Unilateral Absence of the Pulmonary Veins: An Unusual Diagnosis With Characteristic Imaging Findings

BACKGROUND: Congenital unilateral absence of the pulmonary vein (UCAPV) is a rare entity with characteristic clinical and imaging findings. Despite its congenital nature, the radiographic findings and symptoms of UCAPV may not be recognized at birth and patients may present in childhood or early adulthood with findings that may mimic other diagnoses. METHODS: The evolution of imaging findings in UCAPV is presented through two cases, one of which demonstrates the progression of findings over several years. The embryologic basis of this entity is reviewed and the clinical presentation and characteristic imaging findings including radiographs, nuclear scintigraphy, computed tomography, magnetic resonance imaging and cardiac catheterization are demonstrated. RESULTS: Characteristically, normal at birth, radiographs demonstrate the gradual development of a small lung and ipsilateral pulmonary artery over time. In addition to unilateral absence of the pulmonary veins on CT or MRI, a mediastinal soft tissue mass reflecting the development of mediastinal collaterals is a common finding and should be recognized as secondary to the absent ipsilateral pulmonary veins rather than as a primary process causing occlusion of the pulmonary veins. Scintigraphy will show absent perfusion to the affected lung. CONCLUSION: Awareness of the distinctive imaging findings in this unusual condition is critical to avoid misdiagnosis and to prevent the consequences of UCAPV which include pulmonary hypertension and extensive venous collaterals with or without hemoptysis, both of which may prevent definitive repair

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-risk Leukemias: A Report from the LEAP Consortium.

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence, Tier 1 or 2, recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance (VUS), performed ex vivo drug sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)