Novel optical spectral transmission (OST)-guided versus conventionally disease activity-guided treatment: study protocol of a randomized clinical trial on guidance of a treat-to-target strategy for early rheumatoid arthritis.

BACKGROUND: Assessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at 'HandScan remission' (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm). METHODS/DESIGN: The study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered. DISCUSSION: The study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients. TRIAL REGISTRATION: Dutch Trial Register, NTR6388. Registered on 6 April 2017 ( NL50026.041.14 ). Protocol version 3.0, 19-01-2017.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

DCD donor hemodynamics as predictor of outcome after kidney transplantation.

Insufficient hemodynamics during agonal phase-ie, the period between withdrawal of life-sustaining treatment and circulatory arrest-in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at the fingertip) and systolic blood pressure (SBP-with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2 > 60% or SpO2 < 60%, and minutes of SBP > 80 mmHg or SBP < 80 mmHg. Outcome measures were and primary non-function (PNF), delayed graft function (DGF), and three-year graft survival. Primary non-function (PNF) rate was 6.6%, delayed graft function (DGF) rate was 67%, and graft survival at three years was 76%. Longer periods of agonal phase (median 16 min [IQR 11-23]) contributed significantly to an increased risk of DGF (P = .012), but not to PNF (P = .071) and graft failure (P = .528). Multiple logistic regression analysis showed that an increase from 7 to 20 minutes in period of SBP < 80 mmHg was associated with 2.19 times the odds (95% CI 1.08-4.46, P = .030) for DGF. In conclusion, duration of agonal phase is associated with early transplant outcome. SBP < 80 mmHg during agonal phase shows a better discrimination for transplant outcome than SpO2 < 60% does.

Gouty arthritis: decision-making following dual-energy CT scan in clinical practice, a retrospective analysis.

To establish whether dual-energy CT (DECT) is a diagnostic tool, i.e., associated with initiation or discontinuation of a urate lowering drug (ULD). Secondly, to determine whether DECT results (gout deposition y/n) can be predicted by clinical and laboratory variables. Digital medical records of 147 consecutive patients with clinical suspicion of gout were analyzed retrospectively. Clinical data including medication before and after DECT, lab results, and results from diagnostic joint aspiration and DECT were collected. The relationship between DECT results and clinical and laboratory results was evaluated by univariate regression analyses; predictors showing a p < 0.10 were entered in a multivariate logistic regression model with the DECT result as outcome variable. A backward stepwise technique was applied. After the DECT, 104 of these patients had a clinical diagnosis of gout based on the clinical judgment of the rheumatologist, and in 84 of these patients, the diagnosis was confirmed by demonstration of monosodium urate (MSU) crystals in synovial fluid (SF) or by positive DECT. After DECT, the current ULD was modified in 33 (22.4%) of patients; in 29 of them, ULD was started and in 1 it was intensified. Following DECT, the current ULD was stopped in three patients. In the multivariable regression model, cardiovascular disease (OR 3.07, 95% CI 1.26-7.47), disease duration (OR 1.008, 95% CI 1.001-1.016), frequency of attack (OR 1.23, 95% CI 1.07-1.42), and creatinine clearance (OR 2.03, 95% CI 0.91-1.00) were independently associated with positive DECT results. We found that the DECT result increases the confidence of the prescribers in their decision to initiation or discontinuation of urate lowering therapy regimen in of mono- or oligoarthritis. It may be a useful imaging tool for patients who cannot undergo joint aspiration because of contraindications or with difficult to aspirate joints, or those who refuse joint aspiration. We also suggest the use of DECT in cases where a definitive diagnosis cannot be made from signs, symptoms, and MSU analysis alone.

Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis.

OBJECTIVE: There is increasing evidence that adipocytokines may exert proinflammatory and destructive effects in rheumatoid arthritis (RA). Hence, the authors investigated the relationship between adipocytokines and several features associated with RA (inflammation, joint destruction and cardiovascular disease), as well as the effect of treatment with a tumour necrosis factor inhibitor or glucocorticoids (GCs) hereupon. METHODS: Serum levels of adiponectin, leptin, resistin, visfatin, vaspin and lipids were determined in a well-defined cohort of patients with RA before and after 16 weeks of adalimumab treatment (adalimumab cohort). The same parameters were analysed in two other cohorts of patients with RA before and after 2 weeks of high-dose prednisolone (high GC cohort) and before and after 22 weeks of treatment with a combination regimen with tapered high-dose prednisolone (COBRA -GC cohort). Radiographs of hands and feet (adalimumab and COBRA-GC cohorts) were assessed at baseline and after treatment. RESULTS: Treatment with adalimumab or GC showed opposing effects on vaspin and visfatin levels. Lipid levels improved after several months of adalimumab or GC treatment; in the adalimumab cohort, this was related to reduced visfatin levels, independent of C reactive protein levels. After long-term adalimumab or GC treatment, resistin levels declined, which was associated with a decrease in inflammation markers. In the adalimumab cohort, baseline resistin levels were predictive of baseline radiological damage, independent of anticitrullinated peptide antibodies status or C reactive protein levels. CONCLUSION: Changes in serum adipocytokine levels were treatment specific, further strengthening the role of visfatin and resistin in several disease manifestations of RA.

Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss.

OBJECTIVE: To explore the effects of anti-tumour necrosis factor (TNF)alpha antibody therapy on bone mineral density (BMD) of the lumbar spine and femur neck in patients with rheumatoid arthritis (RA). METHODS: A total of 50 patients with active RA (DAS28> or =3.2) who started adalimumab (40 mg subcutaneously/2 weeks) were included in an open label prospective study. All patients used stable methotrexate and were allowed to use prednisone (< or =10 mg/day). The BMD of the lumbar spine and femur neck was measured before and 1 year after start of treatment. RESULTS: Disease activity at baseline (28-joint Disease Activity Score (DAS28)) and disease duration were inversely correlated with femoral neck BMD and lumbar spine BMD (p<0.05). Mean BMD of lumbar spine and femur neck remained unchanged after 1 year of adalimumab therapy (+0.3% and +0.3%, respectively). Of interest, a beneficial effect of prednisone on change in femur neck BMD was observed with a relative increase with prednisone use (+2.5%) compared to no concomitant prednisone use (-0.7%), (p = 0.015). CONCLUSION: In contrast to the progressive bone loss observed after conventional disease-modifying antirheumatic drug therapy, TNF blockade may result in an arrest of general bone loss. Consistent with previous observations, the data also suggest that the net effect of low-dose corticosteroids on BMD in RA may be beneficial, possibly resulting from their anti-inflammatory effects.

Successful management of chronic myeloid leukaemia with leucapheresis during a twin pregnancy.

We present a 36-year-old woman in whom chronic myeloid leukaemia (CML) was diagnosed during a twin pregnancy. Because of hyperleucocytosis, we started leucapheresis also with the goal of gaining time for discussing treatment options. As this strategy was so effective and our patient was reluctant to take medication, we decided to continue this treatment.

[Mixed myelocytic and lymphocytic acute leukemia. Case report]. / Leucemia aguda mixta mieloide y linfoide. Caso clinico.

A patient with acute mixed myelocytic and lymphocytic leukemia is reported. The patient showed two populations of malignant myeloid and lymphoid cells with predominance of myeloid lineage. According to the present knowledge, it is hypothesized that its origin is at a pluripotent transformed stem cell which has the capability of differentiating through myeloid and lymphoid lineages. Its maturation is arrested at certain level, thus raising two monoclonal populations simultaneously in the same patient. The treatment should be combined with drugs used in acute myeloblastic and lymphoblastic leukemia. The response to chemotherapy is generally poor.

Morphological changes on nerves and histopathological effects on liver and kidney of rats by pentachlorophenol (PCP).

1. The chronic toxicity of pentachlorophenol (PCP) was studied in rats after 90-120 days of oral administration ad libitum of 0.3-3 mM PCP aqueous solutions. 2. Morphological studies of their sciatic nerves were performed by optical and electron microscopy. 3. They showed degenerative changes in about 10% of the A and B type of nerve fibers. 4. The myelin sheath was discontinued by complete separation in several concentric rings while some other parts of the nerve exhibited a variable loss of neurotubules, neurofilaments and other axoplasmic components. 5. However, the C type of nerve fibers, the blood vessels and the perineurium did not show any morphologic alteration. 6. It was also found that in the liver PCP caused hemodynamic vein changes and injury in the hepatocytes such as cellular swelling and vacuolar degeneration. 7. The damage in the kidney occurred primarily in the glomeruli and secondarily in the proximal tubules causing turbid tumefaction and the formation of casts in the tubular lumen.

[Bilateral renal agenesis: a 10-year experience]. / Agenesia renal bilateral: experiencia de 10 años.

Bilateral renal agenesis (BRA) is an uniformly lethal malformation occurring in 0.1-0.3/1000 births. This condition is associated with severe oligohydramnios, intrauterine growth retardation (IUGR), extra-renal anomalies, and malpresentation. The aim of this study was to present our experience with 10 cases of BRA seen in a 10-year period. In only one case the prenatal diagnosis was made. Therefore, the clinician was faced with a high-risk pregnancy: 70% of cases presented with malpresentation, oligohydramnios, and severe IUGR. This explain the high rate of cesarean section (40%) and the neonatal intensive care offered to these neonates. The principal methods to improve the prenatal diagnosis of this condition are discussed.