Charlson Co‐morbidity Index and albumin significantly associated with fracture risk in peritoneal dialysis patients

Published literature on fracture in dialysis patients seldom addressed the effect of co‐morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co‐morbidity Index (CCI) and biochemical parameters were also collected. Non‐fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient‐years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty‐four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self‐ambulatory patients (47.1%) became non‐ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non‐ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.     

Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (¹H-MRSI). T1- and T2-weighted MRI images and three-dimensional ¹H-MRSI (480 voxels over 360 cm³, about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18–56 years old, 3–55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This ¹H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.     

Using natural products for drug discovery: the impact of the genomics era

Introduction: Evolutionarily selected over billions of years for their interactions with biomolecules, natural products have been and continue to be a major source of pharmaceuticals. In the 1990s, pharmaceutical companies scaled down their natural product discovery programs in favor of synthetic chemical libraries due to major challenges such as high rediscovery rates, challenging isolation, and low production titers. Propelled by advances in DNA sequencing and synthetic biology technologies, insights into microbial secondary metabolism provided have inspired a number of strategies to address these challenges.

Areas covered: This review highlights the importance of genomics and metagenomics in natural product discovery, and provides an overview of the technical and conceptual advances that offer unprecedented access to molecules encoded by biosynthetic gene clusters.

Expert opinion: Genomics and metagenomics revealed nature’s remarkable biosynthetic potential and her vast chemical inventory that we can now prioritize and systematically mine for novel chemical scaffolds with desirable bioactivities. Coupled with synthetic biology and genome engineering technologies, significant progress has been made in identifying and predicting the chemical output of biosynthetic gene clusters, as well as in optimizing cluster expression in native and heterologous host systems for the production of pharmaceutically relevant metabolites and their derivatives.     

The optimal management of variant histology in muscle invasive bladder cancer

Bladder cancer is a heterogenous disease that is associated with tangible mortality in muscle invasive disease. The WHO 2016 classification of urothelial tumours reflects the contemporary approach towards histological variants in bladder cancer, including variants of urothelial carcinoma (UC) and non-urothelial variants. This review focuses on variant histology in UC, and discusses the importance of accurate histological diagnosis, and subsequent risk stratification and therapeutic decision making based on proper variant recognition. Most urothelial variants are associated with poorer outcomes compared to conventional UC, although some perform reasonably better. However, high quality evidence detailing optimal treatment and survival outcomes are still lacking in literature, due to the rarity of these cases.     

Inflammatory Markers and Risk of Hip Fracture in Older White Women: The Study of Osteoporotic Fractures

Hip fractures are the most devastating consequence of osteoporosis and impact 1 in 6 white women leading to a two‐ to threefold increased mortality risk in the first year. Despite evidence of inflammatory markers in the pathogenesis of osteoporosis, few studies have examined their effect on hip fracture. To determine if high levels of inflammation increase hip fracture risk and to explore mediation pathways, a case‐cohort design nested in a cohort of 4709 white women from the Study of Osteoporotic Fractures was used. A random sample of 1171 women was selected as the subcohort (mean age 80.1 ± 4.2 years) plus the first 300 women with incident hip fracture. Inflammatory markers interleukin‐6 (IL‐6) and soluble receptors (SR) for IL‐6 (IL‐6 SR) and tumor necrosis factor (TNF SR1 and TNF SR2) were measured, and participants were followed for a median (interquartile range) of 6.3 (3.7, 6.9) years. In multivariable models, the hazard ratio (HR) of hip fracture for women in the highest inflammatory marker level (quartile 4) was 1.64 (95% confidence interval [CI], 1.09–2.48, p trend = 0.03) for IL‐6 and 2.05 (95% CI, 1.35–3.12, p trend <0.01) for TNF SR1 when compared with women in the lowest level (quartile 1). Among women with 2 and 3–4 inflammatory markers in the highest quartile, the HR of hip fracture was 1.51 (95% CI, 1.07–2.14) and 1.42 (95% CI, 0.87–2.31) compared with women with zero to one marker(s) in the highest quartile (p trend = 0.03). After individually adjusting for seven potential mediators, cystatin‐C (a biomarker of renal function) and bone mineral density (BMD) attenuated HRs among women with the highest inflammatory burden by 64% and 50%, respectively, suggesting a potential mediating role. Older white women with high inflammatory burden are at increased risk of hip fracture in part due to poor renal function and low BMD. © 2014 American Society for Bone and Mineral Research.     

Effects of laser irradiation on human erythrocytes: Considerations concerning clinical laser angioplasty

Recent studies demonstrate the potential use of laser to vaporize human coronary atherosclerotic plaques. The laser energy is transmitted through flexible quartz fiber and discharged intravascularly. Since red blood cells could be exposed to intense heat, we examined effects of laser irradiation on human erythrocytes. Blood was obtained and placed in 5 ethylene diaminetetracidic acid (EDTA) vials for each normal donor. A flexible 400 diameter core quartz fiber coupled to an argon-ion laser source was positioned 1 cm above the surface of 1.5 ml blood. Four vials were exposed to 5 W laser beam for 5, 10, 15, or 20 s; the remaining vial was left untreated. Packed cell volume fell primarily during the first 5 s of laser exposure (p<0.01) and plateaued beyond 5 s. Plasma hemoglobin (Hgb) rose progressively with each increased duration of exposure (p<0.01). This study indicates that lysis of erythrocytes occurs in cells exposed directly to the laser beam. However, beyond the direct beam, damage to red cell membrane took place as evident by progressive Hgb leakage into plasma despite no further cell lysis. These observations require consideration during clinical laser angioplasty.