SAT-512 Severe Hypocalcemia Presenting as Status Epilepticus after Denosumab Use in Metastatic Prostate Cancer

Introduction: Denosumab decreases the incidence of skeletal-related events in patients with metastatic bone disease and is used routinely as part of the therapeutic strategy for various cancers. However, it is associated with a high risk of hypocalcemia with incidence of high-grade hypocalcemia (defined as total calcium < 7mg/dl) as high as 5.1% in patients with castrate-resistant prostate cancer. We present a case of severe hypocalcemia presenting with status epilepticus 32 days after administration of denosumab. Case: A 83 year old African American man presented to the emergency room with status epilepticus. Initial labs revealed a critically low calcium (Ca) of <5mg/dl (8.5-10.1) with albumin 2.2 g/dl (3.4-5.0), ionized calcium 1.09 mg/dl (4.6-5.1) and creatinine (Cr) 3.68 mg/dl (0.67-1.17). QTC was prolonged at 544ms (<400ms). He was intubated for airway protection and a continuous infusion of intravenous calcium gluconate was initiated. Three months prior, he had been diagnosed with prostate cancer with diffuse osteoblastic metastases to his ribs, cervical, thoracic, lumbar and sacral vertebrae, right humerus and bilateral iliac bones. He received a first dose of conventional chemotherapy and 120mg denosumab subcutaneously 32 days prior to hospital admission. Lab investigations then were pertinent for Ca of 9 mg/dl, Cr 1.46 mg/dl, and alkaline phosphatase 362 Units/L (25-125). A 25-hydroxy vitamin D (25-D) was not checked. Further evaluation demonstrated intact parathyroid hormone 677.2 pg/ml (18.4-80.1), alkaline phosphatase 397 Units/L, phosphorus 3.6 mg/dl (2.5-4.9) and 25-D 18 ng/ml (30-100). He was also found to have metastatic obstruction of both ureters which had resulted in acute kidney injury. He was slowly weaned off the intravenous calcium and started on calcitriol 2mcg twice daily, 4 gram elemental calcium daily via feeding tube and cholecalciferol 6000 units daily. Calcium levels remained stable at 8.0-8.5mg/dl on this regimen. Given the extensive metastatic disease, the patient’s family elected to pursue hospice care, and he passed away 9 days later. Conclusion: Patients with osteoblastic metastases and renal impairment are at particularly increased risk of hypocalcemia after denosumab, which can be potentially life-threatening. Physicians caring for patients with metastatic prostate cancer should ensure that vitamin D levels are replete and calcium levels are normal prior to administration of denosumab, monitor calcium levels closely, and counsel them about the signs and symptoms of hypocalcemia to allow prompt diagnosis and treatment

Economic Policies and the Impact of Natural Disasters on Economic Growth: A Threshold Regression Approach

This paper investigates the impact of natural disasters on the long-term macroeconomic performance of a country. More specifically, we want to see whether the impact of natural disasters on economic growth is uniform across countries or it is differentiated according to the macroeconomic policy environment and other structural characteristics of the countries at hand. In order to test this empirically we use the Threshold Regression (TR) approach of Hansen (2000) and data from 90 countries over the period of 1970 to 2001. Our analysis reveals several interesting patterns such as: countries with higher per capita income, higher government spending, higher degree of openness to trade, less fiscal imbalances and greater financial stability are better able to withstand the disaster shock and further prevent its impact on long-term economic growth.Natural Disasters, Economic Policies, Economic Growth, Threshold Regression

Neural networks and support vector machines based bio-activity classification

Classification of various compounds into their respective biological activity classes is important in drug discovery applications from an early phase virtual compound filtering and screening point of view. In this work two types of neural networks, multi layer perceptron (MLP) and radial basis functions (RBF), and support vector machines (SVM) were employed for the classification of three types of biologically active enzyme inhibitors. Both of the networks were trained with back propagation learning method with chemical compounds whose active inhibition properties were previously known. A group of topological indices, selected with the help of principle component analysis (PCA) were used as descriptors. The results of all the three classification methods show that the performance of both the neural networks is better than the SVM

Directed-polymer systems explored via their quantum analogs: Topological constraints and their consequences

The equilibrium statistical mechanics of classical directed polymers in 2 dimensions is well known to be equivalent to the imaginary-time quantum dynamics of a 1+1-dimensional many-particle system, with polymer configurations corresponding to particle world-lines. This equivalence motivates the application of techniques originally designed for one-dimensional many-particle quantum systems to the exploration of many-polymer systems, as first recognized and exploited by P.-G. de Gennes [J.\ Chem.\ Phys.\ {\bf 48}, 2257 (1968)]. In this low-dimensional setting interactions give rise to an emergent polymer fluid, and we examine how topological constraints on this polymer fluid (e.g., due to uncrossable pins or barriers) and their geometry give rise to strong, entropy-driven forces. In the limit of large polymer densities, in which a type of mean-field theory is accurate, we find that a point-like pin causes a divergent pile-up of polymer density on the high-density side of the pin and a zero-density region (or gap) of finite area on the low-density. In addition, we find that the force acting on a pin that is only mildly displaced from its equilibrium position is sub-Hookean, growing less than linearly with the displacement, and that the gap created by the pin also grows sublinearly with the displacement. By contrast, the forces acting between multiple pins separated along the direction preferred by the polymers are super-Hookean. These nonlinear responses result from effective long-ranged interactions between polymer segments, which emerge via short-ranged interactions between distant segments of long polymer strands. In the present paper, we focus on the case of an infinitely strong, repulsive contact interaction, which ensures that the polymers completely avoid one another. In a companion paper, we consider the effects of a wider set of inter-polymer interactions.Comment: 17 pages, 10 figure