjects with asymptomatic BHR and healthy controls, whereas asthma patients showed small airway dysfunction as reflected by higher R5 -R20 and lower X5 values. During methacholine provocation, small airway dysfunction was more severe in asthma patients than in subjects with asymptomatic BHR. Interestingly, a higher increase in small airway dysfunction during methacholine provocation was associated with a higher increase in Borg dyspnea scores in subjects with asymptomatic BHR, but not in asthma patients. CONCLUSION: Subjects with asymptomatic BHR may experience fewer symptoms in daily life because they have less small airway dysfunction.

The impact of endotracheal intubation on oxygen delivery, trachea pressure and wall deformation.

This paper concerns improving endotracheal tube (ETT) insertion through advanced computational science modelling. The study aims to better understand endotracheal intubation (ETI) and reduce medical errors in intensive and critical care units since ETT insertion is unique for each patient, depending on age, gender, size, physiology, and underlying health conditions. We have employed computational fluid dynamics and biomechanics modelling to investigate the effect of ETT for three ventilation modes on (a) local oxygen delivery to the lungs, (b) air pressure and wall shear stress at the tracheal walls, and (c) oscillatory elastic deformation of the tracheal tissues and muscle. For the first time, we reveal how the ventilation mode and ETT insertion in the trachea may induce major complications, especially in long periods of ETT. We show that rotating the ETT or displacing it by 2 mm only can induce a significant rise in the tracheal pressure up to 177 cmH2O. This study, for the first time, shows the vital role of computers in biology and medicine to provide enhanced decision-making-support to clinicians and medical doctors dealing with ETI.

Training first-year medical residents to break bad news using healthcare role-play and trainees as simulated patients: Experience of the "ADIAMED" program from Lille University School of Medicine.

INTRODUCTION: Several studies suggest the relevance of healthcare simulation to prepare future doctors to deliver bad news. A such, we designed a role-play workshop to train first-year residents enrolled in Lille University School of Medicine to break bad news. The objective of this work is to report on our experience of this training and to assess its educational value through its capacity to satisfy residents' expectations, to induce a feeling of ease towards bad news disclosure, and to change trainees' preconceptions regarding these situations. METHODS: The training consisted of a 45-minute heuristic reflective activity, aimed at identifying residents' preconceptions regarding bad news disclosure, followed by 4 30-min role-plays in which they played the parts of the physician, the patient and/or their relatives. Trainees were asked to answer 2 questionnaires (pre- and post-training), exploring previous experiences, preconceived ideas regarding bad news disclosure and workshop satisfaction. RESULTS: Almost all residents felt very satisfied with the workshop, which they regarded as formative (91%) and not too stressful (89%). The majority felt "more capable" (53% vs. 83%) and "more comfortable" (27% vs. 62%) to deliver bad news, especially regarding "finding the right words" (12% vs. 22%). Trainees tended to overestimate their skills before the workshop and lowered their assessment of their performance after attending the training, especially when they played the role of a patient in the simulation. CONCLUSION: Healthcare role-play seems an interesting technique for training to breaking bad news. Placing residents in the role of patients or relatives is an active approach that encourages reflexivity.

Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.

Construction of an adaptable and specific severity score for prehospital emergencies.

The aim of this study was to design a severity score specific to mobile emergency and resuscitation services (MERS). A prospective, multicentre cohort study including 17 868 patients was performed. The severity reference criterion was determined by multiple correspondence analysis. A multiple linear regression was used for the construction of the severity score. The score performances were analysed in terms of area under the receiver operating characteristics curves (AUC). Twelve variables were identified for the construction of the severity score. The multiple regression (r2 = 0.947; p<0.001) provided a severity score that took on values from 8 to 68. The score performs well in distinguishing the various patient outcomes in terms of AUC. This study develops the first adaptable and specific severity score of MERS activities.

Paraquat poisoning in Western French Guyana: a public health problem persisting ten years after its withdrawal from the French market.

OBJECTIVE: Paraquat poisoning has almost disappeared from metropolitan France following its ban from the European market ten years ago. However, due to neighboring countries still authorizing paraquat use, French Guyana seems in a different situation. Here we aimed to report a series of paraquat-poisoned patients admitted to the emergency department of the Western French Guyana Hospital in Saint-Laurent du Maroni, to raise awareness of national health authorities on this persistent major issue. PATIENTS AND METHODS: We conducted a retrospective observational study describing the clinical features, the prognostic factors and the final outcome of paraquat-poisoned patients admitted to the emergency department between January 2008 and August 2014. RESULTS: Twenty-six paraquat-poisoned patients were included in the study. The median estimated paraquat dose intentionally ingested was 105 mg/kg (interquartile range, IQR: 359). Eighteen patients were treated with the cyclophosphamide/dexamethasone combination and seventeen with N-acetylcysteine in addition to the usual supportive care. Six patients survived and twenty died within a median 36h delay after admission (IQR: 130). Death was associated with cardiovascular (65%) and respiratory (35%) failure. Based on a bivariate analysis, predictive factors of death included (p≤0.05): advanced age, higher ingested paraquat dose, altered renal function, hypokalemia, acidosis, and dark blue dithionite test, observed on hospital admission. CONCLUSIONS: Paraquat poisoning still persists in French Guyana despite its withdrawal from the market. It is possible to determine the probability of death on patient admission based on routine clinical and biological parameters. There is an urgent need to request neighboring countries to ban paraquat with the aim of eradicating this dramatically life-threatening poisoning.

Local recurrence after CO2 laser cordectomy for early glottic carcinoma.

OBJECTIVES: To point out prognosis factors of local recurrence after endoscopic cordectomies for Tis, T1a, T1b, and T2 glottic squamous cell carcinomas. STUDY DESIGN: A cohort of 110 patients treated from January 1990 to December 2000 at a single institution was retrospectively analyzed: 21 had Tis, 76 T1a, 7 T1b, and 6 T2 (mean follow-up 42 mo; range 1-160 mo). METHODS: The depth and extension of the excision were graded according to the European Laryngological Society Classification. Univariate analysis was used to review the impact on disease-free survival of factors related to the host, the tumor, and the treatment. RESULTS: According to the Kaplan-Meier method, the 5 year overall survival and the disease-free survival were 87% and 75%, respectively. The rates of cause-specific survival, ultimate local control with laser alone, and laryngeal preservation were 97%, 84%, and 90%, respectively. Univariate analysis by the log rank test revealed that vocal muscle infiltration (P = .001) and subglottic involvement (P = .02) have a significant impact on disease-free survival. Of the 22 patients with local recurrence (17 T1a, 1 T1b, and 4 T2), 9 were managed with total laryngectomy, 5 with partial laryngectomy, 4 with further laser cordectomy, 2 with radiotherapy, and 2 had no curative treatment. CONCLUSION: Transoral laser surgery for early glottic carcinoma is a valid alternative to radiotherapy and partial laryngectomy in terms of oncologic results. It offers low morbidity and excellent retreatment options in case of local failure. Careful patient selection for laser surgery is essential to secure good results.

[Perioperative evolution of the nutritional status in head and neck surgical patients. Prospective and descriptive case series]. / Evolution périopératoire du statut nutritionnel en chirurgie carcinologique des voies aérodigestives supérieures. Etude prospective et descriptive.

AIM OF THE STUDY: To assess the perioperative evolution of the nutritional status of head and neck surgical patients. DESIGN: Prospective, descriptive case series. PATIENTS AND METHODS: Fifty-four patients candidates for total or partial laryngectomy for malignancy of the neck tract without a past of neck surgery. The nutritional status of all patients hospitalized for total pharyngolaryngectomy, total or partial laryngectomy was assessed by 1) clinical parameters including weight (W), weight variation (WV, percentage of loss), Body Mass Index (BMI), triceps skin fold measurement (T), midarm circumference (M), and 2) biological parameters such as serum albumin (SA), transthyretin (TTR), lymphocytes (Ly). These parameters were noted at the time of diagnostic laryngoscopy (T1), the day before surgery (T2), and 10 days afterward (T3) when patients were authorized to eat normally. All patients had enteral nutrition (EN) support (35 kcal/kg/day) starting at D1 and for 10 days afterward. Only complete data per patient were analyzed. RESULTS: 24 patients were excluded. During the 21 days [7-53] preoperative period (T1-T2), WV was (6.6% [-8,1-+20.0] [T2] vs. 4.7% [-12,9-+20.0] [T1], p<0.05) without difference in T and M. In the postoperative period (T2-T3), all parameters worsened, except T, with: WV (8.2% [-8,1-+20.0] [T3], p<0.05 vs T2), M (27.4 cm [20.0-37.0] [T3] vs 28.3 cm [20.5-39.0] [T2], p<0.05) et TTR (0.21 mg/l [0.09-0.36] [T3] vs. 0.27 mg/l [0.08-0.45] [T2], p<0.05). BMI was 22.9 [15.2-36.7] (T1) vs 22.9 [15.2-35.3] (T2), NS and 22.1 [15.0-34.9] (T3), p<0.05 vs (T2). CONCLUSION: The nutritional status in malignancy head and neck surgical patients seems to be best assessed by loss weight. It worsened mainly during the postoperative period even if a well-conducted EN was performed as defined by the French consensus conference.

Effect of L-arginine on endothelial injury and hemostasis in rabbit endotoxin shock.

To investigate whether impaired endothelial function was related to alteration of nitric oxide (NO) formation during endotoxic shock, we studied the effects of supplementation of L-arginine (L-Arg), D-arginine (D-Arg), and N(G)-nitro-L-arginine methyl ester (L-NAME), on endothelial function and structure in a rabbit model. Endotoxic shock was induced by a single lipopolysaccharide bolus (0.5 mg/kg i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor were determined by functional assays. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess damaged endothelial cell surface of the abdominal aorta. These parameters were studied 5 days after the onset of endotoxic shock and were compared under three conditions: in absence of treatment, with L-Arg or D-Arg supplementation, or with L-NAME. Both L-Arg and D-Arg significantly improved endothelium-dependent relaxation and endothelial morphological injury. L-NAME did not alter endothelial histological injury induced by lipopolysaccharide. These data indicate that arginine supplementation nonspecifically prevents endothelial dysfunction and histological injury in rabbit endotoxic shock. Moreover, L-Arg has no effect on coagulation activation and expression of monocyte tissue factor induced by endotoxic shock.

Complications of surgical closure of tracheo-cutaneous fistula in pediatric patients - two case reports.

Tracheocutaneous fistula is seen frequently in decannulated children and respiratory complications associated with primary surgical closure can be potentially fatal. Cough is a precipitating factor for an air leak and we report two cases in which this occurred. A tracheotomy was performed on a 5-month-old girl for mechanical ventilation. Decannulation was successful at the first attempt. One year later, she presented with a persistent tracheo-cutaneous fistula. After surgical closure without drainage, she developed subcutaneous emphysema during a coughing episode. Sutures were removed. A 9-month-old boy presented with oxygen-dependence after lung disease and a tracheotomy was performed for respiratory support. Decannulation was successful at the first attempt 6 months later. He developed a pneumomediastinum after surgical closure of a tracheo-cutaneous fistula. Sutures were removed but replacement of a tracheotomy tube was required. In both cases the wounds were allowed to heal by secondary intention.

[Recurrent hematomas and normal standard hemostasis tests]. / Hématomes récidivants et bilan d'hémostase standard normal.

The authors report the case of a 22-month-old boy experiencing a voluminous subcutaneous haematoma, 72 hours after a head trauma. Two subsequent drainages of this haematoma were required because of its recurrence. The child, whose parents had blood relations, suffered from recurrent bleeding since his birth. A standard haemostasis assessment including prothrombin time, activated partial thrombopiastin time, bleeding time, concentration of fibrinogen and platelet count was unremarkable. Therefore, coagulation factors were explored. An inherited factor XIII deficiency (less than 2%) was recognized. A new drain was inserted, after administration of factor XIII concentrate. The time course of the haematoma was favourable. After discharge, the prophylactic therapy consisted of an injection of factor XIII concentrate (50 Ul.kg-1) every 5 weeks.

[Unilateral nasal obstruction,. An unusual complication of nasotracheal intubation]. / Obstruction nasale unilatérale. Une complication inhabituelle de l'intubation nasotrachéale.

Partial avulsion of the middle turbinate is an unusual complication of nasotracheal intubation, while minor nasal mucosal trauma is common. We report a case in a 25 year-old healthy-woman, diagnosed four years after nasotracheal intubation for removal of wisdom teeth under general anaesthesia, consisting in a unilateral nasal obstruction related to partial avulsion of the middle turbinate.

[Autoantibodies and anti-factor VIII and Chlamydia pneumoniae infection]. / Auto-anticorps anti-facteur VIII et infection à Chlamydia pneumoniae.

We report the case of a 64-year-old man without hemorrhagic history experiencing epistaxis. The standard hemostasis assessment including prothrombin index, activated partial thromboplastin time (APTT) and platelet count found an isolated abnormal APTT (105 sec vs 33 sec). Therefore, coagulation factors were explored. An acquired factor VIII deficiency (5%) with anti-FVIII antibody (4.5 Bethesda unit.mL-1) was recognised. This anti-FVIII antibody was related to a Chlamydia pneumoniae pulmonary infection. Treatment consisted of: i) Four successive anterior packing and activated factor VII infusion (Novoseven); ii) steroids injection and bi-antibiotherapy. The time course of the epistaxis was favourable under treatment.

[Cerebral fat embolism after closed leg injury]. / Embolie graisseuse cérébrale après traumatisme fermé de la jambe.

A 21-year-old man sustained a closed fracture of the leg from an industrial accident, without associated head trauma. The orthopaedic treatment consisted of immediate immobilization by setting leg in plaster. Two hours after admission, the Glasgow coma scale score was 10. Four hours after admission he developed a coma (Glasgow coma scale score = 7) with repetitive seizures. No lesion was visible on cerebral CT scan. Chest X-ray was unremarkable. Petechiae on the anterior chest wall and abdomen with bilateral mydriasis occurred. Thrombocytopenia with prothrombine time increase were observed. Magnetic resonance imaging, 27 hours after admission, showed high-intensity areas on T2 weighted views due to fat embolism. Retinal haemorrhages were observed. The bronchoalveolar lavage showing fat staining of tracheal aspirates confirmed the diagnosis of fat embolism. This case report emphasizes the possibility of predominant neurologic manifestations of a fat embolism and the diagnostic help of cerebral magnetic resonance imaging.

[Iatrogenic laryngotracheal stenosis. A follow-up of 20 recent cases]. / Sténoses laryngo-trachéales iatrogènes. Suivi de l'évolution de 20 cas récents.

The aim of this study was to analyse the follow-up of patients with a history of endotracheal intubation and/or tracheotomy because of respiratory distress, surgical necessity or long-term resuscitation. Twenty adults were followed up in a ENT facility for laryngeal or tracheal stenosis, of which 7 cases were diagnosed during 1994. This study shows that, in patients with a history of intubation, or intubation followed by tracheotomy, the stenosis developed within two months after resuscitation with a favourable outcome. After tracheotomy only, the stenosis developed later (2 months or more) with more recurrences. The diagnosis of stenosis was made on gradual or acute dyspnea. While respiratory resuscitation methods are essential and often life-saving, they are not without complications. Laryngeal and tracheal stenosis could be largely prevented by more careful techniques of endotracheal intubation and tracheotomy. Periodic endoscopic airway surveillance is useful to detect stenosis even when there is no clinical symptom.

[Patient treated with sub-mental intubation for maxillofacial trauma]. / Intubation sub-mentale chez un patient victime d'un traumatisme maxillo-facial.

Maxillo-facial traumas are frequent and most often occur in young patients. Naso-tracheal or orotracheal intubation may be contraindicated in case of combined occlusal fracture and nasal or ethmoido-nasal fracture. This study was carried out a clinical case of a patient treated at the Lille University Hospital for a maxillofacial trauma associating fracture of nose and maxilla. The purpose was to assess the reliability of submental intubation as an alternative to tracheotomy. Submental intubation is a reliable single and safe technique allowing an one-stage surgical treatment in case of complex association of fractures without using tracheotomy. Its use should be implemented on a larger scale.