Venetoclax: Bcl-2 inhibition for the treatment of chronic lymphocytic leukemia.

Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.

Predictive outcome indexes in neonatal Congenital Diaphragmatic Hernia.

OBJECTIVE: We examined the reliability of the main prenatal and postnatal prognosis-related indexes that can be used to evaluate congenital diaphragmatic hernia (CDH) outcome. METHODS: Seventy-seven neonates with CDH were analyzed according to CDH prognosis-related factors, divided into prenatal findings, postnatal clinical values and postnatal predictive outcome scores applied at birth and within the first 12-24 h. The data are compared between two groups: survivors and non-survivors. RESULTS: During prenatal age, major associated anomalies, intrathoracic stomach, diagnosis prior to 25 weeks of gestational age and lung-to-head ratio < 0.6 were statistically significant, demonstrating their greater incidence in non-survivors. The majority of postnatal values at PICU admission were found to be reliable in identifying the CDH outcome: paO2/FiO2, oxygenation index, alveolar-arterial-O2 gradient, arterial-alveolar-O2 tension ratio, pH, mean blood pressure, body temperature. All the postnatal predictive outcome scores (Apgar 1' and 5', CDH-Study-Group equation, Score for Neonatal-Acute-Physiology II, SNAP-Perinatal-Extension II, Pediatric Risk of Mortality III and Wilford-Hall/Santa-Rosa formula) were statistically significant with more favorable values for prognosis in the survivors group. CONCLUSION: The chances of predicting CDH outcome are fairly high. During prenatal age, only a few findings may be obtained. Conversely, many postnatal indexes and scores can reliably predict such outcome.

Rhabdomyolysis and respiratory failure: rare presentation of carnitine palmityl-transferase II deficiency.

Carnitine palmityl-transferase (CPT) II deficiency is a rare disorder of the fatty acid beta-oxidation cycle. CPT II deficiency can be associated with rhabdomyolysis in particular conditions that increase the requirement for fatty acid oxidation, such as low-carbohydrate and high-fat diet, fasting, exposure to excessive cold, lack of sleep and prolonged exercise. The best known CPT II deficiency is the muscular form with episodic muscle necrosis and paroxysmal myoglobinuria after prolonged exercise. We report a case of a four-year-old male child, who, after one day of hyperthermia and fasting, developed a massive rhabdomyolysis beginning with acute respiratory failure and later complicated by acute renal failure. Appropriate management in Pediatric Intensive Care Unit (PICU) (mechanical ventilatory support, fluid supply combined with mannitol and bicarbonate infusions, administration of acetaminophen and antibiotics, and continuous venovenous haemofiltration) brought about complete resolution with an excellent outcome. Biochemical investigation of muscle biopsy and genetic analysis showed a deficiency of CPT II. The onset of CPT II deficiency with respiratory failure is extremely rare, but a correct and early diagnosis of rhabdomyolysis is the key to successful treatment. A metabolic myopathy such as CPT II deficiency should be suspected in children affected by rhabdomyolysis if trauma, crash, infections, drugs or extreme exertion can be excluded.

Gastric perforation in a newborn.

Gastric perforation in neonates is an uncommon condition. In most cases, it is attributed to peptic ulceration and/or hemorrhagic gastritis. The high mortality rate in such patients can be improved by early diagnosis and prompt resuscitation, followed by surgery. We report a full-term female newborn, who developed a gastric perforation in the first day of life. The possible aetiology and the perioperative management are discussed.

[Problems in anesthesia in pulmonary cystic adenomatosis]. / Problemi di anestesia nell'adenomatosi cistica polmonare.

Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare disease. It is about an abnormal proliferation of mesenchymal elements and failure of maturation of bronchiolar structures, characterized by the replacement of normal pulmonary tissue with "cysts" in variable size and number. These lesions communicate with the tracheobronchial tree. During fetal period hydrops and polyhydramnios can be associated with CCAM. A cystic adenomatoid malformation can be detected by antenatal ultrasound, and, at the birth, it is confirmed by chest radiography. From January 1990 to December 1998, 24 cases with CCAM came to our observation; 16 of these patients underwent surgery and 14 have come to a complete recovery. The newborns, with CCAM, can show early acute respiratory distress for rapid expansion of the cysts leading to compression of normal lung and mediastinal shift. Conventional mechanical ventilation may cause further expansion of the involved lobe with a ball-valve effect: this take a clinical deterioration. Perioperative ventilatory management with high frequency oscillation (HFO) is useful to stabilize and to improve arterial blood gases of this patients. At the moment, thanks to the early prenatal sonographic diagnosis, it is possible, and strongly advisable, after adequate serial checkings during the pregnancy, to refer CCAM cases to a tertiary centre that is properly equipped, where a poly-specialist team consisting of obstetrician, neonatologist, pediatric anesthetist and pediatric surgeon, will be able to plan and arrange in the best treatment necessary for the newborn.