Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control

Clinical Assessment of Functional Recovery Following Nerve Transfer for Traumatic Brachial Plexus Injuries

Surgical reconstruction and postoperative rehabilitation are both important for restoring function in patients with traumatic brachial plexus injuries (BPIs). The current study aimed to understand variations in recovery progression among patients with different injury levels after receiving the nerve transfer methods. A total of 26 patients with BPIs participated in a rehabilitation training program over 6 months after nerve reconstruction. The differences between the first and second evaluations and between C5–C6 and C5–C7 BPIs were compared. Results showed significant improvements in elbow flexion range (p = 0.001), British Medical Research Council’s score of shoulder flexion (p = 0.046), shoulder abduction (p = 0.013), shoulder external rotation (p = 0.020), quantitative muscle strength, and grip strength at the second evaluation for both groups. C5–C6 BPIs patients showed a larger shoulder flexion range (p = 0.022) and greater strength of the shoulder rotator (p = 0.004), elbow flexor (p = 0.028), elbow extensor (p = 0.041), wrist extensor (p = 0.001), and grip force (p = 0.045) than C5–C7 BPIs patients at the second evaluation. Our results indicated different improvements among patients according to injury levels, with quantitative values assisting in establishing goals for interventions

Cyclic Stability of Locking Plate Augmented with Intramedullary Polymethyl Methacrylate (PMMA) Strut Fixation for Osteoporotic Humeral Fractures: A Biomechanical Study

The locking plate may provide improved fixation in osteoporotic bone; however, it has been reported to fail due to varus collapse or screw perforation of the articular surface, especially in osteoporotic bone with medial cortex comminution. Using bone graft as an intramedullary strut together with plate fixation may result in a stronger construct. However, the drawbacks of bone grafts include limited supply, high cost, and infection risk. PMMA (so-called bone cement) has been widely used for implant fixation due to its good mechanical properties, fabricability, and biocompatibility. The risk of donor-site infection and the drawbacks of allografting may be overcome by considering PMMA struts as alternatives to fibular grafts for humeral intramedullary grafting surgeries. However, the potential effects of intramedullary PMMA strut on the dynamic behaviour of osteoporotic humerus fractures remain unclear. This study aimed to investigate the influence of an intramedullary PMMA strut on the stability of unstable proximal humeral fractures in an osteoporotic synthetic model. Two fixation techniques, a locking plate alone (non-strut group) and the same fixation augmented with an intramedullary PMMA strut (with-strut group), were cyclically tested in 20 artificial humeral models. Axially cyclic testing was performed to 450 N for 10,000 cycles, intercyclic motion, cumulated fragment migration, and residual deformation of the constructs were determined at periodic cyclic intervals, and the groups were compared. Results showed that adding an intramedullary PMMA strut could decrease 1.6 times intercyclic motion, 2 times cumulated fracture gap migration, and 1.8 times residual deformation from non-strut fixation. During cycling, neither screw pull-out, cut-through, nor implant failure was observed in the strut-augmented group. We concluded that the plate-strut mechanism could enhance the cyclic stability of the fixation and minimize the residual displacement of the fragment in treating osteoporotic proximal humeral unstable fractures. The PMMA strut has the potential to substitute donor bone and serve as an intramedullary support when used in combination with locking plate fixation. The intramedullary support with bone cement can be considered a solution in the treatment of osteoporotic proximal humeral fractures, especially when there is medial comminution

Casein Kinase 1 Epsilon Expression Predicts Poorer Prognosis in Low T-Stage Oral Cancer Patients

Casein kinase 1 is a group of ubiquitous serine/threonine kinases that are involved in normal cellular functions and several pathological conditions, such as DNA repair, cell cycle progression, cytokinesis, differentiation, and apoptosis. Recent studies have indicated that casein kinase 1-epsilon (CK1ε) and casein kinase 1-delta (CK1δ) expression has a role in human cancers. We investigated the associations between CK1ε and CK1δ expression and the clinical parameters of oral cancer using immunohistochemical study methods on oral squamous cell carcinoma specimens. The results of our immunohistochemical analysis showed that the loss of CK1ε expression was greatly associated with a poor four-year survival rate in oral cancer patients (p = 0.002). A Kaplan-Meier analysis showed that patients who had a loss of CK1ε expression had a considerably poorer overall survival rate than patients who had positive CK1ε expressions (p = 0.022). A univariate analysis revealed that patients who had a loss of CK1ε expression had considerably poorer overall survival (OS) than patients who had positive expression (p = 0.024, hazard ratio (HR) = 1.7). In conclusion, our data indicated that the loss of cytoplasmic CK1ε expression is greatly associated with poor survival and might be an adverse survival factor

Immunoglobulin E and G Levels in Predicting Minimal Change Disease before Renal Biopsy

Purpose. The diagnosis of minimal change disease in adults relies mainly on renal biopsy, but this procedure is not without complications. Despite the advancements in technique of percutaneous renal biopsy, biopsy-related complications still occur. Bleeding is one of the major complications, which may lead to hemodynamic instability and, sometimes, even death. Thus, we developed a model to predict MCD for high-risk patients unsuitable for renal biopsy. Methods. We enrolled 142 patients with nephrotic syndrome who received renal biopsy between October 2007 and April 2011 at one tertiary medical center in this study. Demographic, clinical, and prebiopsy laboratory variables were retrospectively recorded and analyzed. Results. The overall prevalence of MCD was 26.8%. Age, hemoglobin levels, 24-hour urine protein, immunoglobulin (Ig) G, and IgE differed significantly between the MCD and non-MCD groups. Logistic regression analysis showed a significant increase in the risk of developing MCD as the number of Ig risk factors, namely, IgG 110 mg/dl, increased. Having both risk factors significantly increased the chances of receiving a diagnosis of MCD (by 31.84-fold, P =.007) compared with having neither. Combining the aforementioned clinical model and the 2 Ig risk factors was the best in predicting the diagnosis of MCD, with the area under a receiver-operating characteristic curve of 0.91. Conclusions. Combining clinical model and this 2 Ig risk factors provides physicians simple and valuable clinical markers to diagnose MCD

Does a Supplemental Low-Protein Diet Decrease Mortality and Adverse Events After Commencing Dialysis? A Nationwide Cohort Study

Background: A beneficial effect of a ketoanalogue-supplemented low-protein diet (sLPD) in postponing dialysis has been demonstrated in numerous previous studies. However, evidence regarding its effect on long-term survival is limited. Our study assessed the long-term outcomes of patients on an sLPD after commencing dialysis. Methods: This retrospective study examined patients with new-onset end-stage renal disease with permanent dialysis between 2001 and 2013, extracted from Taiwan’s National Health Insurance Research Database. Patients who received more than 3 months of sLPD treatment in the year preceding the start of dialysis were extracted. The outcomes studied were all-cause mortality, infection rate, and major cardiac and cerebrovascular events (MACCEs). Results: After propensity score matching, the sLPD group (n = 2607) showed a lower risk of all-cause mortality (23.1% vs. 27.6%, hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.70–0.84), MACCEs (19.2% vs. 21.5%, HR 0.86, 95% CI 0.78–0.94), and infection-related death (9.9% vs. 12.5%, HR 0.76, 95% CI 0.67–0.87) than the non-sLPD group did. Conclusion: We found that sLPD treatment might be safe without long-term negative consequences after dialysis treatment

Multivariate analysis of the influence of various parameters on overall survival (OS) in oral squamous cell cancer (OSCC) patients according to IL6 expression (337 cases).

<p>Note:¹IL6 high/IL6 (low/negative);²HR: hazard ratio; ³CI: confidence interval. Statistical significance was defined as *P<0.05.</p