The association between physical activity time and neuropathy in longstanding type 1 diabetes: A cross-sectional analysis of the Canadian study of longevity in type 1 diabetes

AimPhysical activity (PA) is recommended to improve glycemic control in T1D; however, the effect of PA on distal symmetric polyneuropathy (DSPN) and cardiac autonomic function in longstanding T1D is unknown.MethodsData from 75 participants were collected as part of the Canadian Study of Longevity in T1D. Participants completed a physical exam, medical history, extensive complications phenotyping and reported their daily PA from the preceding 12-months. Pearson and Spearman correlations were used to assess PA time and complications variables. Linear regression was used to test associations between PA time, neurological and electrophysiological measures. Univariable regression was used to indicate the change in the given independent variables associated with a 30-min increase in PA per week.ResultsParticipants were 66 ± 8 years old with diabetes duration of 54 [52,58] years, HbA_1c was 7.3 ± 0.8, 65(89%) had DSPN. Weekly PA time was 156 ± 132 min, and 35(47%) reported ≧150 min/week. Participants with DSPN reported lower PA time compared to individuals without DSPN (141 ± 124 min/week vs. 258 ± 129 min/week; p = 0.015). PA time was associated with better cooling detection threshold (r = 0.24; p = 0.043), peroneal and sural amplitude (r = 0.36; p = 0.0017, r_s = 0.26; p = 0.024) and conduction velocity (r_s = 0.28; p = 0.015, r = 0.23; p = 0.050). Linear regression adjusting for age and HbA1c, showed that for each 30-min of PA there was a 0.09mv higher peroneal amplitude (p = 0.032) and 0.048 ms lower peroneal F-wave latency (p = 0.022).ConclusionIn longstanding T1D, PA time is associated with superior large nerve fibre function in the lower limbs and some better measures of small nerve fibre function.     

Evaluating the diagnostic value of zoom endoscopic surveillance compared to routine biopsy after intestinal transplantation

BackgroundAfter intestinal transplantation, close allograft monitoring especially during the early postoperative period is crucial since the intestine is a highly immunogenic organ. Current protocols are based on endoscopic and histologic examination with the latter one being linked to the risk of bleeding and perforation.AimsEvaluation of the diagnostic value of endoscopy utilizing magnification to predict acute cellular rejection compared to routine allograft biopsies.MethodsFourteen patients underwent the protocol with longitudinal zoom endoscopic and histological graft monitoring during the first year after transplantation. The intestinal mucosa was analyzed during endoscopy utilizing the SASAKI score while a minimum of two biopsies were taken during each examination. A new graduation of severity for acute cellular rejection based on the findings of the SASAKI score is established.ResultsEndoscopic findings of 385 examinations and more than 1000 intestinal allograft biopsies were analyzed. A total of 7 acute cellular rejection episodes in 6/14 patients occurred. Allograft endoscopy was able to diagnose ACR with a sensitivity of 76% and a specificity of 82%.ConclusionsOur results will be critical for refining protocols for allograft monitoring after intestinal transplantation thus paving the way towards less invasive measures.     

Disparity in Utilization of Multiagent Therapy for Acute Promyelocytic Leukemia in the United States

BackgroundDespite high rate of cure in acute promyelocytic leukemia (APL) in clinical trials, outcomes in real-world practice are dismal. We utilized National Cancer Database (NCDB) to explore utilization of multiagent therapy in APL and identify any disparities in treatment in real-world practices.Patients and MethodsNCDB categorizes use of systemic chemotherapy into single agent versus multiagent therapy. Some patients received hormonal therapy, immunotherapy, and unknown therapy; details of these treatments could not be ascertained. We therefore used multiple logistic regression analysis to evaluate effects of covariates on the probability of multiagent therapy use in 6678 patients.ResultsCompared to patients >60 years, patients aged 0 to 18 years (hazard ratio[HR] 3.2, 95% confidence interval [CI] 1.8-5.5, P< .0001), 19 to 40 years (HR 1.6, 95% CI 1.03-2.54, P= .03), and 41 to 60 years (HR 1.6, 95% CI 1.3-1.9, P< .0001) were more likely to receive multiagent therapy. Patients with Charlson comorbidity index (CCI) of 0 (HR 1.6, 95% CI 1.2-2.3, P= .001) and CCI of 1 (HR 1.4, 95% CI 1.0-1.9, P= .04) had a higher likelihood of receiving multiagent therapy than patients with CCI ≥ 3. Patients treated at academic cancer centers, compared to those treated at community cancer center (HR 0.5, 95% CI 0.3-0.7, P= .001), comprehensive community cancer center (HR 0.7, 95% CI 0.6-0.8, P< .0001), and integrated network cancer center (HR 0.8, 95% CI 0.6-0.9, P= .02) were more likely to be treated with multiagent therapy. Compared to the patients with private insurance, those with Medicaid had increased likelihood (HR 1.2, 95% CI 1.0-1.4, P= .04) whereas uninsured patients had a lower likelihood of receiving multiagent therapy (HR 0.6, 95% CI 0.5-0.8, P= .0005).ConclusionTo our knowledge, this study is the first and the largest scale analysis of treatment practices in APL in real-world practices. Our findings highlight significant disparities in treatment of APL based on age, insurance, and health-system factors.     

Lymph node micrometastasis of poorly differentiated node-negative gastric cancer risks a worse-than-expected survival outcome under standard management algorithm

BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types.Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN.ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78.ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.     

Oncologic benefit of adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and curative surgery with selective lateral pelvic lymph node dissection: An international retrospective cohort study

IntroductionIntensive local treatment comprising total mesorectal excision (TME) with selective lateral pelvic lymph node dissection (LPND) after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) has received attention among clinicians treating rectal cancer. It remains unclear whether adjuvant chemotherapy (ACT) after intensive local treatment is beneficial for these patients. We evaluated the oncologic benefit of ACT for patients with LARC who received intensive local treatment.Materials and methodsThis international multicentre retrospective cohort study included 737 patients treated in Japan and Korea between 2010 and 2017. The effectiveness of ACT on recurrence-free survival (RFS) was evaluated using univariable and multivariable Cox proportional hazards models, with subgroup analyses to identify subpopulations potentially benefiting from ACT.ResultsThe median follow-up was 49 months; the 5-year RFS and local recurrence rates for the entire cohort were 72.1% and 4.9%, respectively; 514 patients (69.7%) received adjuvant chemotherapy, without an oncologic benefit (hazard ratio, 1.14; 95% confidence interval [CI]: 0.79–1.68) demonstrated in the multivariable Cox regression analysis. In subgroup analyses, the distributions of the 95% CI in patients aged ≥70 years and those with ypStage 0 tended to place a disproportionate emphasis that favoured the non-ACT treatment strategy.ConclusionDespite achieving good local control with intensive local treatment strategy, the effectiveness of ACT for the LARC patients with CRT followed by TME with selective LPND was not proved. Elderly patients and those with ypStage0 may not receive benefit from ACT after CRT and TME ± LPND.     

Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke

ObjectiveTo investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health.DesignRandomized controlled trial.SettingThe general communities of Baltimore, Maryland, and Atlanta, Georgia.ParticipantsTwo hundred forty-six older (>50 years), chronic (>6 months) survivors of stroke (N=246) with hemiparetic gait were recruited, with 51 completing pre-intervention testing and 39 completing postintervention testing. Participants were required to have completed all conventional physical therapy and be capable of walking 3 minutes on a treadmill (N=246).InterventionParticipants completed 6 months of 2 times/wk stretching or balance (ST; n=19) or 3 times/wk aerobic treadmill rehabilitation (TM; n=20;).Main Outcome Measure(s)Peak oxygen uptake rate (V?o₂peak), 6-minute walking distance (6MWD), fasting plasma glucose, insulin, oxidative stress, and inflammatory biomarkers were assessed pre- and postintervention. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated.ResultsPhysical function and metabolic health parameters tended to improve after TM but not ST (ST vs TM: V?o₂peak: ?9% vs 24%, P<.01; 6MWD: 1% vs 15%, P=.05; insulin: ?1% vs ?31%, P=.05; HOMA-IR: ?3% vs ?29%, P=.06). Plasma concentrations of nitrotyrosine, protein carbonyls, and oxidized low-density lipoprotein (oxLDL) tended to decrease from pre-intervention concentrations in response to TM compared to ST (ST vs TM: nitrotyrosine: 2% vs ?28%, P=.01; protein carbonyls: ?4% vs ?34%, P=.08; oxLDL: ?3% vs ?32%, P<.01). Changes in circulating concentrations of C-reactive protein, protein carbonyls, and oxLDL were negatively associated with changes in V?o₂peak and 6MWD (r's=?0.40 to ?0.76) and positively associated with fasting plasma insulin and HOMA-IR (r's=0.52-0.81, Ps<.01).ConclusionsSix months of TM tends to be associated with increased functional capacity and reduced oxidative stress in chronic stroke survivors. Our findings identify potentially modifiable systemic markers of inflammation and oxidative stress important to stroke rehabilitation and provide potential targets for novel therapeutics in future studies.     

Effectiveness of a community organizing intervention on mortality and its equity among older residents in Japan: A JAGES quasi-experimental study

Interventions that involve key aspects of community organizing, such as quantitative community assessments and organizational partnership support for the community, may promote residents' health. We evaluated the effectiveness of this form of intervention on mortality and its variability across individual-level household equivalized income tertiles, comparing 52,858 residents aged 65 and above in 12 intervention municipalities to 39,006 residents in nine control municipalities in Japan. During 1,166 days of follow-up, the adjusted hazard ratio for cumulative mortality among men in the intervention municipalities was 0.92 (95% confidence interval: 0.86, 0.99) compared to those in the control group, with similar results being observed across all income levels. Active utilization of data to evaluate communities and building intersectoral partnerships might lower older male residents’ mortality risk, regardless of their income status.