The state of the science on the health benefits of blueberries: a perspective.

Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6-7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.

Pembrolizumab With R-CHOP in Previously Untreated DLBCL: Sustained, High Efficacy, and Safety With Long-Term Follow-Up.

BACKGROUND: While generally ineffective in relapsed diffuse large B cell lymphoma (DLBCL), immune checkpoint inhibitors (ICIs) may hold greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (PR-CHOP) in a phase I trial of untreated DLBCL, noting responses in 90% of patients (complete response 77%) and a 2-year progression-free survival (PFS) of 83%. We herein report long-term safety and efficacy at 5-year follow up. PATIENTS AND METHODS: Adult patients with untreated DLBCL or grade 3b follicular lymphoma, intended to receive 6 cycles of R-CHOP were eligible. Patients (N = 30) were treated with pembrolizumab 200 mg IV and R-CHOP in 21-day cycles for 6 cycles. RESULTS: At median follow up of 4.8 years, 5-year PFS was 71% (CI, 54%-94%) and 5-year overall survival was 83% (CI, 71%-98%). Immune-related adverse events (IRAEs) occurred in 7 (23%) patients (10% grade 3/4). Three IRAEs (rash, thyroiditis, rheumatoid arthritis) occurred beyond 3 months of treatment completion. PD-L1 tumor expression was documented in 19 of 23 (83%) tested patients. None of the 19 patients who had any PD-L1 expression have relapsed, whereas 2 out of the 4 patients with no PD-L1 expression have relapsed. CONCLUSION: PR-CHOP has led to durable responses in most patients, with the best outcomes in PD-L1-expressing disease. Furthermore, the safety profile was manageable, with no consistent pattern of late events. These data support ongoing strategies incorporating ICIs in frontline DLBCL therapy and confirmation of predictive biomarkers including tumor PD-L1 expression.

Multi-omics approach to socioeconomic disparity in metabolic syndrome reveals roles of diet and microbiome.

The epidemy of metabolic syndrome (MetS) is typically preceded by adoption of a "risky" lifestyle (e.g., dietary habit) among populations. Evidence shows that those with low socioeconomic status (SES) are at an increased risk for MetS. To investigate this, we recruited 123 obese subjects (body mass index [BMI] ≥ 30) from Chicago. Multi-omic data were collected to interrogate fecal microbiota, systemic markers of inflammation and immune activation, plasma metabolites, and plasma glycans. Intestinal permeability was measured using the sugar permeability testing. Our results suggest a heterogenous metabolic dysregulation among obese populations who are at risk of MetS. Systemic inflammation, linked to poor diet, intestinal microbiome dysbiosis, and gut barrier dysfunction may explain the development of MetS in these individuals. Our analysis revealed 37 key features associated with increased numbers of MetS features. These features were used to construct a composite metabolic-inflammatory (MI) score that was able to predict progression of MetS among at-risk individuals. The MI score was correlated with several markers of poor diet quality as well as lower levels of gut microbial diversity and abnormalities in several species of bacteria. This study reveals novel targets to reduce the burden of MetS and suggests access to healthy food options as a practical intervention.

Curated and harmonized gut microbiome 16S rRNA amplicon data from dietary fiber intervention studies in humans.

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies.

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma.

Concurrent administration of pembrolizumab with chemotherapy in untreated classic Hodgkin lymphoma (CHL) has not been studied previously. To investigate this combination, we conducted a single-arm study of concurrent pembrolizumab with AVD (doxorubicin, vinblastine, and dacarbazine; APVD) for untreated CHL. We enrolled 30 patients and met the primary safety end point with no observed significant treatment delays in the first 2 cycles. Twelve patients experienced grade 3 or 4 nonhematologic adverse events (AEs), most commonly febrile neutropenia and infection/sepsis. Grade 3 or 4 immune-related AEs, including alanine aminotransferase elevation and aspartate aminotransferase elevation were observed in 3 patients. One patient experienced an episode of grade 2 colitis and arthritis. Six patients missed at least 1 dose of pembrolizumab because of AEs, primarily grade 2 or higher transaminitis. Among 29 response-evaluable patients, the best overall response rate was 100% and the complete response rate was 90%. With a median follow-up of 2.1 years, the 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, no patient who has withheld or discontinued pembrolizumab because of toxicity has progressed. Clearance of circulating tumor DNA (ctDNA) was associated with superior PFS when measured after cycle 2 and at the end of treatment (EOT). None of the 4 patients with persistent uptake by fluorodeoxyglucose positron emission tomography (PET) at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy but may yield spurious PET findings in some patients. This trial was registered at www.clinicaltrials.gov as #NCT03331341.

An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson's disease participants.

A pro-inflammatory intestinal microbiome is characteristic of Parkinson's disease (PD). Prebiotic fibers change the microbiome and this study sought to understand the utility of prebiotic fibers for use in PD patients. The first experiments demonstrate that fermentation of PD patient stool with prebiotic fibers increased the production of beneficial metabolites (short chain fatty acids, SCFA) and changed the microbiota demonstrating the capacity of PD microbiota to respond favorably to prebiotics. Subsequently, an open-label, non-randomized study was conducted in newly diagnosed, non-medicated (n = 10) and treated PD participants (n = 10) wherein the impact of 10 days of prebiotic intervention was evaluated. Outcomes demonstrate that the prebiotic intervention was well tolerated (primary outcome) and safe (secondary outcome) in PD participants and was associated with beneficial biological changes in the microbiota, SCFA, inflammation, and neurofilament light chain. Exploratory analyses indicate effects on clinically relevant outcomes. This proof-of-concept study offers the scientific rationale for placebo-controlled trials using prebiotic fibers in PD patients. ClinicalTrials.gov Identifier: NCT04512599.

Hope and physical health.

This article provides a brief overview of the recent research focusing on hope and physical health. The reviewed research is limited to research primarily on hope as conceptualized by Snyder and colleagues [33] and to those studies in which the researchers measured hope using scales based on Hope Theory proposed by Snyder and colleagues. Studies on hope and health behaviors, as well as specific health outcomes such as pain, cancer, and chronic illness are included. Overall findings indicate that hope is plays an important role in health.

Maternal-Child Microbiome and Impact on Growth and Neurodevelopment in Infants and Children: A Scoping Review.

BACKGROUND: Pathologic changes in the microbiome (dysbiosis) have been implicated in affecting the growth and neurodevelopment of infants and children. There is evidence to suggest that prenatal and postnatal stressors may be a factor in dysbiosis and there is also a growing body of evidence to suggest that interventions may reduce this negative impact. A scoping review was undertaken to identify association between maternal and/or child microbiome with child growth and neurodevelopment. Additionally, intervention studies such as use of nutritional supplementation and its impact on the microbiome, growth and neurodevelopment were reviewed. METHODS: An exhaustive literature search identified 654 relevant citations. After review of abstracts, 557 were eliminated, and 97 remained for full text review. We identified and reported on 42 articles which met inclusion criteria. RESULTS: Seven studies examined associations between microbiome and neurodevelopment and 36 studies evaluated anthropometric measurements, most commonly weight, and microbiota relationships. One study evaluated both growth and neurodevelopment and microbiota. Fourteen studies evaluated supplemental nutrients. Preterm, low birth weight (LBW), and very low birth weight (VLBW) infants were most studied. Findings were inconclusive for consistent associations between microbiota and growth and neurodevelopment. Further, there were no consistent conclusive changes with prescribed treatment interventions. DISCUSSION: There is a need for high-quality longitudinal studies evaluating repeated developmental assessment measures using consistent microbial analysis techniques to inform conclusions regarding the association between microbiome and infant and child growth and neurodevelopment. Additional intervention studies that may mitigate dysbiosis are warranted.

Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas.

The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]-EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.

Efficacy, safety, and molecular response predictors of oral ixazomib and short-course rituximab in untreated iNHL.

Patients with indolent B-cell non-Hodgkin lymphoma (iNHL) generally require treatment but experience normal survival, emphasizing the need for simpler, safer therapies. Proteasome inhibitors target aberrant signaling pathways within iNHL and have manageable toxicities. We evaluated the oral proteasome inhibitor ixazomib as initial monotherapy, and combined with rituximab, for first-line treatment of iNHL. Treatment-naïve patients with iNHL needing therapy received oral ixazomib 4 mg weekly until progressive disease or unacceptable adverse events. A 4-week course of rituximab was added during month 7. The primary end point was overall response rate (ORR) during the ixazomib monotherapy window. Correlations included gene expression profiling and response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Thirty-three patients with follicular lymphoma (FL) (n = 20), marginal zone lymphoma (n = 7), and other iNHL were treated with a median follow-up of 30.3 months. During the 6-month ixazomib window, the ORR was 24%, including 35% in FL. The best ORR over the entire study period was 52% overall and 65% in FL; complete response was achieved in 33% and 45%, respectively. The median duration of response was 25.8 months (range, 0-49.7), and the 24-month progression-free and overall survival rates were 51% (95% confidence interval [CI], 32-67) and 91% (95% CI, 74-97), respectively. Ixazomib was well tolerated. Baseline downregulation of proteasome genes, PSMB9 (P = .03) and PSMB8 (P = .007), were associated with response. All evaluated patients generated anti-S antibodies to SARS-CoV-2 vaccination, with a median of 254.9 binding arbitrary unit per mL. Ixazomib demonstrated efficacy alone and with short-course rituximab in untreated iNHL while exhibiting favorable toxicity, convenience, and retention of the B-cell immune response. This trial is registered at www.clinicaltrials.gov as NCT02339922.

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as ß-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher ß-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, ß-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Psychometric Testing of a Food Timing Questionnaire and Food Timing Screener.

BACKGROUND: Circadian rhythms coordinate multiple biological processes, and time of eating is an important entrainer of peripheral circadian clocks, including those in the gastrointestinal tract and liver. Whereas time of eating can be assessed through valid and reliable tools designed to measure nutrient intake (24-h recalls), currently there is no easily administered, valid, and reliable tool designed to specifically assess both time of food intake and sleep. OBJECTIVES: The objective of this study was to test the validity and reliability of 2 questionnaires developed to measure food and sleep-wake timing, the Food Timing Questionnaire (FTQ) and Food Timing Screener (FTS), and the agreement between these 2 tools. METHODS: The content validity of these tools was assessed by an expert panel of 10 registered dietitian nutritionists. Adult volunteers (n = 61) completed both tools to assess internal consistency and test-retest reliability. Criterion-related validity was determined through the association of FTQ and FTS with 2 valid instruments, the Automated Self-Administered 24-hour recall (ASA24®) Dietary Assessment tool and the Munich Chronotype Questionnaire. Agreement between the FTQ and FTS was tested by calculating the Pearson's correlations for both food and sleep-wake timing. RESULTS: The content validity indexes for both tools were >0.80, and internal consistency and test-retest reliability coefficients were >0.50 for all meals and sleep-wake times. Correlation coefficients were >0.40 between both tools and criterion measures of food intake and sleep except for snacks. Correlations between the FTQ and FTS for all eating events and sleep were >0.60 except for snack 1. CONCLUSIONS: Both the FTQ and FTS are valid and reliable instruments for meal timing and sleep. However, further psychometric testing in a more expansive and diverse sample will improve the ability of these tools to accurately assess food timing and sleep and their impact on health outcomes.

Behavioral circadian phenotypes are associated with the risk of elevated body mass index.

BACKGROUND: Metabolic dysfunction and obesity rates are on the rise. Although the central modes of circadian disruption has been studied in relation to the risk of obesity, the role of eating time has remained unclear. Here, we aimed to assess circadian behavioral phenotypes and their association with the risk of elevated body mass index (BMI). METHODS: This was a prospective cross-sectional study of individuals presenting for colorectal cancer screening colonoscopy. Participants completed demographic questionnaires, The Munich ChronoType Questionnaire (MCTQ), and Food Timing Screener (FTS). The primary outcome of the study was the association between circadian phenotypes and elevated BMI. RESULTS: A total of 488 individuals completed the survey, with a mean (SD) age of 57.5 (10.8) years. The mean body mass index (BMI) was 28.8 (6.1) kg/m2, with 72.3% of individuals met criteria for elevated BMI. Four circadian behavioral phenotypes were generated: early chronotype with regular food timing (ER) (34.7%), early chronotype with irregular food timing (EI) (11.7%), intermediate/late chronotype with regular food timing (LR) (33.9%), and intermediate/late chronotype with irregular food timing (LI) (19.7%). In a multivariable regression analysis, LI phenotype had 2.9 times higher odds of elevated BMI as compared to ER phenotype (OR 2.9, 95% CI 1.3-6.7, P = 0.01). CONCLUSION: The combination of late chronotype and irregular food timing, representative of a behavioral circadian rhythm disruption, is associated with higher rates of elevated BMI. The majority of individuals with this abnormal circadian phenotype were younger than 60 years old. This observation is especially relevant because of the ongoing rise in the obesity rates among young adults. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

Associations of Dietary Lipid-Soluble Micronutrients with Hepatic Steatosis among Adults in the United States.

Lipid-soluble micronutrients may be beneficial to non-alcoholic fatty liver disease due to their important roles in metabolism and maintaining tissue functions. Utilizing 2017-2018 National Health and Nutrition Examination Survey, this study examined the potential overall and race/ethnicity-specific (black, Hispanic and white) associations of dietary lipid-soluble micronutrients (α-tocopherol, retinol, vitamin D, ß-carotene and total carotenoids) with hepatic steatosis. The analysis included 4376 adults (1037 blacks, 981 Hispanics, 1549 whites) aged ≥20 years who completed the transient elastography examination with dietary data available. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regressions. The age-adjusted prevalence of steatosis was 20.9% for blacks, 34.0% for Hispanics and 28.7% for whites. Overall, dietary α-tocopherol was inversely associated with steatosis (highest vs. lowest quartile: OR = 0.51, 95%CI = 0.35-0.74, Ptrend = 0.0003). The associations remained significant among blacks (highest vs. lowest tertile: OR = 0.45, 95%CI = 0.26-0.77, Ptrend = 0.002) and whites (highest vs. lowest tertile: OR = 0.56, 95%CI = 0.33-0.94, Ptrend = 0.02). Higher α-tocopherol intake was associated with lower odds of steatosis among all (Ptrend = 0.016) and black participants (Ptrend = 0.003) classified as never/rare/occasional alcohol drinkers. There was a trend suggesting higher ß-carotene intake with lower odds of steatosis (Ptrend = 0.01). Our results suggest potential protective effects of dietary vitamin E as α-tocopherol on steatosis particularly among blacks.

Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide for second-line treatment of relapsed or refractory classical Hodgkin lymphoma: a single centre, phase 1/2 study.

BACKGROUND: Relapsed or refractory classical Hodgkin lymphoma could be treated with multiagent salvage chemotherapy followed by autologous haematopoietic stem-cell transplantation. The aim of this study is to establish the safety and activity of dose-dense brentuximab vedotin combined with ifosfamide, carboplatin, and etoposide (BV-ICE) chemotherapy in second-line treatment of classical Hodgkin lymphoma. METHODS: We conducted a single-arm, open-label, phase 1/2 study of dose-dense BV-ICE at the Seattle Cancer Care Alliance, University of Washington (Seattle, WA, USA). Eligibility criteria were age 18 years or older; diagnosis of first relapse, primary refractory classical Hodgkin lymphoma after one previous line of therapy; measurable disease of at least 1 cm in the longest axis, CT of chest, abdomen, and pelvis with PET within the past 28 days; Eastern Cooperative Oncology Group performance status of 0-1; and adequate organ function. A 3 + 3 dose escalation study was done for the phase 1 part of the trial to establish the maximum tolerated dose to be used for the phase 2 study. Brentuximab vedotin was delivered on days 1 and 8 at either 1·2 mg/kg (dose level 1) or 1·5 mg/kg (dose level 2) intravenously (capped at 150 mg) with standard dosing of ICE on days 1-3 (ifosfamide 5 g/m2 plus mesna 5 g/m2 intravenously over 24 h on day 2, carboplatin area under the curve 5 on day 2 in one intravenous injection, and etoposide 100 mg/m2 on days 1-3 in one intravenous injection per day) for two 21-day cycles. The primary endpoint was to establish the recommended phase 2 dose (phase 1 part) and complete response rate after two cycles, with a prespecified target of 78% (phase 2 part). Safety analysis was done in all enrolled participants and the primary activity analysis was done in all patients with evaluable response data. This study is registered with ClinicalTrials.gov (NCT02227199); enrolment and study treatment are complete. FINDINGS: Between Oct 16, 2014, and Feb 10, 2020, we enrolled 45 patients with a median age of 31 years (IQR 28-45). The recommended phase 2 dose of brentuximab vedotin was established to be 1·5 mg/kg. After a median follow-up of 3·1 years (IQR 1·7-4·1), 32 (74%; 95% CI 58·8-86·5) of 43 evaluable patients had complete responses after two cycles of treatment. Grade 3-4 haematological toxic effects were common, including neutropenia (33 [73%]), anaemia (six [13%]), and thrombocytopenia (36 [80%]). The most common grade 3-4 non-haematological toxic effects were febrile neutropenia (four [9%]), sepsis (six [13%]), increased alanine aminotransferase (five [11%]), hyperglycaemia (three [7%]), pulmonary embolism (two [4%]), and increased aspartate aminotransferase (two [4%]). There was one (2%) on-treatment death due to multisystem organ failure that was considered treatment related. Serious adverse events occurred in 13 (29%) patients. INTERPRETATION: Our data suggest that dose-dense BV-ICE is a rapidly administered and active salvage regimen for patients with relapsed or refractory classical Hodgkin lymphoma despite a complete response in this trial lower than the prespecified phase 2 target. Although cross-trial comparisons should be made with caution, activity results seem to be similar to previously presented brentuximab vedotin chemotherapy salvage combinations delivered over much longer durations and can be considered in young (<60 years), transplantation-eligible patients for second-line therapy. FUNDING: Seagen, Lymphoma Research Foundation, National Institutes of Health/National Cancer Institute, and generous philanthropic donations to the University of Washington from numerous individuals and families in support of lymphoma research.

Effects of conventional and sugar-free energy drinks intake in runners: a double-blind, randomized, placebo-controlled crossover clinical trial.

BACKGROUND: This study evaluated the effects of two types of energy drinks (ED) intake in trained runners. METHODS: A double-blind randomized placebo-controlled clinical trial was conducted over 6 weeks. Participants and beverages were allocated by randomization. Twelve men 23±2.6 years, 177±3.4 cm, 74.4±5.5 kg, VO2max=59.8±5.5 mL·(kg.min)-1] ingested either a conventional energy drink containing carbohydrates and 3 mg·kg-1 of caffeine, (ED1), a sugar-free energy drink 3 mg·kg-1 of caffeine (ED2), or a carbohydrate-containing, decaffeinated placebo (PL) 40-minutes before an exercise protocol. Sprint time, rate of perceived exertion (RPE), respiratory exchange ratio (RER), blood pressure (BP), heart rate and plasmatic glucose were evaluated during the experimental protocol. RESULTS: Performance improved after consuming both ED (P<0.004 ED1 and P=0.001 ED2) with lower RPE (P<0.05 for ED1 and P<0.05 for ED2) compared to PL. Consumption of ED2 decreased RER values at 0-5 minutes and 40-45 minutes (P<0.001), and ED1 increased systolic BP (P<0.05) during exercise compared to PL. There were no differences in the evaluated parameters between EDs (P>0.05). CONCLUSIONS: Consumption of conventional or sugar free ED represents a valid ergogenic strategy to improve acute performance with reduction of RPE. However, intake of a conventional ED warrants caution, mainly because the effects on systolic BP.

Ibrutinib Monotherapy in Relapsed or Refractory, Transformed Diffuse Large B-cell Lymphoma.

BACKGROUND: Histologic transformation to diffuse large B-cell lymphoma (tDLBCL) occurs in a significant proportion of indolent lymphomas. However, few studies of novel agents inform its management, particularly when relapsed after or refractory (R/R) to prior treatment. PATIENTS AND METHODS: We prospectively evaluated ibrutinib monotherapy in pathologically documented patients with R/R tDLBCL in a single-arm study. The primary endpoint was overall response rate. RESULTS: Twenty patients who had received a median of 4 (range, 2-9) prior lines of therapy overall (median, 2.5; range, 1-9 for tDLBCL) were treated. The overall response rate was 35%, including complete responses in 15%. The median progression-free survival and overall survival were 4.1 months (95% confidence interval, 2.4-6.2 months) and 22.4 months (95% confidence interval, 7.5 months to not reached), respectively. Disease control > 2 months was seen in 75% and > 1 year in 15%. Response was associated with either low tumor bulk or low metabolic tumor volume (P = .05) but not with antecedent lymphoma histology (P = 1.0). Treatment-related adverse events were consistent with prior studies of ibrutinib. CONCLUSIONS: Ibrutinib showed low toxicity and meaningful efficacy in R/R tDLBCL, including short-term disease control in most cases. Results demonstrate the potential utility of ibrutinib in this challenging clinical setting, including as a potential bridge to more definitive treatments.

Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis.

Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients.