Anti-CD20 monoclonal antibodies: reviewing a revolution.

Since the inception of rituximab in the 1990s, anti-CD20 monoclonal antibodies have revolutionised the treatment of B cell hematological malignancies and have become a cornerstone of modern gold-standard practice. Additionally, the potent efficacy of these agents in depleting the B cell compartment has been used in the management of a broad array of autoimmune diseases. Multiple iterations of these agents have been investigated and are routinely used in clinical practice. In this review, we will discuss the physiology of CD20 and its attractiveness as a therapeutic target, as well as the pharmacology, pre-clinical and clinical data for the major anti-CD20 monoclonal antibodies: rituximab, obinutuzumab and ofatumumab.

Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort.

BACKGROUND: Vitamin D status varies with geographic location and no studies of vitamin D in systemic lupus erythematosus (SLE) have been reported in the Southern Hemisphere. OBJECTIVES: To assess the prevalence of vitamin D deficiency in an Australian SLE cohort, and its relationship with disease activity. METHODS: Data were collected prospectively on 119 consecutive patients with SLE in the Monash Lupus Clinic in Melbourne, Australia, between January 2007 and January 2013. Patients had simultaneous serum 25-hydroxyvitamin D concentration and disease activity (SLEDAI-2K) recorded. Statistical methods were used to determine the correlation of serum vitamin D level and disease activity both at baseline and at a subsequent time point. Adjustments were made for the use of glucocorticoids, immunosuppressants and vitamin D supplementation. RESULTS: Vitamin D deficiency (<40 nmol/L) was detected in 27.7% of patients at baseline. Multiple regression analysis showed a significant inverse correlation of SLEDAI-2K with baseline vitamin D level and with vitamin D supplementation. Over a 12-month period of observation, among the 119 patients, there were 464 serial vitamin D measurements with corresponding SLEDAI-2K, representing 266 time intervals. The median change in vitamin D level was an increase of 25 nmol/L and this corresponded with a decline in SLEDAI-2K of 2 units. In regression analysis, there was a significant association between low vitamin D at a prior time point and a rise in SLEDAI-2K at the subsequent time point (univariable OR 3.3, 95% CI 1.5 to 7.7, p=0.005) or having a high disease activity (SLEDAI-2k>10) at the subsequent time point (univariable OR 3.1, 95% CI 1.4 to 6.8, p=0.004). CONCLUSIONS: In Australian patients with SLE, low vitamin D was associated with a higher disease activity and an increase in serum vitamin D was associated with reduced disease activity over time. The therapeutic effect of vitamin D in SLE should be further assessed in interventional studies.

Association of serum B cell activating factor from the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) with central nervous system and renal disease in systemic lupus erythematosus.

INTRODUCTION: The objective of this study is to determine whether serum concentrations of B cell activating factor from the tumour necrosis factor family (BAFF) and/or a proliferation-inducing ligand (APRIL) are associated with clinical manifestations of systemic lupus erythematosus (SLE). METHODS: BAFF and APRIL concentrations were quantified using a commercial ELISA in serum samples obtained at the time of clinical assessment in 98 patients, and on 245 samples from 75 of these patients followed prospectively. RESULTS: Serum BAFF was significantly increased, and APRIL decreased, in patients with either renal or central nervous system (CNS) lupus. In contrast, in cross-sectional analysis, there was no correlation between disease activity (SLEDAI-2k) and serum BAFF or APRIL. In longitudinal follow-up, there was no association between changes in serum BAFF or APRIL and changes in SLEDAI-2k, or between baseline serum BAFF or APRIL and subsequent changes in SLEDAI-2k. However, between-visit changes in BAFF were significantly different in patients with increases in SLEDAI-2k ≥ 4, compared to patients whose SLEDAI-2k did not change. CONCLUSIONS: Although neither serum BAFF nor APRIL correlated with disease activity in the overall population, elevated serum BAFF and reduced APRIL may be markers of renal and CNS disease in SLE patients.

Prevalence of transfusion-acquired hepatitis C in an Australian bleeding disorders population.

In Australia prior to 1992, many patients with bleeding disorders were exposed to hepatitis C through blood products. However, the incidence, complications and response to treatment of chronic hepatitis C (CHC) in this population are poorly characterized. The aim of this study was to examine the prevalence of CHC and response to treatment in an Australian bleeding disorders population. Demographic data, virological data and liver disease status from these 700 patients with inherited bleeding disorders were analysed. Of these 700 patients, 424 (61%) had been tested for CHC infection and 219 (52%) were hepatitis C antibody positive, with the prevalence approaching 100% in patients with severe bleeding disorders. Of 219 patients, 73 (33%) had received treatment for their infection with a response rate of 33/73 (45%) across all genotypes. Of 219 patients, 34 (16%) had spontaneous viral clearance. When measured with transient elastography, 44/98 (45%) patients with CHC had significant liver fibrosis and 15/98 (15%) had liver cirrhosis. Of 130 patients, 38 (29%) with CHC infection had no evidence of follow-up with an appropriate clinician in the past 2 years. This study demonstrates that testing for CHC in this population is incomplete and treatment rates are low. Given the substantial morbidity and mortality associated with CHC and new therapeutic options becoming available, it seems important to reengage patients to diagnose, offer treatment and monitor this infection.

Comparison of curvature-based and Shack-Hartmann-based adaptive optics for the Gemini telescope.

We present the results of independent numerical simulations of adaptive optics systems for 8-m astronomical telescopes that use both Shack-Hartmann and wave-front curvature sensors. Four differents codes provided consistency checks and redundancy. All four simulate a complete system and model noise and servo-lag effects. A common atmospheric turbulence generator was used for consistency. We present the main characteristics of the codes, and we report the system performance in term of Strehl ratio and full width at half-maximum versus the magnitude of the (on-axis) guide star. We show that a Shack-Hartmann plus stacked actuator mirror system with 10 x 10 subapertures or a curvature plus bimorph mirror system with 56 subapertures yields a 50% Strehl ratio at 1.6 mum for a m(R) = 14.7 magnitude star, with almost equivalent performance at both brighter and dimmer light levels.

The closed-loop nature of the tymbal response in the dogbane tiger moth, Cycnia tenera (Lepidoptera, Arctiidae).

The dogbane tiger moth, Cycnia tenera, emits ultrasonic sounds by rhythmically buckling a pair of tymbals when stimulated by pulsed sounds resembling bat echolocation. We monitored the central pattern generator governing this response by recording the motor output of the tymbal branch of the metathoracic leg nerve. The rhythm of the tymbal motor pattern can be altered midway (500 m/sec from its initiation) by changing the period and, to a lesser degree, the intensity of the stimulus. The tymbal response of C. tenera is therefore closed-looped to stimulus pulse period and intensity. Our results suggest that C. tenera relies less on the changes in an attacking bat's echolocation intensity when responding with this behaviour because this acoustic parameter may be a more unreliable indicator of the proximity of the bat than its echolocation call period.

The stability of carboplatin, diamorphine, 5-fluorouracil and mitozantrone infusions in an ambulatory pump under storage and prolonged 'in-use' conditions.

Drug infusions can be exposed for prolonged periods to 'in-use' conditions where the temperature of an infusion in a holster-worn infusion pump may reach 37 degrees C. In this study, the stability of three cytotoxic drug infusions (carboplatin, 5-fluorouracil and mitozantrone) and one analgesic infusion (diamorphine HCl) was determined in Parker Micropump medication reservoirs under refrigerated storage and prolonged in-use conditions. The stability of the three cytotoxic drug infusions was unaffected by 14 days storage at either 4 or 37 degrees C. The diamorphine HCl infusion was stable over 14 days storage at 4 degrees C but under in-use conditions at 37 degrees C, drug degradation became significant (greater than 5%) if storage exceeded 7 days.