Assessing vitamin D levels in an anti-DFS70 positive population: New insights emerging

Abstract

Background: Anti-dense fine speckled 70 (DFS70) autoantibodies have more often been described in apparently healthy individuals than in patients with systemic autoimmune rheumatic diseases (SARD). The aim of this study was to explore the link between anti-DFS70 autoantibodies and vitamin D (25(OH)D) levels in an Italian adult cohort.

Methods: Serum samples from 34 (five males and 29 females) anti-DFS70 positive patients (index cases), 34 ANA-negative healthy controls, 34 ANA-positive anti-DFS70 negative SLE patients, both groups age- and gender-matched with the index cases, 23 ANA-positive anti-DFS70 negative healthy blood donors and six female SARD patients showing mixed DFS positive pattern were collected and tested for 25(OH)D levels. Relevant demographics and lifestyle practices, body mass index (BMI), comorbidities, and use of medication were recorded for patients and healthy controls.

Results: Mean serum levels of 25(OH)D were significantly higher in anti-DFS70 positive subjects (mean?±?SD: 22.1?±?9.8?ng/ml) than in ANA-negative healthy controls (mean?±?SD: 17.3?±?6.7?ng/ml; p?=?.03), ANA-positive healthy controls (mean?±?SD: 15.2?±?6.8?ng/ml; p?=?.01), SLE patients (16.6?±?11.0?ng/ml; p?=?.01) and in patients with SARD (15.0?±?5.6?ng/ml; p?=?.01). No statistically relevant differences in BMI, clinical, or demographic parameters were found.

Conclusions: Our findings showed higher levels of vitamin D in anti-DFS70 positive subjects than in the controls, which is compatible with the hypothesis of the “benign” nature of anti-DFS70 antibodies.     

Computerized acoustic cardiography correlates with echocardiography and invasive haemodynamics after percutaneous transvenous mitral commissurotomy

Background:?Rheumatic mitral stenosis severity has been assessed by the systolic time interval between the QRS onset and the first heart sound (QS1) by phonocardiography. We hypothesized that non-invasive computerized acoustic cardiography could evaluate mitral stenosis severity compared with echocardiography and invasive haemodynamics in patients undergoing percutaneous transvenous mitral commissurotomy (PTMC).

Methods:?27 patients underwent computerized acoustic cardiography, echocardiography, and invasive haemodynamic measurements prior to and after PTMC.

Results:?The mean age was 31?±?10 years, and 21 (78%) were female. By echocardiography, mitral valve area increased from 0.82?±?0.14 to 1.50?±?0.24 cm² (p?<?0.0001). The QS1 interval decreased from 101.7?±?12.9 to 93.2?±?9.2?ms (p?<?0.0001). The change in the QS1 interval correlated with the change in mitral valve area by echocardiography (p?=?0.037), right ventricular systolic pressure (p?<?0.0001), and the invasive mitral valve gradient (p?=?0.076).

Conclusions:?Acoustic cardiography may be used as an adjunctive non-invasive diagnostic tool to assess mitral stenosis severity.     

The pharmacokinetic profile of raltegravir-containing antiretroviral therapy in HIV-infected individuals over 60 years of age

Background:

Antiretroviral safety and efficacy and may differ in older versus younger HIV-infected patients. The objective of this study was to assess the pharmacokinetic (PK) profile in older HIV-infected subjects (>60?years) switching combination antiretroviral therapy (cART) to a raltegravir (RAL) containing regimen.

Methods:

Nineteen HIV-infected patients over 60?years of age on effective cART (HIV-RNA Results:

In HIV-infected subjects over the age of 60 (mean?±?SD age: 66?±?3.4?years, n?=?19) switching to a RAL containing regimen, we observed no safety concerns, no plasma virological rebounds, and no differences in RAL apparent oral clearance when compared to younger HIV-infected populations (mean?±?SD age: 41?±?9.2?years, n?=?38) based on population pharmacokinetic analysis. After 24?weeks of study therapy a decline in cognitive function was observed [change in (SD) global score of (0.91 (1.3), P?=?0.018].

Conclusions:

No significant changes in RAL exposure associated with age were observed.     

Sulfur mustard triggers oxidative stress through glutathione depletion and altered expression of glutathione-related enzymes in human airways

Context: Sulfur mustard (SM) is a lipophilic and reactive chemical compound that targets human airway system.

Objective: Glutathione (GSH) depletion, oxidative stress (OS) status, and changes in expression of GSH-dependent antioxidant enzymes were considered in human mustard lungs.

Materials and methods: Lung biopsies and bronchoalveolar lavage (BAL) were collected from non-exposed (n?=?10) individuals and SM-exposed patients (n?=?12). Alterations in expression of GSH-dependent enzymes were studied using RT² Profiler? PCR array. OS was evaluated by determining BAL fluid levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and GSH.

Results: Mean TAC (0.142?±?0.027?µmol/l) and GSH (4.98?±?1.02?nmol/l) in BAL fluids of control group was significantly higher (p?p?=?.001) higher than that in controls (0.49?±?0.048?nmol/l). Glutathione peroxidases (GPXs), glutathione-s-transferases (GSTs), and glutathione synthetase (GSS) enzymes were overexpressed in mustard lung biopsies, while glutathione reductase (GSR) was significantly downregulated (14.95-fold).

Conclusions: GSH depletion induced by GSR downregulation may be a major mechanism of SM toxicity on human lung. Despite overexpression of GSTs and GPXs genes, GSH depletion may decline the productivity of these enzymes and total antioxidants capacity, which is associated with OS.     

Blood lead levels,pulmonary function and agility in Polish schoolchildren

Background: Reduced vital capacity (VC) and forced vital capacity (FVC) are associated with lead (Pb) exposure.

Aim: The objective of this study is to analyse the effects of Pb on FVC and the shuttle run performance.

Subjects and methods: Data were available for 184 male and 189 female Polish schoolchildren aged 10–15?years. Regression analysis was performed of shuttle run performance (dependent) on Pb and FVC.

Results: Shuttle run time increased by 1.75 (±?0.77) and 1.97 (±?0.77) seconds for each 10?µg/dL increase in Pb blood among males and females, respectively. Higher shuttle run times indicate poorer performance. Average unadjusted blood Pb level in the sample was 5.27?μg/dL (±?0.19 SE) and 3.82?μg/dL (±?0.10 SE), respectively. Path analysis was used to assess the association of Pb level with shuttle run time. Blood Pb had a significant negative effect on VC (B=??13.60?±?3.28 [SE], p?B?=??13.08?±?3.27, p?B?=??0.04?±?0.007, p?B?=?1.59?±?0.75, p?B?=?1.49?±?0.73, p?Conclusions: Thus, Pb had direct and indirect effects that increased shuttle run time, i.e. negatively affected performance.     

The absence of physiological neonatal weight loss on the 1st–5th day is associated with decreased later physical indices

Abstract

Aim: To investigate associations between physiological neonatal weight loss on the 1st–5th day and physical indices from birth up to the age of 17 years.

Methods: Data were derived from the personal health records of healthy, full-term and breastfed children born in Vilnius in 1990 and 1996. Five hundred and thirty children (289 boys and 241 girls) who left a maternity unit on the 1st–5th day after birth were included in the analysis.

Results: Infants left the maternity unit on day 4.62?±?2.33. On the day of leaving a maternity unit, infants lost 105.06?±?130.48 g (2.85?±?3.65%) of birth weight. Girls who did not lose or gained weight after birth had already weighed less at birth (3163?±?547 and 3490?±?403 g, respectively, p?<?0.01) and remained lighter up to the age of 17 years (54.3?±?8.7 and 60.8?±?10.1?kg at the age of 17 years respectively, p?<?0.001). Girls who did not lose or gained weight after birth were also shorter than those who lost weight (164.3?±?5.7 and 168.6?±?5.4?cm at the age of 17 years, respectively, p?<?0.001).

Conclusion: Girls who did not lose or gained weight immediately after birth tended to remain shorter and lighter during childhood and adolescence. Only a few statistically significant differences were obtained in boys.     

Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves’ orbitopathy: A five-year follow-up study

Abstract

The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves’ orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), ^99mTc-labeled diethylene triamine pentaacetic acid (^99mTc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375?mg/m² body surface area for four weeks. The mean follow-up period was 67 (range 58–81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5?±?1.7 and decreased to 3.4?±?1.6 by one month (p?<?0.05) and remained unchanged (3.2?±?1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52?±?4.51?MBq/cm³ and decreased to 11.97?±?2.36?MBq/cm³ at one year (p?<?0.002). The mean of T2 relaxation times before and one year after therapy were 96.91?±?17.61?ms and 84.29?±?9.41?ms, respectively (p?<?0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4?±?3.4?U/L, 5.6?±?4.5?U/L and 1.7?±?1.5?U/L, respectively (p?<?0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.     

Free-living physical activity and energy expenditure of rural children and adolescents in the Nandi region of Kenya

Abstract

Purpose: To examine the relationship between physical activity and energy demands in children and adolescents with highly active lifestyles.

Methods: Physical activity patterns of 30 rural Kenyan children and adolescents (14?±?1 years, mean?±?SD) with median body mass index (BMI) z-score?=??1.06 [?3.29–0.67] median [range] were assessed by accelerometry over 1 week. Daily energy expenditure (DEE), activity-induced energy expenditure (AEE) and physical activity level (PAL) were simultaneously determined using doubly-labelled water (DLW). Active commuting to school was assessed by global positioning system.

Results: Mean DEE, AEE and PAL were 12.2?±?3.4, 5.7?±?3.0?MJ/day and 2.3?±?0.6, respectively. A model combining body mass, average accelerometer counts per minute and time in light activities predicted 45% of the variance in DEE (p?<?0.05) with a standard error of DEE estimate of 2.7?MJ/day. Furthermore, AEE accounted for ～47% of DEE. Distance to school was not related to variation in DEE, AEE or PAL and there was no association between active commuting and adiposity.

Conclusion: High physical activity levels were associated with much higher levels of energy expenditure than observed in Western societies. These results oppose the concept of physical activity being stable and constrained in humans.     

Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease

The anthocyanidin delphinidin reduces psoriasiform lesions and inflammatory mediators in human cell culture systems. Its role in psoriatic disease has not yet been investigated. We assessed delphinidin’s in vitro immunomodulatory effect on ex vivo stimulated peripheral blood mononuclear cells (PBMCs) from 50 individuals [26 with psoriasis, 10 with psoriatic arthritis (PsA) and 14 healthy controls (HCs)]. Cells were either left untreated or stimulated with PMA plus ionomycin in the presence or absence of delphinidin. Intracellular production of interferon-γ (IFNγ), interleukin-17A (IL-17A), and interleukin-10 (IL-10) was measured flow cytometrically. Delphinidin dose-dependently reduced IFNγ⁺ T cells from patients and HCs. The mean IFNγ decrease in CD4⁺ T subpopulations was 42.5?±?28% for psoriasis patients, 51.8?±?21.5% for PsA patients and 49?±?17% for HCs (p?<?0.001 for all). Similarly, IFNγ reduction in CD8⁺ T cells was 34?±?21.6% for psoriasis patients, 47.1?±?22.8% for PsA and 44.8?±?14.3% for HCs (P <?0.001 for all). An inhibitory effect of delphinidin was also noted in IFNγ producing NKs and NKTs from psoriasis individuals. Delphinidin also significantly decreased IL-17⁺ CD4⁺ T cells in all tested subjects, with marginal effect on the increase of IL-10-producing T regulatory subsets. In conclusion, delphinidin exerts a profound in vitro anti-inflammatory effect in psoriasis and psoriatic arthritis by inhibiting IFNγ⁺ innate and adaptive cells and T helper (Th) 17 cells. If this effect is also exerted in vivo, delphinidin may be regarded as a nutraceutical with immunosuppressive potential.

     

Clinical characteristics and outcomes of idiopathic membranous nephropathy with glomerular IgM deposits

Glomerular IgM deposition is commonly shown in idiopathic membranous nephropathy, but the clinicopathological features and outcomes of IMN with IgM deposition are unclear. This single-center prospective cohort study enrolled 210 patients with biopsy-proven IMN from January 2016 to December 2018. Clinicopathological features, treatment responses, and kidney outcomes were compared between patients with and without IgM deposition. In total, 76 (36.2%) patients show glomerular IgM deposition. Patients with IgM deposition were younger (45?±?13.30 vs. 50.59?±?13.65 years, P?=?0.006), had a higher estimated glomerular filtration rate (eGFR) (100.03 [81.31–111.37] vs. 92.67 [74.71–106.63] mL/min/1.73 m², P?=?0.041), and had a lower proportion of nephrotic syndrome (60.5% vs. 75.4%, P?=?0.024) at the time of kidney biopsy. Patients with IgM deposition had a significantly higher proportion of focal segmental glomerular sclerosis (FSGS) lesions (27.6% vs. 13.4%, P?=?0.011) and C1q deposition (72.4% vs. 57.5%, P?=?0.032). Although the treatments and initial treatment responses were comparable, patients with glomerular IgM deposition had a significantly greater proportion of eGFR decline of?≥?5 mL/min/1.73 m² per year (log-rank test, P?<?0.001) and eGFR decrease of?≥?10% from baseline (log-rank test, P?=?0.003). Cox regression analysis showed that IgM deposition was an independent risk factor of eGFR decline of?≥?5 mL/min/1.73 m² per year (HR, 2.442; 95% CI, 1.550–3.848, P?<?0.001) and eGFR decline by?≥?10% from baseline (HR, 2.629; 95% CI, 1.578–4.385, P?<?0.001) during follow-up. IgM deposition in the glomeruli is an independent risk factor for decreased renal function in patients with IMN.

     

Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy

Abstract

Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91?±?7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5?±?322.77 versus 387.27?±?85.11?pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5?±?322.77 versus 567.32?±?92.16?pg/ml). CCL5/RANTES serum doesn’t correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.     

Type-III interferons and rheumatoid arthritis: Correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels

Aim: To assess serum type III or lambda (λ) interferons (IFN) levels and its clinical and laboratory associations in rheumatoid arthritis (RA). Methods: A cross-sectional study including 43 patients with RA (86% females; age 45.3?±?10.3 years) and 43 healthy individuals was performed. Clinical data including disease activity, acute-phase reactants, rheumatoid factor and anticyclic citrullinated peptide (anti-CCP) antibodies were collected. Serum IFNλ1, IFNλ2, IFNλ3, CXCL8 and anti-mutated citrullinated vimentin (anti-MCV) antibody levels were measured. Results: Patients with RA had higher IFNλ1 (113.5?±?118.6?pg/mL versus 55.9?±?122.3?pg/mL; p?<?0.0001) and IFNλ2 (245.4?±?327.7?pg/mL versus 5.1?±?11.0?pg/mL; p?=?0.009) levels than controls, but not IFNλ3 levels. Notably, IFNλ1 levels were found to be higher in both patients with active disease (124.9?±?135.9?pg/mL; p?<?0.001) and quiescent disease (99.0?±?93.7?pg/mL; p?<?0.01), while IFNλ2 levels were higher only in patients with active disease (264.0?±?356.1?pg/mL; p?=?0.02). A noteworthy association between serum IFNλ1 levels and anti-MCV antibody titers (Spearman's rho coefficient 0.36, 95% CI 0.36 to 0.61; p?=?0.02) was observed. Conclusion: Serum IFNλ1 and IFNλ2 levels are abnormally elevated in patients with RA and the former are linearly associated with circulating anti-MCV antibody levels. These results may place type-III IFN as an attractive new therapeutic target in RA.     

Exercise training reduces oxidative stress in people living with HIV/AIDS: a pilot study

Background: Exercise training has been shown to be an effective strategy to balance oxidative stress status; however, this is underexplored in people living with HIV/AIDS (PLWHA).

Objective: To evaluate the effects of exercise training on oxidative stress in PLWHA receiving antiretroviral therapy.

Methods: Patients performed 24 sessions (3 times per week, 8 weeks) of either aerobic (AT), resistance (RT), or concurrent training (CT). Glutathione disulphide to glutathione ratio (GSSG/GSH) in circulating erythrocytes and thiobarbituric acid–reactive substances (TBARS) in plasma samples were assessed as oxidative stress markers. Eight PLWAH completed the training protocol (AT =3, RT =3, CT =2). The GSSG/GSH and TBARS values were logarithmically transformed to approximate a normal distribution. A paired t-test was used to determine the differences between baseline and post-training values.

Results: Data-pooled analysis showed a decrease in GSSG/GSH and TBARS after the training period: log GSSG/GSH= –1.26?±?0.57 versus –1.54?±?0.65, p?=?.01 and log TBARS =0.73?±?0.35 versus 0.43?±?0.21, p?=?.01. This was paralleled by a rise in peak oxygen uptake (VO_2peak?=?29.14?±?5.34 versus 32.48?±?5.75?ml kg^?1 min^?1, p?=?.04). All the subjects who performed resistance exercises showed an average gain of 37?±?8% in muscle strength with no difference between performing single or multiple sets in terms of muscle strength gain. The results reinforce the clinical importance of exercise as a rehabilitation intervention for PLWHA and emphasizes the safety of exercise at the physiological level with the potential to mediate health outcomes.     

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab

Background: The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases.

Aim: We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL).

Methods: Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment.

Results: Seven patients were followed and median age was 56.0?±?5.0?years (range, 41.9–71.6?years). At baseline, the mean level of IgG was 333.7?±?40.8?and IgM 40.9?±?11.3?mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%).

Conclusion: Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.     

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7%?±?5.3% versus 43.4%?±?7.0%, P?=?.015) and chronic graft-versus- host disease (GVHD; 20.1%?±?5.8% versus 46.0%?±?7.9%, P?=?.003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1%?±?3.3% versus 84.4%?±?5.7%, P?=?.235), grades III to IV acute GVHD (3.4%?±?2.4% versus 12.3%?±?4.7%, P?=?.098), moderate to severe chronic GVHD (12.6%?±?4.9% versus 11.5%?±?4.9%, P?=?.905), or graft rejection (7.4%?±?3.6% versus 5.5%?±?3.1%, P?=?.852). There was also no significant difference with regard to the incidence of severe bacterial infection (P?=?.075), invasive fungal disease (P?=?.701), or cytomeglovirus viremia (P?=?.770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.     

Does the antiviral therapy of patients with chronic hepatitis exert nephrotoxic effects?

Introduction: HBV and HCV chronic hepatitis can be accompanied by secondary renal disease. In addition, these patients receive antiviral drugs with potential nephrotoxicity. It is known that interferon (IFN) therapy in HCV-infected kidney transplant recipients is followed by rejection of the transplant in 50% of the cases. Ribavirin is contraindicated in hemodialyzed patients and in patients with a GFR <50?ml/min/1.73 m². IFN therapy requires dosage reduction and close monitoring in patients with a GFR <50?ml/min/1.73 m² and in patients with end stage renal disease. The aim of our study was to assess the nephrotoxicity of antiviral drugs in patients with chronic hepatitis by measuring three renal biomarkers: urinary albumin, N-acetyl-β-d-glucosaminidase (NAG) and α 1-microglobulin, as well as glomerular filtration rate (GFR-MDRD4) before and at 6 months of therapy.

Methods: Fifty-five patients (28 male and 27 female, with a mean age of 47.85?±?12.03 years) with chronic hepatitis (40 patients with HCV, 13 patients with HBV, 1 patient with HBV+HCV, and 1 patient with HBV+HDV) were enrolled into the study. Different antiviral drug associations were used on a case-by-case basis. The 40 patients with HCV chronic hepatitis received either Peg-IFN-α 2a+Ribavirin (37 patients) or Peg-IFN-α 2b+Ribavirin (3 patients). The 13 patients with HBV chronic hepatitis received Peg-IFN-α 2a (9 patients), Lamivudine (2 patients), Entecavir (1 patient), or Adefovir (1 patient). The patient with HBV+HCV chronic hepatitis received Peg-IFN-α 2a+Ribavirin. The patient with HBV+HDV chronic hepatitis received IFN-α 2a. Urinary albumin (ELISA), NAG (colorimetrical method), α 1-microglobulin (ELISA), and serum creatinine were measured before and at 6 months of antiviral therapy. Urinary markers were expressed as either mg/gCr (for albumin and α 1-microglobulin) or U/gCr (for NAG). Statistical analysis (Pearson’s correlation coefficient, paired t-test and χ²-test) was performed.

Results: At 6 months of therapy urinary albumin/gCr did not increase significantly: 16.58?±?23.39 vs. 15.85?±?24.96?mg/gCr before therapy, p?=?0.87. Urinary NAG/gCr did not increase significantly: 4.21?±?3.37 vs. 3.83?±?3.2?U/gCr before therapy, p?=?0.53. Urinary α 1-microglobulin/gCr was almost unchanged: 4.38?±?4.47 vs. 4.38?±?3.57?mg/gCr before therapy, p?=?0.99. The GFR did not decline significantly: 92.41?±?22.21 vs. 94.59?±?36.1?ml/min/1.73 m² before therapy, p?=?0.7. Ten patients (18.18%) were albuminuric before therapy, and 14 patients (25.45%) were albuminuric at 6 months of therapy, a non-significant increase (p?=?0.35). We found a correlation between urinary albumin/gCr and NAG/gCr and between urinary albumin/gCr and α 1-microglobulin/gCr both at baseline and at 6 months of therapy: r?=?0.54, p?=?0.0005; r?=?0.29, p?=?0.03; r?=?0.51, p?=?0.0005; and r?=?0.4, p?=?0.002, respectively. In the patient receiving Adefovir, a known nephrotoxic drug, two of the three biomarkers (urinary albumin/gCr and NAG/gCr) increased, most notably NAG/gCr. Both HCV and HBV chronic hepatitis therapy were associated with non-significant changes in renal biomarker excretion and GFR.

Conclusions: With the exception of Adefovir, all of the drug associations used in this study were safe.     

The role of meniscal tears and meniscectomy in the mechanical stability of the anterior cruciate ligament deficient knee

Background

The role of an intact meniscus in providing mechanical stability to the knee of anterior cruciate ligament (ACL) deficient and ACL reconstructed patients has not been well studied.

Short-term pharmacologically induced growth study of ontogenetic allometry of oxygen uptake in children

Background: A range of allometric coefficients have been proposed in describing the maximal oxygen uptake (VO_2max): body mass relation in children using weight-bearing ergometry. However, a wide deviation in the allometric coefficients for VO_2max may be apparent when selected pediatric cohorts are studied in conjunction with clinical intervention for growth abnormalities.

Aim: The purpose of this study was to determine the allometric coefficients for VO_2max after short-term pharmacologically induced growth in pre- and early pubescent children.

Subjects and methods: The treatment group consisted of nine subjects with non-growth hormone (GH)-deficient short stature and one with GH-deficient short stature (mean age: 13.7?±?1.7 years). Ten pre- and early pubescent children matched for age, height, weight, VO_2max and body mass index (BMI) were controls. The treatment group were evaluated before (Pre-GH) and after (Post-GH) 4 months of subcutaneous GH therapy (0.05?mg?kg^?1day^?1?×?6 days week^?1).

Results: The mean ontogenetic coefficient for the treatment group was 1.50?±?0.20 and for the control group was 0.77?±?0.34. The mean allometric coefficient for body mass relative to VO_2max was significantly higher in the treatment group compared with the control group (p<0.05). Height, weight, fat free mass (FFM), VO_2max indexed to body mass (mL?kg^?1?min^?1) and FFM (mL?kgFFM^?1?min^?1) increased (p<0.05) with GH therapy. GH therapy also increased insulin-like growth factor-I (IGF-I) and served as a biochemical marker of GH therapy (p<0.05). The control group had no significant differences in all the variables tested (p<0.05).

Conclusion: The scaling for oxygen uptake (VO₂) for body mass varies with GH treatment and the increase in VO_2max that commonly occurs in conjunction with physical growth in the pre-and early pubescent individual may be linked to an increase in FFM and linear size.

Résumé. Arrière plan: Une gamme de coefficients d’allométrie a été proposée pour décrire la relation entre consommation d’énergie maximum (VO_2max) et masse corporelle, chez des enfants examinés par ergométrie avec charge pondérale. On observe cependant qu’une large déviation des coefficients d’allométrie pour le VO_2max peut apparaître lorsque des cohortes pédiatriques sont étudiées pour les anomalies de la croissance, en conjonction avec une intervention clinique.

But: Le but de cette étude est de déterminer les coefficients d’allométrie pour le VO_2max à la suite d’une courte poussée de croissance induite par pharmacologie chez des enfants prépubères ou de puberté récente.

Sujets et méthodes: Le groupe sous traitement consiste en neuf sujets de stature courte sans déficience d’hormone de croissance (HC) et d’un sujet de stature courte suite suite à une déficience de l’hormone de croissance (âge moyen?: 13,7?±?1,7?ans). On a pris comme contrôles, dix enfants prépubères et de puberté récente appariés pour l’âge, la stature, le poids, le VO_2max et l’IMC. Le groupe en traitement a été évalué avant (Pré-HC) et après (post-HC) quatre mois d’injections d’HC sous cutanée (0,05?mg?kg^?1?jour^?1?×?6?jours semaine^?1).

Résultats: Le coefficient ontogénique moyen pour le groupe sous traitement est de 1,50?±?0,20 et pour le groupe de contrôle 0,77?±?0,34. Le coefficient allométrique moyen pour la masse corporelle en rapport avec VO_2max est significativement plus élevé dans le groupe traité que dans le groupe contrôle (p<0,05). La stature, le poids, la masse maigre, le VO_2max rapporté à la masse corporelle (mL?kg^?1?min^?1) et à la masse maigre (mL?kg^?1?min^?1) s’accroissent avec la thérapie par HC (p?<?0,05). La thérapie HC accroît également le facteur I de croissance insulino mimétique, lequel sert de marqueur biochimique de la thérapie HC (p?<?0,05). Le groupe de contrôle ne présente pas de différence significative pour toutes les variables examinées (p?<?0,05).

Conclusion: L’échelle de VO₂ en fonction de la masse corporelle, varie avec les traitement par HC et l’augmentation en VO_2max qui se produit en général en conjonction avec la croissance physique chez l’individu prépubère ou pubère récent, peut être liée à l’accroissement de la masse maigre et de la taille linéaire.

Zusammenfassung. Hintergrund: Eine Vielzahl allometrischer Koeffizienten ist vorgeschlagen worden, um die Relation von maximaler Sauerstoffaufnahme (VO_2max) zu Körpermasse im Kindesalter unter Verwendung von gewichtsbezogener Ergometrie zu beschreiben. Allerdings wird eine weite Abweichung allometrischer Koeffizienten für VO_2max offensichtlich, wenn ausgewählte pädiatrische Stichproben in Verbindung mit klinischen Interventionen bei Wachstumsstörungen untersucht werden.

Ziel: Sinn dieser Studie war die Bestimmung von allometrischen Koeffizienten für VO_2max nach kurzzeitigem medikamenteninduzierten Wachstum bei präpubertären Kindern und Kindern in der frühen Pubertät.

Probanden und Methoden: Die Behandlungsgruppe bestand aus neun Probanden mit nicht-wachstumshormonbedingtem Kleinwuchs und einem Patienten mit Kleinwuchs aufgrund eines Wachstumshormonmangels (mittleres Alter: 13,7?±?1,7?Jahre). Die Kontrollgruppe bestand aus zehn gleichaltrigen präpubertären Kindern und Kindern in der frühen Pubertät von vergleichbarer Körperhöhe und vergleichbarem Gewicht, VO_2max und BMI. Die Behandlungsgruppe wurde vor (prä-GH) und nach (post-GH) 4-monatiger subkutaner Wachstumshormontherapie (0,05?mg?kg^?1?Tage^–1?×?6?Tage Woche^?1) untersucht.

Ergebnisse: Der mittlere ontogenetische Koeffizient für die Behandlungsgruppe war 1,50?±?0,20 und für die Kontrollgrupp.,77?±?0,34. Der mittlere allometrische Koeffizient für Körpermasse relativ zu VO_2max war in der Behandlungsgruppe signifikant höher als in der Kontrollgruppe (p?<?0,05). Körperhöhe, Gewicht, fettfreie Masse (FFM), VO_2max in Bezug zu Körpermasse (mL?kg^?1?min^?1) und FFM (mL?kg?FFM^?1?min^?1) stiegen mit Wachstumshormontherapie (p?<?0,05). Die Wachstumshormontherapie führte auch zu einem Anstieg des Insulin-like Growth Factor-I (IGF-I) und diente als biochemischer Marker der Wachstumshormontherapie (p?<?0,05). Die Kontrollgruppe zeigte keine signifikanten Unterschiede bei den getesteten Variablen (p?<?0,05).

Zusammenfassung: Die Anpassung von VO₂ an Körpermasse variiert mit der Wachstumshormontherapie, und der Anstieg von VO_2max, der üblicherweise in Verbindung mit körperlichem Wachstum vor und zu Beginn der Pubertät auftritt, könnte mit einer Vermehrung von FFM und Körperlänge verknüpft sein.

Resumen. Antecedentes: Se ha propuesto un rango de coeficientes alométricos para describir la relación entre el consumo máximo de oxígeno (VO_2max) y la masa corporal en niños, utilizando la prueba de esfuerzo (ergometría “weight-bearing”). Sin embargo, puede ponerse de manifiesto una amplia desviación de los coeficientes alométricos para el VO_2max cuando se estudian las cohortes pediátricas seleccionadas junto con la intervención clínica para las anomalías del crecimiento.

Objetivo: El objetivo de este estudio fue determinar los coeficientes alométricos para el VO_2max tras un crecimiento a corto plazo inducido farmacológicamente en niños pre-puberales y con pubertad temprana.

Sujetos y métodos: El grupo de tratamiento consistió en nueve individuos con baja estatura no deficientes de hormona de crecimiento (GH) y uno con baja estatura y deficiente para la GH (edad media: 13,7?±?1,7 años). Diez niños pre-puberales y con pubertad temprana de la misma edad, estatura, peso, VO_2max e IMC fueron los controles. El grupo de tratamiento fue evaluado antes (Pre-GH) y después (Post-GH) de 4 meses de terapia subcutánea con GH (0,05?mg?kg^?1?día^–1?×?6?días por semana^?1).

Resultados: El coeficientes ontogénico medio para el grupo de tratamiento fue de 1,50?±?0,20 y para el grupo de control de 0,77?±?0,34. El coeficiente alométrico medio para la masa corporal respecto al VO_2max fue significativamente mayor en el grupo que recibía tratamiento que en el grupo control (p?<?0,05). La estatura, el peso, la masa libre de grasa (FFM), el VO_2max indexado para la masa corporal (mL?kg^?1?min^?1) y la FFM (mL?kg?FFM^?1?min^?1) aumentaban (p?<?0,05) con la terapia con GH. Esta terapia también incrementaba el factor de crecimiento semejante a la insulina tipo I (IGF-I) y sirvió como un marcador bioquímico de la terapia con GH (p?<?0,05). El grupo de control no mostró diferencias significativas en ninguna de las variables testadas (p?<?0,05).

Conclusión: la escala del VO_2max para la masa corporal varía con el tratamiento con GH; el incremento en el VO_2max que ocurre habitualmente junto con el crecimiento físico en los individuos pre-puberales y de pubertad temprana puede estar asociado con un incremento de la FFM y del tamaño lineal.     

The maraviroc expanded access program — safety and efficacy data from an open-label study

Purpose:

The maraviroc (MVC) expanded access program (EAP) was initiated to increase MVC availability to patients with limited treatment options. Darunavir (DRV), raltegravir (RAL), and etravirine (ETV) were either recently approved or under regulatory review at study initiation and available for coadministration with MVC. Thus, the safety of MVC in combination with new antiretroviral therapies (ARVs) could be assessed. This open-label safety study of MVC was conducted at 262 sites worldwide in 1032 R5 HIV-positive treatment-experienced patients with limited/no therapeutic options.

Methods:

Study visits included screening, baseline, end of study or early discontinuation, and follow-up 30?days after last dose. Interim visits for HIV-1 RNA and CD4 cell counts occurred according to local HIV infection management guidelines. Safety data were analyzed overall and by subgroup based on ARV combination [MVC+optimized background therapy (OBT), MVC?±?OBT+DRV/r, MVC?±?OBT+RAL, MVC?±?OBT+RAL+DRV/r, MVC?±?OBT+RAL+ETV?±?DRV/r].

Results:

Most (90.3%) adverse events (AEs) were of mild or moderate severity with few grade 3/4 events, discontinuations, or temporary discontinuations/dose reductions due to AEs or serious AEs. Similar results were observed across subgroups. Of treated patients, 79.9% and 50% had HIV-1 RNA Conclusion:

MVC was well tolerated with virologic suppression observed in most patients.     

Effects of raltegravir combined with tenofovir/emtricitabine on body shape,bone density,and lipids in African-Americans initiating HIV therapy

Background:

Raltegravir (RAL) plus tenofovir/emtricitabine (TDF/FTC) is a recommended initial antiretroviral regimen. A substantial proportion of persons diagnosed with HIV infection and starting antiretrovirals in the U.S. are African-American (AA); however, the effects of this regimen on metabolic parameters have largely been studied in white patients.

Methods:

Single-arm, open-label study of untreated AA HIV-infected patients administered RAL with TDF/FTC for 104?weeks. Changes in fasting lipids, insulin resistance, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), limb and trunk fat, and bone mineral density (BMD) were assessed at weeks 56 and 104.

Results:

Thirty (85% men) participants were included. Median entry characteristics included age of 38?years, CD4 323?cells/mm³, HIV RNA level 29?245 copies/ml, and body mass index 28.1?kg/m². At 56 and 104?weeks, significant increases in VAT, trunk fat, limb fat, and overall fat were observed. Bone mineral density decreased by 1.5% by week 104.There were no significant changes in non-HDL-cholesterol, fasting triglycerides, or insulin resistance. A median CD4 cell count increase of 318?cells/mm³ (IQR 179, 403; full range 40, 749) (P?Conclusions:

In this cohort of AAs, initiation of RAL with TDF/FTC was associated with significant general increases in fat. Significant changes in lipids or insulin resistance were not observed and there was a small decline in BMD. Therapy was well tolerated and effective. These results are consistent with findings of studies of initial antiretroviral therapy in racially diverse cohorts and inform treatment selection for AA patients starting therapy for HIV infection.