Treating young adult cannabis use disorder with text message-delivered peer network counseling.

BACKGROUND: Approximately 16.5% of U.S. young adults have a cannabis use disorder (CUD) and are at risk for negative outcomes. Treatment can reduce cannabis use, but young adults are less likely to seek help than older adults. Peer Network Counseling-txt (PNC-txt) is a brief, text-delivered, Motivational Interviewing-informed substance use intervention focusing on peer relations and activity spaces as mechanisms for behavioral change. PNC-txt has shown evidence of reducing tobacco and cannabis use with adolescents and young adults, but it has not been tested in the context of legal cannabis use. The current randomized controlled trial sought to expand the evidence regarding the context of PNC-txt effects, comparing one state in which cannabis is legal (Colorado) and one state in which it is not (Tennessee). We hypothesized that participants randomized to PNC-txt would show significant reductions in cannabis use compared to controls, with larger reductions for females and those in Colorado, and that peer relations and activity space would mediate effects. METHODS: One thousand, seventy eight 18-25 year olds (CO: 551; TN: 527) who met screening criteria for CUD and biologically-verified cannabis use were randomly assigned to PNC-txt or waitlist control condition. Every other day for 4 weeks, participants assigned to PNC-txt received pre-programmed text conversations, tailored via data from the baseline assessment. Self-report and biological indicators of cannabis use were measured at 1-, 3-, and 6-months. DISCUSSION: Data analysis is underway. Results will provide evidence regarding whether, and how, PNC-txt reduces cannabis use in young adults with CUD. TRIAL REGISTRATION: This trial was prospectively registered on September 28, 2020 with ClinicalTrials.gov (NCT04567394).

A Phase 0 Study to Assess the Biodistribution and Pharmacokinetics of a Radiolabeled Antibody Targeting Human Kallikrein 2 in Participants with Metastatic Castration-Resistant Prostate Cancer.

Despite the inclusion of multiple agents within the prostate cancer treatment landscape, new treatment options are needed to address the unmet need for patients with metastatic castration-resistant prostate cancer (mCRPC). Although prostate-specific membrane antigen is the only cell-surface target to yield clinical benefit in men with advanced prostate cancer, additional targets may further advance targeted immune, cytotoxic, radiopharmaceutical, and other tumor-directed therapies for these patients. Human kallikrein 2 (hK2) is a novel prostate-specific target with little to no expression in nonprostate tissues. This first-in-human phase 0 trial uses an 111In-radiolabeled anti-hK2 monoclonal antibody, [111In]-DOTA-h11B6, to credential hK2 as a potential target for prostate cancer treatment. Methods: Participants with progressive mCRPC received a single infusion of 2 mg of [111In]-DOTA-h11B6 (185 MBq of 111In), with or without 8 mg of unlabeled h11B6 to assess antibody mass effects. Sequential imaging and serial blood samples were collected to determine [111In]-DOTA-h11B6 biodistribution, dosimetry, serum radioactivity, and pharmacokinetics. Safety was assessed within a 2-wk follow-up period from the time of [111In]-DOTA-h11B6 administration. Results: Twenty-two participants received [111In]-DOTA-h11B6 and are included in this analysis. Within 6-8 d of administration, [111In]-DOTA-h11B6 visibly accumulated in known mCRPC lesions, with limited uptake in other organs. Two treatment-emergent adverse events unrelated to treatment occurred, including tumor-related bleeding in 1 patient, which led to early study discontinuation. Serum clearance, biodistribution, and tumor targeting were independent of total antibody mass (2 or 10 mg). Conclusion: This first-in-human study demonstrates that tumor-associated hK2 can be identified and targeted using h11B6 as a platform as the h11B6 antibody selectively accumulated in mCRPC metastases with mass-independent clearance kinetics. These data support the feasibility of hK2 as a target for imaging and hK2-directed agents as potential therapies in patients with mCRPC.

College Students' Day-to-Day Maladaptive Drinking Responses to Stress Severity and Stressor-Related Guilt and Anger.

BACKGROUND: Stress is a common part of college students' daily lives that may influence their physical activity (PA) and alcohol use. Understanding features of daily stress processes that predict health behaviors could help identify targets for just-in-time interventions. PURPOSE: This study used intensive longitudinal data to examine whether prior day stress processes predict current day PA or alcohol use. METHODS: Participants (N=58, Mage=20.5, 59% women, 70% White) were 18-to-25-year-old students who engaged in binge drinking at least twice monthly and used cannabis or tobacco in the past year. They wore activity (activPAL4) and alcohol (Secure Continuous Remote Alcohol Monitor) monitors for 11 days to assess daily PA (e.g., step counts) and alcohol use (e.g., drinking day), and completed daily surveys about yesterday's stress, including number of stressors (i.e., frequency), stressor intensity (i.e., severity), and frequency of affective states (e.g., guilt). Multilevel models examined prior day stress predicting current day PA or alcohol use. RESULTS: Participants had higher odds of current day drinking (odds ratio=1.21) and greater area under the curve (B=0.08) when they experienced greater than usual stress severity the prior day. Participants had higher current day peak transdermal alcohol concentration (B=0.12) and area under the curve (B=0.11) when they more frequently experienced guilt due to stressors the prior day. CONCLUSIONS: College students' unhealthy response of increasing alcohol use due to stress could adversely impact health outcomes. There is a critical need for interventions addressing students' ability to effectively manage and respond to the stress-inducing, daily demands of student life.

College students experience stress regularly, which may influence their physical activity (PA) and drinking behaviors. Understanding how daily stress predicts health behaviors could be useful for stress-reduction interventions. This study examined whether prior day stress predicted current day PA or alcohol use. Participants (N = 58) were 18- to 25-year-old college students who binge drank at least twice per month and used cannabis or tobacco in the past year. They wore PA and alcohol sensors for 11 days to assess daily PA and alcohol use, and completed daily surveys about yesterday's stress, including the number of stressors experienced (i.e., frequency), stressor intensity (i.e., severity), and mood responses related to stress (anger, anxiety, guilt, sadness). Participants were 21% more likely to drink and drank at higher intensity when they experienced greater than usual stress severity the prior day. Participants had higher current day alcohol use intensity when they more frequently experienced guilt due to stressors the prior day. College students' unhealthy response of increasing alcohol use due to stress could negatively impact short- and long-term health outcomes. There is a critical need for interventions addressing students' ability to effectively manage and respond to the stress-inducing, daily demands of student life.

Appendiceal neuroendocrine neoplasms and resection of the mesoappendix: a retrospective comparative study.

PURPOSE: Incidental appendiceal neoplasms are identified in approximately 1% of the specimens of suspected appendicitis. The current institutional policy is to perform en bloc mesoappendix resection during routine laparoscopic appendicectomy allowing for staging, reducing the need for oncological right hemicolectomy (ORH). Herein, we review en bloc mesoappendicectomy in clinical practice and its effects on the rate of ORH. METHODS: We reviewed all cases of appendicectomy performed at the Auckland City Hospital between 1 May 2014 and 31 May 2019. Clinical notes and histopathological reports were reviewed. All neoplasms, surgical techniques and the need for further surgery were analysed. RESULTS: A total of 2455 appendicectomies were performed with an approximately similar number of procedures between the sexes and an overall median age of 31 years. Overall, 86% (n = 2098) of the specimens included resection of the mesoappendix, and 58 (2.4%) appendiceal neoplasms were identified. Of them, 33 (1.3%) specimens included neuroendocrine appendiceal neoplasms. Eleven (33%) patients with appendiceal neuroendocrine neoplasms were recommended ORH. One of these patients may have avoided additional surgery, whereas 3 (9.1%) patients with tumours of 10-20 mm avoided ORH because their mesoappendix was resected. CONCLUSION: At our centre, there has been a significant change in the practice of mesoappendix resection, and we support resection of the mesoappendix during appendicectomy. The procedure is technically straightforward and safe, incurs no increases in costs or time, allows for accurate tumour staging and guides decisions regarding further surgical interventions.

The Identification of CELSR3 and Other Potential Cell Surface Targets in Neuroendocrine Prostate Cancer.

Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a significant subset of patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine prostate cancer (NEPC)]. On the basis of RNA sequencing (RNA-seq) data from a clinical cohort of tissue from benign prostate, locally advanced prostate cancer, metastatic castration-resistant prostate cancer and NEPC, we developed a multi-step bioinformatics pipeline to identify NEPC-specific, overexpressed gene transcripts that encode cell surface proteins. This included the identification of known NEPC surface protein CEACAM5 as well as other potentially targetable proteins (e.g., HMMR and CESLR3). We further showed that cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) knockdown results in reduced NEPC tumor cell proliferation and migration in vitro. We provide in vivo data including laser capture microdissection followed by RNA-seq data supporting a causal role of CELSR3 in the development and/or maintenance of the phenotype associated with NEPC. Finally, we provide initial data that suggests CELSR3 is a target for T-cell redirection therapeutics. Further work is now needed to fully evaluate the utility of targeting CELSR3 with T-cell redirection or other similar therapeutics as a potential new strategy for patients with NEPC. Significance: The development of effective treatment for patients with NEPC remains an unmet clinical need. We have identified specific surface proteins, including CELSR3, that may serve as novel biomarkers or therapeutic targets for NEPC.

Characteristics and Long-Term Outcome of Surgically Managed High-Grade Extremity Chondrosarcoma.

Background: Dedifferentiated chondrosarcoma (DCS) is a highly malignant variant that portends a poor prognosis. Although factors such as clinico-pathological characteristics, surgical margin, and adjuvant modalities likely play a role in overall survival, debate continues with varying results on the importance of these indicators. The purpose of this study is (1) To delineate the characteristics, local recurrence (LR), and survival of patients with intermediate (IGCS), high (HGCS) and dedifferentiated (DCS) chondrosarcoma of the extremity by utilizing detailed cases at one tertiary institution. (2) To assess survival between high grade chondrosarcoma and DCS utilizing a less detailed but large cohort from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Twenty-six cases of high-grade (conventional FNCLCC grades 2 and 3, dedifferentiated) chondrosarcoma were identified from an ongoing prospective cohort of 630 sarcoma patients managed surgically at a tertiary referral university hospital between 9/1/2010-12/30/2019. A retrospective review of demographics, tumor characteristics, surgical procedure, treatment course, and survival data was performed to determine prognostic factors for survival. An additional 516 cases of chondrosarcoma were identified from the SEER database. Using the Kaplan-Meier method, both the large database and case series were evaluated, and estimated cause-specific survival was calculated at 1, 2, and 5 years. Results: There were 12 IGCS, 5 HGCS, and 9 DCS patients in the single institution cohort. DCS had a higher stage at diagnosis (p=0.04). Limb salvage was the most common procedure performed in every group (11/12 IGCS, 5/5 HGCS, and 7/9 DCS; p=0.56). Margins included 8/12 wide and 3/12 intralesional for IGCS. For HGCS, there were 3/5 wide, 1/5 marginal, and 1/5 intralesional. A majority of DCS margins were wide (8/9) with only 1 marginal. There was no difference of associated margins between the groups (p=0.85), however there was a difference when margins were classified based on numerical measurement (IGCS: 0.125cm (0.1-0.35); HGCS: 0cm (0-0.1); DCS: 0.2cm (0.1-0.5); p=0.03). The overall median follow-up was 26 months (IQR:16.1-70.8). The time interval from resection to death was lower in DCS (11.5 months (10.7-12.2)), followed by IGCS (30.3 months (16.2-78.2)), and HGCS (55.1 months (32.0-78.2; p=0.047). LR occurred in 5/9 DCS, 1/5 HGCS, and 1/14 IGCS patients. Of the DCS patients only 2/6 who received systemic therapy had LR, while all 3/3 who did not receive systemic therapy had LR. Overall systemic therapy and radiation did not impact incidence of LR (p=0.67; p=0.34). However, patients who had LR were 17.5 times more likely to die within one year (HR=17.5, 95%CI (1.01-303.7), p=0.049), after adjusting for the age at the surgery. There was no correlation with the utilization of systemic therapy, radiation therapy, or margin and overall survival (p=0.63, p=0.52, p=0.74). In the SEER patient cohort, 149 cases (28.9%) were DCS and 367 (71.1%) were HGCS. At final follow-up, 49.6% (n=256) of the cohort had a cause of death due to chondrosarcoma. HGCS was associated with higher chance of 1-year survial (p<0.001), 2-year survival (p<0.001), 5-year survival (p<0.001), and overall survival (p<0.001). Additionally, decreased survival was associated with metastatic disease at presentation (p=0.01). Overall limb salvage was most utilized for both HGCS (76.5%) and DCS (74.3%). In regard to limb salvage vs. amputation, there was no difference in survival at 1 year (p=0.10) or 2 year (p=0.13) between the groups, however those who underwent limb salvage procedure had a significantly better chance of survival at 5 years when compared to amputation (HR=1.49 (1.11-1.99); p=0.002). Conclusion: High-grade chondrosarcoma remains a fatal disease in many patients, particularly if associated with dedifferentiated subtype. Interestingly, all (100%) DCS patients who did not receive systemic therapy had LR. However, chemotherapy and radiation did not significantly increase survival. In this case series and large database study, HGCS had the smallest surgical margin, but with the longest time interval for both LR and death. Additionally, using the SEER database, DCS and amputation had worse prognosis at the 5-year survival time. Further studies on valuable prognostic influences as well as earlier identification of this rare disease may help in developing better management options. Level of Evidence: III.

A non-pharmacological multi-modal therapy to improve sleep and cognition and reduce mild cognitive impairment risk: Design and methodology of a randomized clinical trial.

Aging populations are at increased risk of sleep deficiencies (e.g., insomnia) that are associated with a variety of chronic health risks, including Alzheimer's disease and related dementias (ADRD). Insomnia medications carry additional risk, including increased drowsiness and falls, as well as polypharmacy risks. The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBTi), but access is limited. Telehealth is one way to increase access, particularly for older adults, but to date telehealth has been typically limited to simple videoconferencing portals. While these portals have been shown to be non-inferior to in-person treatment, it is plausible that telehealth could be significantly improved. This work describes a protocol designed to evaluate whether a clinician-patient dashboard inclusive of several user-friendly features (e.g., patterns of sleep data from ambulatory devices, guided relaxation resources, and reminders to complete in-home CBTi practice) could improve CBTi outcomes for middle- to older-aged adults (N = 100). Participants were randomly assigned to one of three telehealth interventions delivered through 6-weekly sessions: (1) CBTi augmented with a clinician-patient dashboard, smartphone application, and integrated smart devices; (2) standard CBTi (i.e., active comparator); or (3) sleep hygiene education (i.e., active control). All participants were assessed at screening, pre-study evaluation, baseline, throughout treatment, and at 1-week post-treatment. The primary outcome is the Insomnia Severity Index. Secondary and exploratory outcomes span sleep diary, actiwatch and Apple watch assessed sleep parameters (e.g., efficiency, duration, timing, variability), psychosocial correlates (e.g., fatigue, depression, stress), cognitive performance, treatment adherence, and neurodegenerative and systemic inflammatory biomarkers.

Key performance indicators for improving outcomes from retroperitoneal sarcoma surgery in New Zealand.

BACKGROUND: Retroperitoneal sarcomas are a rare and heterogenous group of tumours. There is increasing evidence that high volume sarcoma units achieve superior outcomes than low volume units. Due to the relatively small population, New Zealand is unlikely to generate a sufficient case volume to be considered high volume. To our knowledge, no well-established key performance indicators (KPIs) exist for retroperitoneal sarcoma surgery. In order to ensure quality standards we aim to propose KPIs which will act as a benchmark and a target for future quality improvement. METHODS: Potential KPIs were generated by internal discussion within the sarcoma team, taking into consideration available guidelines and evidence. Cases treated through the unit since 2015 were audited to determine historical performance against these KPIs. RESULTS: Eighty-six patients with primary retroperitoneal sarcomas were identified. 69% of patients were discussed at the sarcoma MDM prior to treatment, 62% underwent preoperative core biopsy. 82% of patients were seen and treated within target timeframes set by the Ministry of Health. 53% of patients underwent surgery with a sarcoma trained surgeon. R0/R1 rate was 88%. 90-day mortality was 4.6%. CONCLUSIONS: Surgical treatment of retroperitoneal sarcomas is complex and can be associated with significant morbidity. The proposed KPIs provide a measure of service performance and provide targets for quality improvement.

Mean affect and affect variability may interact to predict inflammation.

INTRODUCTION: Individuals with greater affect variability (i.e., moment-to-moment fluctuations possibly reflecting emotional dysregulation) are at risk for greater systemic inflammation, which is associated with cardiovascular disease. Some evidence suggests that affect variability is linked with poorer health indicators only among those with higher average levels of affect, particularly for positive affect (PA), and that associations may be non-linear. The present study sought to examine whether links between both PA and negative affect (NA) variability and inflammation are moderated by average level of affect. METHODS: Participants (N = 300, 50 % female, ages 21-70, 60 % non-Hispanic White, 19 % Hispanic, 15 % non-Hispanic Black) completed a lab assessment and provided a blood sample to measure systemic inflammation (i.e., TNF-α, IL-6, CRP). Affect was collected via a two-day ecological momentary assessment protocol where reports were collected about every 45-min during waking hours. Momentary affect ratings were averaged across both days (i.e., iM), separately for PA and NA, for each participant. Affect variability was calculated as the person-specific SD (i.e., iSD) of affect reports, separately for PA and NA. Linear and quadratic interactions were tested. Models included covariates for sex, race, and body mass index. RESULTS: There were significant interactions between NA iM and NA iSD predicting TNF-α (b = 6.54; p < 0.05) and between PA iM and PA iSD predicting IL-6 (b = 0.45; p < 0.05). Specifically, the association between these affect variability indicators and inflammatory markers were suggestive of a positive association among those with higher average affect but a negative association among those with lower average affect. There was no evidence of non-linear associations between affect and inflammation. DISCUSSION: Incorporating interactive effects between affect variability and average affect may be an important consideration in understanding affective-inflammatory associations.

Peer Network Counseling Effects on Substance Use: an Individual Participant Data Meta-Analysis Integrating Three Randomized Controlled Trials.

The current study describes an individual participant data meta-analysis (IPDMA) testing the efficacy of a peer-network counseling (PNC) intervention for preventing substance use escalation in adolescents and young adults. PNC has shown efficacy in reducing substance use among adolescents and young adults across small-scale randomized controlled trials (RCTs). Identifying expected large-scale effects and moderators is an important next step in guiding use of PNC in practice. To this end, we combine three small-scale RCTs to test PNC intervention effects on substance use change in a combined sample of 421 adolescents and young adults (50% intervention, 55% female, 69% Black/African-American, M age [SD] = 17.3 [2.2] years). Our approach combines latent change score modeling in a structural equation modeling (SEM) framework with study-level fixed effects to obtain (a) a more generalizable PNC effect than we could obtain with each constituent sample and (b) greater power and precision for individual-level moderation of treatment effects. We found that although PNC main effects on substance use outcomes (past 30-day cannabis, alcohol, tobacco, and drug use) were not significant, PNC effects were moderated by individual-level pre-intervention substance use frequency. PNC more strongly reduced drug use at the 1-month follow-up and cannabis use at the 3-month follow-up among participants who showed higher baseline use of these substances. Implications of our approach and findings for prevention researchers are discussed.

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission.

SARS-CoV-2 is primarily an airborne infection of the upper respiratory tract, which on reaching the lungs causes the severe acute respiratory disease, COVID-19. Its first contact with the immune system, likely through the nasal passages and Waldeyer's ring of tonsils and adenoids, induces mucosal immune responses revealed by the production of secretory IgA (SIgA) antibodies in saliva, nasal fluid, tears, and other secretions within 4 days of infection. Evidence is accumulating that these responses might limit the virus to the upper respiratory tract resulting in asymptomatic infection or only mild disease. The injectable systemic vaccines that have been successfully developed to prevent serious disease and its consequences do not induce antibodies in mucosal secretions of naïve subjects, but they may recall SIgA antibody responses in secretions of previously infected subjects, thereby helping to explain enhanced resistance to repeated (breakthrough) infection. While many intranasally administered COVID vaccines have been found to induce potentially protective immune responses in experimental animals such as mice, few have demonstrated similar success in humans. Intranasal vaccines should have advantage over injectable vaccines in inducing SIgA antibodies in upper respiratory and oral secretions that would not only prevent initial acquisition of the virus, but also suppress community spread via aerosols and droplets generated from these secretions.

A Multicenter Study of Left Ventricular Assist Device-Related Gastrointestinal Bleeding.

INTRODUCTION: Continuous left ventricular assist devices (LVADs) offer hemodynamic support in advanced and decompensated heart failure but are often complicated by gastrointestinal bleeding (GIB) in medically fragile patients. METHODS: We performed a retrospective analysis of 475 consecutive patients who underwent LVAD implantation at the Massachusetts General Hospital and Tufts Medical Center from 2008 to 2019 and identified 128 patients with clinically significant GIB. Clinical characteristics of each bleeding event, including procedures and interventions, were recorded. We examined LVAD patients with overt and occult presentations to determine diagnostic endoscopic yield and analyzed predictors of recurrent GIB. RESULTS: We identified 128 unique patients with LVAD implantation complicated by GIB. No significant difference was observed based on study center, underlying cardiomyopathy, race/ethnicity, serum indices, and medications used. Overt bleeders presented more commonly during LVAD implantation admission ( P = 0.001) than occult bleeders. Occult bleed presentations had only 1 lower and no middle GI bleed source identified, despite similar workups to overt bleeds. Destination therapy (e.g., among nontransplant candidates) LVAD implantation (odds ratio 2.38, 95% confidence interval 1.05-5.58) and a history of GIB (odds ratio 3.85, 95% confidence interval 1.29-12.7) were independently associated with an increased risk of recurrent GIB-related hospitalization. DISCUSSION: Our findings confirm a high rate of GIB, especially in destination LVAD patients, and show a low diagnostic yield for colonoscopy and middle GI bleed assessments in LVAD patients with occult bleeds. Overt bleeding was more common and associated with vascular malformations. Although endoscopic interventions stopped active hemorrhage, GIB often recurred.

Do Pediatric Hospitals Improve Operative Efficiency?

Background: In recent years there has been a push towards developing free standing pediatric facilities to provide care specifically towards pediatric patients. The purpose of this study was to determine if moving pediatric cases from a general hospital to a dedicated pediatric facility improved the quality and efficiency of surgical procedures. Methods: A retrospective review of pediatric patients undergoing posterior spinal fusion (PSF) was performed. All procedures were performed by one orthopaedic surgeon (SLW) from 2015 to 2019. The procedures were performed at a general hospital (GH) the first two years, and at a pediatric hospital (PH) the subsequent years. Data extracted included patient sex, age, and procedure type as well as procedure duration, operative turnover time, hospital length of stay, transfusion requirements, and operative delay. Exclusively pediatric adolescent idiopathic scoliosis (AIS) patients undergoing PSF were included due to the high volume and consistent surgical procedures therefore limiting confounding variables. Results: A total of five hundred PSF pediatric procedures were performed during the time period. After excluding non-adolescent idiopathic scoliosis cases, a total of 208 procedures were reviewed (105 at GH; 103 at PH). There was no statistical difference between the groups in regards to operative time (GH: 200 min, PH: 200 min; p=0.91), room turnover time (GH: 38 min, PH: 38 min; p=0.801), or rate of transfusion (GH: 20% PH: 30%; p=0.09). Length of stay was significantly shorter in the PH cohort compared to the GH cohort (4.35 vs. 3.84 days, p=0.0001). However, a smaller proportion of cases at the PH started on time compared to the GH (34% vs. 58%; p=0.0005). Conclusion: Overall, this study demonstrated that AIS procedures at the PH did show a statistically significant reduction in hospital length of stay. However, timely start of the procedure was less likely at this particular facility. Level of Evidence: III.

Surgical management of Graves' disease: historical context and single institution experience.

AIM: To describe indications and outcomes of total thyroidectomy for Graves' disease in a large New Zealand endocrine surgery unit, and to compare these results to international studies. METHODS: We analysed a prospectively collected database to describe the indications and outcomes of surgery for Graves' disease between December 2001 and January 2021. RESULTS: Among 64 patients who underwent total thyroidectomy at our tertiary centre for Graves' hyperthyroidism, Graves' ophthalmopathy and patient preference/aversion to radioactive iodine were the most common indications for surgery. Total thyroidectomy resulted in long-term control of thyrotoxicosis in all patients. There were no incidences of recurrent laryngeal nerve injury. One patient (1.6%) suffered permanent hypoparathyroidism. CONCLUSION: Total thyroidectomy is a safe and effective treatment for Graves' disease. In our population, total thyroidectomy functions as a second-line treatment for Graves' disease.

Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation.

BACKGROUND: Patients with KRAS-mutant cancers have limited treatment options. Here we present a phase I study of JNJ-74699157, an oral, selective, covalent inhibitor of the KRAS G12C isoform, in patients with advanced cancer harboring the KRAS G12C mutation. METHODS: Eligible patients (aged ≥18 years) who had previously received or were ineligible for standard treatment received JNJ-74699157 once daily on a 21-day cycle. Dose escalation was guided by a modified continual reassessment method. RESULTS: Ten patients (100 mg: 9 and 200 mg: 1) were enrolled. Tumor types included non-small cell lung cancer (n = 5), colorectal cancer (n = 4), and carcinoma of unknown primary site (n = 1). The median age was 65 (range: 36-74) years and median treatment duration was 2.91 (range: 0.5-7.5) months. Dose-limiting toxicities of grades 3-4 increased blood creatinine phosphokinase (CPK) were observed in 100 mg and 200 mg dose levels. The most common adverse event was increased blood CPK (6 patients). No significant clinical benefit was observed; the best response was stable disease in 4 patients (40%). CONCLUSION: Based on dose-limiting skeletal muscle toxicities and the lack of efficacy at the 100 mg dose, further enrollment was stopped. The safety profile of JNJ-74699157 was not considered favorable for further clinical development. CLINICALTRIALS.GOV IDENTIFIER: NCT04006301.

Daily Physical Activity, Sedentary Behavior and Alcohol Use in At-Risk College Students.

BACKGROUND: The college years present an opportunity to establish health behavior patterns that can track across adulthood. Health behaviors tend to cluster synergistically however, physical activity and alcohol have shown a positive association. PURPOSE: This study applied a multi-method approach to estimate between- and within-person associations between daily physical activity, sedentary behavior and alcohol use among polysubstance-using college students. METHODS: Participants were screened for recent binge drinking and either tobacco or cannabis use. They wore an activPAL4 activity monitor and a Secure Continuous Remote Alcohol Monitor continuously in the field for 11 days, and completed daily online questionnaires at the beginning of each day to report previous day physical activity, sedentary behavior, and alcohol consumption. RESULTS: Participants (N = 58, Mage = 20.5 years, 59% women, 69% White) reported meeting national aerobic physical activity guidelines (75%) and drinking 2-4 times in the past month (72%). On days when participants reported an hour more than usual of daily sedentary behavior, they reported drinking for less time than usual (γ = -.06). On days when participants took 1,000 more steps than usual, the longest episode of continuous transdermal alcohol detection was shorter (γ = -.03). CONCLUSIONS: Daily physical activity and sedentary behavior were negatively associated with time-based measures of alcohol use with the lowest risk on days characterized by both activity and sedentary behavior. Intensive longitudinal monitoring of time-based processes can provide new insights into risk in multiple behavior change and should be prioritized for future work.

Racial and ethnic differences in abdominal soft tissue sarcoma incidence in New Zealand: a retrospective audit.

BACKGROUND: Soft tissue sarcomas are a rare and heterogenous group of tumours. Anecdotally there seems to be an over representation of patients of Maori ethnicity presented at the Auckland Regional Sarcoma Multidisciplinary Meeting (MDM). To date no study has reported on ethnicity demographics of abdominal and retroperitoneal sarcoma in New Zealand. The aim of this study is to characterize the ethnicity distribution of patients discussed at the regional MDM. METHODS: A retrospective audit was performed of patients presented at the Auckland Regional Sarcoma MDM between January 2015 and December 2020 with abdominal sarcoma. Ethnicity documentation for these patients was reviewed. RESULTS: One hundred and twenty-four patients with intra-abdominal and retroperitoneal tumours were discussed at MDM with 61 proceeding for resection, of those 43 (70.5%) were primary tumours, 10 (16.4%) were recurrent tumours and 8 (13.1%) had metastatic disease. Liposarcoma made up 56 (45.2%) cases, Leiomyosarcoma 33 (26.6%), Other 35 (28.2%). Ethnicities for this group specifically were European 64 (51.6%), Maori 31 (25.0%), Pacific Peoples 17 (13.7%), Asian 6 (4.8%) and Other/unknown 3(2.4%). This was found to be statistically significantly different to the expected ethnicity distribution based on 2018 census data from North Island DHBs (χ2  = 19.55, p = 0.00), with Maori and Pacific Peoples being over-represented and Asian patients being under-represented. Recommendation for surgery did not appear to be related to ethnicity. CONCLUSION: Our descriptive data shows a higher proportion of patients of Maori ethnicity discussed through the North Island regional sarcoma MDM than we would expect comparted to ethnicity distribution in the general population. It is unclear whether this represents a true difference in incidence based on ethnicity.

A Rare Case of Waldenstrom Macroglobulinemia of the Rectosigmoid Colon.

Waldenstrom macroglobulinemia is an uncommon mature B-cell lymphoma characterized by monoclonal immunoglobulin M protein in peripheral blood and lymphoplasmacytic cells in bone marrow and/or extramedullary sites. The gastrointestinal tract is a rare site of involvement. The diagnosis is based on clinicopathologic findings, although somatic mutations, such as MYD88, can aid in the diagnosis. We present a patient with irregular stools diagnosed with Waldenstrom macroglobulinemia involving the rectosigmoid colon by histopathology and immunohistochemistry on colonic biopsies, immunoglobulin M protein in serum, clonal plasma cells in bone marrow, and MYD88 mutation in colonic and bone marrow specimens.

Alcohol Use as a Function of Physical Activity and Golfing Motives in a National Sample of United States Golfers.

Alcohol and physical inactivity are risk factors for a variety of cancer types. However, alcohol use often co-occurs with physical activity (PA), which could mitigate the cancer-prevention benefits of PA. Alcohol is integrated into the culture of one of the most popular physical activities for adults in the United States (U.S.), golf. This study examined how alcohol use was associated with total PA, golf-specific PA, and motives for golfing in a national sample of golfers in the U.S. Adult golfers (n = 338; 51% male, 81% White, 46 ± 14.4 years) self-reported alcohol use, golfing behavior and motives, and PA. Most (84%) golfers consumed alcohol, averaging 7.91 servings/week. Golf participation, including days/week, holes/week, and practice hours/week, was not associated with alcohol use. Golfers with stronger social motives were 60% more likely to consume alcohol. Weekly walking (incident risk ratio (IRR) = 7.30), moderate-to-vigorous PA (MVPA; IRR = 5.04), and total PA (IRR = 4.14) were associated with more alcohol servings/week. Golfers' alcohol use may be higher than the general adult population in the U.S. and contributes 775 extra kilocalories/week, a surplus that may offset PA-related energy expenditure and cancer-protective effects. Alcohol use interventions targeting golfers may facilitate weight loss and reduce cancer risk, especially for golfers motivated by social status.