Novel Therapeutic Agents for Rare Diseases of Calcium and Phosphate Metabolism.

The last decade has been revolutionary regarding the management of rare bone diseases caused by impaired calcium and phosphate metabolism. Elucidation of the underlying genetic basis and pathophysiologic alterations has been the determinant factor for the development of new, disease-specific treatment agents. The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) possesses a critical role in the pathogenesis of various hypophosphatemic disorders. Among them, the genetic disorder of X-linked hypophosphatemia and the acquired syndrome of tumor-induced osteomalacia, although very rare, have attracted the scientific community's attention towards designing an FGF23-inhibitor as a potential specific therapy. The monoclonal antibody burosumab was approved for the treatment of children and adult patients with X-linked hypophosphatemia and recently for tumor-induced osteomalacia patients, demonstrating benefits regarding their symptoms, biochemical profile and bone mineralization status. Asfotase alfa is a hydroxyapatite-targeted recombinant alkaline phosphatase, an enzymatic replacement therapy, substituting the defective activity of tissue non-specific alkaline phosphatase, in patients suffering from hypophosphatasia. Promising data regarding its favorable effect on survival rate, bone quality, fracture healing, muscle strength, mobility, respiratory function, and general quality of life have led to the approval of the drug for the treatment of childhood-onset hypophosphatasia. Given the high costs of treatment for both agents and their limited clinical use until now, more data are needed to define patients' characteristics that make them ideal candidates for therapy. Long-term safety issues also need to be clarified.

Effects of Mediterranean diet on hospital length of stay, medical expenses, and mortality in elderly, hospitalized patients: A 2-year observational study.

OBJECTIVES: The Mediterranean diet (MedDiet) has been related to reduced overall mortality and improved disease outcome. The aim of this study was to estimate the effects of the MedDiet on hospital length of stay (LOS), financial cost, and mortality (from hospitalization up to 24 mo afterward) in hospitalized patients >65 y of age. METHODS: Participating in this observational study were 183 patients >65 y of age, who were urgently admitted for any cause to the Internal Medicine Department of Argolidos General Hospital. Hospital LOS and its financial cost, mortality (during hospitalization, 6 and 24 mo after discharge), physical activity, and medical and anthropometric data were recorded and correlated with the level of adherence to the MedDiet (MedDiet score). RESULTS: In multivariate analyses, hospital LOS decreased by 0.3 d for each unit increase of MedDiet score (P < 0.0001), 2.1 d for each 1 g/dL increase of albumin (P = 0.001) and increased 0.1 d for each day of previous admissions (P < 0.0001). Extended hospitalization (P < 0.0001) and its interaction with MedDiet score (P = 0.01) remained the significantly associated variables for financial cost. Mortality risk increased 3% per each year increase of age (hazard ratio [HR], 1.03; P = 0.02) and 6% for each previous admission (HR, 1.06; P = 0.04); whereas it decreased 13% per each unit increase of MedDiet score (HR, 0.87; P < 0.0001). CONCLUSION: Adoption of the MedDiet decreases duration of admission and long-term mortality in hospitalized patients >65 y of age, with parallel reduction of relevant financial costs.

Weil's disease with haemoptysis and acute respiratory distress syndrome.

A 35-year-old male patient reached the emergency department after an episode of massive haemoptysis a few hours ago. Fever and dyspnea were mentioned to be present the last 5 days. His medical history included only malaria, successfully treated 2 years ago. Clinical examination revealed high fever, jaundice, cyanosis, tachypnea and bilateral rales on pulmonary auscultation. Laboratory investigation showed high erythrocyte sedimentation rate and C reactive protein, leucocytosis, anaemia, mild thrombocytopaenia, renal impairment, hyperbilirubinaemia and abnormal liver function tests; arterial blood gas analysis showed respiratory alkalosis with severe hypoxia. Thoracic X-ray revealed bilateral pulmonary infiltrates, whereas abdominal and heart ultrasound detected hepatomegaly and small pericardial infusion, respectively. The diagnosis of leptospirosis along with acute respiratory distress syndrome was confirmed by positive IgM Leptospira antibodies. Empirical treatment with triple antibiotic therapy and corticosteroids was applied. The patient was discharged after 1 week, without any symptoms and with almost normal laboratory tests.

Evaluation of the New Centers for Disease Control and Prevention Ventilator-Associated Event Module and Criteria in Critically Ill Children in Greece.

OBJECTIVE To evaluate the new adult Centers for Disease Control and Prevention (CDC) ventilator-associated event (VAE) module in critically ill children and compare with the traditionally used CDC definition for ventilator-associated pneumonia (VAP). DESIGN Retrospective observational study of mechanically ventilated children in a pediatric intensive care unit in Greece January 1-December 31, 2011. METHODS Assessment of new adult CDC VAE module including 3 definition tiers: ventilator-associated condition (VAC), infection-related VAC, and possible/probable ventilator-associated pneumonia (VAE-VAP); comparison with traditional CDC criteria for clinically defined pneumonia in mechanically ventilated children (PNEU-VAP). We recorded Pediatric Risk of Mortality score at admission (PRISM III), number of ventilator-days, and outcome. RESULTS Among 119 patients with mechanical ventilation (median [range] number of ventilator-days, 7 [1-183]), 19 patients experienced VAC. Criteria for VAE-VAP were fulfilled in 12 of 19 patients with VAC (63%). Children with either VAC or VAE-VAP were on ventilation more days than patients without these conditions (16.5 vs 5 d, P=.0006 and 18 vs 5 d, P<.001, respectively), whereas PRISM-III score was similar between them. Mortality was significant higher in patients with new VAE-VAP definition (50%), but not in patients with VAC (31.6%), than the patients without new VAE-VAP (14%, P=.007) or VAC (15%, P=.1), respectively. No significant association was found between PNEU-VAP and death. Incidences of PNEU-VAP and VAE-VAP were similar, but the agreement was poor. CONCLUSIONS VAE-VAP and PNEU-VAP found similar prevalence in critically ill children but with poor agreement. However, excess of death was significantly associated only with VAE-VAP. Infect Control Hosp Epidemiol 2016:1-5.