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If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that ‘actionable’ genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings—so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.

Flexible airway endoscopy (FAE) is an accepted and frequently performed procedure in the evaluation of children with known or suspected airway and lung parenchymal disorders. However, published technical standards on how to perform FAE in children are lacking. The American Thoracic Society (ATS) approved the formation of a multidisciplinary committee to delineate technical standards for performing FAE in children. The committee completed a pragmatic synthesis of the evidence and used the evidence synthesis to answer clinically relevant questions. There is a paucity of randomized controlled trials in pediatric FAE. The committee developed recommendations based predominantly on the collective clinical experience of our committee members highlighting the importance of FAE-specific airway management techniques and anesthesia, establishing suggested competencies for the bronchoscopist in training, and defining areas deserving further investigation. These ATS-sponsored technical standards describe the equipment, personnel, competencies, and special procedures associated with FAE in children.

Technological advances have increased the availability of genomic data in research and the clinic. If, over time, interpretation of the significance of the data changes, or new information becomes available, the question arises as to whether recontacting the patient and/or family is indicated. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with research groups from the UK and the Netherlands, developed recommendations on recontacting which, after public consultation, have been endorsed by ESHG Board. In clinical genetics, recontacting for updating patients with new, clinically significant information related to their diagnosis or previous genetic testing may be justifiable and, where possible, desirable. Consensus about the type of information that should trigger recontacting converges around its clinical and personal utility. The organization of recontacting procedures and policies in current health care systems is challenging. It should be sustainable, commensurate with previously obtained consent, and a shared responsibility between healthcare providers, laboratories, patients, and other stakeholders. Optimal use of the limited clinical resources currently available is needed. Allocation of dedicated resources for recontacting should be considered. Finally, there is a need for more evidence, including economic and utility of information for people, to inform which strategies provide the most cost-effective use of healthcare resources for recontacting.

Immune checkpoint inhibitors (ICIs) frequently result in cutaneous immune-related adverse events (IrAEs). Although the majority of these events are mild-to-moderate in severity, up to 5% are severe, which may lead to morbidity and dose interruption or discontinuation of ICI therapy. In addition, up to 25% of dermatologic IrAEs are corticosteroid-refractory or corticosteroid-dependent. These 2020 MASCC recommendations cover the diagnosis and management of cutaneous IrAEs with a focus on moderate-to-severe and corticosteroid-resistant events. Although the usage of immune-suppressive therapy has been advocated in this setting, there is a lack of randomized clinical trial data to provide a compelling level of evidence of its therapeutic benefit.

BackgroundThe adequacy of leptomeningeal collateral flow has a pivotal role in determining clinical outcome in acute ischemic stroke. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral score is among the most commonly used scales for measuring this flow. It is based on the extent and rate of retrograde collateral flow to the impaired territory on angiography.ObjectiveTo evaluate inter- and intraobserver agreementin angiographic leptomeningeal collateral flow assessment.Materials and methodsThirty pretreatment angiogram video loops (frontal and lateral view), chosen from the randomized controlled trial THRombectomie des Artères CErebrales (THRACE), were sent for grading in an electronic file. 19 readers participated, including eight who had access to a training set before the first grading. 13 readers made a double evaluation, 3 months apart.ResultsOverall agreement among the 19 observers was poor (κ = 0,16 ± 6,5.10 -3), and not improved with prior training (κ = 0,14 ± 0,016). Grade 4 showed the poorest interobserver agreement (κ=0.18±0.002) while grades 0 and 1 were associated with the best results (κ=0.52±0.001 and κ=0.43±0.004, respectively). Interobserver agreement increased (κ = 0,27± 0,014) when a dichotomized score, ‘poor collaterals’ (score of 0, 1 or 2) versus ‘good collaterals’ (score of 3 or 4) was used. The intraobserver agreements varied between slight (κ=0.18±0.13) and substantial (κ=0.74±0.1), and were slightly improved with the dichotomized score (from κ=0.19±0.2 to κ=0.79±0.11).ConclusionInter- and intraobserver agreement of collateral circulation grading using the ASITN/SIR score was poor, raising concerns about comparisons among publications. A simplified dichotomized judgment may be a more reproducible assessment when images are rated by the same observer(s) in randomized trials.

Background: Clinical guidelines are a constructive response to the reality that practicing physicians require assistance in assimilating and applying the exponentially expanding, often contradictory, body of medical knowledge. They attempt to define practices that meet the needs of most patients under most circumstances. Ideally, specific clinical recommendations contained within practice guidelines are systematically developed by expert panels who have access to all the available evidence, have an understanding of the clinical problem, and have clinical experience with the procedure being assessed, as well as knowledge of relevant research methods. The recent development of American Pain Society (APS) guidelines has created substantial controversy because of their perceived lack of objective analysis and recommendations perceived to be biased due to conflicts of interest. Objectives: To formally and carefully assess the APS guidelines’ evidence synthesis for low back pain for therapeutic interventions using the same methodology utilized by the APS authors. The interventions examined were therapeutic interventions for managing low back pain, including epidural injections, adhesiolysis, facet joint interventions, and spinal cord stimulation. Methods: A literature search by 2 authors was carried out utilizing appropriate databases from 1966 through July 2008. Articles in which conflicts arose were reviewed and mediated by a third author to arrive at a consensus. Selections of manuscripts and methodologic quality assessment was also performed by at least 2 authors utilizing the same criteria applied in the APS guidelines. The guideline reassessment process included the evaluation of individual studies and systematic reviews and their translation into practice recommendations. Results: The conclusions of APS and our critical assessment based on grading of good, fair, and poor, agreed that there is fair evidence for spinal cord stimulation in post lumbar surgery syndrome, and poor evidence for lumbar intraarticular facet joint injections, lumbar interlaminar epidural injections, caudal epidural steroids for conditions other than disc herniation or radiculitis, sacroiliac joint injections, intradiscal electrothermal therapy, endoscopic adhesiolysis, and intrathecal therapy. However, our assessment of APS guidelines for other interventional techniques, utilizing their own criteria, showed fair evidence for therapeutic lumbar facet joint nerve blocks, caudal epidural injections in disc herniation or radiculitis, percutaneous adhesiolysis in post lumbar surgery syndrome, radiofrequency neurotomy, and transforaminal epidural injections in radiculitis. Also it is illustrated that inclusion of latest literature will change the conclusions, with improved grading – caudal epidural, adhesiolysis, and lumbar facet joint nerve blocks from fair to good or poor to fair. The present critical assessment review illustrates that APS guidelines have utilized multiple studies inappropriately and have excluded appropriate studies. Our integrity assessment shows deep concerns that the APS guidelines illustrating significant methodologic failures which raise concerns about transparency, accountability, consistency, and independence. Conclusion: The current reassessment, using appropriate methodology, shows evidence similar to APS guidelines for several procedures, but differs extensively from published APS guidelines for multiple other procedures including caudal epidural injections, lumbar facet joint nerve blocks, lumbar radiofrequency neurotomy, and percutaneous adhesiolysis. Key words: Guidelines, evidence-based medicine, systematic reviews, American Pain Society, interventional pain management, interventional techniques

PurposeThe American Cancer Society (ACS) and the American Institute for Cancer Research (AICR) each created dietary and physical activity guidelines to improve cancer survivorship. Despite African American breast cancer survivors (AABCS) having the lowest survival rates of any racial or ethnic group, limited information exists on their adherence to cancer-specific lifestyle recommendations. The study’s purpose was to measure adherence to ACS/AICR dietary recommendations in AABCS.MethodsTwo hundred ten AABCS enrolled in the Moving Forward intervention trial, a randomized, community-based, 6-month weight loss study, were assessed for socio-demographics, dietary intake (via food frequency questionnaire), and related health factors at baseline. We operationalized the dietary recommendations put forth by ACS/AICR and created component and total adherence index scores. Descriptive statistics were used to calculate the proportion of women who met recommendations. Student’s t test and χ2 tests were used to compare participant characteristics by median adherence scores.ResultsThe mean total ACS/AICR score was 12.7 ± 2.5 out of 21 points (median, 13; range, 5 to 21). Over 90% were moderately or completely adherent to limiting alcohol and red & processed meat consumption, but the majority failed to meet the other recommendations to eat whole grains, legumes, fruits, vegetables, and avoid added sugars. Women with total scores below the median were younger, with higher BMI, had fewer years of education, and lower income levels.Implications for Cancer SurvivorsThe present study extends the literature on AABCS adherence to cancer survivor–specific dietary guidelines. Findings will inform future dietary lifestyle interventions in this population.

25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; CV = cardiovascular; GI = gastrointestinal; IOM = Institute of Medicine; PTH = parathyroid hormone; RCT = randomized controlled trial; αTF = α-tocopherol; ucOC = undercarboxylated osteocalcin; VKA = vitamin K antagonist; WHI = Women's Health Initiative.

Abstract Objective Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA). Context Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. Patients and Methods Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. Results Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. Conclusion The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.