A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations.

BACKGROUND: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. PATIENTS AND METHODS: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. RESULTS: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. CONCLUSIONS: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

Implementation of the INTERGROWTH-21st Project in Italy.

Turin, Italy, was one of the two European sites for the INTERGROWTH-21(st) Project. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two obstetric hospitals that together account for 79% of the city's approximately 12,000 births per year. Women were recruited for the Fetal Growth Longitudinal Study (FGLS) from ten antenatal clinics serving the city's largest obstetric hospital, Azienda Ospedaliera OIRM-S. Anna. Special activities to encourage participation and raise awareness of the project in this population included obtaining an endorsement from the coordinator of the city's antenatal care service, and disseminating information about the project to women through posters and leaflets in antenatal clinics. One of the major challenges at this site was the low recruitment rate in the early phase of FGLS because of the high prevalence of smoking and of women >35 years old in the population. The addition of six extra recruiting clinics served to increase the pool of potentially eligible women who could be screened and led to a marked improvement in the recruitment rate.

Is breastfeeding duration influenced by maternal attitude and knowledge? A longitudinal study during the first year of life.

OBJECTIVE: To discuss the duration and types of breastfeeding and to identify the factors associated with the early introduction of formula milk. MATERIALS AND METHODS: This longitudinal study was conducted in the largest birthing centre of Turin. 562 mother-infant pairs were selected randomly and enrolled from among all the births that occurred in our Hospital from January to December 2009. Data was collected by means of a questionnaire filled out by the researcher during a face-to-face interview at mother's bed side during her hospital stay. This questionnaire included data regarding maternal socio-demographic, biomedical and hospital-related characteristics and some questions regarding family support, maternal attitude and current knowledge on breastfeeding. Mothers were interviewed by telephone at 1, 3, 6 and 12 months postpartum using the 24-h recall technique and definitions recommended by the WHO to investigate the type of breastfeeding adopted. RESULTS: At the age of 6 months only 8.9% of the infants involved were still exclusively breastfed and 44.3% had discontinued breastfeeding. By the age of 12 months 25.3% of infants were still receiving some breast milk. The main factors that had a negative impact on the duration of breastfeeding included maternal smoking habits, early pacifier introduction and the maternal infant feeding attitude. CONCLUSIONS: The rate of initiation and overall duration of breastfeeding reached the WHO objectives, but exclusive breastfeeding duration has still not reached satisfactory levels at 6 months. Given that the maternal infant feeding attitude is the only factor independently related to breastfeeding duration for the whole first year of life, reliable measures of maternal attitude could be used as a first step in targeting and assessing interventions that promote and sustain breastfeeding.

Benign transient blueberry muffin baby.

In this case-report a case of severe fetal anemia of unknown origin is presented. Diagnosis of fetal anemia was made at 24 weeks of gestational age, when fetal ascites was identified. Doppler sonography of medium cerebral artery showed a high systolic speed velocity (ACM-PSV), of 65 cm/s (>1.55 MoM). This value predicts a severe fetal anemia. Funicolocentesis confirmed hyporegenerative anemia, low reticulocytosis and low erythroblastosis. A fetal transfusion was performed. At birth anemia was still present and the baby presented blueberry muffin and liver erythropoietic foci. The blueberry muffin morphology presents as non-blanching, blue-red macules or firm, dome-shaped papules (2-8 mm in diameter). The eruption is often generalized but favors the trunk, head, and neck. Infectious (Toxoplasmosis, Cytomegalovirus, Rubella, Herpes, Parvo, Coxackievirus, Ebstein Barr, Syphilis), hematologic (sferocytosis, alloimmunization, foeto-maternal transfusion), metabolic, neoplastic (congenital leukemia, neuroblastome, congenital rhabdomyosarcome) and systemic (histiocytosis, lupus) pathologies indicated until now as possible disease causes were excluded. In the first day of life the neonate received a RBC transfusion for anemia (Hb=5.1 g/dL; Hct 15,7% at birth), followed within 48-72 hours by rapid disappearance of the rash, that wasn't then histologically examined. During two weeks of hospitalization reticulocytes raised spontaneously from 0.8% to 3.17%. Until two years of age the auxologic and clinical course was regular and the child is now in good health conditions. Due to the absence of systematic disease and the complete regression, no exact diagnosis and prognosis could be established in this case.

[Neonatal arteriovenous thrombosis: report of a case]. / Trombosi artero-venosa ad insorgenza prenatale: presentazione di un caso.

UNLABELLED: Limb vascular thrombosis is a severe, rare entity, often needing invasive surgery and sometimes leading to loss of function. An infant with in utero arteiro-venous thrombosis is reported. CASE REPORT: The baby, a female infant, was born at 34 weeks from a mother affected by gestational diabetes. She was referred to Neonatal Care Unit because of mild respiratory distress syndrome. She had no malformations. Spontaneous acute ischemia of right upper limb was noticed soon after admission: the limb appeared pale, cold, atonic and areflexic; no signs were noticed on it. Axillary artery and vein thromboses were soon confirmed by ultrasonography and arteriography. Intravenous administration of recombinant tissue plasminogen activator was carried on for 36 hours and followed by heparin and antithrombin III administration. Partial revascularization was obtained after a few hours: at the beginning of the treatment the limb became cyanotic, then edematous and finally the normal colour appeared everywhere but in the hand, was it became visible after a few days, when edema was reabsorbed. No recurrence of thrombosis occurred with heparin prophylaxis. Pain was treated with analgesic therapy, and motor impairment required physiotherapy. The doppler ultrasonographies which were performed subsequently confirmed a complete revascularization of axillary artery and vein. Coagulation and metabolic parameters (clotting tests, protein C, protein S, prothrombin, aminoacids) were studied but disorders predisposing to thrombosis were not found both in the patient and in her parents. CONCLUSION: Early identification of limb vascular thrombosis through external symptoms is very important, as it can avoid invasive surgical procedures.