Citations

Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.

Purpose: To describe the epidemiology, outcomes, and temporal trends of respiratory failure in the cardiac intensive care unit (CICU). Materials and Methods: Retrospective cohort analysis of 2,986 unique Mayo Clinic CICU patients from 2007 to 2018 with respiratory failure. Temporal trends were analyzed, along with hospital and 1-year mortality. Multivariable logistic regression was used to determine adjusted hospital mortality trends. Results: The prevalence of respiratory failure in the CICU increased from 15% to 38% during the study period ( P < 0.001 for trend). Among patients with respiratory failure, the utilization of invasive ventilation decreased and noninvasive ventilation modalities increased over time. Hospital mortality and 1-year mortality were 24% and 54%, respectively, with variation according to the type of respiratory support (highest among patients receiving invasive ventilation alone: 35% and 46%, respectively). Hospital mortality was highest among patients with concomitant cardiac arrest and/or shock (52% for patients with both). Hospital mortality decreased in the overall population from 35% to 25% ( P < 0.001 for trend), but was unchanged among patients receiving positive-pressure ventilation. Conclusions: The prevalence of respiratory failure in CICU more than doubled during the last decade. The use of noninvasive respiratory support increased, while overall mortality declined over time. Cardiac arrest and shock accounted for the majority of deaths. Further research is needed to optimize the outcomes of high-risk CICU patients with respiratory failure.

Tobacco use is projected to kill 1 billion people in the 21st century. Tobacco Use Disorder (TUD) is one of the most common substance use disorders in the world. Evidence-based treatment of TUD is effective, but treatment accessibility remains very low. A dearth of specially trained clinicians is a significant barrier to treatment accessibility, even within systems of care that implement brief intervention models. The treatment of TUD is becoming more complex and tailoring treatment to address new and traditional tobacco products is needed. The Council for Tobacco Treatment Training Programs (Council) is the accrediting body for Tobacco Treatment Specialist (TTS) training programs. Between 2016 and 2019, n = 7761 trainees completed Council-accredited TTS training programs. Trainees were primarily from North America (92.6%) and the Eastern Mediterranean (6.1%) and were trained via in-person group workshops in medical and academic settings. From 2016 to 2019, the number of Council-accredited training programs increased from 14 to 22 and annual number of trainees increased by 28.5%. Trainees have diverse professional backgrounds and work in diverse settings but were primarily White (69.1%) and female (78.7%) located in North America. Nearly two-thirds intended to implement tobacco treatment services in their setting; two-thirds had been providing tobacco treatment for 1 year or less; and 20% were sent to training by their employers. These findings suggest that the training programs are contributing to the development of a new workforce of TTSs as well as the development of new programmatic tobacco treatment services in diverse settings. Developing strategies to support attendance from demographically and geographically diverse professionals might increase the proportion of trainees from marginalized groups and regions of the world with significant tobacco-related inequities.

Background: In the N-MOmentum trial, the risk of an adjudicated neuromyelitis optica spectrum disorder (NMOSD) attack was significantly reduced with inebilizumab compared with placebo. Objective: To demonstrate the robustness of this finding, using pre-specified sensitivity and subgroup analyses. Methods: N-MOmentum is a prospective, randomized, placebo-controlled, double-masked trial of inebilizumab, an anti-CD19 monoclonal B-cell-depleting antibody, in patients with NMOSD. Pre-planned and post hoc analyses were performed to evaluate the primary endpoint across a range of attack definitions and demographic groups, as well as key secondary endpoints. Results: In the N-MOmentum trial (ClinicalTrials.gov: NCT02200770), 174 participants received inebilizumab and 56 received placebo. Attack risk for inebilizumab versus placebo was consistently and significantly reduced, regardless of attack definition, type of attack, baseline disability, ethnicity, treatment history, or disease course (all with hazard ratios < 0.4 favoring inebilizumab, p < 0.05). Analyses of secondary endpoints showed similar trends. Conclusion: N-MOmentum demonstrated that inebilizumab provides a robust reduction in the risk of NMOSD attacks regardless of attack evaluation method, attack type, patient demographics, or previous therapy. The N-MOmentum study is registered at ClinicalTrials.gov: NCT2200770.

We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10 HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.

Abstract Objective To describe headache characteristics, medication use, disability, and quality of life in a large patient cohort from the United States who have chronic migraine (CM) and medication overuse headache (MOH). Methods In all, 610 adult patients were enrolled into the Medication Overuse Treatment Strategy trial from 34 healthcare clinics, including headache specialty, general neurology, and primary care clinics. Descriptive statistics characterize baseline demographics, headache characteristics, medication use, disability (Headache Impact Test 6 [HIT‐6] and Migraine Functional Impact Questionnaire [MFIQ]), pain interference (PROMIS Pain Interference), and quality of life (EQ‐5D‐5L). Relationships with headache frequency were assessed. Results Mean age was 45 years (SD 13) and 531/608 (87.3%) were females. Mean headache days per 30 was 24.3 (SD 5.5), including 13.6 (SD 7.1) with moderate to severe headache. Daily headaches were reported by 36.1% (219/607) of patients. Acute headache medications were used on 21.5 (SD 7.5) per 30 days. The most commonly overused medications were simple analgesics (378/607, 62% of patients), combination analgesics (246/607, 41%), and triptans (128/607, 21%). HIT‐6, MFIQ, PROMIS Pain Interference, and EQ‐5D‐5L scores demonstrated substantial negative impact from CM with MOH on patient functioning and quality of life. Higher headache frequency was associated with more moderate–severe headache days, more frequent acute headache medication use, greater headache‐related disability, and lower quality of life. Only 272/606 (44.9%) were taking migraine preventive medication. Conclusions CM with MOH is associated with a large burden on patients in the United States. Higher headache frequency is associated with greater impact on functioning, pain interference, and quality of life.

The terrorist attacks on 11 September 2001 potentially exposed more than 400,000 responders, workers, and residents to psychological and physical stressors, and numerous hazardous pollutants. In 2011, the World Trade Center Health Program (WTCHP) was mandated to monitor and treat persons with 9/11-related adverse health conditions and conduct research on physical and mental health conditions related to the attacks. Emerging evidence suggests that persons exposed to 9/11 may be at increased risk of developing mild cognitive impairment. To investigate further, the WTCHP convened a scientific workshop that examined the natural history of cognitive aging and impairment, biomarkers in the pathway of neurodegenerative diseases, the neuropathological changes associated with hazardous exposures, and the evidence of cognitive decline and impairment in the 9/11-exposed population. Invited participants included scientists actively involved in health-effects research of 9/11-exposed persons and other at-risk populations. Attendees shared relevant research results from their respective programs and discussed several options for enhancements to research and surveillance activities, including the development of a multi-institutional collaborative research network. The goal of this report is to outline the meeting’s agenda and provide an overview of the presentation materials and group discussion.

PURPOSE Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin. METHODS In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment. RESULTS A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) ( P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively ( P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone. CONCLUSION LEN restores sensitivity to recombinant erythropoietin in growth factor–insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813 ).