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Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study.
Gross, ND, Miller, DM, Khushalani, NI, Divi, V, Ruiz, ES, Lipson, EJ, Meier, F, Su, YB, Swiecicki, PL, Atlas, J, et al
The Lancet. Oncology. 2023;(11):1196-1205
Abstract
BACKGROUND We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. METHODS This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing. FINDINGS Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. FUNDING Regeneron Pharmaceuticals and Sanofi.
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Effectiveness of restricted diet with a plate in patients with type 2 diabetes: A randomized controlled trial.
Zhang, Y, Han, H, Chu, L
Primary care diabetes. 2022;(3):368-374
Abstract
BACKGROUND In view of the complexity of dietary and nutritional education for most patients with type 2 diabetes mellitus (T2DM), a simplified approach called the "restricted diet with a plate" or "plate model" is recommended. PURPOSE To evaluate whether the plate model can effectively improve glycemic control and cardiovascular risk markers in type 2 diabetes mellitus (T2DM), while reducing the time devoted to education and avoiding weight gain. METHODS The study was a randomized, multicenter, controlled study, conducted between October 2018 and October 2019, among patients with T2DM living in Nanjing. The study included 419 participants who were randomly divided into a plate group and a counting group. The plate model included three components: a low-literacy, color leaflet containing the explanation and composition of the plate model, health education, and medical visits. Patients in the counting group received health education, group medical visits, and a paper booklet containing traditional carbohydrate counting education. Primary outcomes were glycemic control and weight. RESULTS Participants in the plate model reduced HbA1c by 0.7% in the first three months, and reduced to a greater extent at six months (1.44%), but this was not sustained, and HbA1c increased slightly over the following six months. Fasting plasma glucose (FPG) and 2-h postprandial glucose (2hPG) values were significantly reduced at the endpoint in the plate model (9.25 ± 1.72% vs. 7.44 ± 0.88%, P = 0.008; 12.07 ± 2.94 vs. 8.35 ± 1.99%; P = 0.004); however, the 2hPG values decreased most significantly. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly in the plate group, which occurred at six months and lasted for 12 months. In the first three months, the average weight loss in the plate group was 1.2 kg/month (95% CI 0.92-1.48), and in the fourth to twelfth months, the average weight gain was 0.21 kg/month (95% CI 0.08-0.34). There was significant difference in education time between the groups (17.3 ± 4.42 vs. 38.6 ± 12.63; P < 0.001). CONCLUSIONS The plate model is at least as effective as the counting model over the short term for glycemic control and perhaps even better for weight and lipid control. Plate model has the potential to improve education of those with low health literacy by reducing reading demands.
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Impact of hemodialysis and post-dialysis period on granular activity levels.
Larkin, JW, Han, M, Han, H, Guedes, MH, Gonçalves, PB, Poli-de-Figueiredo, CE, Cuvello-Neto, AL, Barra, ABL, de Moraes, TP, Usvyat, LA, et al
BMC nephrology. 2020;(1):197
Abstract
BACKGROUND Physical activity (PA) is typically lower on hemodialysis (HD) days. Albeit intradialytic inactivity is expected, it is unknown whether recovery after HD contributes to low PA. We investigated the impact of HD and post-HD period on granular PA relative to HD timing. METHODS We used baseline data from the HDFIT trial conducted from August 2016 to October 2017. Accelerometry measured PA over 1 week in patients who received thrice-weekly high-flux HD (vintage 3 to 24 months), were clinically stable, and had no ambulatory limitations. PA was assessed on HD days (0 to ≤24 h after start HD), first non-HD days (> 24 to ≤48 h after start HD) and second non-HD day (> 48 to ≤72 h after start HD). PA was recorded in blocks/slices: 4 h during HD, 0 to ≤2 h post-HD (30 min slices), and > 2 to ≤20 h post-HD (4.5 h slices). Blocks/slices of PA were captured at concurrent/parallel times on first/second non-HD days compared to HD days. RESULTS Among 195 patients (mean age 53 ± 15 years, 71% male), step counts per 24-h were 3919 ± 2899 on HD days, 5308 ± 3131 on first non-HD days (p < 0.001), and 4926 ± 3413 on second non-HD days (p = 0.032). During concurrent/parallel times to HD on first and second non-HD days, patients took 1308 and 1128 more steps (both p < 0.001). Patients took 276 more steps and had highest rates of steps/hour 2-h post-HD versus same times on first non-HD days (all p < 0.05). Consistent findings were observed on second non-HD days. CONCLUSIONS PA was higher within 2-h of HD versus same times on non-HD days. Lower PA on HD days was attributable to intradialytic inactivity. The established PA profiles are of importance to the design and development of exercise programs that aim to increase activity during and between HD treatments. TRIAL REGISTRATION HDFIT was prospectively registered 20 April 2016 on ClinicalTrials.gov (NCT02787161).
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Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance.
Most, J, Gilmore, LA, Smith, SR, Han, H, Ravussin, E, Redman, LM
American journal of physiology. Endocrinology and metabolism. 2018;(4):E396-E405
Abstract
Calorie restriction (CR) triggers benefits for healthspan including decreased risk of cardiometabolic disease (CVD). In an ancillary study to CALERIE 2, a 24-mo 25% CR study, we assessed the cardiometabolic effects of CR in 53 healthy, nonobese (BMI: 22-28 kg/m2) men ( n = 17) and women ( n = 36). The aim of this study was to investigate whether CR can reduce risk factors for CVD and insulin resistance in nonobese humans and, moreover, to assess whether improvements are exclusive to a period of weight loss or continue during weight maintenance. According to the energy balance method, the 25% CR intervention ( n = 34) produced 16.5 ± 1.5% (mean ± SE) and 14.8 ± 1.5% CR after 12 and 24 mo (M12, M24), resulting in significant weight loss (M12 -9 ± 0.5 kg, M24 -9 ± 0.5 kg, P < 0.001). Weight was maintained in the group that continued their habitual diet ad libitum (AL, n = 19). In comparison to AL, 24 mo of CR decreased visceral (-0.5 ± 0.01 kg, P < 0.0001) and subcutaneous abdominal adipose tissue (-1.9 ± 0.2kg, P < 0.001) as well as intramyocellular lipid content (-0.11 ± 0.05%, P = 0.031). Furthermore, CR decreased blood pressure (SBP -8 ± 3 mmHg, P = 0.005; DBP -6 ± 2 mmHg, P < 0.001), total cholesterol (-13.6 ± 5.3 mg/dl, P = 0.001), and LDL-cholesterol (-12.9 ± 4.4 mg/dl, P = 0.005), and the 10-yr risk of CVD-disease was reduced by 30%. Homeostasis model assessment of insulin resistance (HOMA-IR) decreased during weight loss in the CR group (-0.46 ± 0.15, P = 0.003), but this decrease was not maintained during weight maintenance (-0.11 ± 0.15, P = 0.458). In conclusion, sustained CR in healthy, nonobese individuals is beneficial in improving risk factors for cardiovascular and metabolic disease such as visceral adipose tissue mass, ectopic lipid accumulation, blood pressure, and lipid profile, whereas improvements in insulin sensitivity were only transient.
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Adherence is a multi-dimensional construct in the POUNDS LOST trial.
Williamson, DA, Anton, SD, Han, H, Champagne, CM, Allen, R, LeBlanc, E, Ryan, DH, McManus, K, Laranjo, N, Carey, VJ, et al
Journal of behavioral medicine. 2010;(1):35-46
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Abstract
Research on the conceptualization of adherence to treatment has not addressed a key question: Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program. This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for promoting weight loss. A sample of 811 overweight/obese adults was recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of energy); (2) High fat (40%), average protein (15%); (3) Low fat (20%), high protein (25%); (4) High fat (40%), high protein (25%). Throughout the first 6 months of the study, a computer tracking system collected data on eight indicators of adherence. Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses. Two factors (accounting for 66% of the variance) were identified and confirmed: (1) behavioral adherence and (2) dietary adherence. Behavioral adherence did not differ across the four interventions, but prescription of a high fat diet (vs. a low fat diet) was found to be associated with higher levels of dietary adherence. The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional, with two dimensions: behavioral and dietary adherence.