Ball, Colleen T.

Abstract Background The mechanisms underlying metastatic latency in renal cell carcinoma (RCC) remain poorly understood. Methods This study evaluated 2 large independent cohorts for differences in tumor biology between patients who developed metastases early (≤1 year after nephrectomy) and those with late onset (>3 years). Results In the discovery cohort (n = 161), late metastatic RCC was associated with clear cell histology (88.9% vs 78.7%), lower pathological stage (pT1-2; 40.3% vs 18.0%), and favorable histopathological features including low grade (40.0% vs 2.3%), less sarcomatoid (5.6% vs 21.8%), and reduced necrosis (37.7% vs 78.3%; all P < .02). Late metastatic RCC tumors exhibited increased angiogenesis (63.5% vs 19.4%) and reduced inflammation (78.8% vs 50.0%; all P < .02) profiles. Genomic driver analyses revealed comparable rates of PBRM1 and SETD2 loss in late and early metastatic RCC, while BAP1 loss was significantly less common in late metastatic RCC (7.5% vs 27.1%; P < .02). In multivariable models, BAP1/PBRM1/SETD2 status and tumor necrosis emerged as key discriminators of late metastatic RCCs. These findings were confirmed in the second cohort (n = 307). Late metastatic RCC was enriched for fatty acid oxidation and angiogenesis pathways, supporting a less aggressive phenotype. This was further evidenced by a lower engraftment rate in murine models (0% vs 36.5%; P < .001) and significantly longer overall survival from the time of metastasis (median survival doubled, P < .001). Interestingly, late metastatic RCC shared genomic and phenotypic features with RCC that metastasizes to the pancreas, suggesting a common underlying biology influencing both metastatic latency and pancreatic tropism. Conclusions Overall, these findings advocate for recognition of late metastatic RCC because of its distinct biology and improved prognosis.

Abstract Women at increased risk for breast cancer may benefit from taking risk-reducing medication (RRM) with tamoxifen (tam). Historical uptake of tam in women who qualify has been low. Recent studies have shown low-dose tam to have similar efficacy to standard dosing, with lower risk for adverse events. In this study, we aimed to evaluate uptake, adherence, and tolerability of low-dose tam in women at increased risk for breast cancer and those with ductal carcinoma in situ (DCIS). In this two-site prospective study, women who qualified for breast cancer RRM were offered participation and received consultation with a breast specialist for discussion of RRM rationale, benefits, side effects, and risks. Patients received baseline and 1-year follow-up surveys. A total of 41 patients consented for participation, and 31 completed 1-year follow-up. After initial consultation, 90% (n = 37) reported good/complete understanding of breast cancer risk. Of patients included in 1-year follow-up, 5 had DCIS, 13 had high-risk intraepithelial lesion, and 13 qualified based on Breast Cancer Risk Assessment Tool/International Breast Intervention Study calculation. Furthermore, 74% (n = 23) of patients reported that they took low-dose tam after consultation, with 78.2% (n = 18) of those still taking medication at 1 year. Patients who continued medication had higher estimated breast cancer risk compared with those who discontinued (International Breast Intervention Study 10-year risk, 12.7% vs. 7.6%; P = 0.027). All patients with DCIS initiated low-dose tam, and only one patient with DCIS had discontinued at 1 year. Uptake of low-dose tam after informed discussion is high. Adherence and tolerability at 1-year follow-up improved compared with those with traditional dosing of tam. Prevention Relevance: tam has been used extensively for breast cancer prevention in high-risk women. Historical uptake has been low because of concern for side effects and poor tolerability. Herein, we demonstrate that in the clinical setting, effective patient education and offering of a low-dose option can improve uptake in this high-risk population. See related Spotlight, p. 545

Background For individuals living with chronic conditions like diabetes mellitus and obesity, there is a need for sustainable behavioral strategies and physiologic tools. These tools support identifying and addressing barriers to healthy eating, reducing body mass index (BMI), and building increased physical resilience in real time. Objective To evaluate whether a 12-week learning management system designed to combine nutritional intervention with education and coaching on improving emotional intelligence (EI) could alter cardiometabolic outcomes. Methods This pre-post prospective study enrolled 37 adult volunteers with BMI greater than 25 to participate in a 12-week learning management system. Primary (BMI, systolic blood pressure, diastolic blood pressure, low-density lipoprotein [LDL], high-density lipoprotein, and fasting glucose levels) and secondary self-reported outcomes were assessed at baseline, 12 weeks, and 6 months after enrollment using Short Form-36, Emotional Quotient Inventory (EQi), and Whole Health Index (WHI). Linear mixed-effects regression models with random effect were used to estimate changes in primary and secondary outcomes. We adjusted for multiple testing using Holm step-down method. Results BMI and LDL were the only primary endpoints lower at program completion and 6-month follow-up compared to baseline levels (−1.63 and −17.77 mg/dL, respectively; P < .001). Secondary outcomes showing statistically significant improvement from baseline to 6-month follow-up included energy/fatigue (Short Form-36), self-regard (EQi), decision-making (EQi), impulse control (EQi), stress management (EQi), Whole Brain – Form A (WHI), Whole Food – Form C (WHI), and Whole Body – Form D (WHI). Conclusion This study provides preliminary evidence that lifestyle programs combining nutritional interventions and EI can have a significant impact on BMI and LDL. Our study highlights the potential importance of both nutrition and EI in programs targeting diet and lifestyle modification.

Abstract Objective: Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. Methods: Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. Results: Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. Conclusion: There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.

Ventilator-associated pneumonia (VAP) has significant effects on patient outcomes, including prolonging the duration of both mechanical ventilation and stay in the intensive care unit (ICU). The aim of this study was to assess the association between non-invasive ventilation/oxygenation (NIVO) prior to intubation and the rate of subsequent VAP. This was a multicenter retrospective cohort study of adult patients who were admitted to the medical ICU from three tertiary care academic centers in three distinct regions. NIVO was defined as continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or high-flow nasal cannula (HFNC) for any duration during the hospitalization prior to intubation. The primary outcome variable was VAP association with NIVO. A total of 17,302 patients were included. VAP developed in 2.6% of the patients (444/17,302), 2.3% (285/12,518) of patients among those who did not have NIVO, 1.6% (30/1879) of patients who had CPAP, 2.5% (17/690) of patients who had HFNC, 8.1% (16/197) of patients who had BiPAP, and 4.8% (96/2018) of patients who had a combination of NIVO types. Compared to those who did not have NIVO, VAP was more likely to develop among those who had BiPAP (adj OR 3.11, 95% CI 1.80–5.37, p < 0.001) or a combination of NIVO types (adj OR 1.91, 95% CI 1.49–2.44, p < 0.001) after adjusting for patient demographics and comorbidities. The use of BiPAP or a combination of NIVO types significantly increases the odds of developing VAP once receiving IMV.

ObjectiveNew‐onset and relapsed dermatomyositis (DM) has been reported following SARS‐CoV‐2 infection or COVID‐19 vaccination. This study aims to show the characteristics of a DM cohort after COVID‐19 infection and vaccination.MethodsA retrospective review was performed on patients treated for DM between March 1, 2020, and October 31, 2022. Charts were evaluated for the presence of new‐onset DM or relapse of preexisting DM following either SARS‐CoV‐2 infection or COVID‐19 vaccination. Data on symptom onset, timing of vaccination, type of vaccination, and disease characteristics were collected.ResultsNinety‐eight patients treated for DM at our institution in the Division of Rheumatology were included. In total, 12 of 98 patients (12.2%) experienced DM symptoms (either incident or relapse) following either infection or vaccination. Of the 12 patients who developed incident disease or relapse, 7 (58.3%) developed postinfection symptoms, and 8 (66.7%) developed symptoms after vaccination (3 patients had symptoms following both infection and vaccination). The mean onset of symptoms following COVID‐19 infection was 3.2 days (median 0.5 days), and mean onset following COVID‐19 vaccination was 5.75 days (median 3.5 days). Nine of 12 patients (75%) had a positive myositis‐specific antibody, and the remaining 3 (25%) had myositis‐associated antibodies. There was no predominant vaccine associated with the development of postvaccination DM symptoms.ConclusionThis retrospective review revealed a strong temporal relationship between DM symptoms and COVID‐19 infection or vaccination in 12.2% of all patients with DM evaluated in our clinic during the pandemic. Additional studies are required to understand the possible pathophysiology behind this association.