Primary CNS small mature B-cell lymphoma with plasmacytic differentiation presenting as an amyloidoma: a case report and review of literature

Primary central nervous system lymphomas (PCNSL) without systemic involvement are rare and account for only 2-3% of all brain tumors and \u3c1% of all non-Hodgkin’s lymphoma (NHL). Close to 40% of PCNSL are associated with immunosuppression, however, the incidence of primary central nervous system (CNS) lymphomas has shown an increasing trend in immunocompetent patients in recent decades due to better control of HIV and drug-induced immunosuppression [2]. Here, we describe a case of a primary CNS non-Hodgkin’s small mature B-cell lymphoma with plasmacytic differentiation in an immunocompetent individual. A previously healthy 87-year-old Caucasian woman presented to the neurology clinic with complaints of slowly progressing left sided weakness, predominantly in the left arm and leg over the last 6 months. Magnetic resonance imaging of the brain revealed a large, confluent white matter T2-hyperintensity in the right frontal lobe with multifocal nodular enhancement involving the left cerebral hemisphere, cerebellum, and leptomeninges, consistent morphologically with lymphoplasmacytic lymphoma. A bone marrow biopsy showed normal trilineage hematopoiesis with no evidence of lymphoma, myeloma or amyloidosis. Our patient was treated with Rituximab but developed an ischemic infarct of the left frontal white matter. She and her family decided to forego further treatment and switch to hospice care

Rigid Internal Fixation of Displaced Distal Radius Fractures

Distal radius fractures, the most common long bone fracture, are treated in several ways, including closed reduction, percutaneous pinning, external fixation, and open reduction and internal fixation. This article presents a surgical technique and a series of patients treated with a novel minimally invasive intramedullary fixation technique. The implant is a partially flexible intramedullary rod that can be locked in a rigid position once it is implanted in the bone. An awl and reamer are passed through a starter hole in the radial styloid using a 2-cm incision between the 1st and 2nd dorsal compartments. The device is then implanted under the articular surface, and the distal end of the curved implant is placed down the intramedullary canal of the radius. After locking the shaft segment rigidly, screws are placed through the implant under the distal radial articular margin to stabilize the fracture site. The sensory branches of the radial nerve are retracted during the case. Patients are treated in a wrist splint for a short period of time (2 to 4 weeks) depending on fracture type. The case examples demonstrate the minimally invasive nature of this procedure, the surgical technique, methods of fracture reduction and implantation, and surgical outcomes. Radiographic outcomes, postoperative motion, postoperative function, and validated outcome measures are demonstrated. This minimally invasive technique is ideally suited for distal radial fractures that do not involve the articular surface. It is a safe and effective technique that can provide excellent results. The authors are from th

Survival of verapamil-poisoned rats treated with triiodothyronine.

Life-threatening toxicity due to calcium channel blocker ingestion is commonly encountered by emergency medicine physicians and toxicologists. Despite a vast array of research on its treatment, results have proven inconsistent. The goal of this study is to evaluate potential vasopressor effects of triiodothyronine (T3) in rats poisoned with verapamil. Following anesthesia and intubation, ten Sprague-Dawley rats were given intravenous verapamil infusion of 10 mg/kg/h. This dose was titrated until a mean arterial pressure (MAP) of 50-55 mmHg was achieved and maintained for a period of at least 5 min. The verapamil infusion was then maintained at that rate. Five rats were randomized to receive a T3 bolus of 0.4 mcg/kg preceding an infusion of 1.5 mcg/kg/day which was doubled every 2 min until any of the following endpoints: systolic blood pressure of 100 mmHg, an elapsed time of 60 min, or death. The other five received an equal volume of normal saline solution. The primary outcome measure was survival with secondary outcomes of MAP and heart rate. The T3 group did have a slightly longer, yet not statistically significant, average time to cessation of electrical activity-30.0 +/- 14.4 min versus 23.8 +/- 9.5 min in the placebo group. Average MAP decreased nearly identically in the two groups. Heart rates were not reliable indicators of toxicity in this rat model as there was little decrease until immediately prior to death in most animals. Despite significant variability in toxicity among individual animals, no statistically significant difference in survival time, heart rate, or MAP was found between groups treated with T3 and those receiving saline

Development and Evaluation of an Online, Patient-Driven, Family Outreach Intervention to Facilitate Sharing of Genetic Risk Information in Families with Lynch Syndrome

Departments of Gastroenterology Research, Behavioral Science, and Gastroenterology, Hepatology, and Nutrition This article has been accepted for publication in the Journal of Medical Genetics, 2021 following peer review, and the Version of Record can be accessed online at https://doi.org/10.1136/jmedgenet-2020-107615https://openworks.mdanderson.org/mdacc_ghn_pubs/1000/thumbnail.jp

Hypothermia: an unusual indication for gastric lavage.

BACKGROUND: Previous reports suggest that gastric lavage holds many risks and is not routinely indicated for decontamination of the overdose patient. OBJECTIVE: To present a case of overdose with concurrent accidental hypothermia where gastric decontamination was utilized. CASE REPORT: A 50-year-old hypothermic, comatose patient was transported to the Emergency Department with a concurrent, massive medication ingestion diagnosed incidentally on a routine abdominal computed tomography scan. Both active and passive rewarming measures, in conjunction with gastric lavage and retrieval of multiple pill fragments, were performed, and the patient survived to hospital discharge without sequelae. Interestingly, the patient admitted to an intentional ingestion of both labetalol and lorazepam. CONCLUSION: Due to hypothermia-mediated changes in metabolism, including gastric atony and decreased hepatic metabolism, gastric lavage may provide additional benefit in the management of severely hypothermic patients with potentially lethal, massive pill ingestions

Multifunctional Graphene–Polymer Nanocomposite Sensors Formed by One-Step In Situ Shear Exfoliation of Graphite

Graphene nanocomposites are a promising class of advanced materials for sensing applications; yet, their commercialization is hindered due to impurity incorporation during fabrication and high costs. The aim of this work is to prepare graphene–polysulfone (G−PSU) and graphene–polyvinylidene fluoride (G−PVDF) nanocomposites that perform as multifunctional sensors and are formed using a one-step, in situ exfoliation process whereby graphite is exfoliated into graphene nanoflakes (GNFs) directly within the polymer. This low-cost method creates a nanocomposite while avoiding impurity exposure since the raw materials used in the in situ shear exfoliation process are graphite and polymers. The morphology, structure, thermal properties, and flexural properties were determined for G−PSU and G−PVDF nanocomposites, as well as the electromechanical sensor capability during cyclic flexural loading, temperature sensor testing while heating and cooling, and electrochemical sensor capability to detect dopamine while sensing data wirelessly. G−PSU and G−PVDF nanocomposites show superior mechanical characteristics (gauge factor around 27 and significantly enhanced modulus), thermal characteristics (stability up to 500 °C and 170 °C for G−PSU and G−PVDF, respectively), electrical characteristics (0.1 S/m and 1 S/m conductivity for G−PSU and G−PVDF, respectively), and distinguished resonant peaks for wireless sensing (~212 MHz and ~429 MHz). These uniquely formed G−PMC nanocomposites are promising candidates as strain sensors for structural health monitoring, as temperature sensors for use in automobiles and aerospace applications, and as electrochemical sensors for health care and disease diagnostics

Effect of the Tyrosine Kinase Inhibitors (Sunitinib, Sorafenib, Dasatinib, and Imatinib) on Blood Glucose Levels in Diabetic and Non-diabetic Patients in General Clinical Practice (Poster)

Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRβ are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option

Posterior-based proposals for speeding up Markov chain Monte Carlo

Markov chain Monte Carlo (MCMC) is widely used for Bayesian inference in models of complex systems. Performance, however, is often unsatisfactory in models with many latent variables due to so-called poor mixing, necessitating development of application specific implementations. This paper introduces "posterior-based proposals" (PBPs), a new type of MCMC update applicable to a huge class of statistical models (whose conditional dependence structures are represented by directed acyclic graphs). PBPs generates large joint updates in parameter and latent variable space, whilst retaining good acceptance rates (typically 33%). Evaluation against other approaches (from standard Gibbs / random walk updates to state-of-the-art Hamiltonian and particle MCMC methods) was carried out for widely varying model types: an individual-based model for disease diagnostic test data, a financial stochastic volatility model, a mixed model used in statistical genetics and a population model used in ecology. Whilst different methods worked better or worse in different scenarios, PBPs were found to be either near to the fastest or significantly faster than the next best approach (by up to a factor of 10). PBPs therefore represent an additional general purpose technique that can be usefully applied in a wide variety of contexts.Comment: 54 pages, 11 figures, 2 table

A missense variant in <i>FTCD</i> is associated with arsenic metabolism and toxicity phenotypes in Bangladesh

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Arsenic metabolism efficiency varies among individuals, in part due to genetic variation near AS3MT (arsenite methyltransferase; 10q24.32). To identify additional arsenic metabolism loci, we measured protein-coding variants across the human exome for 1,660 Bangladeshi individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS). Among the 19,992 coding variants analyzed exome-wide, the minor allele (A) of rs61735836 (p.Val101Met) in exon 3 of FTCD (formiminotransferase cyclodeaminase) was associated with increased urinary iAs% (P = 8x10-13), increased MMA% (P = 2x10-16) and decreased DMA% (P = 6x10-23). Among 2,401 individuals with arsenic-induced skin lesions (an indicator of arsenic toxicity and cancer risk) and 2,472 controls, carrying the low-efficiency A allele (frequency = 7%) was associated with increased skin lesion risk (odds ratio = 1.35; P = 1x10-5). rs61735836 is in weak linkage disequilibrium with all nearby variants. The high-efficiency/major allele (G/Valine) is human-specific and eliminates a start codon at the first 5´-proximal Kozak sequence in FTCD, suggesting selection against an alternative translation start site. FTCD is critical for catabolism of histidine, a process that generates one-carbon units that can enter the one-carbon/folate cycle, which provides methyl groups for arsenic metabolism. In our study population, FTCD and AS3MT SNPs together explain ~10% of the variation in DMA% and support a causal effect of arsenic metabolism efficiency on arsenic toxicity (i.e., skin lesions). In summary, this work identifies a coding variant in FTCD associated with arsenic metabolism efficiency, providing new evidence supporting the established link between one-carbon/folate metabolism and arsenic toxicity

Tibial Loading Increases Osteogenic Gene Expression and Cortical Bone Volume in Mature and Middle-Aged Mice

There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months). We first assessed markers of bone turnover in control (non-loaded) mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001). There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001). We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (−1300 µε endocortical; −2350 µε periosteal). Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month) mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001). In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV) than contralateral control tibias (p<0.05), due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages). In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2–12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice