Suture Tape Augmentation of Posterior Cruciate Ligament Reconstruction Shows Improved Biomechanical Stability With Equivalent Outcome and Complication Rates: A Scoping Review.

PURPOSE: The purpose of this study is to assess the current literature surrounding suture tape augmentation (STA) of posterior cruciate ligament reconstruction (PCLR) with additional evaluation of PCLR+STA in clinical practice. METHODS: A systematic search of three databases (PubMed, EMBASE, and Web of Science Core Collection) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was completed April 2023 to identify studies related to PCLR+STA. Surgical technique, animal, biomechanical, and clinical studies were included for review with quality appraisal conducted according to study design. RESULTS: A total of 380 articles were identified in the search, 6 of which met inclusion criteria. Biomechanical studies showed significant reduction in posterior tibial translation (PTT) with STA of PCLR in multiple studies. STA was found to decrease total elongation by 45-58% in multiple studies; increased load to failure was seen with STA as well in one study. Clinical studies showed equivalent or improved patient reported outcomes with STA of PCLR compared to PCLR alone. CONCLUSIONS: Biomechanical studies offer evidence showing the beneficial load-sharing properties of STA such as increased strength and ultimate load with decreased elongation of the graft, especially with larger forces. Clinical evidence illustrates improved or equivalent patient reported outcomes to standard PCLR with no difference in complication rate. CLINICAL RELEVANCE: STA of PCLR offers an opportunity to improve initial graft stability during the early healing phase through load sharing between the augmentation and the graft.

Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer.

The [A] allele of SNP rs965513 in 9q22 has been consistently shown to be highly associated with increased papillary thyroid cancer (PTC) risk with an odds ratio of ∼1.8 as determined by genome-wide association studies, yet the molecular mechanisms remain poorly understood. Previously, we noted that the expression of two genes in the region, forkhead box E1 (FOXE1) and PTC susceptibility candidate 2 (PTCSC2), is regulated by rs965513 in unaffected thyroid tissue, but the underlying mechanisms were not elucidated. Here, we fine-mapped the 9q22 region in PTC and controls and detected an ∼33-kb linkage disequilibrium block (containing the lead SNP rs965513) that significantly associates with PTC risk. Chromatin characteristics and regulatory element signatures in this block disclosed at least three regulatory elements functioning as enhancers. These enhancers harbor at least four SNPs (rs7864322, rs12352658, rs7847449, and rs10759944) that serve as functional variants. The variant genotypes are associated with differential enhancer activities and/or transcription factor binding activities. Using the chromosome conformation capture methodology, long-range looping interactions of these elements with the promoter region shared by FOXE1 and PTCSC2 in a human papillary thyroid carcinoma cell line (KTC-1) and unaffected thyroid tissue were found. Our results suggest that multiple variants coinherited with the lead SNP and located in long-range enhancers are involved in the transcriptional regulation of FOXE1 and PTCSC2 expression. These results explain the mechanism by which the risk allele of rs965513 predisposes to thyroid cancer.

A novel graph mining approach to predict and evaluate food-drug interactions.

Food-drug interactions (FDIs) arise when nutritional dietary consumption regulates biochemical mechanisms involved in drug metabolism. This study proposes FDMine, a novel systematic framework that models the FDI problem as a homogenous graph. Our dataset consists of 788 unique approved small molecule drugs with metabolism-related drug-drug interactions and 320 unique food items, composed of 563 unique compounds. The potential number of interactions is 87,192 and 92,143 for disjoint and joint versions of the graph. We defined several similarity subnetworks comprising food-drug similarity, drug-drug similarity, and food-food similarity networks. A unique part of the graph involves encoding the food composition as a set of nodes and calculating a content contribution score. To predict new FDIs, we considered several link prediction algorithms and various performance metrics, including the precision@top (top 1%, 2%, and 5%) of the newly predicted links. The shortest path-based method has achieved a precision of 84%, 60% and 40% for the top 1%, 2% and 5% of FDIs identified, respectively. We validated the top FDIs predicted using FDMine to demonstrate its applicability, and we relate therapeutic anti-inflammatory effects of food items informed by FDIs. FDMine is publicly available to support clinicians and researchers.

Anatomic Considerations and Reconstruction of the Thumb Flexor Pulley System.

Disruption to the flexor pulley system of the thumb is an infrequent but devastating injury that can lead to significant compromise in both strength and function. Acute rupture leads to pain, weakness, reduced range of motion (ROM), and potential bowstringing of the flexor tendons. Conservative treatment with a pulley ring should be considered in all patients. However, failure of conservative treatment and bowstringing of the thumb are indications for operative intervention. Reconstruction of the oblique pulley system can be performed either in situ or using a free palmaris longus graft. Care should be taken to identify the neurovascular bundles to avoid compression during the reconstruction. Conscious sedation protocols augmented by ultrasound-guided sheath blocks allow the patient to actively and strongly contract the flexor pollicis longus tendon intraoperatively to appropriately tension the construct for optimal results. Rehabilitation should be performed in a stepwise manner beginning with early passive ROM, active ROM, and finally strengthening at around 8 weeks postoperative.

Genetic predisposition to papillary thyroid carcinoma: involvement of FOXE1, TSHR, and a novel lincRNA gene, PTCSC2.

CONTEXT: By genome-wide association studies, the risk allele [A] of SNP rs965513 predisposes strongly to papillary thyroid carcinoma (PTC). It is located in a gene-poor region of 9q22, some 60 kb from the FOXE1 gene. The underlying mechanisms remain to be discovered. OBJECTIVE: Our objective was to identify novel transcripts in the 9q22 locus and correlate gene expression levels with the genotypes of rs965513. DESIGN: We performed 3' and 5' rapid amplification of cDNA ends and RT-PCR to detect novel transcripts. One novel transcript was forcibly expressed in a cell line followed by gene expression array analysis. We genotyped rs965513 from PTC patients and measured gene expression levels by real-time RT-PCR in unaffected thyroid tissue and matched tumor. SETTING: This was a laboratory-based study using cells from clinical tissue samples and a cancer cell line. MAIN OUTCOME MEASURES: We detected previously uncharacterized transcripts and evaluated the gene expression levels and the correlation with the risk allele of rs965513, age, gender, chronic lymphocyte thyroiditis (CLT), and TSH levels. RESULTS: We found a novel long intergenic noncoding RNA gene and named it papillary thyroid cancer susceptibility candidate 2 (PTCSC2). Transcripts of PTCSC2 are down-regulated in PTC tumors. The risk allele [A] of rs965513 was significantly associated with low expression of unspliced PTCSC2, FOXE1, and TSHR in unaffected thyroid tissue. We also observed a significant association of age and CLT with PTCSC2 unspliced transcript levels. The correlation between the rs965513 genotype and the PTCSC2 unspliced transcript levels remained significant after adjusting for age, gender, and CLT. Forced expression of PTCSC2 in the BCPAP cell line affected the expression of a subset of noncoding and coding transcripts with enrichment of genes functionally involved in cell cycle and cancer. CONCLUSIONS: Our data suggest a role for PTCSC2, FOXE1, and TSHR in the predisposition to PTC.

Ultra-rare mutation in long-range enhancer predisposes to thyroid carcinoma with high penetrance.

Thyroid cancer shows high heritability but causative genes remain largely unknown. According to a common hypothesis the genetic predisposition to thyroid cancer is highly heterogeneous; being in part due to many different rare alleles. Here we used linkage analysis and targeted deep sequencing to detect a novel single-nucleotide mutation in chromosome 4q32 (4q32A>C) in a large pedigree displaying non-medullary thyroid carcinoma (NMTC). This mutation is generally ultra-rare; it was not found in 38 NMTC families, in 2676 sporadic NMTC cases or 2470 controls. The mutation is located in a long-range enhancer element whose ability to bind the transcription factors POU2F and YY1 is significantly impaired, with decreased activity in the presence of the C- allele compared with the wild type A-allele. An enhancer RNA (eRNA) is transcribed in thyroid tissue from this region and is greatly downregulated in NMTC tumors. We suggest that this is an example of an ultra-rare mutation predisposing to thyroid cancer with high penetrance.