The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study

Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCγ receptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone versus rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. The primary endpoint was time to treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence the activity of rituximab as a single agent, did not affect time to treatment failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These results were consistent even when the analysis was conducted by intention to treat, indicating that different chemotherapy regimens and loads did not interact differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time to treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (P=0.001; q<0.1), but not in arms in which patients did not receive doxorubicin (i.e., the rituximab-cyclophosphamide-vincristine-prednisone and rituximab-fludarabine-mitoxantrone arms). The impact of MLH1 on time to treatment failure was independent after adjusting for the Follicular Lymphoma International Prognostic Index and other potential confounding variables by multivariate analysis. These data indicate that MLH1 genotype is a predictor of failure to benefit from rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone treatment in advanced follicular lymphoma and confirm that FCGR2A and FCGR3A polymorphisms have no impact when follicular lymphoma is treated with rituximab plus chemotherapy (clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00774826","term_id":"NCT00774826"}}NCT00774826).     

Physical activity reduces the risk for hospitalizations in patients with type 2 diabetes

The purpose of this study is to examine factors and variables associated with hospitalizations in type 2 diabetes mellitus (T2DM). This is a 2-year follow-up study of 145 patients (87 women/58 men), mean age 55.0 ± 3.3 (40 to 60). At baseline, comorbidity severity was evaluated by the Charlson Comorbidity Index (CCI), depressive symptoms by the Beck Depression Inventory (BDI II), sleep quality by the Pittsburgh Sleep Quality Index, daytime sleepiness by the Epworth Sleepiness Scale, and levels of physical activity by the International Physical Activity Questionnaire (IPAQ). Arterial hypertension (74 %), cardiovascular pathology (30 %), and stroke (10 %) were found at baseline. After 2 years, eight cases (6 %) developed a new stroke. At baseline, 70 % (N = 102) of patients had a sedentary life, and 30 % (N = 43) were irregularly active. Two years later, the number of patients with a sedentary life decreased to 52 % (N = 76), and an increase of irregularly active (35 %, N = 51) and active patients (13 %, N = 18; p < 0.005) was observed. Twenty-four individuals (16 %) reported at least one hospitalization. Logistic regression analysis showed that the presence of hypertension and lower physical activity status (IPAQ levels) were predictors of hospitalizations (OR = 0.34, CI 0.14–0.85, p = 0.02); lower physical activity status remained significant in the presence of hypertension (OR = 0.33, CI 0.13–0.84, p = 0.02). In conclusion, higher physical activity status is an independent predictor of lower hospitalizations in T2DM proving that exercising is an important strategy not only to reduce health care costs but also to improve the human burden of hospitalizations for the patients.

     

Prosthodontic planning in patients with temporomandibular disorders and/or bruxism: A systematic review

Statement of problem

The presence of temporomandibular disorders (TMDs) and/or bruxism signs and symptoms may present multifaceted concerns for the prosthodontist.