Effects of high-intensity interval training on functional performance and maximal oxygen uptake in comparison with moderate intensity continuous training in cancer patients: a systematic review and meta-analysis.

INTRODUCTION: High-intensity interval training (HIIT) is an appropriate training modality to improve endurance and therefore contributes to physical performance. This review investigates the effect of HIIT on functional performance in cancer patients. We reviewed the relative peak oxygen uptake (relV̇O2PEAK) and meta-analytical compared HIIT with moderate intensity continuous training (MICT). Furthermore, we took various training parameters under consideration. METHODS: A systematic literature search was conducted in Scopus, PubMed, and Cochrane Library databases. For the review, we included randomized controlled trials containing HIIT with cancer patients. From this, we filtered interventions with additional MICT for the meta-analysis. Outcomes of interest were various functional performance assessments and V̇O2MAX. RESULTS: The research yielded 584 records which fit the inclusion criteria, of which 31 studies with n=1555 patients (57.4±8.6 years) could be included in the overall review and 8 studies in the meta-analysis (n=268, 59.11±5.11 years) regarding relV̇O2PEAK. Different functional outcomes were found, of which walking distance (+8.63±6.91% meters in 6-min walk test) and mobility (+2.7cm in sit and reach test) improved significantly due to HIIT. In terms of relV̇O2PEAK, the performance of cancer patients was improved by HIIT (10.68±6.48%) and MICT (7.4±4.29%). HIIT can be favored to increase relV̇O2PEAK (SMD 0.37; 95% CI 0.09-0.65; I2=0%; p=0.009). Effect sizes for relV̇O2PEAK improvements correlate moderately with total training volume (Spearman's ρ=0.49; p=0.03), whereas percentage increases do not (Spearman's ρ=0.24; p=0.14). CONCLUSION: Functional and physical outcomes were positively altered by different HIIT protocols and forms of implementation, whereas a tendency toward more effectiveness of HIIT vs. MICT was found for relV̇O2PEAK. Future studies should include functional parameters more often, to finally allow a comparison between both training protocols in this regard.

Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa.

Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4+ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8+ α/ß intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRß-rearrangements derived from gluten-specific CD4+ T-cells and gluten-triggered peripheral blood CD8+ T-cells. We show, that in addition to TCRs from gluten-specific CD4+ T-cells, TCRs of gluten-triggered CD8+ T-cells are significantly enriched in CeD duodenal tissue samples. TCRß-rearrangements of gluten-triggered CD8+ T-cells were even more expanded in patients than TCRs from gluten-specific CD4+ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.

The effects of menstrual cycle phases on immune function and inflammation at rest and after acute exercise: A systematic review and meta-analysis.

The immune system plays an important role in mediating exercise responses and adaptations. However, whether fluctuating hormone concentrations across the menstrual cycle may impact these processes remains unknown. The aim of this systematic review with meta-analysis was to compare baseline concentrations as well as exercise-induced changes in immune and inflammatory parameters between menstrual cycle phases. A systematic literature search was conducted according to the PRISMA guidelines using Pubmed/MEDLINE, ISI Web of Science, and SPORTDiscus. Of the 159 studies included in the qualitative synthesis, 110 studies were used for meta-analysis. Due to the designs of the included studies, only the follicular and luteal phase could be compared. The estimated standardized mean differences based on the random-effects model revealed higher numbers of leukocytes (-0.48 [-0.73; -0.23], p < 0.001), monocytes (-0.73 [-1.37; -0.10], p = 0.023), granulocytes (-0.85 [-0.1.48; -0.21], p = 0.009), neutrophils (-0.32 [-0.52; -0.12], p = 0.001), and leptin concentrations (-0.37 [-0.5; -0.23], p = 0.003) in the luteal compared to the follicular phase at rest. Other parameters (adaptive immune cells, cytokines, chemokines, and cell adhesion molecules) showed no systematic baseline differences. Seventeen studies investigated the exercise-induced response of these parameters, providing some indications for a higher pro-inflammatory response in the luteal phase. In conclusion, parameters of innate immunity showed cycle-dependent regulation at rest, while little is known on the exercise responses. Due to a large heterogeneity and a lack of cycle phase standardization among the included studies, future research should focus on comparing at least three distinct hormonal profiles to derive more specific recommendations for exercise prescription.

Microbial community shifts induced by plastic and zinc as substitutes of tire abrasion.

Aquatic environments serve as a sink for anthropogenic discharges. A significant part of the discharge is tire wear, which is increasingly being released into the environment, causing environmental disasters due to their longevity and the large number of pollutants they contain. Main components of tires are plastic and zinc, which therefore can be used as substitutes for tire abrasion to study the effect on microbial life. We investigate environmentally realistic concentrations of plastic and zinc on a freshwater microeukaryotic community using high-throughput sequencing of the 18S V9 region over a 14-day exposure period. Apart from a generally unchanged diversity upon exposure to zinc and nanoplastics, a change in community structure due to zinc is evident, but not due to nanoplastics. Evidently, nanoplastic particles hardly affect the community, but zinc exposure results in drastic functional abundance shifts concerning the trophic mode. Phototrophic microorganisms were almost completely diminished initially, but photosynthesis recovered. However, the dominant taxa performing photosynthesis changed from bacillariophytes to chlorophytes. While phototrophic organisms are decreasing in the presence of zinc, the mixotrophic fraction initially benefitted and the heterotrophic fraction were benefitting throughout the exposure period. In contrast to lasting changes in taxon composition, the functional community composition is initially strongly imbalanced after application of zinc but returns to the original state.

Cardiorespiratory Adaptations in Elderly Men Following Different Concurrent Training Regimes.

BACKGROUND: This study aimed to investigate the effects of different intra-session exercise orders during concurrent training (CT) on endurance performance in elderly men, as well as to verify its influence on individual responses in endurance performance. DESIGN: Twenty-five healthy elderly men (64.7 ± 4.1 years) were placed into two groups: strength training prior to endurance training (SE, n=13), and one in the reverse order (ES, n=12). CT was performed three times a week during 12 weeks. Before and after training, peak oxygen uptake (VO2peak), maximal workload (Wmax), absolute and relative cycling economy at 25, 50, 75 and 100 W (i.e., average VO2 at different stages) were assessed. RESULTS: Similar increases in VO2peak were observed in the SE and ES groups (SE: 8.1 ± 9.9%; ES: 9.3 ± 9.8%; P<0.001), as well as in Wmax (SE: 19.9 ± 19.3%; ES: 24.1 ± 24.0%; P<0.001). Moreover, significant reductions were observed in the absolute VO2 at 100 W (P<0.05) in the SE and ES groups. No difference between groups was observed. In the ES group, one subject did not respond positively in terms of both VO2max and Wmax, whereas 4 subjects did not respond positively in terms of both VO2max and Wmax in SE group. CONCLUSIONS: CT improved maximal and submaximal endurance performance in elderly men, independent of intra-session exercise order. However, it seems that the ES order elicited more individual responsiveness in terms of maximal endurance performance than SE order.

Effects of physical exercise on breast cancer-related secondary lymphedema: a systematic review.

PURPOSE: The aim of this systematic review is to assess the effect of different types of exercise on breast cancer-related lymphedema (BCRL) in order to elucidate the role of exercise in this patient group. METHODS: A systematic data search was performed using PubMed (December 2016). The review is focused on the rehabilitative aspect of BCRL and undertaken according to the PRISMA statement with Levels of Evidence (LoE) assessed. RESULTS: 11 randomized controlled trials (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in aftercare were included. The different types of exercise consisted of aqua lymph training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive exercise. Four of the studies measured a significant reduction in BCRL status based on arm volume and seven studies reported significant subjective improvements. No study showed adverse effects of exercise on BCRL. CONCLUSION: The evidence indicates that exercise can improve subjective and objective parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise appearing to provide the most positive effects.

Combined aerobic and resistance training decreases inflammation markers in healthy men.

Our primary aim was to study the effects of 24 weeks of combined aerobic and resistance training performed on the same day or on different days on inflammation markers. Physically active, healthy young men were randomly divided into three groups that performed: aerobic and resistance training consecutively in the same training session (SS) 2-3 days wk-1 or on alternating days (AD) 4-6 days wk-1 as well as control (C). The total training volume was matched in the training groups. The control group was asked to maintain their habitual physical activity and exercise level. Maximal leg press strength (1RM) and peak oxygen uptake (VO2peak ) were measured. Abdominal fat mass was estimated with dual-energy absorptiometry (DXA). High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and adipocytokines resistin, adiponectin, and leptin were analyzed from plasma samples. Training significantly reduced circulating hs-CRP, leptin, and resistin in both training groups (P<.05), whereas MCP-1 and TNF-α decreased only in AD (P<.05). Significant correlations were observed between changes in abdominal fat mass and corresponding changes in MCP-1, leptin, adiponectin, and resistin. Long-term combined aerobic and resistance training reduced markers of subclinical inflammation in healthy young men. The results indicate that a higher frequency of individual exercise sessions might be more beneficial with respect to the anti-inflammatory effects of physical activity. The decreases in inflammation markers seem to be related to decreases in abdominal fat mass.

Neuromuscular Adaptations to Same-Session Combined Endurance and Strength Training in Recreational Endurance Runners.

This study examined neuromuscular adaptations in recreational endurance runners during 24 weeks of same-session combined endurance and strength training (E+S, n=13) vs. endurance training only (E, n=14). Endurance training was similar in the 2 groups (4-6x/week). Additional maximal and explosive strength training was performed in E+S always after incremental endurance running sessions (35-45 min, 65-85% HRmax). Maximal dynamic leg press strength remained statistically unaltered in E+S but decreased in E at week 24 (-5±5%, p=0.014, btw-groups at week 12 and 24, p=0.014 and 0.011). Isometric leg press and unilateral knee extension force, EMG of knee extensors and voluntary activation remained statistically unaltered in E+S and E. The changes in muscle cross-sectional (CSA) differed between the 2 groups after 12 (E+S+6±8%, E -5±6%, p<0.001) and 24 (E+S+7±7%, E -6±5%, p<0.001) weeks. 1 000 m running time determined during an incremental field test decreased in E+S and E after 12 (-7±3%, p<0.001 and -8±5%, p=0.001) and 24 (-9±5%, p=0.001 and -13±5%, p<0.001) weeks. Strength training performed always after an endurance running session did not lead to increased maximal strength, CSA, EMG or voluntary activation. This possibly contributed to the finding of no endurance performance benefits in E+S compared to E.

[Jejunal ulcerations - a diagnostic challenge in a patient with coeliac disease]. / Jejunale Ulzerationen - eine diagnostische Herausforderung bei einem Patienten mit Zöliakie.

A subset of patients with coeliac disease (CD) suffers persistent or recurrent complaints despite a strict adherence to a gluten-free diet (GFD) that can be caused by refractory coeliac disease (RCD). We present a patient with weight loss and signs of malassimilation secondary to villous atrophy and jejunal ulcerations complicating known CD. We demonstrate a stepwise approach to the diagnosis and subtyping of RCD and to rule out important alternative causes of jejunal ulcerations. RCD can be classified as type I based on the absence or as type II based on the presence of an aberrant intestinal mucosal lymphocyte population. RCD type I shows a more benign course as these patients usually improve on a treatment consisting of nutritional support and immunosuppressive therapies such as budesonide or azathioprine. In contrast, clinical response to standard therapies in RCD type II is less certain and the prognosis is poor. Several groups suggest that RCD type II should be regarded as low-grade intraepithelial lymphoma which frequently transforms into an aggressive enteropathy associated T-cell lymphoma with a high mortality rate. Therefore, a rapid differentiation of RCD type I and RCD type II is a major clinical challenge to early initiate appropriate treatment modalities.

Neuromuscular adaptations to different modes of combined strength and endurance training.

The present study investigated neuromuscular adaptations between same-session combined strength and endurance training with 2 loading orders and different day combined training over 24 weeks. 56 subjects were divided into different day (DD) combined strength and endurance training (4-6 d·wk(-1)) and same-session combined training: endurance preceding strength (E+S) or vice versa (S+E) (2-3 d·wk(-1)). Dynamic and isometric strength, EMG, voluntary activation, muscle cross-sectional area and endurance performance were measured. All groups increased dynamic one-repetition maximum (p<0.001; DD 13±7%, E+S 12±9% and S+E 17±12%) and isometric force (p<0.05-0.01), muscle cross-sectional area (p<0.001) and maximal power output during cycling (p<0.001). DD and S+E increased voluntary activation during training (p<0.05-0.01). In E+S no increase in voluntary activation was detected after 12 or 24 weeks. E+S also showed unchanged and S+E increased maximum EMG after 24 weeks during maximal isometric muscle actions. A high correlation (p<0.001, r=0.83) between the individual changes in voluntary activation and maximal knee extension force was found for E+S during weeks 13-24. Neural adaptations showed indications of being compromised and highly individual relating to changes in isometric strength when E+S-training was performed, while gains in one-repetition maximum, endurance performance and hypertrophy did not differ between the training modes.

The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.

Primary T cell activation and effector cell differentiation is required for rejection of allogeneic grafts in naïve recipients. It has become evident, that mitochondria play an important role for T cell activation. Expression of several mitochondrial proteins such as TCAIM (T cell activation inhibitor, mitochondrial) is down-regulated upon T cell receptor triggering. Here we report that TCAIM inhibited spontaneous development of memory and effector T cells. CD4(+) T cells from Tcaim knock-in (KI) mice showed reduced activation, cytokine secretion and proliferation in vitro. Tcaim KI T cells tolerated allogeneic skin grafts upon transfer into Rag-1 KO mice. CD4(+) and CD8(+) T cells from these mice did not infiltrate skin grafts and kept a naïve or central memory phenotype, respectively. They were unable to acquire effector phenotype and functions. TCAIM altered T cell activation-induced mitochondrial distribution and reduced mitochondrial reactive oxygen species (mROS) production. Thus, TCAIM controls T cell activation and promotes tolerance induction probably by regulating TCR-mediated mitochondrial distribution and mROS production.

Soil application of an encapsulated CO2 source and its potential for management of western corn rootworm larvae.

Western corn rootworm (Diabrotica virgifera virgifera LeConte) larvae use carbon dioxide (CO2) to locate the roots of their hosts. This study investigated whether an encapsulated CO2 source (CO2-emitting capsules) is able to outcompete CO2 gradients established by corn root respiration in the soil. Furthermore, the following two management options with the capsules were tested in semifield experiments (0.5- to 1-m2 greenhouse plots): the disruption of host location and an "attract-and-kill" strategy in which larvae were lured to a soil insecticide (Tefluthrin) between the corn rows. The attract-and-kill strategy was compared with an application of Tefluthrin in the corn rows (conventional treatment) at 33 and 18% of the standard field application rate. Application of the CO2-emitting capsules 30 cm from the plant base increased CO2 levels near the application point for up to 20 d with a peak at day 10. Both the disruption of host location and an attract-and-kill strategy caused a slight but nonsignificant reduction in larval densities. The disruption of host location caused a 17% reduction in larval densities, whereas an attract-and-kill strategy with Tefluthrin added at 33 and 18% of the standard application rate caused a 24 and 27% reduction in larval densities, respectively. As presently formulated, the CO2-emitting capsules, either with or without insecticide, do not provide adequate control of western corn rootworm.

Tracheal intubation in patients with odentogenous abscesses and reduced mouth opening.

BACKGROUND: Odentogenous abscesses with involvement of the facial or cervical spaces can be life-threatening and often have to be drained under general anaesthesia. Trismus and swelling can make intubation with a Macintosh laryngoscope difficult or even impossible. However, indirect laryngoscopy has been successful when conventional direct laryngoscopy has failed. Therefore, we evaluated the efficacy of the Glidescope laryngoscope in patients with odentogenous abscesses and the improvement in mouth opening after neuromuscular block. METHODS: After approval of the ethics committee, 100 patients with odentogenous abscesses were randomized to undergo tracheal intubation with the Glidescope or Macintosh laryngoscope. Success rate, visualization of the glottis, intubation duration, and need for supporting manoeuvres were evaluated. RESULTS: Intubation with the Glidescope was always successful, while conventional intubation failed in 17 out of 50 patients (P<0.0001). In all patients in whom conventional tracheal intubation failed, a subsequent attempt with the Glidescope was successful. The view at the glottis (according to Cormack and Lehane; P<0.0001), intubation duration [34 s (CI 27-41) vs 67 s (CI 52-82), mean (95% confidence interval); P=0.0001], and need for supporting manoeuvres (P<0.0001) were significantly different. The inter-incisor distance improved overall with induction of anaesthesia from 2.0 cm (CI 1.8-2.2) to 2.6 cm (CI 2.3-2.9; P<0.0001) and was correlated with the duration of symptoms. CONCLUSIONS: In patients with odentogenous abscesses, the use of a Glidescope laryngoscope was associated with significantly faster tracheal intubation, with a better view, fewer supporting manoeuvres, and a higher success rate than with a conventional laryngoscope. Improvement of the inter-incisor distance after induction of anaesthesia correlated with the duration of symptoms.

Treatment of metastatic colorectal cancer with cetuximab: influence on the quality of life.

BACKGROUND: Epidermal Growth Factor Receptor (EGFR) antibodies are innovative anti-cancer drugs prolonging survival in metastatic colocrectal cancer. However, due to adverse drug reactions, patients develop acneform skin toxicities. We hypothesized that the skin reaction leads to a decline in general (QOL) and dermatological health related quality of life (HQOL). Furthermore, we aimed at evaluating predictors for QOL and HQOL to improve individual adjustment of therapy. METHODS: 40 outpatients with metastatic colocrectal cancer were involved in this study. According to their KRAS status, patients were allocated to 2 groups: The CTCX group (n = 20; KRAS wild-type) was treated with the EGFR-antibody Cetuximab plus chemotherapy, the CT group (n = 20; KRAS mutation) was receiving chemotherapy only. Psychological assessment consisted of questionaires to evaluate QOL and HQOL, depression, coping-styles, health beliefs and the patient´s personality. RESULTS: Between the two groups, no significanct difference in QOL was found, QOL remained stable over the course of treatment. Yet, the severity of the skin reactions had a significant influence on HQOL. Internal health beliefs and high compliance were found to be protective factors, while passive coping strategies, depression and the personality trait neuroticism were identified as risk factors. DISCUSSION: Interdisciplinary cooperation between medical professionals and psycho-oncologists is strongly recommended to encourage patients to embark on and to retain EGFR-antibody therapy. If risk factors are present, psycho-oncological therapy should focus on the minimization of depression and on the development of active coping strategies.

Determination of the weak axial vector coupling λ = gA/gV from a measurement of the ß-asymmetry parameter A in neutron beta decay.

We report on a new measurement of the neutron ß-asymmetry parameter A with the instrument Perkeo II. The main enhancements are the high neutron polarization of P = 99.7(1)% from a novel arrangement of supermirror polarizers and reduced background from improvements in beam line and shielding. The leading corrections were thus reduced by a factor of 4, pushing them below the level of statistical error and resulting in a significant reduction of systematic uncertainty compared to our previous experiments. We derive the ß-asymmetry parameter A0 = -0.11972(45)(stat)((-44)(+32))(sys) = -0.11972((-65)(+53)) and the ratio of the axial vector to the vector coupling constant λ = gA/gV = -1.2761(12)(stat)((-12)(+9))(sys) = -1.2761((-17)(+14)).

Diffuse gastric cancer with peritoneal carcinomatosis can mimic Crohn's disease.

In some cases the diagnosis of gastric cancer is difficult and the endoscopic presentation may be misleading. Diffuse type gastric carcinoma with peritoneal metastasis may present primarily with abdominal pain, colonic infiltration and/or diarrhea, thus other differential diagnoses like Crohn's disease (CD) may be considered at first. Therefore intensive diagnostic work-up is important. We report two cases of gastric cancer with ascites due to peritoneal carcinomatosis who were first diagnosed as CD. The patients were hospitalized in different institutions for weight loss, abdominal pain and nausea. The first colonoscopy, upper endoscopy with multiple biopsies and ascites puncture were negative for malignant disease, but macroscopic lesions resembling CD were described. Both patients were released on a prednisolone-based treatment for suspected CD. They presented to our hospital for further evaluation due to persistent symptoms. Neither lower nor upper endoscopy were suggestive of CD and endoscopic ultrasound was suspicious of malignancy in one case. Histology was diagnostic and showed gastric infiltration by a poorly differentiated adenocarcinoma. Diffuse type gastric cancer (gastric linitis plastica) with peritoneal metastasis may mimic certain clinical, endoscopic and CT imaging features of CD. Repeated biopsies and endoscopic investigations are often necessary to confirm a malignant process, especially in case of an inconclusive clinical and endoscopic picture. Endoscopic ultrasound may be useful to evaluate the risk of malignancy in patients with macroscopic suspicion of malignancy and negative biopsies.

Mesenteric fat - control site for bacterial translocation in colitis?

In Crohn's disease bacteria could be detected in the adjacent mesenteric fat characterized by hypertrophy of unknown function. This study aimed to define effector responses of this compartment induced by bacterial translocation during intestinal inflammation. Dextran sulfate sodium-induced colitis served as a model of intestinal inflammation. Translocation of peptides and bacteria into mesenteric fat was evaluated. Innate functions of mesenteric fat and epithelium were characterized at whole tissue, cellular, and effector molecule levels. Orally applied peptides translocated in healthy wild-type (WT) mice. Bacterial translocation was not detected in healthy and acute but increased in chronic colitis. Mesenteric fat from colitic mice released elevated levels of cytokines and was infiltrated by immune cells. In MyD88(-/-) mice bacterial translocation occurred in health and increased in colitis. The exaggerated cytokine production in mesenteric fat accompanying colonic inflammation in WT mice was less distinct in MyD88(-/-) mice. In vitro studies revealed that fat not only increases cytokine production following contact with bacterial products, but also that preadipocytes are potent phagocytes. Colonic inflammation is accompanied by massive cytokine production and immune cell infiltration in adjacent adipose tissue. These effects can be considered as protective mechanisms of the mesenteric fat in the defense of bacterial translocation.

RF positivity has substantial influence on the peripheral memory B-cell compartment and its modulation by TNF inhibition.

OBJECTIVES: The role of B cells in rheumatoid arthritis (RA) has been well established with the advent of B-cell targeted therapies. Alterations of peripheral B-cell subsets in RA and heterogeneous modulations of the B-cell compartment under tumour necrosis factor (TNF) inhibition have been described. In this study we examined the influence of rheumatoid factor (RF) positivity on the peripheral B-cell compartment and its modulation under TNF blockade. METHODS: Consecutive patients with RA and inadequate response to methotrexate (MTX) were stratified according to RF status and a subset of them was included in a prospective study of weekly etanercept treatment. RESULTS: At baseline, RF-negative patients had a significant higher percentage of overall CD27+ B cells compared to healthy controls (HC) and RF-positive patients. In detail, RF-negative patients had 46.6% (range 15.7-86.8%) CD27+ B cells compared to 31.3% (12.9-56.9%, p = 0.026) in HC and 29.8% (19-73.3%, p = 0.04) in RF-positive patients. Within the CD27+ compartment, CD27+/immunoglobulin (Ig)D+ memory B cells were significantly increased to 26.4% (range 5.9-54.7%) in RF-negative patients compared to 14.9% (4.1-27.3%, p = 0.006) in HC and 10.5% (3.4-41.1%, p = 0.003) in RF-positive patients. During anti-TNF therapy, memory B cells increased significantly in relative and absolute numbers only in RF-negative patients. CONCLUSIONS: In RF-negative patients, we observed an enhanced frequency of peripheral memory B cells and an accumulation of pre-switch memory B cells. During anti-TNF therapy, memory B cells increased significantly only in RF-negative patients, suggesting that the peripheral memory B-cell compartment is more amenable to TNF inhibition in these patients.