Treatment of Symptomatic Lymphedema in the Hand with Omental Flow-through Flap.

Vascularized lymph node transfer (VLNT) is a surgical option to improve physiologic lymphatic drainage. This technique transfers healthy vascularized lymphatic tissue from various available donor sites to the existing lymphatics of the affected area. Here, we present a successful case halting the size progression and reversing lymphedema symptoms in a patient treated with vascularized omental lymph node transfer. A 56-year-old man presented with stage III malignant sarcoma of his left medial upper arm. Two-years after excision, flap reconstruction, and radiation brachytherapy, worsening diffuse left arm edema developed, causing pain, decreased range of motion, and paresthesia. A vascularized omental lymph node transfer was performed. The omental flap required a flow-through design, requiring anastomosis of both gastroepiploic arteries to obtain Dopplerable signals. The patient experienced progressive relief of lymphedema symptoms after this transfer. Treatment outcomes with the use of VLNT have been largely encouraging; however, objective measures of improvement and timing of neolymphangiogenesis in recipient lymph node sites still need to be defined. Understanding omental VLNT flow dynamics and expected time point changes during the postoperative course will define expected outcomes and allow for treatment of a greater number of patients affected by lymphedema.

A Quantitative Systematic Review of Clinical Outcome Measure Use in Peripheral Nerve Injury of the Upper Limb.

BACKGROUND: Peripheral nerve injury (PNI) is common, leading to reduced function, pain, and psychological impact. Treatment has not progressed partly due to inability to compare outcomes between centers managing PNI. Numerous outcome measures exist but there is no consensus on which outcome measures to use nor when. OBJECTIVE: To perform a systematic review in order to describe and classify outcome measures used in PNI. METHODS: A search of Ovid Medline, Ovid Embase, Allied and Complementary Medicine Database (AMED), and CENTRAL (Cochrane Clinical Trials) was conducted. Randomized control trials (RCTs), cohort studies, and case-controlled and case series (≥5 participants) published from inception of the database until 2019 investigating adult patients with a traumatic upper limb PNI in which an outcome measurement was utilized were included. RESULTS: A total of 96 studies were included (15 RCTs, 8 case-control studies, 18 cohort studies, 5 observational studies, and the remainder were case series or retrospective reviews). A total of 56 individual outcome measures were identified, utilized across 28 different countries and 7097 patients. Ten core domains were defined: sensory subjective, sensory objective, motor subjective, motor objective, sensorimotor function, psychology and well-being, disability, quality of life, pain and discomfort, and neurotrophic measures. CONCLUSION: Lack of consensus on outcome measure use hinders comparison of outcomes between nerve injury centers and the development of novel treatments. Development of a core outcome set will help standardize outcome reporting, improve translation of novel treatments from lab to clinical practice, and ensure future research in PNI is more amenable to systematic review and meta-analysis.

Genomic characterisation of the effector complement of the potato cyst nematode Globodera pallida.

BACKGROUND: The potato cyst nematode Globodera pallida has biotrophic interactions with its host. The nematode induces a feeding structure - the syncytium - which it keeps alive for the duration of the life cycle and on which it depends for all nutrients required to develop to the adult stage. Interactions of G. pallida with the host are mediated by effectors, which are produced in two sets of gland cells. These effectors suppress host defences, facilitate migration and induce the formation of the syncytium. RESULTS: The recent completion of the G. pallida genome sequence has allowed us to identify the effector complement from this species. We identify 128 orthologues of effectors from other nematodes as well as 117 novel effector candidates. We have used in situ hybridisation to confirm gland cell expression of a subset of these effectors, demonstrating the validity of our effector identification approach. We have examined the expression profiles of all effector candidates using RNAseq; this analysis shows that the majority of effectors fall into one of three clusters of sequences showing conserved expression characteristics (invasive stage nematode only, parasitic stage only or invasive stage and adult male only). We demonstrate that further diversity in the effector pool is generated by alternative splicing. In addition, we show that effectors target a diverse range of structures in plant cells, including the peroxisome. This is the first identification of effectors from any plant pathogen that target this structure. CONCLUSION: This is the first genome scale search for effectors, combined to a life-cycle expression analysis, for any plant-parasitic nematode. We show that, like other phylogenetically unrelated plant pathogens, plant parasitic nematodes deploy hundreds of effectors in order to parasitise plants, with different effectors required for different phases of the infection process.

Bioinformatic analysis of expression data to identify effector candidates.

Pathogens produce effectors that manipulate the host to the benefit of the pathogen. These effectors are often secreted proteins that are upregulated during the early phases of infection. These properties can be used to identify candidate effectors from genomes and transcriptomes of pathogens. Here we describe commonly used bioinformatic approaches that (1) allow identification of genes encoding predicted secreted proteins within a genome and (2) allow the identification of genes encoding predicted secreted proteins that are upregulated at important stages of the life cycle. Other approaches for bioinformatic identification of effector candidates, including OrthoMCL analysis to identify expanded gene families, are also described.

Immunosuppressive effects of the traditional Chinese herb Qu Mai on human alloreactive T cells.

Current therapies for transplant rejection are suboptimally effective. In an effort to discover novel immunosuppressants we used cytokine ELISPOT and ELISAs to screen extracts from 53 traditional Chinese herbs for their ability to suppress human alloreactive T cells. We identified a dichloromethane-soluble fraction (Qu Mai fraction AD [QMAD]) of Qu Mai (Dianthus superbus) as a candidate. High-performance liquid chromatography (HPLC) analysis of QMAD revealed three dominant peaks, each with a MW ~600 Daltons and distinct from cyclosporine and rapamycin. When we added QMAD to human mixed lymphocyte cultures, we observed dose-dependent inhibition of proliferation and IFNγ production, by naïve and memory alloreactive T cells, and observed an increased frequency of Foxp3(+) CD4(+) T cells. To address whether QMAD induces regulatory T cells we added QMAD to anti-CD3/CD28-stimulated naïve CD4 T cells and observed a dose-dependent upregulation of Foxp3 associated with new suppressive capacity. Mechanistically, QMAD did not induce T cell IL-10 or TGFß but blocked T cell AKT phosphorylation, a key signaling nexus required for T cell proliferation and expansion, that simultaneously prevents Foxp3 transcription. Our findings provide novel insight into the antiinflammatory effects of one traditional Chinese herb, and support the need for continued isolation, characterization and testing of QMAD-derived components as immune suppressants for transplant rejection.