Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.

A Multicentre Italian Study on the Psychological Impact of an Inconclusive Cystic Fibrosis Diagnosis after Positive Neonatal Screening.

BACKGROUND: An inconclusive diagnosis of cystic fibrosis (CF) after positive newborn screening (NBS) may cause parental distress. We compared the psychological impact of CF transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID), and clear CF diagnosis, on parents. METHODS: The participants were administered the Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, and the Italian version of the Impact of Event Scale-Revised as quantitative tools and semi-structured interviews as qualitative tools. Parental experience, child representation, relationships, future information, and perception of health status were investigated. Interviews were recorded and transcribed verbatim maintaining anonymity. RESULTS: Thirty-two families were enrolled: sixteen with CF and CRMS/CFSPID, respectively. Anxiety and depression values were high in both groups, as were the measurement of traumatic impact subscales: avoidance, intrusiveness, and hyperarousal. The children's health was evaluated by respective parents as being nearly healthy. CONCLUSIONS: Our results highlight negative psychological impacts, including emotional and affective representations, on parents of children with inconclusive CF diagnosis compared with those with clear diagnosis.