Citations

Abstract Purpose: Mucosal melanoma is a rare, aggressive form of melanoma with extremely high recurrence rates despite definitive surgical resection with curative intent. Currently there is no consensus on adjuvant therapy. Data on checkpoint inhibitors for adjuvant therapy are lacking. Patients and Methods: We performed a single-arm, multicenter clinical trial using “flip dose” ipilimumab (1 mg/kg q3w × 4 cycles), and nivolumab (3 mg/kg q3w × 4 cycles), then nivolumab 480 mg q4w × 11 cycles to complete a year of adjuvant therapy. Participants must have had R0/R1 resection ≤90 days before registration, no prior systemic therapy (adjuvant radiotherapy allowed), ECOG 0/1, and no uncontrolled autoimmune disease or other invasive cancer. Patients were recruited through the Midwest Melanoma Partnership/Hoosier Oncology Network. Results: From September 2017 to August 2021, 35 patients were enrolled. Of these, 29 (83%) had R0 resections, and 7 (20%) received adjuvant radiotherapy. Median age was 67 years, 21 (60.0%) female. Recurrence-free survival (RFS) rates at 1 and 2 years were 50% [95% confidence interval (CI), 31%–66%] and 37% (95% CI, 19%–55%), respectively. Overall survival rates at 1 and 2 years were 87% (95% CI, 68%–95%) and 68% (95% CI, 46%–83%), respectively. Median RFS was 10.3 months (95% CI, 5.7–25.8). Most common grade 3 toxicities were diarrhea (14%), hypertension (14%), and hyponatremia (11%), with no grade 4/5 toxicities. Conclusions: Flip-dose ipilimumab and nivolumab after resection of mucosal melanoma is associated with outcomes improved over that of surgical resection alone. Long-term follow-up, subgroup analyses and correlative studies are ongoing.

PURPOSE Breast-conserving therapy (BCT) is the preferred treatment for unifocal breast cancer (BC). The oncologic safety of BCT for multiple ipsilateral breast cancer (MIBC) has not been demonstrated in a prospective study. ACOSOG Z11102 (Alliance) is a phase II, single-arm, prospective trial designed to evaluate oncologic outcomes in patients undergoing BCT for MIBC. PATIENTS AND METHODS Women age 40 years and older with two to three foci of biopsy-proven cN0-1 BC were eligible. Patients underwent lumpectomies with negative margins followed by whole breast radiation with boost to all lumpectomy beds. The primary end point was cumulative incidence of local recurrence (LR) at 5 years with an a priori rate of clinical acceptability of <8%. RESULTS Among 270 women enrolled between November 2012 and August 2016, there were 204 eligible patients who underwent protocol-directed BCT. The median age was 61 years (range, 40-87 years). At a median follow-up of 66.4 months (range, 1.3-90.6 months), six patients developed LR for an estimated 5-year cumulative incidence of LR of 3.1% (95% CI, 1.3 to 6.4). Patient age, number of sites of preoperative biopsy–proven BC, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories were not associated with LR risk. Exploratory analysis showed that the 5-year LR rate in patients without preoperative magnetic resonance imaging (MRI; n = 15) was 22.6% compared with 1.7% in patients with a preoperative MRI (n = 189; P = .002). CONCLUSION The Z11102 clinical trial demonstrates that breast-conserving surgery with adjuvant radiation that includes lumpectomy site boosts yields an acceptably low 5-year LR rate for MIBC. This evidence supports BCT as a reasonable surgical option for women with two to three ipsilateral foci, particularly among patients with disease evaluated with preoperative breast MRI.

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P &lt; 0.001) and autoimmune disease multimorbidity (AIDm) (P &lt; 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P &lt; 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

ObjectiveTo discuss a case of hyaluronic acid filler displaying as PET avid resulting in a false positive for local recurrence and review of the literature of how filler presents on PET.Study DesignCase report and literature review.MethodsRetrospective case review of a patient with angiosarcoma with PET‐MRI positivity after hyaluronic acid filler injection. Review of the literature was performed.ResultsA 49‐year‐old female with low grade angiosarcoma of the right cheek pT1N0M0 was treated with wide local excision and staged reconstruction with cervicofacial advancement flap with subsequent adjuvant radiation therapy. Surveillance PET/MRI scans were conducted every 3 months. After one year without recurrence, HA injectable filler was offered to correct resultant right facial soft tissue defect. The patient proceeded with HA filler and was counseled on the risk of local increased SUV on imaging. Her PET/MRI 3 months later revealed postsurgical changes in the right premaxillary soft tissues with associated low‐grade hypermetabolism with max SUV 1.8, which elevated from prior max SUV 0.9. Contralateral left maxillary soft tissues revealed max SUV 0.8. Biopsy was initially favored for concern of local recurrence until the potential for filler to be associated with elevated SUV was discussed. Further evaluation with MRI showed diffusely increased T2 signal with some trace enhancement in the region of PET activity, confirming that findings were consistent with HA filler augmentation per the neuroradiologist team.ConclusionsFillers, including hyaluronic acid, are associated with elevated SUV on PET‐CT. Otolaryngologists should be aware of these features to improve patient counseling, avoid unnecessary procedures, and reduce patient anxiety. Laryngoscope, 133:2951–2953, 2023

Objectives: Administrative criteria are often used to define COVID-19 outcomes despite challenges in differentiating hospitalization “for” vs “with” COVID-19 and unknown reliability for identifying COVID-related cardiopulmonary complications. We implemented a protocol to adjudicate COVID-related events across 14 studies participating in C4R. Methods: C4R cohorts ascertained COVID-related hospitalizations and deaths via questionnaires or ongoing surveillance. Medical records were reviewed by C4R physicians using a standardized protocol to assign COVID-related diagnoses as definite or probable. C4R diagnoses were compared against ICD codes assigned to the events. This report includes data from events centrally adjudicated by C4R as of September 2022. Results: Among 144 events ascertained across 7 cohorts as potentially COVID-related, SARS-CoV-2 infection was confirmed in 107/117 (91%) non-fatal hospitalizations and 26/27 (96%) deaths. Of confirmed infections, COVID-19 illness was diagnosed as the cause of 101/107 (94%) hospitalizations and 24/26 (92%) deaths ( Table ). Of non-fatal hospitalizations with infection, 72% were diagnosed with severe or critical COVID-19, 78% with COVID-associated pneumonia, and 29% with renal failure; other complications were less common. C4R review did not validate diagnoses indicated by ICD codes for 1 COVID-19 infection, 5 pneumonias, 1 stroke, and 7 renal failure cases. C4R review did identify diagnoses that were not ICD-coded for 13 infections, 31 pneumonias, 6 myocardial infarctions, 5 venous thromboses, and 21 renal failure cases. Conclusions: Protocolized medical records review by C4R confirmed COVID-19 as the cause of hospitalization or death in 87% of events ascertained as potentially COVID-related and 94% of those in which SARS-CoV-2 infection was confirmed. Both false-positive and false-negative misclassification by ICD criteria was observed. Protocolized review may be useful to identify and validate COVID-related events for epidemiologic research.

Background: African-American (AA) adults have a higher prevalence of cardiovascular (CV) risk factors, leading to higher CV disease mortality than White adults. Prior findings of our mobile health (mHealth) lifestyle intervention (FAITH! App) demonstrated efficacy in promoting ideal cardiovascular health (CVH) in AAs. Hypothesis: We hypothesized that the intervention group with preexisting CV risk factors would have a greater increase in LS7 scores than the control group with the same risk factors following use of the FAITH! App. Methods: A cluster randomized controlled trial was conducted among AAs from 16 churches in Minnesota. The intervention included culturally relevant, LS7-focused education modules, diet/physical activity self-monitoring and a group sharing board. A subgroup of participants with ≥1 diagnosis of overweight/obesity, hyperlipidemia, hypertension (HTN) or diabetes was examined. The primary outcome was change in LS7 score—a measure of CVH ranging from poor to ideal (range 0-14 points)—at 6 months post-intervention. Results: Forty-nine participants (75.5% female) were included in the intervention (n=20; mean age [SD]: 58.8 [9.5]) or control (n=29, mean age [SD]: 52.5 [10.7]) groups (Table 1). There was no significant difference in the CV risk factor prevalence between the two groups. There was a greater increase in LS7 score in the intervention vs. control group across all CV risk factors, with significant differences among those with overweight/obesity (1.77, p<.0001) and with 2+ or 3+ CV risk factors (1.00, p=.03; 1.09, p=.04). Compared to the control group, the increase in the percentage of participants with ideal LS7 scores in the intervention group was higher among those with overweight/obesity, HTN, diabetes and 3+ CV risk factors. Conclusions: Our culturally tailored mHealth lifestyle intervention was associated with notable increases in LS7 scores among AAs with preexisting CV risk factors, suggesting its efficacy in improving CVH among this population.

Background: Black women demonstrate higher levels of stress over the life course compared to Black men, White men, and White women, which may help to explain their higher cardiovascular disease (CVD) morbidity and mortality. Despite implications for primary and secondary CVD prevention and racial disparities, few interventions have targeted psychosocial stress to improve blood pressure (BP) levels among Black women. Objective: To test whether a theory-driven, culturally tailored, community intervention focused on the stress experiences of Black women improves psychological outcomes and BP levels. Methods: The “Art for Hearts” pilot trial sought to examine the feasibility, acceptability, and preliminary efficacy of a novel intervention encouraging creative self-expression. This individual level, single-arm pilot trial recruited self-identified Black women ≥18 years. Women participated in an 8-week program, including 4 art sessions with a community artist (a self-identified Black woman) accompanied by a moderated focus group discussion and 4 heart health education sessions (facilitated by a Black woman researcher) on home BP monitoring, stress management techniques, diet/physical activity, and patient-clinician communication. All sessions were conducted in-person in a community space. Participants completed a survey including self-rated stress (scale of 0 to 7), perceived stress (PSS-10), depressive symptoms (PHQ-8), and anxiety symptoms (GAD-7) at baseline and 8 weeks. BP was measured by a trained assessor at baseline and 8 weeks as well as before and after each session. We examined within-participant changes in psychological measures as well as mean systolic and diastolic BP from baseline to 8 weeks. Results: The study included 18 Black women with a mean age of 44.1 (SD=15.4) years. Women were highly educated (36.8% with a graduate/professional degree) and 11.1% earned an income of ≥$100,000. Mean systolic BP was 114 mmHg and mean diastolic BP was 66 mmHg at baseline. From baseline to 8 weeks, self-rated stress level decreased by 1-point (from 4.36 to 3.18; p=0.005) (scale range: 0 -7). Perceived stress (-1.08; p=0.58) and anxiety (-1.33; p=0.09) decreased from baseline to 8 weeks; however, these changes did not achieve statistical significance. Depressive symptoms significantly improved from baseline to 8 weeks (19.13 to 13.38; p=0.044). There were no differences in systolic or diastolic BP from baseline to follow-up. The intervention was deemed feasible and acceptable with an attendance rate of >80%; participants expressed high overall satisfaction with the intervention. Conclusion: A tailored 8-week pilot intervention using painting self-expression demonstrated feasibility, acceptability, and preliminary efficacy for improving self-rated stress and depressive symptoms. No effects were demonstrated on BP in this sample.

Introduction: The prevalence of nonalcoholic fatty liver disease (NAFLD) in US adults is over 25%, yet the etiology of lifestyle factors in the development of NAFLD remains understudied. We examined the independent and joint associations among aerobic physical activity (PA) intensity (moderate, vigorous) and PA type (aerobic, muscle strengthening), television viewing (TV), and odds of NAFLD. Hypothesis: Higher levels of aerobic and muscle strengthening PA are associated with lower odds of NAFLD, and higher levels of TV are associated with higher odds of NAFLD. Methods: We analyzed data from Year 25 of the CARDIA cohort study. Our exposures (moderate and vigorous aerobic and muscle strengthening PA, TV; hr/wk) were assessed using validated questionnaires. Our outcome (NAFLD) was measured using non-contrast computed tomography. We constructed multivariable logistic regression models to examine the independent and joint associations between PA (moderate or vigorous aerobic and strength), TV, and odds of NAFLD. Covariates were sex, age, race, study center, education, diet, smoking status, alcohol consumption, and waist circumference. Results: 2726 participants (648 with NAFLD) were analyzed (mean (SD) age, 50.1 (3.6) years; 49% Black; 43% male). Fully adjusted odds ratios per IQR-standardized continuous PA and TV were: moderate aerobic PA (IQR = 4.3), 0.93 (95% CI, 0.81-1.07); vigorous aerobic PA (IQR = 1.9), 0.63 (95% CI, 0.55-0.73); muscle strengthening PA (IQR = 3.3), 0.80 (95% CI, 0.07-0.92); and TV (IQR = 14.0), 1.20 (95% CI, 1.10-1.32). Only vigorous aerobic PA remained statistically significant after waist circumference adjustment, 0.83 (95% CI, 0.70-0.98). A PA-TV index model (Figure) indicated the combination of higher vigorous aerobic and muscle strengthening PA and lower TV resulted in an odds ratio of 0.23 (95% CI, 0.15-0.37). Conclusion: Concurrent higher levels of vigorous aerobic PA (≥2 hr/wk), muscle strengthening PA (≥2 hr/wk), and lower levels of TV (<7 hr/wk) were associated with 77% lower odds of NAFLD.