Publications

OBJECTIVE

To assess the relationship between treatment response, baseline biomarker levels, and atacicept exposure in patients with systemic lupus erythematosus (SLE) in the phase II/III APRIL-SLE study.

METHODS

We performed a post hoc analysis of patients who received placebo, atacicept 75 mg, or atacicept 150 mg in a randomized, controlled, 52-week trial. Serum levels of BlyS and APRIL were measured at baseline, and serum levels of Ig and the numbers of naive B cells and plasma cells were measured at baseline and during treatment. Atacicept exposure was determined by assessment of the serum trough concentrations throughout the 52-week trial period. Associations between these parameters, treatment response (reduction in British Isles Lupus Assessment Group A or B flare), and infection rates were explored.

RESULTS

Recurrent high baseline levels of both BLyS (≥1.6 ng/ml) and APRIL (≥2.2 ng/ml) correlated with a greater treatment response (flare rate 75.7% with placebo, and 50.0% and 32.0% with atacicept 75 mg and atacicept 150 mg, respectively) compared with lower baseline levels of both. Increased atacicept exposure correlated with reduced flare rates (60.5% with placebo; 63.4%, 61.0%, 48.8%, and 29.3% in the 4 quartiles, from lowest to highest atacicept exposure). Greater pharmacodynamic responses (reduced Ig levels and naive B cell and plasma cell numbers) were associated with greater reductions in the flare rate. Infection rates were similar regardless of biomarker levels at baseline or at the time of atacicept exposure.

CONCLUSION

These post hoc analyses demonstrate a dose-response relationship between atacicept concentrations, reduced Ig levels, and reduced flare rates and suggest that baseline biomarkers such as elevated serum levels of BLyS and APRIL may help to identify the patients who are most likely to benefit from atacicept treatment.

Regulatory agencies face daunting challenges identifying emerging chemical hazards because of the large number of chemicals in commerce and limited data on exposure and toxicology. Evaluating one chemical at a time is inefficient and can lead to replacement with uncharacterized chemicals or chemicals with structural features already linked to toxicity. The Office of Environmental Health Hazard Assessment (OEHHA) has developed a process for constructing and assessing chemical groups for potential biomonitoring in California. We screen for chemicals with significant exposure potential and propose possible chemical groups, based on structure and function. To support formal consideration of these groups by Biomonitoring California’s Scientific Guidance Panel, we conduct a detailed review of exposure and toxicity data and examine the likelihood of detection in biological samples. To date, 12 chemical groups have been constructed and added to the pool of chemicals that can be selected for Biomonitoring California studies, including p,p´-bisphenols, brominated and chlorinated organic compounds used as flame retardants, non-halogenated aromatic phosphates, and synthetic polycyclic musks. Evaluating chemical groups, rather than individual chemicals, is an efficient way to respond to shifts in chemical use and the emergence of new chemicals. This strategy can enable earlier identification of important chemicals for monitoring and intervention.

Radiation recall dermatitis (RRD) is an inflammatory reaction in a previously irradiated field subsequent to the administration of pharmacologic or promoting agents. Herein, we describe a 47-year-old man with NSCLC who was treated with radiotherapy and pemetrexed-based chemotherapy three years prior to developing RRD upon resumption of pemetrexed-based chemotherapy. RRD with pemetrexed is rare and consists of five cases reported thus far. Although RRD is a rare phenomenon, it should be considered in any patient with dermatologic reactions that occur at the site of previous exposure to radiation therapy. When severe, RRD can pose a significant, and possibly life-threatening, impediment to the treatment and care of oncology patients. We discuss the time course, natural history, and management of this condition, as well as a connection to internal organ involvement, such as pneumonitis in thoracic oncology patients.

Internists are called upon on a daily basis to address a range of women's health issues. Staying up to date with the evidence in this wide field can be challenging. This article reviews important studies published in 2015 and early 2016 pertinent to urinary tract infection, osteoporosis, ovarian cancer screening, and contraception.

PURPOSE

Electromagnetic navigation bronchoscopy (ENB) provides improved targeting accuracy during transbronchial biopsies of suspicious nodules. The greatest weakness of ENB-based guidance is the registration divergence that exists between the planning CT, acquired days or weeks before the intervention, and the patient on the table on the day of the intervention. Augmenting ENB guidance with real-time tomosynthesis imaging during the intervention could mitigate the divergence and further improve the yield of ENB-guided transbronchial biopsies. The real-time tomosynthesis prototype, the scanning-beam digital x-ray (SBDX) system, does not currently display images reconstructed by the iterative algorithm that was developed for this lung imaging application. A protocol using fiducial markers was therefore implemented to permit evaluation of potential improvements that would be provided by the SBDX system in a clinical setting.

METHODS

Ten 7 mm lesions (5 per side) were injected into the periphery of each of four preserved pig lungs. The lungs were then placed in a vacuum chamber that permitted simulation of realistic motion and deformation due to breathing. Standard clinical CT scans of the pig lung phantoms were acquired and reconstructed with isotropic resolution of 0.625 mm. Standard ENB-guided biopsy procedures including target identification, path planning, CT-to-lung registration and navigation to the lesion were carried out, and a fiducial marker was placed at the location at which a biopsy would have been acquired. The channel-to-target distance provided by the ENB system prior to fiducial placement was noted. The lung phantoms were then imaged using the SBDX system, and using high-resolution conebeam CT. The distance between the fiducial marker tip and the lesion was measured in SBDX images and in the gold-standard conebeam-CT images. The channel-to-target divergence predicted by the ENB system and measured in the SBDX images was compared to the gold standard to determine if improved targeting accuracy could be achieved using SBDX image guidance.

RESULTS

As expected, the ENB system showed poorer targeting accuracy for small peripheral nodules. Only 20 nodules of the 40 injected could be adequately reached using ENB guidance alone. The SBDX system was capable of visualizing these small lesions, and measured fiducial-to-target distances on SBDX agreed well with measurements in gold-standard conebeam-CT images (p = 0.0001). The correlation between gold-standard conebeam-CT distances and predicted fiducial-to-target distances provided by the ENB system was poor (p = 0.72), primarily due to inaccurate ENB CT-to-body registration and movement due to breathing.

CONCLUSIONS

The SBDX system permits visualization of small lung nodules, as well as accurate measurement of channel-to-target distances. Combined use of ENB with SBDX real-time image guidance could improve accuracy and yield of biopsies, particularly of those lesions located in the periphery of the lung.