Telemonitoring-guided ambulatory fixed CPAP titration versus ambulatory APAP titration in moderate obstructive sleep apnea: A non-inferiority randomized controlled trial.

The present study aimed to evaluate whether titration of fixed continuous positive airway pressure at home using telemonitoring produces patient outcomes equal to auto-adjusting positive airway pressure titration at home for patients with moderate obstructive sleep apnea. Patients were randomized with a 1:1 allocation ratio to receive either auto-adjusting positive airway pressure titration based on the median of the 95th percentile pressure across seven nights or fixed continuous positive airway pressure titration based on a fixed calculated pressure and specific adaptations after telemonitoring of device data after 3 and 7 nights. The results of the ambulatory titration were evaluated with in-laboratory polysomnography after 2 weeks. We hypothesized that fixed continuous positive airway pressure titration would be non-inferior to auto-adjusting positive airway pressure titration in respect to continuous positive airway pressure adherence at a 3-month follow-up. A non-inferiority margin of -0.75 hr was prespecified. One-hundred and four patients were randomly allocated to fixed continuous positive airway pressure (n = 52) and auto-adjusting positive airway pressure (n = 52) titration. The mean difference and the 95% confidence intervals in continuous positive airway pressure adherence after 3 months between the two arms were 0.80 (-0.08, 1.69) hr. The non-inferiority hypothesis was confirmed as the lower one-sided 97.5% confidence interval for the mean difference was above the prespecified margin. Patients in the fixed continuous positive airway pressure titration arm were titrated at significantly lower pressure level and had a significantly lower amount of average leaks compared with auto-adjusting positive airway pressure-titrated patients, while there was no difference in residual obstructive apnea-hypopnea index on polysomnography. Telemonitoring enables ambulatory continuous positive airway pressure titration with fixed pressure that is non-inferior to ambulatory titration with auto-adjusting pressure in patients with moderate obstructive sleep apnea.

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Early lung ultrasound assessment for the prognosis of patients hospitalized for COVID-19 pneumonia. A pilot study.

OBJECTIVE: SARS CoV-2 is an epidemic viral infection that can cause mild to severe lung involvement. Newly apprehended knowledge on thoracic imaging abnormalities and the growing clinical experience on the evolution of this disease make the radiographic follow-up of hospitalized patients relevant. The value of consecutive bedside lung ultrasonography in the follow-up of hospitalized patients with SARS CoV-2 pneumonia and its correlation with other clinical and laboratory markers needs to be evaluated. METHODS: We assessed 39 patients [age: 64 y(60.1-68.7)] with confirmed SARS CoV-2 pneumonia. A total of 24 patients were hospitalized until the follow-up test, 9 were discharged early and 6 required a transfer to critical care unit. Two ultrasound scans of the lung were performed on day 1 and 4 of patients' hospitalization. Primary endpoint was the magnitude of association between a global lung ultrasound score (LUS) and clinical and laboratory markers. Secondary endpoint was the association between the evolution of LUS with the corresponded changes in clinical and laboratory outcomes during hospitalization period. RESULTS: LUS score on admission was higher among the deteriorating patients and significantly (P=0.038-0.0001) correlated (Spearman's rho) with the levels of C-reactive protein (0.58), lymphocytes (-0.33), SpO2 (-0.48) and oxygen supplementation (0.48) upon admission. The increase in LUS score between the two scans was significantly correlated (0.544, P=0.006) with longer hospital stay. CONCLUSION: Lung ultrasound assessment can be a useful as an imaging modality for SARS CoV-2 patients. Larger studies are needed to further investigate the predictive role of LUS in the duration and the outcome of the hospitalization of these patients.

Diaphragm plication for unilateral diaphragm paralysis: a case report and review of the literature.

Unilateral diaphragm paralysis is an often not recognised cause of dyspnoea. We present a patient with a unilateral phrenic nerve paralysis treated with diaphragmatic plication. Patient presented with life-style limiting dyspnoea and pulmonary function showed a decrease in FVC when lying down. Since there was no improvement after respiratory muscle training, plication of the hemidiaphragm was performed by a small thoracotomy. The patient improved with regard to respiratory complaints and lung function. Furthermore, we also demonstrate for the first time a significant improvement in exercise capacity with accompanying striking amelioration of quality of life. The patient is now in follow up up for more than 2 years and the impressive improvement in exercise capacity remains present. Surgical treatment of unilateral diaphragm paralysis has been described in case reports and in small series since 1985. Although comparison of the available data is difficult a diaphragm plication seems an effective and safe procedure for patients with symptomatic, acquired unilateral diaphragm paralysis. Improvement of dyspnoea is present in the majority of patients and we even observed an impressive amelioration in exercise capacity. Consequently, it seems appropriate to propose plication to patients with clear symptoms from the moment spontaneous recovery seems unlikely; yet, prospective randomised controlled studies are needed to prove this.

Late recurrent ovarian carcinoma metastatic to the thoracic wall.

Ovarian cancer is the second most common gynaecologic malignancy. Ovarian carcinomas typically metastasize to multiple sites via exfoliation, lymphatic spread or direct invasion. We present a rare case of a very late recurrence of ovarian carcinoma into the thoracic wall, heralded by thoracic pain in a patient otherwise disease-free for 23 years. This unusual and late presentation of an ovarian cancer metastasis underscores the need for continued awareness and attention to new symptoms in patients with ovarian cancer who show prolonged disease-free intervals.

Atrophy and hypertrophy signalling in the diaphragm of patients with COPD.

We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients. We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitin-proteasome pathway, nuclear factor (NF)-kappaB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD. Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased. The cross-sectional area of all fibre types was reduced in the COPD patients. In addition, MAFbx mRNA was higher in the diaphragm of COPD patients while Nedd4 mRNA decreased. Cytoplasmatic levels of inhibitor protein IkappaBalpha and IkappaBbeta were decreased in the COPD patients as was NF-kappaB p50 DNA-binding activity. MyoD mRNA and its nuclear protein content were decreased in the diaphragm of COPD patients and myogenin mRNA and protein levels remained unchanged. Myostatin mRNA was decreased but its protein levels in the nuclear and cytoplasmic fraction were significantly increased in the COPD patients. These data show that the ubiquitin-proteasome pathway, the NF-kappaB pathway and myostatin protein were up-regulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.