Background-The rate of failure of noninvasive mechanical ventilation (NIMV) in patients with chronic obstructive pulmonary disease (COPD) with acute respiratory insuYciency ranges from 5% to 40%. Most of the studies report an incidence of "late failure" (after >48 hours of NIMV) of about 10-20%. The recognition of this subset of patients is critical because prolonged application of NIMV may unduly delay the time of intubation. Methods-In this multicentre study the primary aims were to assess the rate of "late NIMV failure" and possible associated predictive factors; secondary aims of the study were evaluation of the best ventilatory strategy in this subset of patients and their outcomes in and out of hospital. The study was performed in two respiratory intensive care units (ICUs) on patients with COPD admitted with an episode of hypercapnic respiratory failure (mean (SD) pH 7.23 (0.07), PaCO 2 85.3 (15.8) mm Hg). Results-One hundred and thirty seven patients initially responded to NIMV in terms of objective (arterial blood gas tensions) and subjective improvement. After 8.4 (2.8) days of NIMV 31 patients (23%; 95% confidence interval (CI) 18 to 33) experienced a new episode of acute respiratory failure while still ventilated. The occurrence of "late NIMV failure" was significantly associated with functional limitations (ADL scale) before admission to the respiratory ICU, the presence of medical complications (particularly hyperglycaemia), and a lower pH on admission. Depending on their willingness or not to be intubated, the patients received invasive ventilation (n=19) or "more aggressive" (more hours/day) NIMV (n=12). Eleven (92%) of those in this latter subgroup died while in the respiratory ICU compared with 10 (53%) of the patients receiving invasive ventilation. The overall 90 day mortality was 21% and, after discharge from hospital, was similar in the "late NIMV failure" group and in patients who did not experience a second episode of acute respiratory failure.Conclusions-The chance of COPD patients with acute respiratory failure having a second episode of acute respiratory failure after an initial (first 48 hours) successful response to NIMV is about 20%. This event is more likely to occur in patients with more severe functional and clinical disease who have more complications at the time of admission to the ICU. These patients have a very poor inhospital prognosis, especially if NIMV is continued rather than prompt initiation of invasive ventilation.

Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide-based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRalpha, PDGFRbeta, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.

Rationale: The role of inspiratory effort still has to be determined as a potential predictor of noninvasive mechanical ventilation (NIV) failure in acute hypoxic de novo respiratory failure. Objectives: To explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients. Methods: Thirty consecutive patients with acute hypoxic de novo respiratory failure admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal change in esophageal pressure (DPes), tidal change in dynamic transpulmonary pressure (DPL), expiratory VT, and respiratory rate were recorded on admission and 2-4 to 12-24 hours after NIV start and were tested for correlation with outcomes. Measurements and Main Results: DPes and DPes/DPL ratio were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (n = 18) compared with those who needed endotracheal intubation (n = 12) (median [interquartile range], 11 [8-15] cm H 2 O vs. 31.5 [30-36] cm H 2 O; P , 0.0001), whereas other variables differed later. DPes was not related to other predictors of NIV failure at baseline. NIV-induced reduction in DPes of 10 cm H 2 O or more after 2 hours of treatment was strongly associated with avoidance of intubation and represented the most accurate predictor of treatment success (odds ratio, 15; 95% confidence interval, 2.8-110; P = 0.001 and area under the curve, 0.97; 95% confidence interval, 0.91-1; P , 0.0001). Conclusions: The magnitude of inspiratory effort relief as assessed by DPes variation within the first 2 hours of NIV was an early and accurate predictor of NIV outcome at 24 hours. Clinical trial registered with www.clinicaltrials.gov (NCT 03826797).

Background: Lung cancer initially manifesting as gastrointestinal (GI)-tract metastasis is exceedingly rare, representing a diagnostic challenge and a late-stage disease sign. The clinicopathologic characteristics of the largest series of lung carcinomas initially presenting with GI involvement were described, focusing on differential diagnosis and therapeutic options. Methods: Eighteen consecutive cases of lung cancer (11 surgical specimens and 7 biopsies) initially diagnosed on GI histologic samples were identified during routine pathologist practice. All cases were immunostained with thyroid transcription factor-1 (TTF-1), caudalrelated homeobox 2 (CDX2), and cytokeratins 7 (CK7) and 20 (CK20). Clinical and radiological data were obtained in all cases. Results: There were 10 women and 8 men with a mean age of 68.5 years. The small bowel was the most common GI involved site (12 cases), followed by the stomach (four) and large intestine (two). Only half of cases were correctly diagnosed on GI biopsies. Fourteen patients died shortly from disease (mean follow-up, 3 months); two are still alive with multiple metastases, and two patients with the GI tract as the unique site of metastasis underwent pulmonary lobectomy and chemotherapy and are alive without evidence of disease. At morphology, there were 10 large cell undifferentiated carcinomas and eight adenocarcinomas. All cases were immunostained for CK7 and 89% for TTF-1, whereas CK20 and CDX2 were completely negative. Conclusion: Lung cancer presenting as GI-tract metastasis is probably more frequent than expected, and pathologists should always keep in mind this possibility when dealing with undifferentiated GI carcinoma. Immunostaining with TTF-1, CDX2, CK7, and CK20 is helpful in highlighting lung primary. Although GI metastasis from lung cancer is associated with dismal outcomes, pulmonary resection coupled with chemotherapy might represent a therapeutic option in selected patients with a solitary GI-tract metastasis.

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