The efficacy and safety of venetoclax therapy in elderly patients with relapsed,refractory chronic lymphocytic leukaemia

Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and <75 years treated in the relapsed, refractory non-trial setting. We demonstrate that venetoclax has equivalent efficacy and safety in relapsed/refractory CLL patients who are elderly, the majority of whom are previous ibrutinib-exposed and therefore may otherwise have few clear therapeutic options.     

Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy

Tumor programmed death-ligand 1 (PD-L1) expression in diffuse large B-cell lymphoma (DLBCL) is associated with inferior outcomes. The first-line immunologically-replete setting may be an opportune time for PD-1 inhibition. We evaluated pembrolizumab in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in untreated patients with DLBCL. Eligible patients were age 18 or older, had adequate organ function, and had DLBCL requiring full-course therapy. Patients received pembrolizumab 200 mg/cycle with R-CHOP, primarily to assess toxicity. Response assessment utilized standard criteria, and PD-L1 staining was performed at a validated central laboratory. Among 30 patients, toxicity was comparable to standard R-CHOP but with two grade ≥3 immune related adverse events (rash, pneumonitis). The overall and complete response rate was 90% and 77%. With 25·5 months of median follow-up, 2-year progression-free survival (PFS) is 83%. PD-L1 expression was associated with non-GCB subtype, and improved PFS and survival. Pembrolizumab can safely be added to R-CHOP, and is associated with a high CR rate and 2-year PFS. Improved PFS with PR-CHOP in PD-L1 expressing tumors contradicts historical data in R-CHOP treated patients, supporting evaluation of PD-L1 as a biomarker to identify DLBCL patients who may benefit from this first-line strategy.     

Steady state levels of transforming growth factor-beta1 and -beta2 mRNA and protein expression are elevated in colonic tumors in vivo irrespective of dietary lipids intervention

Colonic tumors of human origin produce abundant transforming growth factor (TGF)-beta suggesting that TGF-beta is critical to their growth. Dietary lipids regulate a number of growth factors including TGF-beta. Whether elevated TGF-beta levels are consistently expressed in colonic tumors irrespective of the environmental milieu in an in vivo model is not known and forms the main objective of the present study. Male F344 rats were injected with azoxymethane, 10 weeks later, rats bearing preneoplastic lesions were fed a low fat (5% corn oil) diet and 3 high fat (5% corn oil with 18% corn oil, fish oil or beef tallow) diets for 16 weeks. Colonic tumors and mucosae were processed and assessed for TGF-beta status. TGF-beta1 and -beta2 mRNA levels were upregulated in colonic tumors more than in mucosae of all diet groups. Dietary lipids modulated TGF-beta mRNA in both tumors and mucosae, high corn and fish oil diets upregulated TGF-beta1 significantly more than the low fat corn oil or high fat beef tallow diets. Immunohistochemical assessments of tissues with different biological features revealed that TGF-beta1 and -beta2 were elevated in tumors and in selected microscopic preneoplastic lesions compared to normal mucosae. This is the first in vivo study, documenting that developing colonic tumors acquire upregulated TGF-beta phenotype even in the presence of lipid environments capable of differentially regulating TGF-beta in normal mucosae. Elevated expression of TGF-beta in a selected subset of microscopic preneoplastic lesions suggests that TGF-beta plays an important role on both early and late stages of colon carcinogenesis.     

Gender differences in handedness and speech lateralization related to early neurologic insults

Left-handedness is a normal variant but also may result from early-life brain insults. Speech typically resides in the left cerebral hemisphere in normal subjects. In 170 subjects with past brain injuries, bilateral or right hemisphere speech lateralization, determined by the intracarotid amobarbital procedure, was more frequent in females (19 vs 5, p = 0.003) as was left-handedness (26 vs 10, p = 0.004). This could be attributed to greater plasticity or functional symmetry in females.     

Effects of an antimicrobial additive to toothbrushes on residual periodontal pathogens

OBJECTIVE: Previous studies have reported the link between residual microbial contamination of toothbrushes and periodontal diseases. The goal of this pilot study was to evaluate the effects of an antimicrobial additive (Microban) to toothbrushes on residual retention of periodontal pathogens. METHODOLOGY: Twenty patients had one side of their mouths brushed with a toothbrush containing the antimicrobial agent (experimental side), and the other side with a toothbrush containing no agent (control). Toothbrushes were air-dried (25 degrees C) for four or 24 hours. Toothbrush heads were vortexed and cultured for Prevotella species (Ps), Porphyromonas gingivalis (Pg), Actinobacillus actinomycetemcomitans (Aa), and non-specific colony-forming units (NS). The plates were incubated and counted. Means and standard deviations were calculated, and data were analyzed using a series of t-tests (paired and unpaired) and Wilcoxon matched-pairs signed-rank test. RESULTS: No significant inter- or intra-group differences in mean counts were found; however, when four-hour and 24-hour data for Aa, Pg, or NS were combined, experimental counts were lower than controls in 39/50 (78%) of the matched pairs (Wilcoxon signed-rank test p = 0.01). CONCLUSION: Toothbrushes containing the antimicrobial additive showed lower microbial counts than those without, but between-group means were not statistically significant.