Research Spotlight

Cortazar, F. B., D. E. Leaf, C. T. Owens, K. Laliberte, W. F. Pendergraft, 3rd and J. L. Niles (2017). “Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: A case series.” BMC Nephrol 18(1): 44.

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BACKGROUND: Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. METHODS: We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline. Complete remission was defined as a UPCR < 0.3 g/g. Secondary outcomes were serious adverse events and the change in proteinuria, serum creatinine, serum albumin, cholesterol, triglycerides, and immunoglobulin G levels after 1 year of treatment. RESULTS: Over a median follow-up time of 37 (IQR, 34-44) months, 100% of patients achieved partial remission and 93% of patients achieved complete remission at a median time of 2 and 13 months, respectively. After 1 year of treatment, median (IQR) UPCR declined from 8.2 (6.6-11.1) to 0.3 (0.2-0.7) g/g (P < 0.001). Three serious adverse events occurred over 51 patient years. No patients died or progressed to ESKD. CONCLUSIONS: Treatment of idiopathic membranous nephropathy with RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

Corzo, G. and G. P. Espino-Solis (2017). “Selected scorpion toxin exposures induce cytokine release in human peripheral blood mononuclear cells.” Toxicon 127: 56-62.

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A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx’s) was performed in order to evaluate their effect on human immune cells. The ScTx’s chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin). A Luminex multiplex analysis was performed in order to determine the amounts chemokines and cytokines IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12-p40, IL-13, interferon alpha (IFN-alpha), interferon gamma (IFN-gamma), tumor necrosis factor alpha TNF-alpha, and interferon-inducible protein-10 (IP-10) secreted from human PBMCs exposed to these toxins. Although, the ScTx Cn5 is not lethal for mammals, it was able to induce the secretion of cytokines IL-1beta, IL-6, and TNF-alpha, IL-10 and IP-10 in comparison to the lethal CssII, which was able to induce only IP-10 secretion. Discrepin also was able to induce only IP-10. Interestingly, only low amounts of interferons alpha and beta were induced in the presence of the ScTx’s assayed. In a synergic experiment, the combination of Discrepin and Cn5 displayed considerable reverse effects on induction of IL-1beta, IL-6, IL-10 and TNF-alpha, but they had a slight synergic effect on IP-10 cytokine production in comparison with the single effect obtained with the Cn5 alone. Thus, the results obtained suggest that the profile of secreted cytokines promoted by ScTx Cn5 is highly related with a cytokine storm event, and also it suggests that the mammalian lethal neurotoxins are not solely responsible of the scorpion envenomation symptomatology.

Dixon-Ibarra, A., S. Driver, H. VanVolkenburg and K. Humphries (2017). “Formative evaluation on a physical activity health promotion program for the group home setting.” Eval Program Plann 60: 81-90.

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Physical inactivity and high rates of chronic conditions is a public health concern for adults with intellectual disability. Few health promotion programs target the group home setting which is the pre-dominant form of residential accommodation for persons with intellectual disability. A process evaluation of a physical activity health promotion program, Menu-Choice, was conducted with five group home sites for adults with intellectual and developmental disabilities. Menu-Choice assists group home staff in including physical activity goals within resident schedules. The physical activity program was designed based on theoretical frameworks, community-based participatory approaches, and established health promotion guidelines for adults with disabilities. Fourteen program coordinators (age M 39; 77% females), 22 staff (age M 39; 82% females), and 18 residents (age M 59; 72% females; 56% ambulatory) participated. Results from the fidelity survey and program completion highlight potential challenges with implementation. Findings will assist with the refinement of the program for continued implementation trials in the group home community.

Downey, L. C., C. M. Cotten, C. P. Hornik, M. M. Laughon, V. N. Tolia, R. H. Clark and P. B. Smith (2017). “Association of in utero magnesium exposure and spontaneous intestinal perforations in extremely low birth weight infants.” J Perinatol: 2017 Jan [Epub ahead of print].

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OBJECTIVE: The objective of this study is to determine whether antenatal exposure to magnesium is associated with spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants (1000 g). STUDY DESIGN: We identified all ELBW infants admitted to 1 of 323 neonatal intensive care units from 2007 to 2013. We used multivariable conditional logistic regression to compare outcomes in the first 21 days after birth between infants exposed and unexposed to magnesium in utero. RESULTS: Of the 28 035 infants, 11 789 (42%) were exposed to antenatal magnesium (AM). There was no difference in the risk of SIP, odds ratio=1.08 (95% confidence interval; 0.91 to 1.29), between infants exposed and unexposed to AM. Mortality in the first 21 days after birth was lower in the magnesium-exposed infants, odds ratio=0.76 (0.70 to 0.83). CONCLUSION: AM exposure in ELBW infants was not associated with increased risk of SIP.

Fendler, T. J., M. E. Nassif, K. F. Kennedy, S. M. Joseph, S. C. Silvestry, G. A. Ewald, S. J. LaRue, J. M. Vader, J. A. Spertus and S. V. Arnold (2017). “Global outcome in patients with left ventricular assist devices.” Am J Cardiol: 2017 Jan [Epub ahead of print].

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Left ventricular assist devices (LVADs) improve survival and quality of life (QOL) for most, but not all, patients with advanced heart failure. We described a broader definition of poor outcomes after LVAD, using a novel composite of death, QOL, and other major adverse events. We evaluated the frequency of poor global outcome at 1 year after LVAD among 164 patients (86% Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 2; shock or declining despite inotropes) at a high-volume center. Poor global outcome (comprising death, poor QOL [Kansas City Cardiomyopathy Questionnaire <45], recurrent heart failure [>/=2 heart failure readmissions], or severe stroke) occurred in 58 patients (35%): 37 died, 17 had poor QOL, 3 had recurrent heart failure, and 1 had a severe stroke. Patients with poor global outcomes were more likely designated for destination therapy (46% vs 24%, p = 0.01), spent more days hospitalized per month alive (median [interquartile range] 18.6 [5.0 to 31.0] vs 3.7 [1.8 to 8.3], p <0.001), and had higher intracranial (12% vs 2%, p = 0.031) and gastrointestinal (44% vs 28%, p = 0.056) hemorrhage rates over the year after implant. Although LVADs often improve survival and QOL, approximately 1/3 of high-acuity patients experienced a poor global outcome over the year after LVAD. In conclusion, composite outcomes may better capture events that matter to patients with LVADs and thus support informed decisions about pursuing LVAD therapy.