Purpose The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytoma and paragangliomas (PCC/PGL). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes. Methods The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were re-reviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence free survival (RFS) and disease specific survival (DSS). Results From 143 subjects, 106 tumors were PCC, and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (IQR:4.0-8.0) and median GAPP score was 3.0 (IQR:2.0-4.0). Interrater reliability was low-moderate for PASS (ICC:0.6082) and good for GAPP (ICC:0.7921). Older age (OR:0.969, p=0.0170) was associated with longer RFS. SDHB germline pathogenic variant (OR:8.205, p=0.0049), extra-adrenal tumor (OR:6.357, p&0.0001), Ki-67 index 1-3% (OR:4.810, p=0.0477), and higher GAPP score (OR:1.537, p=0.0047) were associated with shorter RFS. PASS score was not associated with RFS (p=0.1779). On Cox regression, a GAPP score in the moderately-differentiated range was significantly associated with disease recurrence (HR:3.367, p=0.0184) compared to well-differentiated score. Conclusion Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant inter-observer variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.

In this article, we analyze qualitative data from a purposeful sample of limited English proficiency (LEP) asthma health caregivers. We used ethnically concordant, semistructured, in-depth Spanish-language interviews and a follow-up focus group to explore issues related to communication during pediatric asthma encounters in medical settings. Inductive coding of Spanish transcripts by a bilingual research team was performed until thematic saturation was reached. Several key findings emerged. LEP caregivers encountered significant asthma burdens related to emotional stress, observed physical changes, and communication barriers. Language-discordant communication and the use of ad hoc interpreters were common. This finding is complex, and was influenced by perceptions of interpreter availability, delays in care, feelings of mistrust toward others, and individual emotional responses. Language-concordant education and suitable action plans were valued and desired. We discuss a revealing depiction of the LEP caregiver experience with asthma health communication and recommend areas for further inquiry.

Implementation of a community-based AEF with action plan administration can be beneficial for LEP caregivers and their children. QoL improvements to emotional wellbeing and activity limitations were observed, and lower rates of school absenteeism were reported. Caregiver ability to accurately identify medications was not enhanced.

Histone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.

Context Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. Objective The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1C (HA1C). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. Design A retrospective cohort study was performed (1999–2020). Wilcoxon rank-sum tests compared non-parametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HA1C. The median study duration was 54.2 months (IQR: 19.0–95.1). Setting Tertiary academic hospital. Patients 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR: 45–67) and 56.4% (N=203) were female. Main outcome measures The primary and secondary outcomes were weight and HA1C, respectively. Results On multivariable MEM, norepinephrine (p<0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (p<0.0005) correlated when only metanephrines were included. In the surgical cohort (N=272), normetanephrine decreased postoperatively and was inversely associated with weight (p<0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (p<0.0005) directly correlated with HA1C. Conclusion Plasma norepinephrine and its metabolite directly correlate with HA1C and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HA1C despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.