TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the ‘myopathic form’ of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients. The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency.

We assessed whether prolongation of nocturnal noninvasive ventilation (NIV) after recovery from acute hypercapnic respiratory failure (AHRF) in chronic obstructive pulmonary disease (COPD) patients with NIV could prevent subsequent relapse of AHRF.A randomised controlled trial was performed in 120 COPD patients without previous domiciliary ventilation, admitted for AHRF and treated with NIV. When the episode was resolved and patients tolerated unassisted breathing for 4 h, they were randomly allocated to receive three additional nights of NIV (n=61) or direct NIV discontinuation (n=59). The primary outcome was relapse of AHRF within 8 days after NIV discontinuation.Except for a shorter median (interquartile range) intermediate respiratory care unit (IRCU) stay in the direct discontinuation group (4 (2–6)versus5 (4–7) days, p=0.036), no differences were observed in relapse of AHRF after NIV discontinuation (10 (17%)versus8 (13%) for the direct discontinuation and nocturnal NIV groups, respectively, p=0.56), long-term ventilator dependence, hospital stay, and 6-month hospital readmission or survival.Prolongation of nocturnal NIV after recovery from an AHRF episode does not prevent subsequent relapse of AHRF in COPD patients without previous domiciliary ventilation, and results in longer IRCU stay. Consequently, NIV can be directly discontinued when the episode is resolved and patients tolerate unassisted breathing.

Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.

BACKGROUND: Noninvasive ventilation (NIV) titration may be difficult when dynamic airway obstruction episodes persist, even with high expiratory positive airway pressure (EPAP). We aimed to determine the usefulness of videolaryngoscopy during NIV for identifying mechanisms and sites of obstruction and for providing a guide for their resolution in difficult-to-titrate subjects. METHODS: When obstructions during NIV were present in the built-in software, EPAP was raised to 12 cm H ₂ O. If obstructions persisted, a polygraphy during NIV was performed; if the events occurred with effort, a videolaryngoscopy with nasal and oronasal masks in awake subjects was performed. RESULTS: In a population of 208 subjects in whom NIV was initiated, 13 were identified as difficult to titrate with persistent obstructions during NIV despite an EPAP of 12 cm H ₂ O. Videolaryngoscopy during NIV was able to identify the mechanism and the site of obstruction in all cases. The obstruction under oronasal mask ventilation was due to soft-palate (velum) collapse in 4 subjects, to epiglottic backward movement in 5 other subjects, and to tongue-base obstruction reducing the retroglossal space in 3 more. Videolaryngoscopy during NIV demonstrated improvement in 9 subjects (69%) upon changing to nasal mask and suggested a possible surgical approach in 2 (15%); in one of these 2 subjects, a successful uvulopalatopharyngoplasty was performed. CONCLUSIONS: The use of videolaryngoscopy during NIV in difficult-to-titrate patients may help to identify the sites and mechanisms of obstruction and in some cases may improve quality of ventilation.

Objective: To evaluate the effect of comorbidity as an independent prognostic factor in lung cancer. Method: Data on 2991 consecutive cases of lung cancer were collected prospectively from 19 Spanish hospitals between 1993 and 1997 by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). To evaluate the effect of comorbidity on survival, 1121 patients with non-small cell lung cancer (NSCLC) in pathological stage I who underwent complete resection were selected, excluding operative mortality. The presence of specific comorbidities at the time of thoracotomy was registered prospectively. Results: Cox regression analysis showed that tumour size (0–2, 2–4, 4–7, >7 cm) (HR 1.45 95% CI 1.08 to 1.95), 1.86 (95% CI 1.38 to 2.51), 2.84 (95% CI 1.98 to 4.08)), the presence of a previous tumour (HR 1.45 (95% CI 1.17 to 1.79)) and age (HR 1.02 (95% CI 1.01 to 1.03)) had a significant prognostic association with survival. This study excluded the presence of visceral pleural involvement or other comorbidities as independent variables. Conclusion: The presence of a previous tumour is an independent prognostic factor in pathological stage I NSCLC with complete resection, increasing the probability of death by 1.5 times at 5 years. It is independent of other comorbidities, TNM classification and age.