The relationship of three-dimensional joint space width on weight-bearing CT with pain and physical function

Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. Three-dimensional (3D) joint space width (JSW), measured from weight-bearing computed tomography (CT) images, may yield a more accurate correlation with patients’ symptoms. We assessed the cross-sectional association between 3D JSW and self-reported pain and physical function. Five hundred twenty eight knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight-bearing CT scanner was used to acquire bilateral, weight-bearing, fixed-flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and JSW was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with JSW less than 2.0 and 2.5 mm, respectively, were calculated. Pain and physical function were measured using Western Ontario and McMaster Universities Osteoarthritis Index. Participants who reported greater pain severity tended to have a greater joint area with JSW less than 2.0 mm (P = .07 for the highest vs the lowest tertile). Participants who reported greater functional limitations had a greater joint area with JSW less than 2.0 mm (P = .02 for the highest vs the lowest tertile). There appears to be an association between the medial tibiofemoral area with JSW less than 2.0 mm and pain and physical function.     

Accuracy of sentinel node biopsy in esophageal carcinoma: a systematic review and meta-analysis of the pertinent literature

The use of sentinel node surgery for esophageal carcinoma is still under investigation. We evaluated the data available in the literature on this topic, and herein present the results in a systematic review format. PUBMED, SCOPUS, the ISI web of knowledge and the information from the annual meetings of the Japan Esophageal Society were searched using the search terms: “(esophagus OR esophageal) AND sentinel”. The outcomes of interest were the detection rate and sensitivity. Overall, 18 studies were included. The pooled detection rate was 89.2 % [82.6–93.5]. Patients with T1 and two tumors had a 17 % higher detection rate compared to those with T3 and four tumors. The pooled sensitivity was 84 % [78–88 %]. The sensitivity was higher for adenocarcinoma compared to squamous cell carcinoma (SCC) (91 vs. 81 %). In the SCC patients, there was a trend toward decreased sensitivity associated with an increasing tumor depth (T1:88 %, T2:76 %, T3:50 %). Our analysis indicated that sentinel node biopsy is useful in adenocarcinoma patients. For SCC patients, including only cN0 patients (preferably T1 and 2) would increase the detection rate and sensitivity. Due to the limited number of high-quality studies, drawing any more definite conclusions is impossible. Large cohort studies with a standardized and consistent design will be needed in the future.     

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.     

Epicardial Versus Endocardial Pacemakers in the Pediatric Population: A Comparative Inquiry

Background: Most children in need of cardiac pacemakers remain dependent on the function of the permanent from childhood to adulthood. We sought to evaluate and compare the function between epicardial and endocardial pacemakers in pediatric groups with different conditions. Methods: Between 2012 and 2018, this single-canter study evaluated 44 pediatric patients with indications for epicardial or endocardial pacemakers. Results: The 2 groups, at a median age of 5 (0.1–16) years, were compared concerning the characteristics of the leads used (n = 80: bipolar, unipolar, steroid-eluting, and non–steroid-eluting), survival data, and complications. The reason for pacemaker implantation was congenital complete heart block in 11 (25%) cases and postoperative heart block in 33 (75%) cases. The commonest congenital heart disease accompanied by postoperative block was the ventricular septal defect. In the endocardial lead group, the mean ventricular pacing threshold immediately after the implantation and during the follow-up was less than that in the epicardial lead group (0.75 vs. 0.81 V; P = 0.01 and 0.8 vs. 2.4 V; P = 0.001). During the follow-up, the mean battery longevity was better in the endocardial group (last visit: 6.7 endocardial vs. 3.3 years epicardial). Lead failure was commoner in the epicardial pacemaker, and chronic high-pacing threshold pattern was seen in 14 patients in this group. After 3 years, freedom from lead failure was 94% and 63% in the endocardial and epicardial leads. Conclusions: Pacemakers with endocardial bipolar steroid-eluting leads showed better lead characteristics regarding survival and battery longevity than epicardial pacemakers without these lead characteristics. An appropriate pacemaker type should be selected based on the patient’s condition.     

Atherogenic consequence of antiepileptic drugs: a study of intima-media thickness

We intended to evaluate the carotid intima-media thickness (CA-IMT) as a surrogate factor for atherogenesis in epileptic patients on enzyme inducer (EI) antiepileptic drugs (AEDs) or valproate (VA). The study included 71 patients with epilepsy (37 females) aged 27.7 ± 8.1 and 71 age- and sex-matched non-epileptic subjects. Patients with history of at least 2 years antiepileptic treatment were enrolled. Subjects with known history of cardiovascular risk factors were not included. Thirty-eight patients (21 females) were treated with EI medications and 33 (16 females) with VA. CA-IMTs were measured by a single sonography system in all participants. CA-IMT values were compared between patients with epilepsy and the controls and within the patients with epilepsy on VA or EI medications. Duration of epilepsy was 10.1 ± 7.1 years. Patients were treated with their current AED for 6.9 ± 4.8 years. The CA-IMT of patients with epilepsy was higher than non-epileptic control subjects on either left (0.502 ± 0.079 vs. 0.470 ± 0.073 mm; p = 0.012) or right side (0.524 ± 0.078 vs. 0.458 ± 0.068 mm; p < 0.001). Patients on VA were younger than those receiving EI medications (25.8 ± 7.1 vs. 29.4 ± 8.7 years). Age adjusted CA-IMT values of patients on VA did not differ from the values of patients receiving EI medications. Duration of drug administration did not correlate with CA-IMT values. Patients with epilepsy on AEDs are at higher risk for atherogenesis. In the population of this study the increased risk of atherogenesis was not attributable to the administered AED or duration of treatment.     

High nodal FDG uptake increases risk of distant metastasis in patients with oropharyngeal squamous cell carcinoma

European Journal of Nuclear Medicine and Molecular Imaging - The purpose of this study was to investigate if FDG uptake metrics in primary tumor and lymph node metastases in patients with...     

Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis beyond the CLL international prognostic index

Next-generation sequencing identified about 60 genes recurrently mutated in chronic lymphocytic leukemia (CLL). We examined the additive prognostic value of the total number of recurrently mutated CLL genes (i.e., tumor mutational load [TML]) or the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed CLL and high-count monoclonal B-cell lymphocytosis (HC MBL). We sequenced 59 genes among 557 individuals (112 HC MBL/445 CLL) in a multi-stage design, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time-to-first treatment (TTT), adjusted for CLL-IPI and sex. TML was associated with shorter TTT in the discovery and validation cohorts, with a combined estimate of continuous HR = 1.27 (CI:1.17-1.39, P = 2.6 × 10⁻⁸; c-statistic = 0.76). When stratified by CLL-IPI, the association of TML with TTT was stronger and validated within low/intermediate risk (combined HR = 1.54, CI:1.37-1.72, P = 7.0 × 10⁻¹⁴). Overall, 80% of low/intermediate CLL-IPI cases with two or more mutated genes progressed to require therapy within 5 years, compared to 24% among those without mutations. TML was also associated with shorter TTT in the HC MBL cohort (HR = 1.53, CI:1.12-2.07, P = .007; c-statistic = 0.71). TML is a strong prognostic factor for TTT independent of CLL-IPI, especially among low/intermediate CLL-IPI risk, and a better predictor than any single gene. Mutational screening at early stages may improve risk stratification and better predict TTT.     

Predictive ability of C-reactive protein for early mortality after ischemic stroke: comparison with NIHSS score

We aimed to compare the association of high-sensitivity C-reactive protein (CRP) and National Institutes of Health Stroke Scale (NIHSS) score with mortality risk and to determine the optimal threshold of CRP for prediction of mortality in ischemic-stroke patients. A series of 162 patients with first-ever ischemic-stroke admitted within 24 h after onset of symptoms was enrolled. CRP and NIHSS score were estimated on admission and their predictive abilities for mortality at 7 days were determined by logistic-regression analyses. Receiver-Operating Characteristic (ROC) curves were depicted to identify the optimal cut-off of CRP, using the maximum Youden-index and the shortest-distance methods. Deceased patients had higher levels of CRP and NIHSS on admission (8.87 ± 7.11 vs. 2.20 ± 4.71 mg/l for CRP, and 17.31 ± 6.36 vs. 8.70 ± 4.85 U for NIHSS, respectively, P < 0.01). CRP and NIHSS were correlated with each other (r ² = 0.39, P < 0.001) and were also independently associated with increased risk of mortality [odds ratios (95 % confidence interval) of 1.16 (1.05–1.28) and 1.20 (1.07–1.35) for CRP and NIHSS, respectively, P < 0.01]. The areas under the ROC curves of CRP and NIHSS for mortality were 0.82 and 0.84, respectively. The CRP value of 2.2 mg/l was identified as the optimal cut-off value for prediction of mortality within 7 days (sensitivity: 0.81, specificity: 0.80). Thus, CRP as an independent predictor of mortality following ischemic-stroke is comparable with NIHSS and the value of 2.2 mg/l yields the optimum sensitivity and specificity for mortality prediction.