Disease activity-guided tapering of biologics in patients with inflammatory arthritis: a pragmatic, randomized, open-label, equivalence trial.

OBJECTIVE: To evaluate whether disease activity-guided tapering of biologics compared to continuation as usual care enables a substantial dose reduction while disease activity remains equivalent. METHOD: In this pragmatic, randomized, open-label, equivalence trial, adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in low disease activity on stable-dose biologics for ≥ 12 months were randomized 2:1 into either the tapering group, i.e. disease activity-guided prolongation of the biologic dosing interval until flare or withdrawal, or the control group, i.e. maintaince of baseline biologics with a possible small interval increase at the patients request. The co-primary outcome in the intention-to-treat population was met if superiority in ≥ 50% biologic reduction at 18 months was demonstrated and disease activity was equivalent (equivalence margins ± 0.5). RESULTS: Ninety-five patients were randomized to tapering and 47 to control, of whom 37% (35/95) versus 2% (1/47) achieved ≥ 50% biologic reduction at 18 months. The risk difference was statistically significant [35%, 95% confidence interval (CI) 24%-45%], while disease activity remained equivalent [mean difference 0.05, 95% CI -0.12-0.29]. A statistically significant flare risk was observed [tapering 41% (39/95) vs control 21% (10/47), risk difference 20%, 95% CI 4%-35%]; but, only 1% (1/95) and 6% (3/47) had persistent flare and needed to switch to another biological drug. CONCLUSIONS: Disease activity-guided tapering of biologics in patients with inflammatory arthritis enabled one-third to achieve ≥ 50% biologic reduction, while disease activity between groups remained equivalent. Flares were more frequent in the tapering group but were managed with rescue therapy.

Does light-based tertiary treatment prevent the spread of antibiotic resistance genes? Performance, regrowth and future direction.

The common occurrence of antibiotic-resistance genes (ARGs) originating from pathogenic and facultative pathogenic bacteria pose a high risk to aquatic environments. Low removal of ARGs in conventional wastewater treatment processes and horizontal dissemination of resistance genes between environmental bacteria and human pathogens have made antibiotic resistance evolution a complex global health issue. The phenomenon of regrowth of bacteria after disinfection raised some concerns regarding the long-lasting safety of treated waters. Despite the inactivation of living antibiotic-resistant bacteria (ARB), the possibility of transferring intact and liberated DNA containing ARGs remains. A step in this direction would be to apply new types of disinfection methods addressing this issue in detail, such as light-based advanced oxidation, that potentially enhance the effect of direct light interaction with DNA. This study is devoted to comprehensively and critically review the current state-of-art for light-driven disinfection. The main focus of the article is to provide an insight into the different photochemical disinfection methods currently being studied worldwide with respect to ARGs removal as an alternative to conventional methods. The systematic comparison of UV/chlorination, UV/H2O2, sulfate radical based-AOPs, photocatalytic processes and photoFenton considering their mode of action on molecular level, operational parameters of the processes, and overall efficiency of removal of ARGs is presented. An in-depth discussion of different light-dependent inactivation pathways, influence of DBP and DOM on ARG removal and the potential bacterial regrowth after treatment is presented. Based on presented revision the risk of ARG transfer from reactivated bacteria has been evaluated, leading to a future direction for research addressing the challenges of light-based disinfection technologies.

Disentangling the effects of age and mild traumatic brain injury on brain network connectivity: A resting state fMRI study.

INTRODUCTION: Cognitive complaints are common shortly after mild traumatic brain injury (mTBI) but may persist up to years. Age-related cognitive decline can worsen these symptoms. However, effects of age on mTBI sequelae have scarcely been investigated. METHODS: Fifty-four mTBI patients (median age: 35 years, range 19-64 years, 67% male) and twenty age- and sex-matched healthy controls were studied using resting state functional magnetic resonance imaging in the sub-acute phase. Independent component analysis was used to identify intrinsic connectivity networks (ICNs). A multivariate approach was adopted to evaluate the effects of age and group on the ICNs in terms of (static) functional network connectivity (FNC), intensities of spatial maps (SMs) and time-course spectral power (TC). RESULTS: We observed significant age-related changes for a) FNC: changes between 10 pairs of ICNs, mostly involving the default mode (DM) and/or the cognitive-control (CC) domains; b) SMs: intensity decrease in clusters across three domains and intensity increase in clusters across two domains, including the CC but not the DM and c) TC: spectral power decrease within the 0-0.15 Hz range and increase within the 0.20-0.25 Hz range for increasing age within networks located in frontal areas, including the anterior DM. Groups only differed for TC within the 0.065-0.10 Hz range in the cerebellar ICN and no age × group interaction effect was found. CONCLUSIONS: We showed robust effects of age on connectivity between and within ICNs that are associated with cognitive functioning. Differences between mTBI patients and controls were only found for activity in the cerebellar network, increasingly recognized to participate in cognition. Our results suggest that to allow for capturing the true effects related to mTBI and its effects on cognitive functioning, age should be included as a covariate in mTBI studies, in addition to age-matching groups.

Particulate substrate retention in plug-flow and fully-mixed conditions during operation of aerobic granular sludge systems.

Particulate substrate (XB) is the major organic substrate fraction in most municipal wastewaters. However, the impact of XB on aerobic granular sludge (AGS) systems is not fully understood. This study evaluated the physical retention of XB in AGS sequencing batch reactor (SBR) during anaerobic plug-flow and then aerobic fully-mixed conditions. The influence of different sludge types and operational variables on the extent and mechanisms of XB retention in AGS SBR were evaluated. XB mass-balancing and magnetic resonance imaging (MRI) were applied. During the anaerobic plug-flow feeding, most XB was retained in the first few cm of the settled sludge bed within the interstitial voids, where XB settled and accumulated ultimately resulting in the formation of a filter-cake. Sedimentation and surface filtration were thus the dominant XB retention mechanisms during plug-flow conditions, indicating that contact and attachment of XB to the biomass was limited. XB retention was variable and influenced by the XB influent concentration, sludge bed composition and upflow feeding velocity (vww). XB retention increased with larger XB influent concentrations and lower vww, which demonstrated the importance of sedimentation on XB retention during plug-flow conditions. Hence, large fractions of influent XB likely re-suspended during aerobic fully-mixed conditions, where XB then preferentially and rapidly attached to the flocs. During fully-mixed conditions, increasing floc fractions, longer mixing times and larger XB concentrations increased XB retention. Elevated XB retention was observed after short mixing times < 60 min when flocs were present, and the contribution of flocs towards XB retention was even more pronounced for short mixing times < 5 min. Overall, our results suggest that flocs occupy an environmental niche that results from the availability of XB during aerobic fully-mixed conditions of AGS SBR. Therefore, a complete wash-out of flocs is not desirable in AGS systems treating municipal wastewater.

Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial.

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.

Plasma concentrations of alpha-1-acid glycoprotein in preterm and term newborns: influence of mode of delivery and implications for plasma protein binding of local anaesthetics.

BACKGROUND: Alpha-1-acid glycoprotein (AAGP) is an acute-phase protein with high affinity for amide local anaesthetics (LAs), and a major determinant of free and potentially toxic concentrations of LAs in plasma. Neonates are known to have lower plasma concentrations of AAGP than adults, and are at risk of developing high free concentrations of LAs. Data regarding AAGP in newborns are so far sparse. The aim of this study was to determine plasma concentrations of AAGP after delivery of preterm and term infants, and to investigate correlations between AAGP and gestational age, birth weight, gender, and mode of delivery. METHODS: In this prospective observational study, blood was sampled from umbilical cords of 70 newborn infants born at gestational weeks 27-42 immediately after delivery. Blood samples were subsequently analysed for AAGP plasma concentrations with an immunoturbidimetric assay. RESULTS: We found higher concentrations of AAGP in infants born vaginally compared with those who were delivered by elective Caesarean section [median (inter-quartile range) 0.189 g litre-1 (0.142-0.263 g litre-1) vs 0.110 g litre-1 (0.094-0.157 g litre-1; P=0.0003)], respectively. There was a correlation between gestational age and AAGP concentrations (r=0.50; P=0.011), with significantly higher concentrations in the more mature infants. Gender and birth weight did not appear to influence the plasma concentrations of AAGP. CONCLUSIONS: Alpha-1-acid glycoprotein concentrations in newborns are influenced both by gestational age and mode of delivery. Thus, when dosing local anaesthetics in a parturient, these factors should be taken into account.

From 'miserable minority' to the 'fortunate few': the other end of the mild traumatic brain injury spectrum.

OBJECTIVES: This study, as part of the UPFRONT-study, aimed to study the patients that report zero complaints early after injury, a group that we named the 'fortunate few'. We focused on their demographic, clinical and premorbid characteristics, and examined whether they would remain asymptomatic. Moreover, we investigated the influence of anxiety and depression (HADS), and determined outcome (GOS-E) and quality of life (WHOQOL-BREF) 1 year after injury. METHODS: Patients with MTBI (Glasgow Coma Scale score 13-15), without complaints 2 weeks after injury were included. Follow-up took place at 3, 6 and 12 months after injury. RESULTS: Of the entire UPFRONT-cohort (n = 1151), 10% (n = 119) reported zero complaints 2 weeks after injury. More than half of these patients (57%) developed complaints at a later stage (M = 2, p < .001). Patients with secondary complaints had higher anxiety (p = .004) and depression (p = .002) scores, leading to less favourable outcome (p = .014) and a lower quality of life (p = .006) 1 year after injury compared to patients that remained asymptomatic. CONCLUSION: One in 10 patients with mTBI report zero complaints early after injury. Although they seem fully recovered early after injury, a substantial part may develop secondary complaints leading to less favourable outcome and lower quality of life, warranting further research of this interesting group.

Differences between BCL2-break positive and negative follicular lymphoma unraveled by whole-exome sequencing.

Depending on disease stage follicular lymphoma (FL) lack the t(14;18) in ~15-~50% of cases. Nevertheless, most of these cases express BCL2. To elucidate mechanisms triggering BCL2 expression and promoting pathogenesis in t(14;18)-negative FL, exonic single-nucleotide variant (SNV) profiles of 28 t(14;18)-positive and 13 t(14;18)-negative FL were analyzed, followed by the integration of copy-number changes, copy-neutral LOH and published gene-expression data as well as the assessment of immunoglobulin N-glycosylation sites. Typical FL mutations also affected t(14;18)-negative FL. Curated gene set/pathway annotation of genes mutated in either t(14;18)-positive or t(14;18)-negative FL revealed a strong enrichment of same or similar gene sets but also a more prominent or exclusive enrichment of immune response and N-glycosylation signatures in t(14;18)-negative FL. Mutated genes showed high BCL2 association in both subgroups. Among the genes mutated in t(14;18)-negative FL 555 were affected by copy-number alterations and/or copy-neutral LOH and 96 were differently expressed between t(14;18)-positive and t(14;18)-negative FL (P<0.01). N-glycosylation sites were detected considerably less frequently in t(14;18)-negative FL. These results suggest a diverse portfolio of genetic alterations that may induce or regulate BCL2 expression or promote pathogenesis of t(14;18)-negative FL as well as a less specific but increased crosstalk with the microenvironment that may compensate for the lack of N-glycosylation.

Clinical relevance of microhemorrhagic lesions in subacute mild traumatic brain injury.

Magnetic resonance imaging (MRI) is often performed in patients with persistent complaints after mild traumatic brain injury (mTBI). However, the clinical relevance of detected microhemorrhagic lesions is still unclear. In the current study, 54 patients with uncomplicated mTBI and 20 matched healthy controls were included. Post-traumatic complaints were measured at two weeks post-injury. Susceptibility weighted imaging and T2*-gradient echo imaging (at 3 Tesla) were performed at four weeks post-injury. Microhemorrhagic lesions (1-10 mm) were subdivided based on depth (superficial or deep) and anatomical location (frontal, temporoparietal and other regions). Twenty-eight per cent of patients with mTBI had ≥1 lesions compared to 0 % of the healthy controls. Lesions in patients with mTBI were predominantly located within the superficial frontal areas. Number, depth and anatomical location of lesions did not differ between patients with and without post-traumatic complaints. Within the group of patients with complaints, number of complaints was not correlated with number of lesions. In summary, microhemorrhages were found in one out of four patients with uncomplicated mTBI during follow-up at four weeks post-injury, but they were not related to early complaints.

Outpatient follow-up after mild traumatic brain injury: Results of the UPFRONT-study.

OBJECTIVE: To investigate outpatient follow-up after mild traumatic brain injury (mTBI) by various medical specialists, for both hospitalized and non-hospitalized patients, and to study guideline adherence regarding hospital admission. METHODS: Patients (n = 1151) with mTBI recruited from the emergency department received questionnaires 2 weeks (n = 879), 3 months (n = 780) and 6 months (n = 668) after injury comprising outpatient follow-up by various health care providers, and outcome defined by the Glasgow Outcome Scale Extended (GOS-E) after 6 months. RESULTS: Hospitalized patients (60%) were older (46.6 ± 19.9 vs. 40.6 ± 18.5 years), more severely injured (GCS <15, 50% vs. 13%) with more Computed Tomography (CT) abnormalities on admission (21% vs. 2%) compared to non-hospitalized patients (p < 0.01) . Almost half of the patients visited a neurologist at the outpatient clinic within six months (60% of the hospitalized and 25% of the non-hospitalized patients (χ2 = 67.10, p < 0.01)), and approximately ten per cent consulted a psychiatrist/psychologist. Outcome was unfavourable (GOS-E <7) in 34% of hospitalized and 21% of non-hospitalized patients (χ2 = 11.89, p < 0.01). CONCLUSION: Two-thirds of all mTBI patients consult one or more specialists within six months after injury, with 30% having an unfavourable outcome. A quarter of non-hospitalized patients was seen at the outpatient neurology clinic, underling the importance of regular follow-up of mTBI patients irrespective of hospital admittance.

Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial.

BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up. PATIENTS AND METHODS: Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. RESULTS: Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. CONCLUSIONS: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. TRIAL NUMBERS: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).

Distinct resting-state perfusion patterns underlie psychomotor retardation in unipolar vs. bipolar depression.

OBJECTIVE: Psychomotor abnormalities characterize both unipolar (UP) depression and bipolar (BP) depression. We aimed to assess their neurobiological correlates in terms of motor activity (AL) and resting-state cerebral blood flow (rCBF) and investigate their association in BP, UP, and healthy controls (HC). METHOD: We enrolled 42 depressed patients (22 BP, 20 UP) and 19 HC matched for age, gender, education, income. AL and rCBF were objectively assessed with the use of wrist actigraphy and arterial spin labeling. Group differences and the association of AL and rCBF were computed. RESULTS: Activity level was significantly reduced in patients, but no difference was found between BP and UP. Increased perfusion was found in BP compared with UP and HC, in multiple brain areas. We found positive correlations of rCBF and AL in BP and UP, in different parts of the insula and frontal regions. Only BP showed a cluster in the left precentral gyrus. In HC, only inverse correlations of AL and rCBF were found. CONCLUSION: The differences in rCBF and in the localization of the clusters of positive AL/rCBF correlations between BP and UP suggest that different neural impairments may underlie motor symptoms in the two disorders, but finally converge in phenotypically similar manifestations.

Subacute posttraumatic complaints and psychological distress in trauma patients with or without mild traumatic brain injury.

OBJECTIVE: To identify the frequency, nature and profile of complaints for trauma patients with and without mild traumatic brain injury (mTBI), and to assess their relation to anxiety and depression. METHODS: A prospective cohort study in a level-one trauma centre was conducted. Mild traumatic brain injury patients and trauma controls were approached for participation. Two weeks after injury, The Head Injury Symptom Checklist (HISC) and the Hospital Anxiety and Depression Scale (HADS) were administered. RESULTS: Two-hundred seventy two patients with mTBI and 125 TC patients completed the questionnaires. Differences were demonstrated between the two trauma populations on frequency and nature of reported complaints. Ordinal common factor analysis on the mTBI scores yielded three factors: mental distress, physical discomfort, and sensory disbalance, which were all significantly correlated to anxiety and depression scores. Discriminant analyses identified a subset of complaints which could allocate almost 80% of patients to the correct group. CONCLUSIONS: Patients with mTBI showed a different pattern of complaints than orthopaedic control patients. A mental distress factor consisting of both somatic and cognitive complaints proved to be most discriminating and showed high correlations with anxiety and depression.

Similar clinical features in follicular lymphomas with and without breaks in the BCL2 locus.

Approximately 15% of follicular lymphomas (FLs) lack breaks in the BCL2 locus. The aim of this study was to better define molecular and clinical features of BCL2-breakpoint/t(14;18)-negative FLs. We studied the presence of BCL2, BCL6 and MYC breaks by fluorescence in situ hybridization and the expression of BCL2, MUM1, CD10, P53 and Ki67 in large clinical trial cohorts of 540 advanced-stage FL cases and 116 early-stage disease FL patients treated with chemotherapy regimens and radiation, respectively. A total of 86% and 53% of advanced- and early-stage FLs were BCL2-breakpoint-positive, respectively. BCL2 was expressed in almost all FLs with BCL2 break and also in 86% and 69% of BCL2-breakpoint-negative advanced- and early-stage FLs, respectively. CD10 expression was significantly reduced in BCL2-breakpoint-negative FLs of all stages and MUM1 and Ki67 expression were significantly increased in BCL2-break-negative early-stage FLs. Patient characteristics did not differ between FLs with and without BCL2 breaks and neither did survival times in advanced-stage FLs. These results suggest that the molecular profile differs to some extent between FLs with and without BCL2 breaks and support the notion that FLs with and without BCL2 breaks belong to the same lymphoma entity.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression.

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study was to investigate FAA and its correlation with resting-state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant to reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left-lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients), in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right-lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.

Phototransformation of sulfamethoxazole under simulated sunlight: Transformation products and their antibacterial activity toward Vibrio fischeri.

Sulfamethoxazole (SMX) is a bacteriostatic antibiotic ubiquitously found in the aquatic environment. Since conventional biological wastewater treatment is not efficient to remove SMX, photolysis in natural waters can represent an important transformation pathway. It was recently shown that SMX transformation products can retain antibiotic activity. Therefore, it is crucial to better understand photochemical processes occurring in natural water just as the formation of active transformation products (TPs). During long-term SMX photolysis experiments (one week), nine TPs were identified by reference standards. Moreover, five further TPs of photodecomposition of SMX were found. For the first time, a TP with m/z 271 [M+H](+) was observed during photolysis and tentatively confirmed as 4,x-dihydroxylated SMX. The DOC mass balance clearly showed that only around 5 to 10% were mineralized during the experiment emphasizing the need to elucidate the fate of TPs. Bacterial bioassays confirmed that the mixture retains its antibiotic toxicity toward luminescence (24h) and that there is no change over the treatment time on EC50. In contrast, growth inhibition activity was found to slightly decrease over the irradiation time. However, this decrease was not proportional to the transformation of the parent compound SMX.

Different biological risk factors in young poor-prognosis and elderly patients with diffuse large B-cell lymphoma.

Prognostically relevant risk factors in patients with diffuse large B-cell lymphoma (DLBCL) have predominantly been evaluated in elderly populations. We tested whether previously described risk factors are also valid in younger, poor-prognosis DLBCL patients. Paraffin-embedded samples from 112 patients with de novo DLBCL, enrolled in the R-MegaCHOEP trial of the German High Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using immunohistochemistry (MYC, FOXP1, LMO2, GCET1, CD5, CD10, BCL2, BCL6, IRF4/MUM1) and fluorescence in situ hybridization (MYC, BCL2, BCL6). MYC, BCL2 and BCL6 breaks occurred in 14, 21 and 31%, respectively. In the majority of cases, MYC was simultaneously rearranged with BCL2 and/or BCL6. The adverse impact of MYC rearrangements was confirmed, but the sole presence of BCL2 breaks emerged as a novel prognostic marker associated with inferior overall survival (OS) (P=0.002). Combined overexpression of MYC and BCL2 showed only limited association with inferior OS. All immunohistochemical cell of origin classifiers applied failed to predict survival time. DLBCL tumors with significant proportion of immunoblastic and/or immunoblastic-plasmacytoid cells had inferior OS, independently from from BCL2 break. Younger, poor-prognosis DLBCL patients, therefore, display different biological risk factors compared with an elderly population, with BCL2 translocations emerging as a powerful negative prognostic marker.

Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA: cost-effectiveness based on a 2-year randomized trial.

OBJECTIVES: To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). METHOD: In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient clinics and general practice, prescription and non-prescription medicine, dietary supplements, other health-care resources, and complementary and alternative care. Measures of effectiveness and costs were collected by self-reported questionnaires at inclusion and after 12 and 24 months. Incremental cost-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. RESULTS: Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. CONCLUSIONS: Shared care and nurse care seem to cost less but provide broadly similar health outcomes compared with rheumatologist outpatient care. However, it is still uncertain whether nurse care and shared care are cost-effective in comparison with rheumatologist outpatient care.

The biocidal effect of a novel synthesized gemini surfactant on environmental sulfidogenic bacteria: planktonic cells and biofilms.

A cationic gemini surfactant was synthesized and characterized. The surfactant was successfully applied as a biocide against environmental sulfidogenic bacteria in the bulk phase (planktonic) and on the surface (biofilm). The activity of the synthesized surfactant was discussed based on the redox potential and the sulfide productivity in the bulk phase. The cultivated biofilm structure analysis and corrosion rate were estimated on the metal surface. The lowest metal corrosion rate was recognized at a concentration of 1mM with a metal corrosion inhibition efficiency of 95%. The synthesized gemini surfactant prevented the biofilm formation at a concentration of 0.1mM. The synthesized gemini surfactant displayed a broad spectrum antibacterial activity against Gram-positive and Gram-negative bacteria.