Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat-and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort (p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation (p < 0.001) whereas no differences were observed with regard to deaths (p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes

Anabolic Deficiencies in Heart Failure: Ready for Prime Time?

“Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment. The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF. Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF. There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy.

Hormonal Replacement Therapy in Heart Failure: Focus on Growth Hormone and Testosterone

A growing body of evidence led to the hypothesis that heart failure (HF) could be considered a multiple hormone deficiency syndrome. Deficiencies in the main anabolic axes cannot be considered as mere epiphenomena, are very common in HF, and are clearly associated with poor cardiovascular performance and outcomes. Growth hormone deficiency and testosterone deficiency play a pivotal role and the replacement treatment is an innovative therapy that should be considered. This article appraises the current evidence regarding growth hormone and testosterone deficiencies in HF and reviews novel findings about the treatment of these conditions in HF

Biomarkers and Imaging: Complementary or Subtractive?

Heart failure is a life-threatening disease. Its prevalence is characterized by a slow, steady increase, with unacceptable high mortality. Slowing disease progression is imperative. One of the most active field is the development of novel biomarkers. Biomarkers are used in routine clinical care for diagnosis, monitoring (response to treatment), and risk stratification of patients with heart failure. In this review, we consider in 2 different sections: blood-derived and imaging biomarkers. Finally, we analyze the effect of combining these 2 categories of biomarkers available in heart failure, aiming at understanding whether their role is complementary or subtractive

DiGeorge-like syndrome in a child with a 3p12.3 deletion involving miRNA-4273 born to a diabetic mother

INTRODUCTION: Chromosome 22q11.2 deletion is the most commonly chromosomal alteration associated with DiGeorge syndrome (DGS). However, 22q11.2 deletion is not the only underlying cause of DGS. Recently it has been reported that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and the Bmp-signalling. OBJECTIVE: To describe the immunological and molecular phenotype of a child with DGS-like syndrome born to a diabetic mother. METHODS: Cytogenetic and molecular analysis includes fluorescent in situ hybridization (FISH), Array-CGH and TBX1 sequencing. Lymphocyte subpopulations were studied by flow-cytometry and PBMC proliferation by standard method. RESULTS: a 6-year-old Caucasian male was admitted for thymic aplasia, recurrent airway infections, hypoparathyroidism, renal agenesis, patent oval foramen, septum pellucidum cyst, language delay and dysmorphisms. The immunological evaluation revealed normal serum Ig levels. The immunophenotype revealed a reduction of CD3+ (373cell/mm3), CD4+ (163cells/mm3), CD8+ (388cells/mm3), CD3+CD4+CD45RA (47cells/mm3), CD3+CD4+CD45RO (116cells/mm3) cells. B-lymphocytes were increased (1352cells/mm3), while CD56+ were normal. The proliferative response to PHA and Pockweed was decreased, corresponding to the 45% and 39% of the control, respectively. FISH analysis and TBX1 sequencing were negative. Array CGH revealed a 371Kb-interstitial deletion at 3p12.3 involving the ZNF717, MiRNA-1243 and 4273 genes. Among the MiRNA-4273 predicted target-genes, we found Bone Morphogenetic protein-3 (BMP-3), involved in several steps of embryogenesis, as in kidney and lung organogenesis. CONCLUSIONS: We report on a novel association between a DG-like phenotype and a 3p12.3 chromosomal deletion in an infant born to a diabetic mother, although the causal relationship remains to be proved

Gamma chain is prominently overexpressed in B-pre acute lymphoblastic leukemia cells

INTRODUCTION: The gamma-chain (gc) is a transducing element shared between several cytokine receptors, that plays a prominent role in immunological functions and cell survival. It is directly involved in the regulation of self-sufficient growth and cell cycle progression in continuous human malignant hematopoietic cell lines, in a concentration dependent manner. OBJECTIVE: To evaluate the role of gc in the biology of different types of leukemia, through the analysis of gc-expression profile and gc-signaling in different leukemic cells. METHODS: Leukemic cells were obtained from the bone marrow of 39 newly diagnosed patients with CML, AML, B-pre ALL and T-ALL and healthy controls. Total RNA was extracted and IL2RG, D-type cyclins, BCL-XL and BECLIN-1expression levels were evaluated through Real-Time PCR. The amount of BECLIN-1 protein was evaluated through western blot, using the specific primary antibody. RESULTS: IL2RG expression was increased, as compared to controls, in ALL cells and, in particular, in B-pre ALL (2.55 fold increase vs 1.57 in T-ALL). A positive correlation between IL2RG and cyclins D2 (R = 0.82) and D3 (R = 0.76) expression levels was found. BCL-XL expression was 57% than controls, while BECLIN-1 expression was 4.73-times higher than controls, suggesting the involvement of autophagy in gc-induced cell survival. CONCLUSIONS: The gc is prominently over-expressed in B-pre ALL, with a direct correlation with D-type cyclins. The up-regulation of gc also associates with increased BECLIN-1 expression, which is a potent mediator of autophagy

Metabolic Syndrome in Heart Failure: Friend or Foe?

The interplay between metabolic syndrome (MetS) and heart failure (HF) is intricate. Population studies show that MetS confers an increased risk to develop HF and this effect is mediated by insulin resistance (IR). However, obesity, a key component in MetS and common partner of IR, is protective in patients with established HF, although IR confers an increased risk of dying by HF. Such phenomenon, known as "obesity paradox," accounts for the complexity of the HF-MetS relationship. Because IR impacts more on outcomes than MetS itself, the former may be considered the actual target for MetS in HF patients

Chronic mucocutaneous candidiasis, recurrent herpetic infections and suppurative eyelid infections in a patient carrying a novel gain-of-function mutation in the STAT1 DNA-binding domain

Chronic mucocutaneous candidiasis (CMCC) is characterized by noninvasive persistent Candida infections. Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) cause impaired STAT1 dephosphorylation, diminished IL-17-producing T-cells, and CMCC. We report on a 17-year-old boy with CMCC. At 7 years of age he developed mucocutaneous candidiasis. At 8 years he suffered from severe varicella infection and since 11 he experienced recurrent herpetic infections involving genitals and limbs, recurrent abscesses and suppurative eyelid infections. Familial history was negative. The physical examination revealed oral thrush, onichomycosis, suppurative eyelid infection (figure), furunculosis and parodontitis. Azole-sensitive Candida Albicans grew from oral lesions, nails and esophageal mucosa cultures. Prophylactic treatment with fluconazole resulted in a decrease of frequency and severity of fungal infections. Laboratory evaluation revealed normal white blood cell, T- and B-lymphocyte counts, T-lymphocyte proliferation, Ig and IgG subclasses serum levels and responses to vaccines. HIV serology was negative and IgE levels were persistently elevated (684 KU/L). Transitional (8.2%), mature (79.8%) and memory (12%) B cell levels were normal. Memory B cells mostly included IgM and only few switched cells (88 and 12%, respectively). CD4 and CD8 naïve and memory T cells were normal. IL-17-producing T-cell numbers were 0%. Toll like receptor stimulation resulted in high levels of IL-10, IL1 beta, TNF alpha, IFN-gamma, IL-6 and IL-8. Full-length sequencing of STAT1 genomic DNA identified a T387A heterozygous mutations in the DNA-binding domain, not identified in the unaffected parents. This mutation has not been previously reported