Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study.

The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe pulmonary hypertension and extensive pulmonary fibrosis and were treated with parenteral prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (-)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher DLCO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03-1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10-0.70); p < 0.01). Gas exchange was not adversely affected by parenteral prostacyclin therapy. In the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis treated with pulmonary arterial hypertension-specific therapy, AI is independently associated with increased transplant-free survival. Pulmonary hypertension/pulmonary fibrosis associated with AI should be considered in future clinical trials of pulmonary arterial hypertension-specific therapy in Group 3 pulmonary hypertension.

Emergence of Bruton's tyrosine kinase-negative Hodgkin lymphoma during ibrutinib treatment of chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a chronic B-cell lympho-proliferative disorder in which lymphomatous transformations occur in 5%-15% of patients. Histologically these cases resemble diffuse large B-cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67-year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers. Bone marrow trephine, and lymph node biopsy revealed classical HL with negative immuno-histochemistry for Btk in HL cells, on a backdrop of CLL. The patient commenced treatment with Adriamycin, Vinblastine and Dacarbazine (AVD), which resulted in an excellent response. Hodgkin transformation of CLL is rare with a single retrospective study of 4121 CLL patients reporting only 18 cases. Btk expression in HL cells is recently recognised in classical HL; however, the majority of HLs are Btk negative. Given that Btk inhibitors have recently been shown to induce genomic instability in B cells, in the context of their widespread use, such emerging cases are increasingly relevant.

Interleukin-11 levels in healthy and thrombocytopenic neonates.

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response.