Risk Factors for Secondary Revision After Finger Amputations.

BACKGROUND: Digit amputations are relatively simple and are often performed in the setting of trauma or infection. However, it is not uncommon for digit amputations to undergo secondary revision due to complications or patient dissatisfaction. Identifying factors associated with secondary revision may alter treatment strategy. We hypothesize that the secondary revision rate is affected by digit, initial level of amputation, and comorbidities. METHODS: A retrospective chart review was conducted on patients undergoing digit amputations in operating rooms at our institution from 2011 to 2017. Secondary revision amputations were defined as a separate return to the operating room following initial surgical amputation, excluding emergency room amputations. Patient demographics, comorbidities, level of amputation, and complications were collected. RESULTS: In all, 278 patients were included with a total of 386 digit amputations and mean follow-up of 2.6 months. Three hundred twenty-six primary digit amputations were performed in 236 patients (group A). Sixty digits were secondarily revised in 42 patients (group B). The secondary revision rate was 17.8% for patients and 15.5% for digits. Patients with heart disease and diabetes mellitus were associated with secondary revision, with wound complications being the leading indication overall (73.8%). Medicare covered 52.4% of patients in group B versus 30.1% in group A (P = .005). CONCLUSION: Risk factors for secondary revision include Medicare insurance, comorbidities, previous digit amputations, and initial amputation of either the index finger or the distal phalanx. These data may serve as a prediction model to aid surgical decision-making by identifying patients at risk of secondary revision amputation.

Metaanalysis Reveals Genetic Correlates of Osteoporosis Pathogenesis.

OBJECTIVE: Osteoporosis is a growing healthcare burden. By identifying osteoporosis-promoting genetic variations, we can spotlight targets for new pharmacologic therapies that will improve patient outcomes. In this metaanalysis, we analyzed mesenchymal stem cell (MSC) biomarkers in patients with osteoporosis. METHODS: We employed our Search Tag Analyze Resource for the Gene Expression Omnibus (STARGEO) platform to conduct a metaanalysis to define osteoporosis pathogenesis. We compared 15 osteoporotic and 14 healthy control MSC samples. We then analyzed the genetic signature in Ingenuity Pathway Analysis. RESULTS: The top canonical pathways identified that were statistically significant included the serine peptidase inhibitor kazal type 1 pancreatic cancer pathway, calcium signaling, pancreatic adenocarcinoma signaling, axonal guidance signaling, and glutamate receptor signaling. Upstream regulators involved in this disease process included ESR1, dexamethasone, CTNNß1, CREB1, and ERBB2. CONCLUSION: Although there has been extensive research looking at the genetic basis for inflammatory arthritis, very little literature currently exists that has identified genetic pathways contributing to osteoporosis. Our study has identified several important genes involved in osteoporosis pathogenesis including ESR1, CTNNß1, CREB1, and ERBB2. ESR1 has been shown to have numerous polymorphisms, which may play a prominent role in osteoporosis. The Wnt pathway, which includes the CTNNß1 gene identified in our study, plays a prominent role in bone mass regulation. Wnt pathway polymorphisms can increase susceptibility to osteoporosis. Our analysis also suggests a potential mechanism for ERBB2 in osteoporosis through Semaphorin 4D (SEMA4D). Our metaanalysis identifies several genes and pathways that can be targeted to develop new anabolic drugs for osteoporosis treatment.

Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis.

AIMS: Dermatomyositis (DM) is a progressive, idiopathic inflammatory myopathy with poorly understood pathogenesis. A hallmark of DM is an increased risk for developing breast, ovarian, and lung cancer. Since autoantibodies against anti-TIF-1-γ, a member of the tripartite motif (TRIM) proteins, has a strong association with malignancy, we examined expression of the TRIM gene family to identify pathways that may be contributing to DM pathogenesis. MATERIALS AND METHODS: We employed the Search Tag Analyze Resource for GEO platform to search the NCBI Gene Expression Omnibus to elucidate TRIM family gene expression as well as oncogenic drivers in DM pathology. We conducted meta-analysis of the data from human skin (60 DM vs 34 healthy) and muscle (71 DM vs 22 healthy). KEY FINDINGS: We identified genes involved in innate immunity, antigen presentation, metabolism, and other cellular processes as facilitators of DM disease activity and confirmed previous observations regarding the presence of a robust interferon signature. Moreover, analysis of DM muscle samples revealed upregulation of TRIM14, TRIM22, TRIM25, TRIM27, and TRIM38. Likewise, analysis of DM skin samples showed upregulation of TRIM5, TRIM6, TRIM 14, TRIM21, TRIM34, and TRIM38 and downregulation of TRIM73. Additionally, we noted upregulation of oncogenes IGLC1, IFI44, POSTN, MYC, NPM1, and IDO1 and related this change to interferon signaling. While the clinical data associated with genetic data that was analyzed did not contain clinical data regarding malignancy in these cohorts, the observed genetic changes may be associated with homeostatic and signaling changes that relate to the increased risk in malignancy in DM. SIGNIFICANCE: Our results implicate previously unknown genes as potential drivers of DM pathology and suggest certain TRIM family members may have disease-specific roles with potential diagnostic and therapeutic implications.

Impact of Casting and Splinting Manipulations on Below-Dressing Pressures: An Experimental Model.

BACKGROUND: We tested how different applications of casts and splints affect underlying below-dressing pressures and how these dressings respond to swelling. METHODS: A 3-in polyvinyl chloride pipe with an attached 100 mL saline bag to the outer surface was used to simulate a human forearm. A pressure transducer was attached to the bag and connected to a monitor providing continuous pressure measurements. Either a circumferential fiberglass cast or single-sided plaster splint was applied around the bag. To simulate the dressing's compliance to soft tissue swelling, change in pressure was measured after 25 mL of saline was injected into the bag. Compliance was determined by calculating change in volume over change in pressure as volume was added. RESULTS: In our 150 mL model, cast bivalving reduced pressure up to 28%, and splitting the cotton padding of a splint reduced pressures up to 33%. The mean compliance (ability to accommodate swelling) across all volume intervals was 182% greater in a bivalved cast versus a cast and 21% greater in a cotton-split splint versus a splint. Below-dressing pressure of a tightly wrapped elastic bandage was up to 2.76× greater than a medium tension bandage and up to 6.44× greater than a loosely applied bandage. A splint with real cotton padding had a 28% greater pressure than a splint with synthetic soft-roll padding. CONCLUSIONS: Splitting a dressing, utilizing synthetic cotton padding, and applying an elastic bandage cautiously can help reduce surface pressures and allow the construct to be more accommodating to soft tissue swelling.

Prophylactic muscle flap reconstruction after complex spine surgery for degenerative disease: case series and institutional protocol.

BACKGROUND: Wound complications can occur in up to 20% of patients following multilevel posterior spinal fusion. Currently, the use of local flaps has been reported in high-risk patients with a history of spinal neoplasm, radiation therapy, exposed hardware, multiple spine surgeries, or wound infections. However, there are no reports of prophylactic muscle flap wound closure in patients undergoing multi-level spinal fusion for degenerative pathology. Given the extensive soft tissue dissection for exposure compounded by patient comorbidities, there is potential to minimize the risk of wound complications with prophylactic trapezius and/or paraspinal flap coverage. We sought to describe the utility and outcomes of prophylactic muscle flaps for wound coverage after instrumented posterior spinal fusion for multi-level degenerative spine disease and spinal deformity. METHODS: An institutional review board (IRB)-approved retrospective review of 26 consecutive patients who underwent a multi-level posterior spinal fusion for degenerative pathology with concurrent muscle flap coverage at a single institution (August 2016 to February 2017) was done. Patient demographics, clinical profile, procedures, and outcomes at a minimum 6-month post-operatively have been described. RESULTS: Patients had a mean age of 59.7±13.0 years with a mean body mass index (BMI) of 31.0±8.6 kg/m2. Paraspinous muscle flap (61.5%), trapezius (3.8%), and combination flaps (34.6%) were used for coverage of an average wound defect of 325 cm2 extending over average 10.2 vertebral levels. All wounds healed completely with no complications at an average of 9.1 months follow-up. Only 1 patient (3.8%) developed a seroma for which interventional radiology (IR)-drainage was sufficient. CONCLUSIONS: Prophylactic trapezius and/or paraspinous muscle flap coverage using a team approach can reduce the risk of wound complications after extensive spinal fusion for multi-level degenerative disease or adult spinal deformity (ASD). Preliminary results from our institution suggest that routine use of such a protocol has the potential to improve quality of care and reduce healthcare expenditure associated with this relatively morbid procedure.

Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics.

Adenosine Monophosphate-Activated Protein Kinase or AMPK is a highly-conserved master-regulator of numerous cellular processes, including: Maintaining cellular-energy homeostasis, modulation of cytoskeletaldynamics, directing cell growth-rates and influencing cell-death pathways. AMPK has recently emerged as a promising molecular target in cancer therapy. In fact, AMPK deficiencies have been shown to enhance cell growth and proliferation, which is consistent with enhancement of tumorigenesis by AMPK-loss. Conversely, activation of AMPK is associated with tumor growth suppression via inhibition of the Mammalian Target of Rapamycin Complex-1 (mTORC1) or the mTOR signal pathway. The scientific communities' recognition that AMPK-activating compounds possess an anti-neoplastic effect has contributed to a rush of discoveries and developments in AMPK-activating compounds as potential anticancer-drugs. One such example is the class of compounds known as Biguanides, which include Metformin and Phenformin. The current review will showcase natural compounds and their derivatives that activate the AMPK-complex and signaling pathway. In addition, the biology and history of AMPK-signaling and AMPK-activating compounds will be overviewed, their anticancer-roles and mechanisms-of-actions will be discussed, and potential strategies for the development of novel, selective AMPK-activators with enhanced efficacy and reduced toxicity will be proposed.