Citations

Background: The purpose of this study was to determine whether prominent radial shaft screws in volar locked plating of distal radius fractures increase the risk of tendon irritation, tendon rupture, or hardware removal. Methods: Patients who underwent volar locked plating of distal radius fractures from April 2002 to March 2016 with at least 6 months of follow-up were evaluated. Variables examined included demographics, extensor tendon irritation, extensor tendon rupture, and hardware removal. The most prominent cortical screws on postoperative lateral radiographs were identified and measured from the dorsal cortex of the radial shaft to the tip of the screw. Results: In all, 261 distal radius fractures in 255 patients were identified. Thirty-nine patients (14.9%) underwent subsequent hardware removal at a mean 15.8 ± 18.6 months. Nine patients (3.45%) were found to have clinically significant extensor tendon irritation including one patient (0.38%) with extensor tendon rupture. The average screw was 1.48 mm proud of the dorsal radial cortex. In all, 22.6% of screws were greater than 2 mm proud. Comparing patients who underwent hardware removal with those who did not, there was no statistically significant difference in mean screw prominence or proportion of patients with screws greater than 2 mm. There was no statistically significant difference between shaft screw prominence and extensor tendon irritation. Conclusions: The effect of dorsal screw prominence of radial shaft screws is not significant. This study does not support the downsizing of prominent screws 2 mm or less.

Aims The aim of this study was to evaluate two hypotheses. First, that disruption of posterior bundle of the medial collateral ligament (PMCL) has to occur for the elbow to subluxate in cases of posteromedial rotatory instability (PMRI) and second, that ulnohumeral contact pressures increase after disruption of the PMCL. Materials and Methods Six human cadaveric elbows were prepared on a custom-designed apparatus which allowed muscle loading and passive elbow motion under gravitational varus. Joint contact pressures were measured sequentially in the intact elbow (INTACT), followed by an anteromedial subtype two coronoid fracture (COR), a lateral collateral ligament (LCL) tear (COR + LCL), and a PMCL tear (COR + LCL + PMCL). Results There was no subluxation or joint incongruity in the INTACT, COR, and COR + LCL specimens. All specimens in the COR + LCL + PMCL group subluxated under gravity-varus loads. The mean articular contact pressure of the COR + LCL group was significantly higher than those in the INTACT and the COR groups. The mean articular contact pressure of the COR + LCL + PMCL group was significantly higher than that of the INTACT group, but not higher than that of the COR + LCL group. Conclusion In the presence of an anteromedial fracture and disruption of the LCL, the posterior bundle of the MCL has to be disrupted for gross subluxation of the elbow to occur. However, elevated joint contact pressures are seen after an anteromedial fracture and LCL disruption even in the absence of such subluxation. Cite this article: Bone Joint J 2018;100-B:1060–5.

AbstractWe aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical‐grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis‐associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47–2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30–2.75, p = 0.004), while absence was associated with shorter OS in low‐grade serous carcinomas (HR: 2.95, 95% CI 1.61–5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype‐specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low‐grade serous carcinoma justifies CDK4 inhibition.

Background Navigable, large diameter aspiration catheters demonstrate markedly improved recanalization rates over smaller lumen devices in suction embolectomy. We evaluated the performance of a novel aspiration catheter system designed to maximize lumen size, and compare it to other commercially available aspiration catheters. Methods The 6F R4Q aspiration catheter system comprises a proximal pusher wire of 117 cm length connected to a distal catheter of 25 cm length. When placed through standard guide catheters and into the cerebral circulation, the proximal catheter makes a tight seal between its outer surface and the guide catheter’s inner surface. During aspiration, in vitro flow rates and tip suction force under gentle retraction were compared among 10 commercially available aspiration catheters and the R4Q system. Results The R4Q 6F, 5F, 4F, and 3F catheters achieved flow rates at least 21.9%, 24.7%, 61.9%, and 244.7% greater than the other catheters tested respectively and the R4Q 6F produced a 140.2% higher tip force than a catheter of similar size. Fluid flow rate in the R4Q 6F increased on retraction into the guide catheter, delivering a 58.2% increase from fully extended to fully retracted. Conclusion The R4Q design demonstrates a substantial increase in aspirated flow rate and suction force due to an increased effective diameter than standard tubular catheter designs tested. The prominent increase in the aspiration parameters measured in vitro supports the potential for improved clinical results during stroke thrombectomy procedures.

Objectives: Early results following arthroscopic superior capsular reconstruction(SCR) in patients with massive, irreparable rotator cuff tears are promising. However, no studies have compared patient reported outcomes between SCR or reverse total shoulder(rTSA) and rotator cuff debridement for these patients. Therefore, the purpose of this study was to compare 1-year outcomes between patients with massive irreparable rotator cuff tears who underwent a SCR, rTSA, or rotator cuff debridement with a concurrent biceps tenotomy or tenodesis. Methods: Patients(n=63) who underwent either SCR(n=21), rTSA(21), or cuff debridement(n=21) and biceps tenotomy or tenodesis for a massive, irreparable rotator cuff tear treated with a minimum 1-year follow up were retrospectively reviewed. Age, sex, BMI, smoking status, Charlson Index, Hamada classification, and ASES scores were recorded and compared using a multivariate ANOVA were used to compare between surgical approaches. A Chi Square analyses were used to compare sex distribution and the Charlson Deyo Index between groups (α=0.05). Results: Overall, patients across the 3 groups were not statistically different in age or follow up ASES score at minimum 14 month follow up ( P> 0.05). There was a significant interaction effect between surgery group and sex (P=0.02) on ASES score but not age ( P=0.08). Univariate F tests revealed that male patients who received an SCR displayed a 10-14% better outcome at follow up compared to other groups (Table 1) which exceeds the reported ASES score MCID. Conclusion: Our results show comparable results across surgical options for massive irreparable cuff tears with good patient reported outcomes. Male patients displayed clinically important greater ASES scores at 1 year follow up. Future studies should evaluate these preliminary results to assess if these preliminary results hold up at longer follow up times.

Abstract Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P &lt; 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P &lt; 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.

This study aimed to determine the outcome of free vascularized medial femoral condyle bone grafts in the primary treatment of scaphoid nonunions with scaphoid foreshortening or carpal collapse and intraoperatively documented avascular necrosis. Thirty-two patients (28 male, four female) met the inclusion criteria. Median time from injury to surgery was 70 weeks. Thirty of 32 patients healed at a median of 12 weeks. There was significant improvement from preoperative to postoperative lateral intrascaphoid angle, scapholunate angle, and radiolunate angle. Two scaphoids failed to unite; one patient underwent scaphoidectomy and four-corner fusion 15 months postoperatively after suffering a subsequent injury. Another patient underwent 1,2-intercompartmental supraretinacular artery-based vascularized bone grafting at 4 months postoperatively and then scaphoid excision with four-corner fusion 4 years later. The free vascularized medial femoral condyle bone graft restores scaphoid vascularity and architecture while promoting union in a subset of scaphoid nonunions that has historically been a clinical challenge. Level of evidence: IV

An automated method for specific factor assays has been developed using a novel thrombin-specific chromogenic substrate (developed by A. Aiyappa, Ph. D., Abbott Labs). For factors VIII, IX, XI and XII, the test system includes an ellagic acid activator and brain phospholipid in a calcium containing tris buffer pH 7.4. These are mixed with a plasma sample consisting of a mixture of specific factor deficient substrate and test plasma for 5 minutes and then the chromogenic substrate is added. After another 5 minutes the increase in optical density ΔOD is recorded. Normal plasma serially diluted in specific factor deficient substrate is used to construct a standard graph and test plasma results are interpolated from this.Fifty-four comparative assays have been done for factors VIII and IX and correlated with the results obtained from conventional clotting assays. For factor VIII the correlation coefficient (r)=0.935 (N=35) and for factor IX r=0.941 (N=19). While insufficient data exists to date for factors XI and XII, these assays appear to be comparable to the VIII and IX results.The assays for factors V, VII and X use a simplified system in that the chromogenic substrate and phospholipid are added together. The ΔOD is again recorded after 5 minutes. Test plasma results are interpolated from a standard graph constructed using serially diluted normal plasma as before. To date only the factor V assay has enough data to do a correlation with the clotting assays and r=0.953 (N=13) which is similar to the r value for the VIII and IX assays.Because of the widespread availability of the automated analyzer used in the assay and the standardization of end point determination it provides, specific factor assays might be made more widely available outside specialized coagulation centers.

BackgroundGraft‐versus‐host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature.MethodsWe performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT‐associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017).ResultsOf nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11‐162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0‐54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow‐up period.ConclusionsSOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

Abstract Background The assessment of kidney function and detection of acute kidney injury (AKI) remain cumbersome. On the one hand, because of limited accuracy of established tests: The most widely used methods are creatinine based, which lack in sensitivity, as creatinine is not purely filtrated by the kidney and rises relatively late after onset of AKI. On the other hand, because of labor-intensiveness: Gold standard inulin clearance and comparable methods involve intravenous compound infusion, blood sampling at several time points, and have error-sensitive determination methods. In recent years, several biomarkers have been put forward (e.g., NGAL, KIM-1, TIMP-2*IGFBP-7), but clinical implementation is limited up to now. Content Proenkephalin (PENK) represents a new candidate to determine kidney function. This peptide is cleaved from the precursor peptide preproenkephalin A alongside enkephalins (endogenous opioids) and is filtrated in the glomerulus. PENK plasma concentration appears to accurately represent glomerular filtration rate in patients diagnosed with sepsis or cardiac diseases. Moreover, increased PENK concentration is found to be associated with longer-term outcome concerning AKI and cardiac diseases. Lastly, the predominant receptor of enkephalins, the δ-opioid receptor, is expressed with the highest density in the kidney, suggesting that enkephalins could also exert a direct effect on kidney function. Summary In this review, we present an overview of enkephalins and the assessment of kidney function using this possible new functional biomarker PENK and compare it with established and novel biomarkers.