Metastatic Melanoma to a Neurofibroma.

ABSTRACT: We present an extraordinary case of metastatic cutaneous melanoma to a pre-existing neurofibroma in a 75-year-old man with a history of primary invasive melanoma in an anatomically close vicinity. Histological examination of the metastatic melanoma showed a well-circumscribed intradermal nodule of frankly malignant epithelioid melanocytes without an intraepidermal component, surrounded and sharply demarcated from a diffuse spindle cell proliferation with morphological features of a neurofibroma. The spindle cell component showed bland cytologic features, with no mitotic activity or lymphocytic inflammation and no features of malignancy. By immunohistochemistry, both components expressed S100, while HMB45 positivity and complete loss of p16 were only observed in the epithelioid cells. The morphologically distinct areas were analyzed by fluorescent in situ hybridization, which demonstrated an abnormal profile (gain of RREB1 and homozygous loss of CDKN2A) in the epithelioid nodule; however, no abnormalities were detected in the spindle cell component. Next-generation sequencing showed somatic NRAS and PTEN mutations in the melanoma cells only. The overall molecular findings supported the immunomorphological diagnosis of metastatic melanoma within a neurofibroma over the potential differential diagnosis of melanoma with a neurofibroma-like spindle/desmoplastic component.

A Modified Delphi Study to Establish Essential Clinical Pharmacology Competencies.

INTRODUCTION: Competency-based education has been commonly used to enhance the healthcare workforce for some time. A translational discipline that is integral to drug development and impactful on healthcare and public health is clinical pharmacology. With such contribution, it is essential that the clinical pharmacology workforce is adequately equipped to address the demands of emerging trends of drug development. OBJECTIVES: The primary objective of this study was to determine the most significant competencies needed for a clinical pharmacologist in the regulatory environment. METHODS: A two round modified Delphi technique was administered to 29 clinical pharmacologists within the Office of Clinical Pharmacology (OCP) between November 2021-January 2022. A questionnaire consisting of core and technical competencies was administered electronically using SurveyMonkey ® to gain consensus about essential clinical pharmacology competencies. Participants used a Likert scale to rank importance of competencies from strongly agree (1), agree (2), neutral (3), disagree (4), strongly disagree (5). Participants also suggested topics to be included in the next round. Consensus was set at 60%. The competencies receiving the most consensus at 60% in round one and the new topics proceeded to the second round. In the second and final round, participants ranked the suggested competencies. Descriptive statistics and a McNemar change test were utilized to analyze data. Only data from the participants who completed both rounds was used in the study. RESULTS: In round one participants ranked all fifty-six core and technical competencies as essential with consensus of at least 60%. In round two, participants ranked sixty-two competencies as essential with consensus of at least 60%. A McNemar change test demonstrated stability of ranking between rounds. CONCLUSION: Essential core and technical competencies can build education programs to sustain the emerging clinical pharmacology workforce in the Office of Clinical Pharmacology. The Delphi technique is a suitable approach to determine essential competencies because it cultivates consensus and gains insight from experts in the forefront of drug development.

Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary.

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA-approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke-Margolis Center for Health Policy collaborated with the FDA to host a two-day virtual public workshop entitled "Pharmacodynamic Biomarkers for Biosimilar Development and Approval" on September 20-21, 2021. The public workshop was a forum for global regulators, biopharmaceutical developers, and academic researchers to discuss the current and future role of PD biomarkers in improving the efficiency of biosimilar development and approval. The workshop objectives included: (i) discuss the current and potential future state of leveraging PD biomarkers for biosimilar development and approval; (ii) summarize the FDA's initiatives to advance biosimilar development; (iii) describe stakeholders' experience with PD biomarkers in biosimilar development; and (iv) explain research efforts to promote broader application of PD biomarkers in biosimilar development. This document summarizes presentations and panel discussions from each session of the two-day September 2021 public workshop covering the application of PD biomarkers for biosimilar development.

The effect of a walking program on perceived benefits and barriers to exercise in postmenopausal African American women.

PURPOSE: Rates of exercise participation among African Americans is low. Identifying and overcoming perceived benefits/ barriers unique to African American women (AAW) may increase their exercise participation. The purpose of this study was to describe perceived benefits/barriers to exercise in AAW before and after participation in a walking program. METHOD: Thirty-five postmenopausal AAW participated in a 7-week structured walking program with 2 walking goals. Perceived benefits and barriers to exercise were assessed using the Exercise Benefits/Barriers Scale at the beginning and end of the program. Participants engaged in a postintervention interview to further assess benefits/barriers to exercise participation. RESULTS: Perceived benefits/barriers to exercise did not change significantly with participation in a walking program. Lack of time due to work and family responsibilities affected achievement of the brisk walking goal. CONCLUSIONS: Postmenopausal AAW in this study strongly believed in the benefits of exercising and had increased levels of participation in a walking program when lack of time was not a barrier. Overcoming this barrier is the true challenge to health care professionals.

Small for gestational age neonates--are we missing some by only using standard population growth standards and does it matter?

OBJECTIVES: Birth weight below the 10th percentile on growth charts based on population norms or small for gestational age (SGA) is associated with adverse perinatal outcome. We compare the association among neonatal mortality, morbidity and SGA as determined by currently used percentiles based on population standards (method A) and customised birth weight percentiles (method B). METHODS: Study of outcomes of SGA neonates from a cohort of 6125 consecutive pregnancies, analysed in function of the method (A or B) used to diagnose SGA. RESULTS: There were 831 SGA infants, 84% were born at term and the majority were of European origin (61.4%). By method A, there was a sixfold decrease in the prevalence of SGA babies (2.3%) compared with method B (13.5%). After correcting for prematurity, SGA infants diagnosed by method B alone (not identified by standard population method) still constituted a high proportion of infants with hypothermia and hypoglycaemia (p < 0.05). CONCLUSION: Customised charts identified six times more SGA infants than standard charts. These infants, considered appropriately grown by standard charts, are at a significantly higher risk of morbidity.