Diffuse alveolar hemorrhage in children with interstitial lung disease: Determine etiologies!

OBJECTIVE: Diffuse alveolar hemorrhage (DAH) in children is a rare condition resulting from different underlying diseases. This study aimed at describing characteristics and diagnostic measures in children with ILD (children's interstitial lung disease, chILD) and DAH to improve the diagnostic approach by increasing clinician's awareness of diagnostic shortcomings. PATIENTS AND METHODS: A retrospective data analysis of patients with ILD and DAH treated in our own or collaborating centers between 01/07/1997 and 31/12/2020 was performed. Data on clinical courses and diagnostic measures were systematically retrieved as case-vignettes and investigated. To assess suitability of diagnostic software-algorithms, the Human Phenotype Ontology (HPO) was revised and expanded to optimize conditions of its associated tool the "Phenomizer." RESULTS: For 97 (74%) of 131 patients, etiology of pulmonary hemorrhage was clarified. For 34 patients (26%), no underlying condition was found (termed as idiopathic pulmonary hemorrhage, IPH). Based on laboratory findings or clinical phenotype/comorbidities, 20 of these patients were assigned to descriptive clusters: IPH associated with autoimmune features (9), eosinophilia (5), renal disease (3) or multiorgan involvement (3). For 14 patients, no further differentiation was possible. CONCLUSION: Complete and sometimes repeated diagnostics are essential for establishing the correct diagnosis in children with DAH. We suggest assignment of patients with IPH to descriptive clusters, which may also guide further research. Digital tools such as the Phenomizer/HPO are promising, but need to be extended to increase diagnostic accuracy.

Vaccinating in Pregnancy: Opportunities and Challenges.

The continuum of preconception, antenatal period, fourth trimester, and interconception period are a critical time for comprehensive care to advance maternal-child health and deliver family-centered care. Immunizations are a key component of this care delivery; however, there are intricacies around indications of vaccinations during this key period. Both active immunity to the individual receiving the vaccine as well as passive immunity passed to the fetus during pregnancy highlight the benefits of this care. Understanding the indications and benefits of vaccine administration during this continuum is critical for providers caring for individuals of reproductive age.

Primary Care Practice Redesign: Challenges in Improving Behavioral Health Care for a Vulnerable Patient Population.

This study examined a program focused on integrating mental health in a family medicine practice in an economically challenged urban setting. The program included using a behavioral health technology platform, a behavioral health collaborative composed of community mental health agencies, and a community health worker (CHW). Of the 202 patients screened, 196 were used for analysis; 56% were positive for anxiety, 38% had scores consistent with moderate to severe depression, and 34% were positive for post-traumatic stress disorder. There was a statistically significant difference in the diagnosis of depression when comparing the screened group to a control group. Only 27% of patients followed through with behavioral health referrals despite navigational assistance provided by a CHW and assured access to care through a community agency engaged with the Behavioral Health Alliance. Further qualitative analysis revealed that there were complex patient factors that affected patient decision making regarding follow-up with behavioral health care.

Tyrphostin AG490 reduces inflammation and fibrosis in neonatal obstructive nephropathy.

BACKGROUND: Congenital obstructive nephropathy is the main cause of end-stage renal disease in infants and children. Renal insufficiency is due to impaired growth and maturation in the developing kidney with obstruction. Congenital obstructive nephropathy leads to cytokine mediated inflammation and the development of interstitial fibrosis. The Janus kinase-2 (JAK-2) and Signal Transducer and Activator of Transcription'-3 (STAT3) are involved in cytokine production, inflammation, and interstitial fibrosis. METHODS: We studied the role of JAK2/STAT3 in a model of congenital obstructive nephropathy using unilateral ureteral obstruction (UUO) in neonatal mice at the second day of life. Cytokine production, inflammation, and interstitial fibrosis were analyzed in obstructed and sham operated kidneys of neonatal mice treated with or without JAK2/STAT3 inhibitor Tyrphostin AG490. To mimic obstruction and distension, proximal tubular cells were stretched in vitro. RESULTS: We show that STAT3 is highly activated in the developing kidney with obstruction and in proximal tubular cells following stretch. JAK2/STAT3 activation mediates cytokine release and leukocyte recruitment into neonatal kidneys after UUO. Pharmacological blockade of JAK2/STAT3 by Tyrphostin AG490 reduced inflammation, tubular apoptosis, and interstitial fibrosis. JAK2/STAT3 blockade decreased pro-inflammatory and profibrotic mediators in tubular cells. CONCLUSION: Our findings provide evidence that JAK2/STAT3 mediates inflammation and fibrosis in the developing kidney with obstruction. Blocking JAK2/STAT3 may prove beneficial in congenital obstructive nephropathy in children.