Development and validation of COVID-19 Radiological Risk Score (COVID-RRS): a multivariable radiological score to estimate the in-hospital mortality risk in COVID-19 patients.

OBJECTIVE: To develop and validate in-hospital mortality risk score comprising radiological aberrances in chest computed tomography (CT) performed on admission. PATIENTS AND METHODS: Single-center, longitudinal cohort study in adult patients admitted with Coronavirus Disease 2019 (COVID-19) to our ward. Patients were followed-up during hospitalization until discharge or death. Eligibility criteria for the study comprised positive real-time reverse transcription-polymerase chain reaction test (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ground-glass opacities in chest CT. In-hospital death was the outcome of interest. Radiological, laboratory, and clinical data were analyzed. Radiological determinants of mortality were used as variables in multivariate logistic regression analysis, and results were used to build a radiological risk score. RESULTS: 371 patients were enrolled in development and validation cohorts (181 and 190 respectively), with a total of 47 non-survivors. Univariate analysis data determined 12 predictive factors (nine risk and three protective). In multivariate analysis, we developed COVID-RRS (COVID-19 Radiological Risk Score) - a radiological score predicting in-hospital COVID-19 mortality risk comprising estimated lung involvement percentage, pleural effusion, and domination of consolidation-type changes in chest CT. Our score was superior in the prediction of COVID-19 mortality to the percentage of lung involvement alone, Chest Computed Tomography Severity Score (CTSS), and Total Severity Score (TSS) in both groups with AUC of 0.910 and 0.902, respectively (p <0.001). CONCLUSIONS: Additional imaging features independently contribute to COVID-19 mortality risk. Our model comprising lung involvement estimation, pleural effusion, and domination of consolidations performed significantly better than scores based on the extent of the changes alone. COVID-RRS is a simple, reliable, and ready-to-use tool for clinical practice.

Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency.

The role of genetic background in childhood-onset combined pituitary hormone deficiency (CPHD) has been extensively studied. The major contributors are the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes coding transcription factors implicated in pituitary organogenesis. The clinical consequences of mutations encompass impaired synthesis of a growth hormone (GH) and one or more concurrent pituitary hormones (i.e. LH, FSH, TSH, PRL). Manifestation of the disorder may vary due to various mutation impacts on the final gene products or an influence of environmental factors during pituitary organogenesis. We describe the clinical and molecular characteristics of two brothers aged 47 and 39 years presenting an uncommon manifestation of congenital hypopituitarism. Sequencing of the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes was performed to confirm the genetic origin of the disorder. A compound heterozygosity in the PROP1 gene has been identified for both probands. The first change represents a mutational hot spot (c.150delA, p.R53fsX164), whereas the second is a novel alteration (p.R112X) that leads to protein disruption. Based on precise genetic diagnosis, an in silico prediction of a p.R112X mutation on protein architecture was performed. The resulting clinical phenotype was surprisingly distinct compared to most patients with genetic alterations in PROP1 reported in the current literature. This may be caused by a residual activity of a newly identified p.R112X protein that preserves over 70 % of the homeodomain structure. This examination may confirm a key role of a DNA-binding homeodomain in maintaining PROP1 functionality and suggests a conceivable explanation of an unusual phenotype.

Circulating adipokines and organ involvement in patients with systemic sclerosis.

BACKGROUND: In recent years, mediators synthesized in the adipose tissue, the so-called adipokines, have been reported to play important roles in the pathogenesis of autoimmune rheumatic diseases. OBJECTIVE: To compare serum leptin, adiponectin and resistin levels in patients with systemic sclerosis (SSc) and healthy controls. To find possible relationship between serum levels of adipokines and organ involvement with focus on interstitial lung disease in SSc patients. PATIENTS AND METHODS: Lung involvement was assessed functionally (body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO) and six-minute walk test) and radiologically (using average disease extent on high resolution computed tomography (HRCT) of the lungs according to the percentage of interstitial changes) in 29 SSc patients. Quantitative sandwich ELISA was used to measure resistin, leptin and adiponectin concentrations in sera of patients and 30 healthy controls. RESULTS: We found no statistically significant differences in serum resistin, leptin and adiponectin levels between SSc patients and the controls. However, serum adiponectin concentrations were significantly lower in active than in inactive patients, they also correlated positively with vital capacity (VC) (p=0.04) and negatively with Valentini activity score (p=0.04). Serum resistin levels were significantly elevated in patients with digital ulcers (p=0.03) and serum concentrations of leptin were associated with the duration of SSc symptoms other than Raynaud's phenomenon (p<0.01) CONCLUSIONS: Serum adiponectin should be further investigated as a candidate for SSc activity marker and resistin may play a role in ulcer development in SSc patients.

Absence of the suprarenal segment of the inferior vena cava with a coexisting absence of the right brachiocephalic vein in a 22-year-old Caucasian male with arterial hypertension.

Congenital anomalies of the inferior vena cava (IVC) are rarely observed malformations of the venous system, occurring in 0.3% of otherwise healthy individuals, and in 0.6% to 2% of patients with coexisting cardiovascular defects. They are usually asymptomatic and recognised incidentally during imaging, operations or dissection studies. In this paper we report an extremely rare case of a 22-year-old Caucasian male, admitted for the purpose of excluding secondary causes of hypertension. During imaging of the abdomen and the thorax we found a complete lack of the suprarenal segment of the IVC, with a coexisting absence of the right brachiocephalic vein. We discuss the problem of congenital defects of the IVC and we review the relevant literature.

Gray matter volume in relation to cardio-vascular stiffness.

BACKGROUND: Hemodynamic disturbances are associated with aging as well as the chronic process of left ventricular and arterial stiffening. This process can influence gray matter volume and thereby contribute to brain atrophy. We performed a comprehensive assessment of left ventricular and arterial function as well as central hemodynamics. These data were correlated with gray matter volume (GMV) as evaluated by magnetic resonance imaging (MRI). METHODS: GMV and aortic stiffness were estimated using MRI. Left ventricular end-systolic elastance or stiffness (Ees), arterial elastance (Ea) and total arterial compliance (TAC) were determined by echocardiography. Central hemodynamics were assessed using pulse wave analysis. RESULTS: Seventy-five healthy subjects (42 women, 33 men, mean age of 58 years) were recruited. The clinical analyses showed that GMV correlates significantly and inversely with age (r=-0.37, P=0.001), end-systolic LV stiffness (r=-0.39, P=0.0009), augmentation pressure (r=-0.48, P<0.0001), arterial elastance (r=-0.27, P=0.02) and aortic stiffness (r=-0.23, P=0.04), as determined by aortic pulse wave velocity (aPWV). GMV correlated significantly with total arterial compliance (r=0.23, P=0.04). Stepwise forward multiple regression analysis revealed that 35% of variance (P<0.0001) in GMV is attributed to aPWV, Ees and AP. CONCLUSIONS: Left ventricular end-systolic stiffness, augmentation of central arterial pressure and aortic stiffness are associated independently and negatively with GMV. These associations suggested that brain atrophy is influenced by hemodynamic factors.

Cushing's syndrome in pregnancy: a case report and mini review of the literature.

Adrenal diseases in pregnant women are diagnosed relatively rarely. The main cause of hypercortisolemia during pregnancy is Cushing's syndrome related to adrenal adenoma. It is important to diagnose Cushing's syndrome in pregnant women because it can lead to significant maternal and foetal complications and morbidity. However, due to physiological endocrine changes and symptoms in pregnant women the diagnosis of this disorder can be a challenge. One current case describes a 38-year-old pregnant woman with hypertension, oedema and an adrenal tumour. At the beginning, Conn syndrome was suspected, but after careful analysis Cushing's syndrome (with an adenoma of the right adrenal gland) was diagnosed. After delivery and 5 weeks of pharmacological treatment the patient underwent right side adrenalectomy by laparoscopy.