Multiple Sustainable Benefits of a Rehabilitation Program in Therapeutic Management of Hypermobile Ehlers-Danlos Syndrome: A Prospective and Controlled Study at Short- and Medium-Term.

OBJECTIVE: To evaluate the effects of a 9-week rehabilitation program (RP) for patients with hypermobile Ehlers-Danlos syndrome (hEDS) in the short- and medium-term. DESIGN: Nonrandomized controlled trial with 6 months follow-up. SETTING: Outpatient rehabilitation program. PARTICIPANTS: A referred sample of 36 hEDS patients were assessed for eligibility (N=36), 25 were included, 22 completed the RP and 19 completed the follow-up. INTERVENTIONS: A 9 -week control period without intervention followed by a 9-week RP. MAIN OUTCOME MEASURE: Functional exercise capacity was used as a primary outcome measure. Balance, kinesiophobia, fatigue, pain, quality of life, anxiety, depression, and hyperventilation were measured as secondary outcomes. RESULTS: No significant change was observed during the 9-week control period before the RP. There was a significant improvement immediately after the RP for the functional exercise capacity, balance with eyes closed, fatigue, and quality of life (P<.05). Even more improvements were found 6 weeks after the end of the RP, and there was still an improvement after 6 months in functional exercise capacity, kinesiophobia, depression, hyperventilation, and some components of the quality of life. CONCLUSION: This study supports the effectiveness of an RP as a useful management tool for hEDS patients.

Endoscopic follow-up of low-grade precancerous bronchial lesions in high-risk patients: long-term results of the SELEPREBB randomised multicentre trial.

BACKGROUND: 3-9% of low-grade preinvasive bronchial lesions progress to cancer. This study assessed the usefulness of an intensive bronchoscopy surveillance strategy in patients with bronchial lesions up to moderate squamous dysplasia. METHODS: SELEPREBB (ClinicalTrials.gov NCT00213603) was a randomised study conducted in 17 French centres. After baseline lung computed tomography (CT) and autofluorescence bronchoscopy (AFB) to exclude lung cancer and bronchial severe squamous dysplasia or carcinoma in situ (CIS), patients were assigned to standard surveillance (arm A) with CT and AFB at 36 months or to intensive surveillance (arm B) with AFB every 6 months. Further long-term data were obtained with a median follow-up of 4.7 years. RESULTS: 364 patients were randomised (A: 180, B: 184). 27 patients developed invasive lung cancer and two developed persistent CIS during the study, with no difference between arms (OR 0.63, 95% CI 0.20-1.96, p=0.42). Mild or moderate dysplasia at baseline bronchoscopy was a significant lung cancer risk factor both at 3 years (8 of 74 patients, OR 6.9, 95% CI 2.5-18.9, p<0.001) and at maximum follow-up (16 of 74 patients, OR 5.9, 95% CI 2.9-12.0, p<0.001). Smoking cessation was significantly associated with clearance of bronchial dysplasia on follow-up (OR 0.12, 95% CI 0.01-0.66, p=0.005) and with a reduced risk of lung cancer at 5 years (OR 0.15, 95% CI 0.003-0.99, p=0.04). CONCLUSION: Patients with mild or moderate dysplasia are at very high risk for lung cancer at 5 years, with smoking cessation significantly reducing the risk. Whereas intensive bronchoscopy surveillance does not improve patient outcomes, the identification of bronchial dysplasia using initial bronchoscopy maybe useful for risk stratification strategies in lung cancer screening programmes.

Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.

RATIONALE: Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP). OBJECTIVES: To determine the impact of continuous control of tracheal cuff pressure (P(cuff)) on microaspiration of gastric contents. METHODS: Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P(cuff) using a pneumatic device (intervention group, n = 61) or routine care of P(cuff) (control group, n = 61). MEASUREMENTS AND MAIN RESULTS: The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P(cuff). Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log(10) cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups. CONCLUSIONS: Continuous control of P(cuff) is associated with significantly decreased microaspiration of gastric contents in critically ill patients.

Management of postintubation tracheobronchial ruptures.

STUDY OBJECTIVES: To determine whether nonoperative management can be applied to iatrogenic postintubation tracheobronchial rupture (TBR). DESIGN: Prospective cohort study. PATIENTS AND INTERVENTIONS: Thirty consecutive patients with TBR complicating intubation between June 1993 and December 2005 entered the study. Patients not receiving mechanical ventilation at time of diagnosis were treated nonsurgically. Patients receiving mechanical ventilation who were judged operable underwent surgical repair, while nonoperable candidates had their TBR bridged by endotracheal tubes. RESULTS: Fifteen patients not requiring mechanical ventilation underwent simple conservative management. TBR length measured 3.85 +/- 1.46 cm (mean +/- SD). Eight TBRs showed full-thickness rupture with frank anterior intraluminal protrusion of the esophagus. In three patients, transient noninvasive positive pressure ventilatory support (NIV) was necessary. All lesions healed without sequelae. Two patients receiving mechanical ventilation underwent surgical repair and died. Thirteen patients receiving mechanical ventilation were considered at high surgical risk, and TBR bridging was attempted as salvage therapy. Complete bridging was achieved in five patients by simply advancing the endotracheal tube distal to the injury. Separate bilateral mainstem endobronchial intubation was necessary in six patients whose TBRs were too close to the carina. Nine of 13 patients (69%) treated with nonoperative therapy completely recovered. CONCLUSION: We conclude that conservative nonoperative therapy should be considered in patients with postintubation TBR who are breathing spontaneously, or when extubation is scheduled within 24 h from the time of diagnosis, or when continued ventilation is required to treat an underlying respiratory status. Surgical repair should be reserved for cases in which NIV or bridging the lesion is technically not feasible.

Successful orthotopic transplantation of short tracheal segments without immunosuppressive therapy.

OBJECTIVES: Results of tracheal transplantation have been disappointing due to of ischaemia and rejection. It has been experimentally demonstrated that results of tracheal autograft/allograft transplantation were correlated with both graft length and revascularization method. Recently, we demonstrated that heterotopic epithelium-denuded-cryopreserved tracheal allograft (TA) displayed satisfactory immune tolerance. We aimed at evaluating the results of such allografts in orthotopic transplantation according to graft length and prior heterotopic or single-stage orthotopic revascularization in a rabbit model. METHODS: Twenty New Zealand rabbits were used. Six females served as donors. Tracheal mucosa was mechanically peeled off and then the TAs were cryopreserved. Male recipients were divided into three groups receiving: (i) long TA segment with prior heterotopic revascularization (10-12 tracheal rings, n = 3); (ii) average TA segment with single-stage orthotopic revascularization (6-8 tracheal rings, n = 4); (iii) short TA segment with single-stage orthotopic revascularization (4-5 tracheal rings, n = 7). No immunosuppressive therapy was administered. Grafts were assessed bronchoscopically and upon death or sacrifice by macroscopic evaluation, histology and immunohistochemical staining for apoptosis. RESULTS: Four animals were sacrificed from Day 33 to Day 220. The survival time of other recipients was 0-47 days (mean 19.6 ± 16.7 days). Aside from three animals that died from complications, all TA segments had satisfactory stiffness, were well vascularized, showed varying levels of neoangiogenesis and inflammatory infiltration devoid of lymphocytes, and showed evidence of only low levels of apoptosis. Varying degrees of fibroblastic proliferation originating from the lamina propria were observed in the lumen of all TAs and evolved over time into collagenized fibrosis in animals surviving over 45 days. Likewise, cartilage tracheal rings exhibited central calcification deposits, which started on Day 16 and increased over time. Epithelial regeneration was constantly observed. Intense fibroblastic proliferation led to stenosis in all animals from Groups (i) and (ii) but only one of seven animals from Group (iii). CONCLUSIONS: Our results suggest that short segments of epithelium-denuded-cryopreserved TA may be reliable for tracheal transplantation in the rabbit model without problems related to graft stiffness or immune rejection. Before considering clinical applications, investigations should be conducted in larger mammals.

[Exercise-induced vocal cord dysfunction in asthma: a new diagnostic method]. / Diagnostic de la dysfonction des cordes vocales à l'exercice dans l'asthme sévère.

OBJECTIVE: Vocal cord dysfunction (VCD) is an under-recognized cause of dyspnea and is difficult to diagnose. The symptoms caused by exercise-induced VCD (IEVCD) often falsely suggest asthma, but there is sometimes a real association between the two diseases. The objective of this study was to evaluate a new, simple method for analyzing vocal cord behavior in the diagnosis of IEVCD, and to clarify the prevalence of IEVCD in an uncontrolled asthma population with unexplained exertional dyspnea. METHODS: This single-center study was conducted prospectively between April 2012 and March 2013. The main inclusion criterion was uncontrolled asthma with unexplained dyspnea. The assessment included cardiopulmonary exercise testing and supraglottal laryngoscopy during exercise with measurement of the vocal cord-opening angle (VCOA). Data from 15 asthmatic patients were compared with those from 10 non-asthmatic dyspneic patients (controls) to define specific criteria for the endoscopic diagnosis of IEVCD. RESULTS: Endoscopy during bicycle exercising was well tolerated. Normal value of inspiratory VCOA (itVCOA) was>49°. Values for the itVCOA were lower for asthmatics than for controls when exercising at 50% maximal power (52.8°±13.3° and 64.5°±8.3°, respectively). Four of the 15 asthmatics (26%) demonstrated IEVCD characterized with itVCOApeak of less than 49°. CONCLUSION: Measurement of VCOA represents a new, simple method for obtaining objective data in the exploration of VCD. The prevalence of IEVCD in uncontrolled asthmatic patients is important (26% in our small sample). IEVCD is probably an under-diagnosed aggravating factor in asthma, and its diagnosis and management could avoid the therapeutic climbing in asthma. This method of analysis may help to accurately and objectively assess vocal cord dysfunction.

Intubation-related tracheal ischemic lesions: incidence, risk factors, and outcome.

PURPOSE: To determine incidence, risk factors and outcome of tracheal ischemic lesions related to intubation. METHODS: Planned post hoc analysis using patients from a previous randomized controlled study. Fiberoptic tracheoscopy was performed during the 24 h following extubation. In patients with >2 ischemic lesions, ulcer or tracheal rupture, fiberoptic tracheoscopy was repeated 2 weeks after the last extubation. Tracheal ischemic lesions were predefined based on a quantitative score. RESULTS: Ninety-six adult patients were included in this study. Eighty (83 %) patients had at least one tracheal ischemic lesion. Thirty-seven (38 %) patients had a tracheal ischemia score > median score (5; IQ 1, 7). The most common tracheal ischemic lesion was ischemia (68 %), followed by hyperemia (54 %), ulcer (10 %), and tracheal rupture (1 %). Univariate analysis identified duration of neuromuscular-blocking agent use, overinflation of tracheal cuff (>30 cmH2O), percentage of P cuff determination >30 cmH2O, duration of assist-control ventilation, and plateau pressure as risk factors for having a tracheal ischemia score >5. Duration of assist-control mechanical ventilation was the only factor independently associated with tracheal ischemia score >5 [OR (95 % CI) 1.10 per hour (1.02-1.20)]. A fiberoptic tracheoscopy was performed 2 weeks after extubation in 22 patients. This examination was normal in all patients, except the one with tracheal rupture who had marked improvement. CONCLUSION: Tracheal ischemic lesions are common in intubated, critically ill patients. Duration of assist-control mechanical ventilation through a tracheal tube is the only independent risk factor. These lesions healed in the majority of patients 2 weeks after extubation.

Endoscopic ultrasound guided transbronchial fine needle aspiration: a French Department of Pathology's 4-year experience.

BACKGROUND: Endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA) is an accurate outpatient procedure used to explore mediastinal lymph nodes for lung cancer staging and unexplained mediastinal masses. AIMS AND METHODS: A retrospective study was conducted over four years on EBUS-TBNA sampled lymph nodes investigated for the staging of lung cancer or unexplained mediastinal lymphadenopathies, first using the conventional method (CM) and then a liquid based cytology (LBC). RESULTS: Of the 628 specimens (355 patients) collected, the overall rate of adequacy was 88% and the diagnosis of malignancy was achieved in 43% of cases. The inadequate rate was 6% with LBC and 21% with CM. A paraffin cytoblock was available in 80% with LBC and 62% with CM. Of the 628 aspirates, 270 (43%) were categorised as negative for malignancy including 26 cases consistent with sarcoidosis, 272 (43%) as malignant, 9 (1.4%) as suspicious for non-small-cell carcinoma and 77 as inadequate samples (12%). Of the 272 cases diagnosed as malignant, 87 (32%) were classified as non-small-cell carcinoma, 106 (39%) as adenocarcinoma, 48 (18%) as squamous cell carcinoma and 20 (7%) as small cell carcinoma. Five lymphomas, four metastatic melanomas and two carcinoids were also diagnosed. CONCLUSIONS: EBUS-TBNA is a reliable method for the staging of lung cancer and for unexplained mediastinal mass exploration. The LBC has a lower rate of inadequate samples, a better yield of cytoblock for immunohistochemistry and a dramatically reduced time requirement for interpretation as compared to CM.

Endoscopic management of idiopathic tracheal stenosis.

BACKGROUND: Idiopathic tracheal stenosis (ITS) is a rare condition representing a difficult therapeutic challenge. Endoscopic management is a therapeutic option but long-term results are not established. The aim of this retrospective multicenter study was to analyze long-term outcome after endoscopic management of ITS. METHODS: Nine institutions involved in interventional bronchoscopy were contacted and asked to identify ITS endoscopically treated. A standard form was used to report the main characteristics and long-term outcome after endoscopic management. RESULTS: Twenty-three patients, 96% women, aged 45±16 years, were endoscopically treated for ITS. Time between first symptoms and diagnosis was 19±18 months. Bronchoscopy showed a weblike (61%) or complex (39%) stenosis, located in the upper part of the trachea, mainly in the cricoid area. Endoscopic treatment included mechanical dilation only (52%) or associated with laser or electrocoagulation (30%) and stent placement (18%). All procedures were efficient. The follow-up after endoscopic management was 41±34 months. The ITS recurrence occurred in 30% at 6 months, 59% at 2 years, and 87% at 5 years, with a delay of 14±16 months. The treatment of recurrence (n=13) included endoscopic management in 12 cases. CONCLUSIONS: Endoscopic management of ITS provides a safe and efficient therapeutic option but late recurrences are frequent and require long-term follow-up.