Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

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Cortical Porosity Identifies Women With Osteopenia at Increased Risk for Forearm Fractures

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high‐resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10‐year fracture probability using the country‐specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age‐matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact‐appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact‐appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. © 2014 American Society for Bone and Mineral Research.     

Death within the first year after kidney transplantation – an observational cohort study

The risk of death within the first year postkidney transplantation is not well described in the contemporary era. We extracted data on all kidney transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed between Hospital Episode Statistics and the Office for National Statistics to identify all deaths. Cox proportional hazard models were performed to identify factors associated with 1‐year mortality. 566 deaths (3.0%) occurred within the first year post‐transplant (from 19 103 kidney transplant procedures analysed). Infection, cardiovascular events and malignancy were classified in 21.6%, 18.3% and 7.4% of death certificates, respectively. Among recipients with prior myocardial infarct history who died within the first year, 38.8% of deaths were attributed to a cardiac‐related event. Malignancy‐related death was responsible for 61.5% of 1‐year mortality for allograft recipients with pretransplant cancer history. 22.1% of deaths included kidney failure as a contributory factor on the death certificate (3.3% specifically stated allograft failure). Variables associated with 1‐year mortality included deceased‐donor kidney, increasing age, residence in socioeconomically deprived area and history of select medical comorbidities pre‐operatively. We conclude 1‐year mortality postkidney transplantation is low, but in select allograft recipients, the risk of death increases considerably.     

Cover Image,Volume 40, Issue 4

The abysmal success rate of anticancer drugs in clinical trials, is in part, attributable to discordance between cultured cancer cells and patient tumors. While tumors in vivo, display a lower mitotic index, patient tumors portray much higher centrosomal aberrations, relative to in vitro cultured cells. The microenvironment too differs considerably between the in vitro and in vivo scenarios. Notably, another hallmark of cancer, hypoxia, is not recapitulated in cell lines cultured under normoxic conditions. These observations raise the possibility that hypoxia may be the missing link that explains the discordance between cell biological phenomena in vitro versus physiological conditions. Further, the interplay between hypoxia and centrosome amplification (CA) is relatively understudied. Recent research from our laboratory, geared toward examining the biological link between the two, has uncovered that hypoxia induces the expression of proteins (Plk4, Aurora A, Cyclin D) implicated in CA, in a hypoxia-inducible factor 1α (HIF-1α)-dependent context. Our studies evidence that hypoxia fuels CA that underlie intratumoral heterogeneity and metastatic potential of cancer cells. Given the advent of HIF-1α inhibitors, this research has ramifications in aiding patient risk stratification and designing new cancer drug therapies to facilitate clinical decision-making.     

Patterns of attendances to the hospital emergency eye care service: a multicentre study in England

Background/ObjectivesTo characterise the patterns of presentation and diagnostic frequencies in Hospital Emergency Eye Care Services (HEECS) across 13 hospitals in England.MethodsRetrospective, cross-sectional, observational multi-centre (n = 13) study to assess HEECS attendances over a 28-day study period. Data derived included: number of consecutive attendances, patient demographics and diagnoses. Age and gender variations, the impact of day of the week on attendance patterns, diagnostic frequencies and estimates of the annual incidence and attendance rates were evaluated.ResultsA total of 17,667 patient (mean ± standard deviation age = 49.6 ± 21.8 years) attendances were identified with an estimated HEECS annual new attendance rate of 31.0 per 1,000 population. Significantly more females (53%) than males (47%) attended HEECS (p < 0.001). Female attendances were 13% higher in those ≥50 years of age. Weekends were associated with a significant reduction in attendances compared to weekdays (χ² = 6.94, p < 0.001). Among weekdays, Mondays and Fridays were associated with significantly higher attendances compared with midweek (χ² = 2.20, p = 0.032). Presenting pathologies involving the external eye, cornea and conjunctiva accounted for 28.6% of the caseload.ConclusionThis is the largest multicentre study assessing attendance patterns in HEECS in England. We have, for the first time, observed a “weekend effect” in relation to attendance to HEECS. Differences in health-seeking behaviour and lack of awareness of HEECS weekend services may be partly attributed to the differences observed. Our findings, along with the type of presentations, have the potential to guide commissioners with future planning of HEECS.Subject terms: Epidemiology, Epidemiology     

Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia

Abstract

Imatinib-induced tyrosine kinase inhibition extends beyond the BCR-ABL mutation, resulting in adverse effects. We evaluated hypogammaglobulinemia as a potential ‘off-target’ action of imatinib in children with CML. A cross-sectional, observational study was performed. Patients with CML in chronic phase, age <18-years at diagnosis, receiving imatinib for a duration exceeding 6-months were enrolled. Serum immunoglobulin G, A, and M were measured by end-point nephelometry. Thirty patients were enrolled. The mean age at diagnosis was 10.4?±?3.1?years (range: 5-18). The mean age at enrollment was 16.4?±?4.1?years (range: 9-23). The median dose of imatinib was 287.5?mg/m² (IQR: 267.3, 345.0). The median duration of imatinib-therapy was 6-years (IQR: 3.0, 10.3). The median (IQR) normalized levels of IgG, IgA, and IgM were 33.0% (IQR: ?12.8, 58.7), 28.1% (IQR: ?17.0, 90.1) and 15.9% (IQR: ?9.3, 40.5), respectively. The IgG, IgA, and IgM levels were reduced in 9 (30%), 8 (27%), and 10 (33%) patients, respectively. Five (17%) patients had pan-hypogammaglobulinemia. We suggest checking immunoglobulin levels in patients with CML receiving imatinib with recurrent/unusual infections.     

Protein Energy Wasting in a Cohort of Maintenance Hemodialysis Patients in Dhaka,Bangladesh

Malnutrition is associated with high rates of mortality among patients with end stage kidney disease (ESKD). There is a paucity of data from Bangladesh, where around 35,000–40,000 people reach ESKD annually. We assessed protein-energy wasting (PEW) amongst 133 patients at a single hemodialysis setting in Dhaka. Patients were 49% male, age 50 ± 13 years, 62% were on twice-weekly hemodialysis. Anthropometric, biochemical, and laboratory evaluations revealed: BMI 24.1 ± 5.2 kg/m², mid-arm muscle circumference (MAMC) 21.6 ± 3.6 cm, and serum albumin 3.7 ± 0.6 g/dL. Based on published criteria, 18% patients had PEW and for these patients, BMI (19.8 ± 2.4 vs. 25.2 ± 5.2 kg/m²), MAMC (19.4 ± 2.4 vs. 22.2 ± 3.8 cm), serum albumin (3.5 ± 0.7 vs. 3.8 ± 0.5 g/dL), and total cholesterol (135 ± 34 vs. 159 ± 40 mg/dL), were significantly lower as compared to non-PEW patients, while hand grip strength was similar (19.5 ± 7.6 vs. 19.7 ± 7.3 kg). Inflammatory C-reactive protein levels tended to be higher in the PEW group (20.0 ± 34.8 vs. 10.0 ± 13.9 p = 0.065). Lipoprotein analyses revealed PEW patients had significantly lower low density lipoprotein cholesterol (71 ± 29 vs. 88 ± 31 mg/dL, p < 0.05) and plasma triglyceride (132 ± 51 vs. 189 ± 103 mg/dL, p < 0.05), while high density lipoprotein cholesterol was similar. Nutritional assessments using a single 24 h recall were possible from 115 of the patients, but only 66 of these were acceptable reporters. Amongst these, while no major differences were noted between PEW and non-PEW patients, the majority of patients did not meet dietary recommendations for energy, protein, fiber, and several micronutrients (in some cases intakes were 60–90% below recommendations). Malnutrition Inflammation Scores were significantly higher in PEW patients (7.6 ± 3.1 vs. 5.3 ± 2.7 p < 0.004). No discernible differences were apparent in measured parameters between patients on twice- vs. thrice-weekly dialysis. Data from a larger cohort are needed prior to establishing patient-management guidelines for PEW in this population.     

Congenital intramedullary spinal ependymal cyst

A rare case of congenital intramedullary ependymal cyst of the dorsal cord in a 7-year-old boy associated with kyphoscoliosis and rachidian malformations of the dorsal spine is reported. Myelography suggested an intramedullary lesion. The posterior location and presence of a clear plane of cleavage from the medullary tissue enabled total enucleation of the cyst. Histological differentiation from other similar intradural cysts is discussed and the relevant literature is reviewed. This is the fifth such case reported in the literature.