Global Metabolomics in Allogeneic Hematopoietic Cell Transplantation Recipients Discordant for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

A systematic review of direct oral anticoagulant use in chronic kidney disease and dialysis patients with atrial fibrillation.

Background: There is a lack of clear benefit and a potential risk of bleeding with direct oral anticoagulant (DOAC) use in chronic kidney disease (CKD) and dialysis patients with atrial fibrillation. The objective of this study was to evaluate how treatment with DOACs affects stroke and bleeding outcomes compared with warfarin or aspirin. Methods: We conducted a systematic review of randomized controlled trials, cohort studies and case series, and searched electronic databases from 1946 to 2017. Studies evaluating stroke and bleeding outcomes with DOAC use in CKD and dialysis patients were included. Results: From 8008 studies, 10 met the inclusion criteria. For moderate CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2), there was no difference in stroke outcomes between dabigatran 110 mg [hazard ratio (HR) 0.78, 95% confidence interval (95% CI) 0.51-1.21], rivaroxaban (HR 0.82-0.84, 95% CI 0.25-2.69) and edoxaban (HR 0.87, 95% CI 0.65-1.18) versus warfarin. Dabigatran (150 mg twice daily) and apixaban reduced risk of stroke or systemic embolism significantly more than warfarin for moderate CKD patients (HR 0.55, 95% CI 0.34-0.89 and HR 0.61, 95% CI 0.39-0.94, respectively). Edoxaban and apixaban were associated with reduced major bleeding events (HR 0.50-0.76) compared with warfarin. Rivaroxaban and dabigatran 110 mg and 150 mg showed no significant difference in major bleeding versus warfarin. In hemodialysis (HD) patients, there was no difference in stroke outcomes between apixaban, dabigatran [relative risk (RR) 1.71, 95% CI 0.97-2.99] or rivaroxaban (RR 1.8, 95% CI 0.89-3.64) versus warfarin. In HD patients, rivaroxaban and dabigatran were associated with an increased major bleeding risk (RR 1.45-1.76), whereas there was no major bleeding difference with apixaban compared to warfarin. Limitations: The heterogeneity of major bleeding and stroke definitions of the 10 included studies. Conclusions: Clinicians should continue to weigh the risk of stroke versus bleeding before prescribing DOACs in the CKD and dialysis population.

Primary Cutaneous Anaplastic Large Cell Lymphoma With Gastric Metastasis.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a subtype of non-Hodgkin lymphoma (NHL) that is localized to the skin. Disseminated disease is rare, and visceral organ involvement is even more so. We report a unique case of PCALCL with gastric metastasis. A 75-year-old man with a history of cutaneous left lower extremity PCALCL status post radiation therapy initially presented with abdominal pain and was found to have diffuse celiac axis and retroperitoneal lymphadenopathy. Endoscopy, initially done to biopsy an involved lymph node (LN), demonstrated a friable gastric nodular lesion with telangiectasias. Biopsy of the lesion and LN revealed anaplastic large cell lymphoma, identical in pathology to the known skin lesion. The patient was treated with systemic chemotherapy with a good response. PCALCL has been thought of as a localized malignancy with a good prognosis and low potential for extracutaneous spread. To our knowledge, this is the first instance of metastatic PCALCL involving the stomach.

Metabolomic Differentials in Women With and Without Fibromyalgia.

A nontargeted plasma metabolomic analysis was conducted to compare differentially expressed metabolites in women with and without fibromyalgia (FM) using data and samples collected from two parent studies in women with FM (n = 20) and comparative data collected from newly recruited age-matched women (n = 20). Blood plasma samples were analyzed for metabolite content using liquid chromatography mass spectrometry. Consolidation of positive and negative ion mode metabolomics data with fold change (>2 or <0.5) and variable importance of projection scores ≥1 revealed statistically significant metabolites comparing samples from women with and without FM. Metabolite profiles in patients with FM differed from the comparison group in energy, lipid and amino acid metabolites reflecting heightened oxidative stress, inflammation, and tryptophan degradation in patients with FM. Study results may contribute to further identification of unique metabolomic profiles enhancing understanding of the pathophysiology of FM and for the development of effective therapeutic options.

Low Incidence of Neurovascular Complications After Placement of Proximal Tibial Traction Pins.

Skeletal tibial traction is a temporizing measure used preoperatively for femoral fractures to improve the length and alignment of the limb and provide pain relief. The goal of this study was to identify possible neurovascular morbidity associated with the use of bedside skeletal tibial traction to treat femur fractures. All femoral fractures treated with proximal tibial traction during a 10-year period at an urban level I trauma center were retrospectively reviewed. The medical record was reviewed to determine whether a pin-related complication had occurred. Records also were reviewed to identify ipsilateral multi-ligamentous knee injuries that were not diagnosed until after the application of traction. In total, 303 proximal tibial traction pins were placed. A total of 7 (2.3%; 95% confidence interval, 0.60%-4.0%) pin-related neurologic complications and zero vascular complications were noted. All complications involved motor and/or sensory deficits in the distribution of the peroneal nerve. Of the 7 complications, 6 resolved fully after surgery and removal of the pin. After traction placement, 6 (2.0%) ipsilateral multiligamentous knee injuries were diagnosed. None of these patients had a neurovascular complication. This study suggests that bedside placement of proximal tibial traction for femoral fractures is associated with a low incidence of neurovascular complications and that traction can be safely placed at the bedside by residents. A thorough neurovascular examination should be performed before insertion, and care should be taken to identify the proper starting point and reduce soft tissue trauma during pin placement. [Orthopedics. 2017; 40(6):e1004-e1008.].