Usefulness of contrast enhanced FLAIR imaging for predicting the severity of meningitis

The aim of this study was to evaluate whether contrast enhanced fluid attenuated inversion recovery (CE-FLAIR) imaging can be used to predict the severity of meningitis based on leptomeningeal enhancement (LE) score and cerebrospinal fluid signal intensity (CSF-SI) on CE-FLAIR. We retrospectively analyzed data collected from 43 consecutive patients admitted to our hospital due to meningitis. Clinical factors including initial Glasgow Coma Scale (GCS) score, CSF glucose ratio, log CSF protein, log CSF WBC, and prognosis were evaluated. The LE score was semi-quantitatively scored, and we evaluated CSF-SI ratio at the interpeduncular or quadrigerminal cisterns on CE-FLAIR. We evaluated the differences in clinical variables, LE scores and CSF-SI ratios between the recovery and the complication group. We assessed the correlation between clinical variables, LE scores and CSF-SI ratios. The values of log CSF protein, CSF-SI ratio, and LE score were significantly higher in the complication group (p value <0.05). GCS score and CSF glucose ratio were significantly lower in the complication group (p value <0.01). The LE scores had significant negative correlation with GCS scores and CSF glucose ratios (p value <0.001). The LE score was significantly positively correlated with the value of log CSF protein and CSF-SI ratio (p value <0.01). The CSF-SI ratio was negatively correlated with GCS score and CSF glucose ratio (p value <0.01). The CSF-SI ratio was positively correlated with the value of log CSF protein (p value <0.05). Our results suggest that LE score and CSF-SI ratio are well correlated with clinical prognostic factors. We may predict the clinical severity of meningitis by using LE scores and CSF-SI ration on CE-FLAIR imaging.     

Intracellular distribution of differentially phosphorylated dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A)

The gene encoding dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome 21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton, and nucleus. Its overexpression is a contributing factor to the developmental alterations and age‐associated pathology observed in DS. We hypothesized that the intracellular distribution of DYRK1A and cell‐compartment‐specific functions are associated with DYRK1A posttranslational modifications. Fractionation showed that, in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two‐dimensional gel analysis of the fractions revealed DYRK1A with distinct isoelectric points: 5.5–6.5 in the nucleus, 7.2–8.2 in the cytoskeleton, and 8.7 in the cytosol. Phosphate‐affinity gel electrophoresis demonstrated several bands of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis disclosed one phosphorylated site in the cytosolic DYRK1A and multiple phosphorylated residues in the cytoskeletal DYRK1A, including two not previously described. This study supports the hypothesis that intracellular distribution and compartment‐specific functions of DYRK1A may depend on its phosphorylation pattern. © 2013 Wiley Periodicals, Inc.     

Sequencing of LRP2 Reveals Multiple Rare Variants Associated with Urinary Trefoil Factor-3

Novel biomarkers are being investigated to identify patients with kidney disease. We measured a panel of 13 urinary biomarkers in participants from the Offspring Cohort of the Framingham Heart Study. Using an Affymetrix chip with imputation to 2.5 M single-nucleotide polymorphisms (SNPs), we conducted a GWAS of these biomarkers (n=2640) followed by exonic sequencing and genotyping. Functional studies in zebrafish were used to investigate histologic correlation with renal function. Across all 13 biomarkers, there were 97 significant SNPs at three loci. Lead SNPs at each locus were rs6555820 (P=6.7×10⁻⁴⁹; minor allele frequency [MAF]=0.49) in HAVCR1 (associated with kidney injury molecule-1), rs7565788 (P=2.15×10⁻¹⁶; MAF=0.22) in LRP2 (associated with trefoil factor 3 [TFF3]), and rs11048230 (P=4.77×10⁻⁸; MAF=0.10) in an intergenic region near RASSF8 (associated with vascular endothelial growth factor). Validation in the CKDGen Consortium (n=67,093) showed that only rs7565788 at LRP2, which encodes megalin, was associated with eGFR (P=0.003). Sequencing of exons 16–72 of LRP2 in 200 unrelated individuals at extremes of urinary TFF3 levels identified 197 variants (152 rare; MAF<0.05), 31 of which (27 rare) were nonsynonymous. In aggregate testing, rare variants were associated with urinary TFF3 levels (P=0.003), and the lead GWAS signal was not explained by these variants. Knockdown of LRP2 in zebrafish did not alter the renal phenotype in static or kidney injury models. In conclusion, this study revealed common variants associated with urinary levels of TFF3, kidney injury molecule-1, and vascular endothelial growth factor and identified a cluster of rare variants independently associated with TFF3.Serum creatinine, as used in most GFR estimating equations, is the primary biomarker of CKD.¹ Creatinine has significant limitations as a biomarker. It is insensitive to early declines in kidney function, and there are important extrarenal factors that influence its concentration, thus increasing the potential for misclassification when it is used to diagnose renal disease.² As a result, novel biomarkers are being investigated that could allow earlier and more accurate diagnosis of CKD.³ It is likely, however, that these biomarkers also have non-GFR determinants, including genetic factors. For example, levels of cystatin C, a novel GFR biomarker, are known to be influenced by both nongenetic factors, such as adiposity and the metabolic syndrome,⁴ and the presence of specific genetic variants in the cystatin C-gene cluster.⁵Genome-wide association studies (GWAS) allow for the evaluation of genetic associations of biomarkers in an unbiased manner. These studies could illuminate previously unrecognized pathways for CKD pathogenesis, thus identifying new potential molecular targets for therapeutic intervention. Multiple variants have been identified in association with kidney function through GWAS,⁶ whereas a variant in CUBN encoding cubilin, a proximal tubular transport protein, has been associated with albuminuria.⁷ Recently, a GWAS identified a locus at PTGDS in association with another kidney biomarker, β-trace protein.⁸To gain additional insight into biologic pathways of renal function and kidney injury, we measured a panel of 13 urinary biomarkers in participants from the Framingham Heart Study (FHS) and performed a GWAS of their levels. Here, we report the primary results from these studies as well as follow-up work to identify whether rare variants in LRP2 are associated with levels of trefoil factor 3 (TFF3).     

From amputation to limb salvage reconstruction: evolution and role of the endoprosthesis in musculoskeletal oncology

In 1943, Austin Moore developed the first endoprosthesis fashioned from Vitallium, providing the first alternative to traditional amputation as primary treatment of bone tumors. The success of the Vitallium endoprosthesis has since then led to the development of new materials and designs further advancing limb salvage and reconstructive surgery. Combined with the advent of chemotherapy use and imaging advances, conservative treatment of musculoskeletal tumors has expanded greatly. As the implantable options increased with the development of the Lewis expandable adjustable prosthesis and the noninvasive Phenix Growing prosthesis, receiving the diagnosis of a bone tumor no longer equates to automatic limb loss. Our review details the history and development of endoprostheses throughout orthopedic oncology in the treatment of musculoskeletal tumors.     

A prospective randomised comparison of two insertion methods for i‐gel™ placement in anaesthetised paralysed patients: standard vs rotational technique

In this prospective randomised study, we compared two techniques for i‐gel^? insertion. One hundred and eighty‐one anaesthetised, paralysed adult patients were randomly allocated into one of two groups. In the standard group (n = 91), the i‐gel was inserted using the standard technique. In the rotation group (n = 90), the i‐gel was rotated 90° anticlockwise in the mouth and re‐rotated in the hypopharynx to the original alignment. The success rate, insertion time, air leak pressure and complications were assessed. The success rate for insertion at the first attempt was lower for the standard technique, 78 (86%) vs 87 (97%; p = 0.016). The mean (SD) insertion time was longer (26.9 (14.5) s vs 22.4 (10.2) s; p = 0.016) and air leak pressure was lower (22.5 (10.4) cmH₂O vs 27.1 (9.4) cmH₂O; p = 0.002) in the standard group. The incidence of bloodstaining was higher with the standard technique (8 (9%) vs 1 (1%); p = 0.034). This study suggests that the rotational technique is superior to the standard technique for i‐gel insertion.     

The Natural History of Arteriovenous Access and Risk Factors Associated With Access Thrombosis After Successful Kidney Transplantation

Introduction

The purpose of this study was to determine the natural history of arteriovenous (AV) access after successful kidney transplantation (KT) and to identify the risk factors of spontaneous access closure in kidney transplant recipients.

Methods

We performed a retrospective review of 115 patients who underwent KT with functioning access from June 2010 to July 2012. AV access patency was checked and recorded daily during the hospital stay and at every visit to the outpatient clinic. Patients were divided into 2 groups according to the patency of access, and risk factors of access thrombosis were assessed. Access patency was followed up until patency was lost or the study was closed.

Results

At the end of follow-up, 18 (15.7%) AV accesses had spontaneously closed. Mean time to closure was 119 ± 163 days, and 12 of 18 were closed within 90 days after KT. AV access spontaneously closed in 8.5% of male patients, compared with 27.3% of female patients (P = .007), 12.2% of cases with native access compared with 35.3% of cases with artificial access (P = .016), and 11.3% of cases with wrist access compared with 25.7% of cases with elbow access (P = .049). Spontaneously closed AV accesses tended to have a lower mean access flow compared with functioning accesses (P = .019). On multivariate analysis, female sex and AV access flow volume affected spontaneous AV access closure (odds ratio 4.749, 95% confidence interval 1.919–35.383, P = .008; odds ratio 0.998, 95% confidence interval 0.996–0.999, P = .010, respectively).

Conclusions

Our results suggest that AV access thrombosis occurs more frequently during the early postoperative period, particularly in female patients or patients with low flow access, whereas it is a rare event in male patients or patients with high access flow, especially in the late postoperative period.