Role of a Chest X-ray Severity Score in a Multivariable Predictive Model for Mortality in Patients with COVID-19: A Single-Center, Retrospective Study.

Predicting the mortality risk of patients with Coronavirus Disease 2019 (COVID-19) can be valuable in allocating limited medical resources in the setting of outbreaks. This study assessed the role of a chest X-ray (CXR) scoring system in a multivariable model in predicting the mortality of COVID-19 patients by performing a single-center, retrospective, observational study including consecutive patients admitted with a confirmed diagnosis of COVID-19 and an initial CXR. The CXR severity score was calculated by three radiologists with 12 to 15 years of experience in thoracic imaging, based on the extent of lung involvement and density of lung opacities. Logistic regression analysis was used to identify independent predictive factors for mortality to create a predictive model. A validation dataset was used to calculate its predictive value as the AUROC. A total of 628 patients (58.1% male) were included in this study. Age (p < 0.001), sepsis (p < 0.001), S/F ratio (p < 0.001), need for mechanical ventilation (p < 0.001), and the CXR severity score (p = 0.005) were found to be independent predictive factors for mortality. We used these variables to develop a predictive model with an AUROC of 0.926 (0.891, 0.962), which was significantly higher than that of the WHO COVID severity classification, 0.853 (0.798, 0.909) (one-tailed p-value = 0.028), showing that our model can accurately predict mortality of hospitalized COVID-19 patients.

Macrophage migration inhibitory factor mediates hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a devastating disease leading to progressive hypoxemia, right ventricular failure, and death. Hypoxia can play a pivotal role in PH etiology, inducing pulmonary vessel constriction and remodeling. These events lead to increased pulmonary vessel wall thickness, elevated vascular resistance and right ventricular hypertrophy. The current study examined the association of the inflammatory cytokine macrophage migration inhibitory factor (MIF) with chronic lung disease and its role in the development of hypoxia-induced PH. We found that plasma MIF in patients with primary PH or PH secondary to interstitial lung disease (ILD) was significantly higher than in the control group (P = 0.004 and 0.007, respectively). MIF involvement with hypoxia-induced fibroblast proliferation was examined in both a human cell-line and primary mouse cells from wild-type (mif⁺/⁺) and MIF-knockout (mif⁻/⁻) mice. In vitro, hypoxia-increased MIF mRNA, extracellular MIF protein accumulation and cell proliferation. Inhibition of MIF inflammatory activity reduced hypoxia-induced cell proliferation. However, hypoxia only increased proliferation of mif⁻/⁻ cells when they were supplemented with media from mif⁺/⁺ cells. This growth increase was suppressed by MIF inhibition. In vivo, chronic exposure of mice to a normobaric atmosphere of 10% oxygen increased lung tissue expression of mRNA encoding MIF and accumulation of MIF in plasma. Inhibition of the MIF inflammatory active site, during hypoxic exposure, significantly reduced pulmonary vascular remodeling, cardiac hypertrophy and right ventricular systolic pressure. The data suggest that MIF plays a critical role in hypoxia-induced PH, and its inhibition may be beneficial in preventing the development and progression of the disease.

Correlation of pulmonary hypertension severity with metrics of comorbid sleep-disordered breathing.

PURPOSE: We performed nocturnal polysomnography in patients with pulmonary hypertension (PH) of varying etiologies to determine the association of metrics describing sleep-disordered breathing (SDB) with measures of PH severity. METHODS: Consecutive patients referred for evaluation of dyspnea on exertion and elevated pulmonary arterial pressure >30 mmHg on echocardiography, who underwent right and left heart catheterization and polysomnography, were included. Patients were not pre-selected for symptoms of sleep-disordered breathing. RESULTS: Twenty-eight patients including 22 females and six males with a mean age of 55.2 ± 11.9 years were evaluated. Etiologies of PH were idiopathic (32%) and PH associated with other diseases (68%). Most were World Health Organization (WHO) Functional class II (39%) and III (39%). The group mean pulmonary arterial pressure (mPAP) was 40.9 ± 15.1 mmHg. Diurnal resting and exercise arterial oxygen saturations (SaO(2)) were 94.9 ± 3.7% and 88.3 ± 8.9%. The mean apnea-hypopnea index (AHI) was 11.4 ± 19.8/h; 50% of all patients had an AHI ≥ 5/h; 30.6 ± 36.0% of total sleep time was spent with SaO(2) < 90% (T90%); 66% of subjects with an AHI ≥ 5/h of sleep reported snoring, and 60% noted daytime somnolence; however, only 29% had an Epworth Sleepiness Scale ≥10. Right atrial pressure and mPAP were significantly correlated with AHI and T90%. The best predictive model relating PH severity to metrics of SDB was a highly significant association (p = 0.005) between mPAP and a linear combination of AHI and T90%. CONCLUSIONS: SDB comprised of obstructive apneas, hypopneas, and nocturnal hypoxemia is prevalent in PH and cannot be accurately predicted by sleep apnea signs and symptoms or diurnal rest and exercise SaO(2). The association of AHI and T90% with mPAP suggests a potential relationship between the pathophysiology of sleep-disordered breathing and PH.

Repeated phlebotomies improve and stabilise renal function in cyanotic nephropathy.

Patients over 10 years of age with cyanotic congenital heart disease (CCHD) risk developing significant glomerular proteinuria, a condition called cyanotic nephropathy. Even though the pathogenesis of glomerulopathy associated with CCHD is still unclear, a potential mechanism is hyperviscosity-induced decrease in peritubular capillary blood flow leading to an increase in glomerular capillary pressure, in turn resulting in proteinuria. Although angiotensin-converting enzyme (ACE) inhibitors have been traditionally used in the treatment of these patients with cyanotic nephropathy, they may, however, not be well tolerated. Here we present a case of an adult patient with CCHD who could not tolerate an ACE inhibitor but showed improvement and stabilisation of her renal function following treatment with repeated phlebotomies.