Selective nerve transfers to restore shoulder abduction and flexion in acute flaccid myelitis: A case report.

Acute flaccid myelitis (AFM) is a polio-like condition predominantly affecting children that is characterized by acute-onset, asymmetric flaccid paralysis, often preceded by a prodromal fever or viral illness. With prompt diagnosis and early surgical referral, nerve transfers may be performed to improve function. Highly selective nerve transfers are ideal to preserve existing functions while targeting specific deficits. In this report, we present a case of a double fascicular nerve transfer of median and ulnar nerve fascicles to the axillary nerve, combined with selective transfer of the spinal accessory nerve to the supraspinatus branch of the suprascapular nerve, performed for a 5-year-old girl who developed AFM after an upper respiratory infection. Six months after the onset of the patient's symptoms, the patient had continued weakness of shoulder flexion and abduction, atrophy of the deltoid, and supraspinatus muscles, though needle electromyography revealed a functioning infraspinatus muscle. The patient had no post-operative complications and at 2 years of postoperative follow up achieved shoulder abduction and flexion Active Movement Scale scores of 7/7 compared to preoperative scores of 2/7, with no loss of function in the donor nerve domains. The patient showed active shoulder abduction against gravity to 90° from 30° preoperatively and shoulder flexion to 180° from 15° preoperatively. This case report shows that highly selective nerve transfers may preserve existing functions while targeting specific deficits. A double fascicular transfer from the median and ulnar nerves to axillary nerve may provide abundant axons for functional recovery.

Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer.

OBJECTIVE: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described. DESIGN: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and H3K9me3 for heterochromatin. RESULTS: We demonstrate that H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumour-specific enhancers for crucial oncogenes, such as ASCL2 and FZD10, was required for excessive proliferation. Consistently, combination of MEK plus bromodomain inhibition was found to have synergistic effects in CRC patient-derived xenograft models. Probing intertumour heterogeneity, we identified four distinct enhancer subtypes (EPIgenome-based Classification, EpiC), three of which correlate well with previously defined transcriptomic subtypes (consensus molecular subtypes, CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, TGFßi, mTORi and SRCi) for EpiC groups. CONCLUSION: Our data suggest that the dynamics of active enhancer underlies CRC progression and the patient-specific enhancer patterns can be leveraged for precision combination therapy.

Methylation-eQTL analysis in cancer research.

MOTIVATION: DNA methylation is a key epigenetic factor regulating gene expression. While promoter methylation has been well studied, recent publications have revealed that functionally important methylation also occurs in intergenic and distal regions, and varies across genes and tissue types. Given the growing importance of inter-platform integrative genomic analyses, there is an urgent need to develop methods to discover and characterize gene-level relationships between methylation and expression. RESULTS: We introduce a novel sequential penalized regression approach to identify methylation-expression quantitative trait loci (methyl-eQTLs), a term that we have coined to represent, for each gene and tissue type, a sparse set of CpG loci best explaining gene expression and accompanying weights indicating direction and strength of association. Using TCGA and MD Anderson colorectal cohorts to build and validate our models, we demonstrate our strategy better explains expression variability than current commonly used gene-level methylation summaries. The methyl-eQTLs identified by our approach can be used to construct gene-level methylation summaries that are maximally correlated with gene expression for use in integrative models, and produce a tissue-specific summary of which genes appear to be strongly regulated by methylation. Our results introduce an important resource to the biomedical community for integrative genomics analyses involving DNA methylation. AVAILABILITY AND IMPLEMENTATION: We produce an R Shiny app (https://rstudio-prd-c1.pmacs.upenn.edu/methyl-eQTL/) that interactively presents methyl-eQTL results for colorectal, breast and pancreatic cancer. The source R code for this work is provided in the Supplementary Material. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bayesian adaptive trial design for a continuous biomarker with possibly nonlinear or nonmonotone prognostic or predictive effects.

As diseases like cancer are increasingly understood on a molecular level, clinical trials are being designed to reveal or validate subpopulations in which an experimental therapy has enhanced benefit. Such biomarker-driven designs, particularly "adaptive enrichment" designs that initially enroll an unselected population and then allow for later restriction of accrual to "marker-positive" patients based on interim results, are increasingly popular. Many biomarkers of interest are naturally continuous, however, and most existing design approaches either require upfront dichotomization or force monotonicity through algorithmic searches for a single marker threshold, thereby excluding the possibility that the continuous biomarker has a nondisjoint and truly nonlinear or nonmonotone prognostic relationship with outcome or predictive relationship with treatment effect. To address this, we propose a novel trial design that leverages both the actual shapes of any continuous marker effects (both prognostic and predictive) and their corresponding posterior uncertainty in an adaptive decision-making framework. At interim analyses, this marker knowledge is updated and overall or marker-driven decisions are reached such as continuing enrollment to the next interim analysis or terminating early for efficacy or futility. Using simulations and patient-level data from a multi-center Children's Oncology Group trial in Acute Lymphoblastic Leukemia, we derive the operating characteristics of our design and compare its performance to a traditional approach that identifies and applies a dichotomizing marker threshold.

Microsurgical Resection of a Primary Intraosseous Meningioma Encasing the Superior Sagittal Sinus.

Primary intraosseous meningiomas (PIMs) are an infrequent variant of meningiomas characterized by hyperostosis and brain compression. En bloc surgical resection of giant PIMs involving critical structures such as venous sinuses or cranial nerves could be associated with significant morbidity. The objective of this report is to demonstrate the safety and feasibility of piecemeal resection of PIMs involving the superior sagittal sinus and frontal sinus. A 54-year-old female with a large 5 cm thick bifrontal primary intra-osseous meningioma encasing the anterior segment of the superior sagittal sinus and frontal sinus underwent a bifrontal craniotomy with piecemeal microsurgical resection of the lesion, complete frontal sinus exoneration, and a synthetic cranioplasty. Clinical outcome was measured by extent of resection, preservation of cortical draining veins and postoperative course. A Simpson grade I resection of the lesion was achieved following piecemeal resection of the giant PIM without clinical or radiographic evidence of venous infarct or injury. The postoperative course was uncomplicated, and the patient was discharged home 3 days after cranioplasty. A complete resection of a giant bifrontal PIM with superior sagittal sinus encasement and frontal sinus involvement can be achieved safely via a piecemeal approach without significant intra-operative morbidity.

Clinical and molecular characterization of early-onset colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early-onset CRC that differentiate these patients from patients 50 years old or older. METHODS: Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence. RESULTS: This retrospective review of more than 36,000 patients with CRC showed that early-onset patients were more likely to have microsatellite instability (P = .038), synchronous metastatic disease (P = .009), primary tumors in the distal colon or rectum (P < .0001), and fewer BRAF V600 mutations (P < .001) in comparison with patients 50 years old or older. Patients aged 18 to 29 years had fewer adenomatous polyposis coli (APC) mutations (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35-0.90; P = .015) and an increased prevalence of signet ring histology (OR, 4.89; 95% CI, 3.23-7.39; P < .0001) in comparison with other patients younger than 50 years. In patients younger than 40 years, CMS1 was the most common subtype, whereas CMS3 and CMS4 were uncommon (P = .003). CMS2 was relatively stable across age groups. Early-onset patients with inflammatory bowel disease were more likely to have mucinous or signet ring histology (OR, 5.54; 95% CI, 2.24-13.74; P = .0004) and less likely to have APC mutations (OR, 0.24; 95% CI, 0.07-0.75; P = .019) in comparison with early-onset patients without predisposing conditions. CONCLUSIONS: Early-onset CRC is not only distinct from traditional CRC: special consideration should be given to and further investigations should be performed for both very young patients with CRC (18-29 years) and those with predisposing conditions. The etiology of the high rate of CMS1 in patients younger than 40 years deserves further exploration.

Vascularized Composite Allotransplantation of the Elbow Joint: A Cadaveric Study.

BACKGROUND: Surgical options for the unreconstructable elbow are limited to arthrodesis, total arthroplasty, or osteoarticular allograft reconstruction. Each of these options is limited by severe functional impairment and/or high complication rates. Vascularized allotransplantation of the elbow joint has the potential to mitigate these complications. In this study, we describe our technique for harvesting the elbow for vascularized joint transplantation and demonstrate the flap's vascularity using contrast angiography. METHODS: Anatomical studies were used to design and harvest a vascularized elbow joint flap pedicled on the brachial vessels in 10 cadaveric arms. Diaphyseal blood supply is provided by 3 nutrient arteries, and periarticular supply arises from the various collateral arteries of the arm and recurrent arteries of the forearm. The brachialis and supinator, and their respective nerves, were included as functional muscles because of their intimate association with critical vasculature. Tendinous insertions of the biceps and triceps, as well as the flexor/pronator and extensor origins, were preserved for repair in the transplant recipient. Both lateral arm and radial forearm flaps were preserved to aid in soft tissue inset as well as vascular/immunologic monitoring. Contrast angiography of each dissected specimen was performed to assess the location of the nutrient vessels and assess flap vascularity, as indicated by filling of the critical extraosseous and endosteal vessels. RESULTS: Angiographic imaging of 10 specimens demonstrated that this flap dissection preserves the nutrient endosteal supply to the humeral, radial, and ulnar diaphysis, in addition to the critical extraosseous arterial structures perfusing the elbow joint and periarticular tissues. From proximal to distal, these arteries are the musculoperiosteal radial, posterior branch of the radial collateral, inferior ulnar collateral, recurrent interosseous, radial recurrent, and the anterior and the posterior ulnar recurrent. CONCLUSIONS: Vascularized composite allotransplantation of the elbow joint holds promise as a motion and function preserving option for young, high-demand patients with a sensate and functional hand, who would otherwise be limited by the restrictions of total elbow arthroplasty or fusion. In this study, we propose a flap design and technique for harvest and also offered vascular imaging-based evidence that this flap is adequately vascularized.

EGFR of platelet regulates macrophage activation and bacterial phagocytosis function.

BACKGROUND: Beyond their crucial role in hemostasis, platelets possess the ability to regulate inflammation and combat infections through various mechanisms. Stringent control of macrophage activation is essential during innate immune responses in sepsis. Macrophages are considered crucial phagocytic cells that aid in the elimination of pathogens. Platelet interactions with monocytes-macrophages are known to be significant in the response against bacterial infections, but the primary mediator driving these interactions remains unclear. EGFR plays critical role in the regulation of inflammation and infection through various mechanisms. RESULTS: The overexpression of platelets by thrombopoietin (TPO) leads to the sequestration of both pro-inflammatory (IL-6/IL-1) and anti-inflammatory (IL-10) cytokines in the organ tissue of septic mice. Epidermal growth factor receptor (EGFR) is critical for platelet activation in sepsis. EGFR-licensed platelets enhance macrophage immune function, including the production of reactive oxygen species (ROS) and the clearance of bacteria. Platelet EGFR also induces M1 macrophage polarization by increasing the expression of inducible nitric oxide synthase (iNOS) and CD64. CONCLUSION: EGFR can activate platelet immune function. Moreover, activated platelets efficiently regulate bacterial phagocytosis and pro-inflammatory function of macrophages through an EGFR-dependent pathway.

Targeted muscle reinnervation and regenerative peripheral nerve interfaces for pain prophylaxis and treatment: A systematic review.

OBJECTIVE: Nerve pain frequently develops following amputations and peripheral nerve injuries. Two innovative surgical techniques, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI), are rapidly gaining popularity as alternatives to traditional nerve management, but their effectiveness is unclear. LITERATURE SURVEY: A review of literature pertaining to TMR and RPNI pain results was conducted. PubMed and MEDLINE electronic databases were queried. METHODOLOGY: Studies were included if pain outcomes were assessed after TMR or RPNI in the upper or lower extremity, both for prophylaxis performed at the time of amputation and for treatment of postamputation pain. Data were extracted for evaluation. SYNTHESIS: Seventeen studies were included, with 14 evaluating TMR (366 patients) and three evaluating RPNI (75 patients). Of these, one study was a randomized controlled trial. Nine studies had a mean follow-up time of at least 1 year (range 4-27.6 months). For pain treatment, TMR and RPNI improved neuroma pain in 75%-100% of patients and phantom limb pain in 45%-80% of patients, averaging a 2.4-6.2-point reduction in pain scores on the numeric rating scale postoperatively. When TMR or RPNI was performed prophylactically, many patients reported no neuroma pain (48%-100%) or phantom limb pain (45%-87%) at time of follow-up. Six TMR studies reported Patient-Reported Outcomes Measurement Information System (PROMIS) scores assessing pain intensity, behavior, and interference, which consistently showed a benefit for all measures. Complication rates ranged from 13% to 31%, most frequently delayed wound healing. CONCLUSIONS: Both TMR and RPNI may be beneficial for preventing and treating pain originating from peripheral nerve dysfunction compared to traditional techniques. Randomized trials with longer term follow-up are needed to directly compare the effectiveness of TMR and RPNI with traditional nerve management techniques.

DISSECTING TUMOR TRANSCRIPTIONAL HETEROGENEITY FROM SINGLE-CELL RNA-SEQ DATA BY GENERALIZED BINARY COVARIANCE DECOMPOSITION.

Profiling tumors with single-cell RNA sequencing (scRNA-seq) has the potential to identify recurrent patterns of transcription variation related to cancer progression, and so produce new therapeutically-relevant insights. However, the presence of strong inter-tumor heterogeneity often obscures more subtle patterns that are shared across tumors, some of which may characterize clinically-relevant disease subtypes. Here we introduce a new statistical method to address this problem. We show that this method can help decompose transcriptional heterogeneity into interpretable components - including patient-specific, dataset-specific and shared components relevant to disease subtypes - and that, in the presence of strong inter-tumor heterogeneity, our method can produce more interpretable results than existing widely-used methods. Applied to data from three studies on pancreatic cancer adenocarcinoma (PDAC), our method produces a refined characterization of existing tumor subtypes (e.g. classical vs basal), and identifies a new gene expression program (GEP) that is prognostic of poor survival independent of established prognostic factors such as tumor stage and subtype. The new GEP is enriched for genes involved in a variety of stress responses, and suggests a potentially important role for the integrated stress response in PDAC development and prognosis.

5-HT(1B) autoreceptor regulation of serotonin transporter activity in synaptosomes.

Serotonin-1B (5-HT(1B) ) autoreceptors are located in serotonin (5-HT) terminals, along with serotonin transporters (SERT), and play a critical role in autoregulation of serotonergic neurotransmission and are implicated in disorders of serotonergic function, particularly emotional regulation. SERT modulates serotonergic neurotransmission by high-affinity reuptake of 5-HT. Alterations in SERT activity are associated with increased risk for depression and anxiety. Several neurotransmitter receptors are known to regulate SERT K(m) and V(max) , and previous work suggests that 5-HT(1B) autoreceptors may regulate 5-HT reuptake, in addition to modulating 5-HT release and synthesis. We used rotating disk electrode voltammetry to investigate 5-HT(1B) autoreceptor regulation of SERT-mediated 5-HT uptake into synaptosomes. The selective 5-HT(1B) antagonist SB224289 decreased SERT activity in synaptosomes prepared from wild-type but not 5-HT(1B) knockout mice, whereas SERT uptake was enhanced after pretreatment with the selective 5-HT(1B) agonist CP94253. Furthermore, SERT activity varies as a function of 5-HT(1B) receptor expression-specifically, genetic deletion of 5-HT(1B) decreased SERT function, while viral-mediated overexpression of 5-HT(1B) autoreceptors in rat raphe neurons increased SERT activity in rat hippocampal synaptosomes. Considered collectively, these results provide evidence that 5-HT(1B) autoreceptors regulate SERT activity. Because SERT clearance rate varies as a function of 5-HT(1B) autoreceptor expression levels and is modulated by both activation and inhibition of 5-HT(1B) autoreceptors, this dynamic interaction may be an important mechanism of serotonin autoregulation with therapeutic implications.

Osteoplastic Thumb Reconstruction in the Immediate Setting: A Case Series.

Background: Traumatic thumb amputation can have devastating effects on residual hand function. When replantation is not possible, thumb reconstruction is often performed in a delayed manner and may require multiple stages. Furthermore, reconstruction techniques often require microsurgical skills and equipment, which are not readily available at all institutions. This case series illustrates our technique for immediate osteoplastic thumb reconstruction following traumatic amputation. Methods: This is a case series involving all patients who sustained unreplantable thumb amputations and underwent immediate osteoplastic thumb reconstruction with bone autograft and pedicled groin flap by the senior author from September 2016 through August 2018. Results: Five patients underwent immediate osteoplastic thumb reconstruction during the study period. Total operative time for the initial osteoplastic reconstruction averaged 158 minutes (range 96-290 minutes). In addition to flap division surgery, patients underwent an average of 1.2 revision procedures (range 0-2), primarily for debulking and hardware removal. Patients achieved an average gain in length of 3.3 cm compared with the maximum anticipated length with revision amputation at the time of injury, and had stable clinical outcomes for a minimum of 12 months. Conclusions: Osteoplastic thumb reconstruction is a useful technique for thumb reconstruction for select patients following traumatic thumb amputation. Advantages of this approach include shorter overall operative times and hospital length of stay, minimal donor site morbidity, and a straightforward, reproducible technique.

Surface Electromyography-Driven Therapeutic Gaming for Rehabilitation of Upper Extremity Weakness: A Pilot Study.

SUMMARY: In patients with severe upper extremity weakness that may result from peripheral nerve injuries, stroke, and spinal cord injuries, standard therapy in the earliest stages of recovery consists primarily of passive rather than active exercises. Adherence to prescribed therapy may be poor, which may contribute to suboptimal functional outcomes. The authors have developed and integrated a custom surface electromyography device with a video game to create an interactive, biofeedback-based therapeutic gaming platform. Sensitivity of the authors' custom surface electromyography device was evaluated with simultaneous needle electromyography recordings. Testing of this therapeutic gaming platform was conducted with a single 30-minute gameplay session in 19 patients with a history of peripheral nerve injury, stroke, spinal cord injury, and direct upper extremity trauma, including 11 patients who had undergone nerve and/or tendon transfers. The device was highly sensitive in detecting low levels of voluntary muscle activation and was used with 10 distinct muscles of the arm, forearm, and hand. Nerve and tendon transfer patients successfully activated the donor nerve/muscle and elicited the desired movement to engage in gameplay. On surveys of acceptability and usability, patients felt the system was enjoyable, motivating, fun, and easy to use, and their hand therapists expressed similar enthusiasm. Surface electromyography-based therapeutic gaming is a promising approach to rehabilitation that warrants further development and investigation to examine its potential efficacy, not only for building muscle strength and endurance but also for facilitating motor relearning after nerve and tendon transfer surgical procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Responses of soil respiration and microbial community structure to fertilizer and irrigation regimes over 2 years in temperate vineyards in North China.

Fertilizer and irrigation regimes can profoundly affect soil carbon (C) emissions, which influence soil organic carbon (SOC) storage. However, information regarding the effects of fertilizer and irrigation management on the components of soil respiration (Rs) and the underlying microbial community characteristics in vineyard ecosystems remains limited. Therefore, a 2-year field experiment was conducted in a wine-grape vineyard (WGV) and a table-grape vineyard (TGV). Each vineyard included two fertilizer and irrigation regimes: farmers' practice (FP) and recommended practice (RP). The trenching method was employed to separate Rs into heterotrophic respiration (Rh) and autotrophic respiration (Ra). Additionally, the SOC storage and soil microbial community structure at 0-20 cm soil depth were determined after the 2-year experiment. The results showed that the fertilizer and irrigation regimes caused no effect on Ra. Compared with the FP treatment in WGV and TGV, the RP treatment significantly (P < 0.05) decreased the average daily Rh by 15.13 % and 17.11 %, which contributed to the annual Rs values at the whole-vineyard scale decreased by 8.93 % and 11.78 %, respectively. Besides, compared with the initial value, the SOC storage under RP treatment were effectively increased by 6.39 % and 6.33 % in WGV and TGV, respectively. Low annual total Rh was partially ascribed to the significant (P < 0.05) decline in Proteobacteria and Bacteroidetes relative abundance, thus reducing the decomposition rate of SOC. Compared with WGV, the fertilizer and water input was higher in the TGV, which resulted in the annual total Rs and Rh values at the whole-vineyard scale was increased by 11.53 % and 15.74 %, respectively, while the annual total Ra was decreased by 18.83 % due to the lower grapevine density and more frequent summer pruning. Overall, RP treatment was found to be a suitable strategy for reducing soil C emissions and benefiting SOC storage in vineyards around North China.

Nonsurgical Approaches to Neuroma Management.

Symptomatic neuromas and chronic neuropathic pain are significant problems affecting patients' quality of life and independence that are challenging to treat. These symptoms are due to structural and functional changes that occur peripherally within neuromas, as well as alterations that occur centrally within the brain and spinal cord. A multimodal approach is most effective, with goals to minimize opioid use, to capitalize on the synergistic effects of nonopioid medications and to explore potential benefits of novel adjunctive treatments.

OryzaGP 2021 update: a rice gene and protein dataset for named-entity recognition.

Due to the rapid evolution of high-throughput technologies, a tremendous amount of data is being produced in the biological domain, which poses a challenging task for information extraction and natural language understanding. Biological named entity recognition (NER) and named entity normalisation (NEN) are two common tasks aiming at identifying and linking biologically important entities such as genes or gene products mentioned in the literature to biological databases. In this paper, we present an updated version of OryzaGP, a gene and protein dataset for rice species created to help natural language processing (NLP) tools in processing NER and NEN tasks. To create the dataset, we selected more than 15,000 abstracts associated with articles previously curated for rice genes. We developed four dictionaries of gene and protein names associated with database identifiers. We used these dictionaries to annotate the dataset. We also annotated the dataset using pre-trained NLP models. Finally, we analysed the annotation results and discussed how to improve OryzaGP.

Targeted Peripheral Nerve Interface: Case Report with Literature Review.

Nerve transection injuries can result in painful neuromas that adversely affect patient recovery. This is especially significant following amputation surgeries in the setting of prosthetic wear and function. Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface (RPNI) are 2 modern surgical techniques that provide neuromuscular targets for these transected nerve endings to reinnervate. These strategies have been previously shown to reduce phantom limb pain, residual limb pain, and neuroma-related pain.1,2,7,11 Two recent articles described technical adaptations of combining targeted muscle reinnervation and RPNI to create a hybrid procedure.3,12 In this article, we propose a different modification of targeted muscle reinnervation and RPNI, where the transected nerve stump is coapted to a recipient unit consisting of an intact distal nerve branch with its associated muscle graft. We called this recipient unit a targeted peripheral nerve interface because it contains a distal nerve branch for nerve coaptation and can guide axonal regeneration from the donor nerve to its target muscle graft. We theorize that targeted peripheral nerve interface may lead to more even distribution of regenerating axons with potentially less pain and stronger signals for prosthetic control when compared with standard RPNI.

Closed Ring Avulsion Injury With Isolated Arterial Insufficiency.

Ring avulsion injuries are an uncommon, often catastrophic, pattern of digit injuries that result from sudden traction onto a ring-bearing digit. The reconstructive treatment of these injuries can be complex because of the characteristic involvement of nerves, muscles, vasculature, and bone. There is paucity of literature describing isolated arterial injuries in the absence of overlying soft tissue and underlying bone involvement. We present an unusual case of a closed ring avulsion injury, wherein a patient initially presented to his local urgent care center with a cool and pale digit without wounds or fractures, and abnormal pulse oximetry readings prompted his transfer to a tertiary care center for further evaluation. Surgical exploration demonstrated isolated disruption of both digital arteries and the preservation of both digital nerves. The digit was successfully revascularized with venous autografting and stripping of arterial thrombi.

Occult primary breast cancer presenting with brachial plexopathy: A case report.

Breast cancer affects about one in eight women over the course of her lifetime. Occult breast cancer, in which primary breast cancer is detected without evidence of disease in the breast itself, comprises up to 1% of new diagnoses; this is typically detected from abnormal axillary lymph nodes, and distant metastases are rare. Here, we present an unusual case of occult breast cancer presenting as upper extremity pain, edema, and weakness, with a metastatic mass to the brachial plexus being the only site of disease.

Development and Validation of a Gene Signature Classifier for Consensus Molecular Subtyping of Colorectal Carcinoma in a CLIA-Certified Setting.

PURPOSE: Consensus molecular subtyping (CMS) of colorectal cancer has potential to reshape the colorectal cancer landscape. We developed and validated an assay that is applicable on formalin-fixed, paraffin-embedded (FFPE) samples of colorectal cancer and implemented the assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. EXPERIMENTAL DESIGN: We performed an in silico experiment to build an optimal CMS classifier using a training set of 1,329 samples from 12 studies and validation set of 1,329 samples from 14 studies. We constructed an assay on the basis of NanoString CodeSets for the top 472 genes, and performed analyses on paired flash-frozen (FF)/FFPE samples from 175 colorectal cancers to adapt the classifier to FFPE samples using a subset of genes found to be concordant between FF and FFPE, tested the classifier's reproducibility and repeatability, and validated in a CLIA-certified laboratory. We assessed prognostic significance of CMS in 345 patients pooled across three clinical trials. RESULTS: The best classifier was weighted support vector machine with high accuracy across platforms and gene lists (>0.95), and the 472-gene model outperforming existing classifiers. We constructed subsets of 99 and 200 genes with high FF/FFPE concordance, and adapted FFPE-based classifier that had strong classification accuracy (>80%) relative to "gold standard" CMS. The classifier was reproducible to sample type and RNA quality, and demonstrated poor prognosis for CMS1-3 and good prognosis for CMS2 in metastatic colorectal cancer (P < 0.001). CONCLUSIONS: We developed and validated a colorectal cancer CMS assay that is ready for use in clinical trials, to assess prognosis in standard-of-care settings and explore as predictor of therapy response.