Inspiratory Effort and Respiratory Mechanics in Patients with Acute Exacerbation of Idiopathic Pulmonary fibrosis: A Preliminary Matched Control Study.

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.

Association between respiratory distress time and invasive mechanical ventilation in COVID-19 patients: A multicentre regional cohort study.

AIM: To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. MATERIALS AND METHODS: An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO2/FiO2 ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. MEASUREMENTS AND MAIN RESULTS: We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p < 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p < 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. DISCUSSION: Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting.

INTRODUCTION: Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified. METHODS: An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. RESULTS: Chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC = 0.92 p < 0.0001). CONCLUSIONS: Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome.

Breast granulomatosis with polyangiitis mimicking breast cancer.

Inflammatory lesions of the breast encompass primary reactive processes and local manifestation of systemic diseases. They are very rare and they are generally treated without resort to biopsy. Nevertheless they could be clinically challenge mimicking malignant process and needing surgery to reach a correct diagnosis. Here we describe a rare case of breast granulomatosis with polyangiitis, which presented with radiological and clinical alarming features that immediately raised the suspicious of malignancy leading to breast-conserving surgery.

[Differentiated thyroid cancers. Thyroid recurrence after limited surgery]. / Cancers thyroïdiens différenciés. Récidives thyroïdiennes après chirurgie limitée.

Twenty-eight patients with differentiated thyroid cancer presented with local relapse 6 months to 24 years (mean: 7 years) after limited surgery. The tumour was clinically undetectable in 7 cases. Among 22 patients reoperated upon, one died post-operatively, 17.8% had permanent recurrent nerve paralysis and 14.3%, permanent hypoparathyroidism. Metastases were discovered in 15 patients (53.8%), 4 1/2 years on average after the relapse; they resulted in death within less than 2 years in 11 (39.2%) and the survival rate was moderate (26.7%). The mean survival of the 12 patients now in remission is 7 years since the relapse and 13 years since the initial tumour.

[Clinical and functional sequelae of bronchiolitis]. / Sequele cliniche e funzionali della bronchiolite.

The authors carried out a follow-up on twenty-five children, affected with bronchiolitis in the early years of life, at seven years of age, in order to evaluate their clinical status and pulmonary function. Their parents were questioned about diseases of the small airways following to acute bronchiolitis. PRIST and RAST were effected in fourteen children; an evaluation of the pulmonary function with spirometry, flow-volume curve and body-plethysmography was done in every child. Then the flow-volume curve was repeated after bronchial provocation test with exercise (free running). Abnormalities of the pulmonary function at resting significant for small airways' obstruction were observed. A great number of children with bronchial hyperreactivity (60%) was observed after bronchial provocation test with exercise, particularly in those with genetic predisposition; 6/14 (43%) showed sensitization to many inhalant allergens, without correlation with genetic predisposition, clinical sequences and bronchial hyperreactivity.

Bronchial selective ventilation in a wide tracheocutaneous fistula.

We present the treatment and management of a wide tracheocutaneous fistula after tracheotomy correlated with excessive cuff pressure in a 36-year-old woman with cerebral palsy since infancy in which persistent type II respiratory failure required continuous ventilatory support. We discuss the surgical treatment adopted for the management of this particularly wide lesion. At the end of surgery, mechanical ventilation through a tracheal cannula was hindered by the reduced length of the residual trachea below the tracheotomy. The need to guarantee mechanical ventilation to the patient led to the implementation of a cuff securing system in the two main bronchi. We describe the approach that may be attempted under extreme conditions, when traditional ventilation methods cannot be applied for anatomical reasons.

PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract.

AIMS: To investigate the value of platelet-derived growth factor receptors (PDGFRs) by immunohistochemistry in discriminating KIT-negative gastrointestinal stromal tumours (GISTs) from other soft-tissue neoplasms of the digestive tract. METHODS AND RESULTS: One-hundred and sixty-seven primary gastrointestinal mesenchymal tumours (125 GISTs, 15 intra-abdominal desmoids, 12 leiomyomas, eight leiomyosarcomas, three schwannomas, two solitary fibrous tumours, and one case each of inflammatory pseudotumour and fibroid polyp) were reclassified based on morphology and on the immunohistochemical panel recommended by the National Institutes of Health consensus on GIST. All cases were then tested with antibodies specific for PDGFR alpha and beta. Of 125 GISTs, 117 were KIT-positive (93.6%) and eight KIT-negative (6.4%). All the KIT-positive GISTs were negative for both PDGFRs, while all the eight KIT-negative GISTs expressed PDGFR-alpha, with two of them also coexpressing PDGFR-beta. Among the 42 non-GIST tumours, only a small percentage (26.6%) of desmoids immunostained for PDGFR-alpha, two of them coexpressing PDGFR-beta. CONCLUSIONS: Immunostaining with PDGFR-alpha is a helpful marker in discriminating between KIT-negative GISTs and other gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for PDFGR-alpha, while none of the other gastrointestinal mesenchymal tumours analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These preliminary data demonstrate the suitability of commercially available antibodies to detect immunohistochemically the mutually exclusive expression of KIT and PDGFR-alpha previously reported in GISTs by molecular biological techniques. Since PDGFR exists in the form of a homodimer (alphaalpha, betabeta) or heterodimer (alphabeta) and two of the KIT-negative GISTs coexpressed both PDGFR isoforms, further investigations are required to elucidate the role of PDGFR-beta in GISTs.

Incidence and causes of non-invasive mechanical ventilation failure after initial success.

BACKGROUND: The rate of failure of non-invasive mechanical ventilation (NIMV) in patients with chronic obstructive pulmonary disease (COPD) with acute respiratory insufficiency 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 in-hospital prognosis, especially if NIMV is continued rather than prompt initiation of invasive ventilation.