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Background and Aims Platelet‐stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin’s impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection. Approach and Results Consecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07‐2.31; severe morbidity OR, 1.86; 95% CI, 1.22‐2.79; LD OR, 1.96; 95% CI, 1.23‐3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03‐4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90‐day mortality and 1‐year overall survival. Conclusions We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.

PURPOSE To describe the characteristics of the members of the ASCO-sponsored Oncology Student Interest Groups (OSIGs) in Latin America. METHODS This was a multicenter cross-sectional study. We surveyed 97 OSIG members from three medical schools in Peru and Mexico. We administered a 60-question survey covering topics including personal background, oncology training experience, and professional practice expectations and preferences. RESULTS A little more than one half of the surveyed OSIG members were female. More than one half had a visa to visit the United States and had an advanced level of English. One half of the OSIG members were also ASCO members. Most participants agreed or strongly agreed that participation in their OSIG increased their interest in cancer-related specialties (94%) and provided professional networking opportunities (94%) and that it was accessible to all students (91%). Most participants believed that their OSIG had sufficient resources to carry out its activities. Students were asked to rate their interest when they entered medical school versus at the time of the survey. Most of the members were strongly interested in pursuing surgical oncology. The majority of members were somewhat interested or very interested in palliative care and medical oncology. CONCLUSION To our knowledge, this is the first study that provides data on medical student perceptions of the Latin American OSIGs sponsored by ASCO. Student perceptions of medical oncology and the impact of OSIGs were generally positive. Given the shortages of oncology specialists in Latin American and elsewhere, strategies to engage medical students in the pursuit of cancer-related careers are becoming increasingly essential.

Abstract Objectives Pure erythroid leukemia (PEL) is exceptionally rare in the pediatric setting. Four pediatric PEL cases with t(1;16)(p31;q24) NFIA-CBFA2T3 were reported previously. We present a case of an infant with PEL presenting with erythroblastic sarcoma and harboring a novel t(1;8)(p31.3;q21.3) NFIA-RUNX1T1 fusion detected by RNA sequencing and conventional karyotype. Methods Bone marrow (BM) and abdominal mass biopsies from the patient were evaluated with extensive immunohistochemical, flow cytometric, cytogenetic, and molecular studies. Results The patient was a female infant who presented between 2 and 5 months of age with cytopenias and an enlarging abdominal mass. Blasts in the BM and abdominal mass expressed CD71 and CD117 with focal expression of CD43, E-cadherin, epithelial membrane antigen, and hemoglobin A. They were negative for additional myeloid, lymphoid, and nonhematolymphoid markers. These findings were most consistent with PEL and erythroblastic sarcoma. RNA sequencing revealed the novel NFIA-RUNX1T1 fusion. Conclusions Along with the previously reported PELs with NFIA-CBFA2T3 fusions, we describe a subset of PELs that occur in children, that frequently display extramedullary disease, and that harbor rearrangements of NFIA with core binding factor genes. We hypothesize that, together, these cases represent a rare but distinct clinicopathologic group of pediatric PELs with recurrent genetic abnormality.

Purpose of review Sarcopenia is a progressive generalized decline in skeletal muscle mass, strength, and function. This condition is highly prevalent in critically ill patients and is associated with poor outcomes in the ICU. In this review, we describe the use, evidence, and limitations of the most common validated imaging studies used to assess muscle mass in ICU, and we provide an overview of the benefits of using the sarcopenia index [(serum creatinine/serum cystatin C) × 100]) in the ICU. Recent findings Currently, the determination of muscle mass using anthropometric measurements and serum biomarkers is unreliable. Several new techniques, including a dual-energy X-ray absorptiometry, computed tomography scan, ultrasonography, and bioimpedance analysis, have been studied and validated for the diagnosis and prognosis of sarcopenia in the ICU. However, these techniques are often not accessible for the majority of critically ill patients. The sarcopenia index constitutes an accurate method to diagnose sarcopenia, predict ICU outcomes, and nutritional status in critically ill patients. Summary Diagnosis of sarcopenia has substantial implications in ICU patients. Choosing the correct test to identify patients who may need preventive or therapeutic support for this condition will favorably impact ICU outcomes.

Precision oncology is the field that places emphasis on the diagnosis and treatment of tumors that harbor specific genomic alterations susceptible to inhibition or modulation. Although most alterations are only present in a minority of patients, a substantial effect on survival can be observed in this subgroup. Mass genome sequencing has led to the identification of a specific driver in the translocations of the tropomyosin receptor kinase family (NTRK) in a subset of rare tumors both in children and in adults, and to the development and investigation of Larotrectinib. This medication was granted approval by the US Food and Drug Administration for NTRK-positive tumors, regardless of histology or age group, as such, larotrectinib was the first in its kind to be approved under the premise that molecular pattern is more important than histology in terms of therapeutic approach. It yielded significant results in disease control with good tolerability across a wide range of diseases including rare pediatric tumors, salivary gland tumors, gliomas, soft-tissue sarcomas, and thyroid carcinomas. In addition, and by taking different approaches in clinical trial design and conducting allocation based on biomarkers, the effects of target therapies can be isolated and quantified. Moreover, and considering developing nations and resource-limited settings, precision oncology could offer a tool to reduce cancer-related disability and hospital costs. In addition, developing nations also present patients with rare tumors that lack a chance of treatment, outside of clinical trials. This, in turn, offers the possibility for international collaboration, and contributes to employment, education, and health service provisions. The reviews of this paper are available via the supplemental material section.

Basilar invagination is a challenging dilemma that neurosurgeons may face. Herein, we present a case of a 65-year-old female with a history of rheumatoid arthritis and status post a previous C4–7 ACDF who presented to our clinic with progressive weakness in her bilateral upper and lower extremities. Imaging revealed basilar invagination. She underwent an endoscopic endonasal odontoidectomy followed by an occiput–C6 fusion. We present the endonasal portion of the procedure and have highlighted the technical nuances of this approach. Our goal is to provide better insight into this surgical strategy when dealing with basilar invagination. The video can be found here: https://youtu.be/aeMbvI_zYQA

11539 Background: Ripretinib is a novel switch-control TKI that broadly inhibits KIT and PDGFRA kinase signaling. In INVICTUS (NCT03353753), a randomized, double-blind, placebo (PBO)-controlled trial of ripretinib in ≥4th-line advanced GIST, ripretinib reduced the risk of disease progression or death by 85% vs PBO with a favorable overall safety profile. Common ( > 20%) adverse events (AEs) included, but were not limited to, alopecia and PPES. Exploratory analyses evaluated the impact of alopecia and PPES on quality of life (QoL). Methods: Patients (pts) with advanced GIST previously treated with at least imatinib, sunitinib, and regorafenib were randomized (2:1) to ripretinib 150 mg QD or PBO. AEs were graded using CTCAE v4 and PROs collected using EQ-5D-5L (EQ5D) and EORTC QLQ-C30 (C30). Repeated measures (RM) models assessed the impact of alopecia and PPES on 5 PROs (EQ5D visual analogue scale; and C30 physical functioning, role functioning, and the overall health and overall QoL questions) within the ripretinib arm. Fixed effects were sex, alopecia/PPES, and ECOG scores at baseline. Results: 128/129 randomized pts received treatment (85 ripretinib 150 mg QD; 43 PBO). Alopecia, regardless of causality, occurred in 44 (51.8%) on ripretinib (34 [40.0%] grade 1; 10 [11.8%] grade 2) and 2 (4.7%) on PBO (both grade 1). PPES occurred in 18 (21.2%) on ripretinib (11 [12.9%] grade 1; 7 [8.2%] grade 2); none on PBO. The median times in days to first occurrence and worst severity grade with ripretinib were 57.0 and 62.5 for alopecia; 56.5 and 57.0 for PPES. The RM models showed a slight trend towards improvement in PRO score over time for pts with alopecia; the only association reaching a P-value of < 0.05 was between alopecia and increased overall QoL. None of the associations between PPES and PRO scores reach P < 0.05. All PRO p-values are nominal, and no statistical significance is being claimed. Conclusions: Ripretinib had a favorable overall safety and tolerability profile. When stratified by alopecia and PPES, patient-reported assessments of function, overall health, and overall QoL were maintained over time. For both alopecia and PPES, onset and maximum severity occurred almost simultaneously, indicating that these events generally did not progressively worsen. These results suggest that alopecia and PPES are manageable and do not have a negative effect on function, overall health, and QoL. Clinical trial information: NCT03353753 .

11535 Background: Ripretinib is a novel switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and PDGFRA kinase signaling through a dual mechanism of action. In INVICTUS (NCT03353753), a randomized, double-blind, placebo-controlled trial of ripretinib in ≥4th-line advanced GIST, ripretinib reduced the risk of disease progression or death by 85% vs placebo and had a favorable overall safety profile in patients previously treated with ≥3 prior TKIs. Methods: As part of the INVICTUS trial, patient reported outcome (PRO) measures were collected using EQ-5D-5L (EQ5D) and EORTC QLQ-C30 (C30). In prespecified and additional analyses, ANCOVA models were built to compare changes from baseline to cycle 2 day 1 (C2D1) for PRO measures within the ripretinib and placebo arms and determine the difference between treatment arms. PRO measures included the EQ5D visual analogue scale (VAS) and the C30 physical functioning (PF) and role functioning (RF) scales (all scores range from 0–100; higher scores are better). The C30 overall health and overall QoL questions were also assessed (scores range from 1–7; higher scores are better). Fixed effects included treatment arm, number of previous anticancer treatments (3 vs ≥4), and ECOG score at baseline (0 vs 1/2). Results: Overall, 129 patients were randomized and 128 received treatment (85 to ripretinib 150 mg QD; 43 to placebo). All PRO p-values are nominal, and no statistical significance is being claimed. VAS scores improved an average 3.7 points from baseline to C2D1 with ripretinib vs an average decline of 8.9 with placebo (P = 0.004; improvement or no change, 67% vs 41% of patients, respectively). Similarly, the average PF score improved 1.6 points with ripretinib and decreased 8.9 with placebo (P = 0.004; improvement or no change, 68% vs 44%). RF scores also improved an average of 3.5 points with ripretinib vs a decrease of 17.1 with placebo (P = 0.001; improvement or no change, 77% vs 50%). For the overall health and overall QoL questions, scores increased with ripretinib an average of 0.20 and 0.28, respectively, and decreased 0.78 and 0.76 with placebo (both P = 0.001; improvement or no change, 74% vs 47% and 79% vs 59%, respectively). Conclusions: Based on the 5 PRO measures assessed, when compared with placebo and best supportive care, ripretinib provided patient-benefit in advanced GIST with PRO measures of role and physical function, VAS, overall health, and overall QoL remaining stable. Clinical trial information: NCT03353753 .

Background and objectives Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically. Results Across 16 focus groups, 134 participants (range, 19–85 years old; 51% women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked outcomes were kidney function (importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: constraining day-to-day experience, impaired agency and control over health, and threats to future health and family. Conclusions Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact.

In 2017, the International Headache Society convened a Global Patient Advocacy Summit (GPAS-1) to begin a collaborative effort involving patients, patient advocates, patient advocacy organizations, healthcare professionals, scientists, professional pain, neurology, and headache societies, pharmaceutical manufacturers, and regulatory agencies to advance issues of importance to patients affected by headache worldwide. In September 2019, the second Global Patient Advocacy Summit (GPAS-2) was convened to revisit issues from the inaugural meeting, assess the progress of the International Headache Society Global Patient Advocacy Coalition (IHS-GPAC) in meeting the goals set forth therein, and discuss strategies for achieving established goals and supporting future development. Short- and long-term mandates from the first Summit were realized, including publishing the Vancouver Declaration on Global Headache Patient Advocacy 2018, determining the governing and operational structures of the IHS-GPAC, and helping to facilitate the first World Federation of Neurology World Brain Day dedicated to migraine. Another short-term mandate, creating a unified advocacy strategy, was fulfilled by the Coalition’s decision to focus on encouraging support from employers and implementing employee support programs for people with migraine. To help execute the strategy, the Coalition is developing an employer engagement toolkit that will educate employers and employees about the impact of migraine in the workplace, reduce stigma directed toward employees with migraine, and facilitate the care of employees with migraine to reduce the burden of illness and improve workplace productivity. Coalition members will disseminate the toolkit and encourage the adoption of migraine workplace programs by employers worldwide. The Coalition has established an alliance with two global, multinational employers to expand migraine awareness and support among policy makers and other stakeholders around the world. The IHS-GPAC met many of the goals established at GPAS-1, and it has initiated a global strategy focused on the psychosocial and economic toll of headache disorders, especially migraine, in the workplace. Ongoing and future activities will explore a range of opportunities with employers and across the full spectrum of advocacy goals.