Implant Prophylaxis: The Next Best Practice Toward Asepsis in Spine Surgery.

Study designA literature review.ObjectivesAn evaluation of the contaminants prevalent on implants used for surgery and the aseptic methods being employed against them.MethodsPubMed was searched for articles published between 2000 and 2017 for studies evaluating the contaminants present on spine implants, and associated pre- and intraoperative implant processing and handling methodology suggested to avoid them. Systematic reviews, observational studies, bench-top studies, and expert opinions were included.ResultsEleven studies were identified whose major focus was the asepsis of implants to reduce the incidence of surgical site infection incidences during surgery. These studies measured the colony forming units of bacteria on sterilized implants and/or gloves from the surgeon, scrub nurse, and assistants, as well as reductions of surgical site infection rates in spine surgery due to changes in implant handling techniques. Additionally, the search included assessments of endotoxins and carbohydrates present on reprocessed implants. The suggested changes to surgical practice based on these studies included handling implants with only fresh gloves, keeping implants covered until the immediate time of use, reducing operating room traffic, avoiding reprocessing of implants (ie, providing terminally sterilized implants), and avoiding touching the implants altogether.ConclusionsBoth reprocessing (preoperative) and handling (intraoperative) of implants seem to lead to contamination of sterilized implants. Using a terminally sterilized device may mitigate reprocessing (preoperative implant prophylaxis), whereas the use of fresh gloves for handling each implant and/or a permanent shielding technique (intraoperative implant prophylaxis) could potentially avoid recontamination at the theatre

Possible Association between Expression of Chemokine Receptor-2 (CCR2) and Amyotrophic Lateral Sclerosis (ALS) Patients of North India

BACKGROUND AND OBJECTIVES: We earlier reported elevated chemokine ligand-2 (CCL2) in Indian amyotrophic lateral sclerosis (ALS) patients. We now analysed chemokine receptor-2 (CCR2), the receptor of CCL2, in these ALS patients. METHODS: Indian sporadic ALS patients (n=50) were included on the basis of El Escorial criteria. Percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. Real Time Polymerase Chain Reaction (PCR) was used to quantitate CCR2 mRNA expression in PBMCs. Normal controls (n = 40) were also included for comparison. RESULTS: Flow Cytometry revealed significantly reduced CCR2 expressing PBMCs in the ALS patients. We also found a significant decline in number of CCR2 expressing PBMCs in limb onset ALS when compared to bulbar onset ALS. PBMCs from ALS patients showed substantial down-regulation of CCR2 mRNA. CCR2 mRNA expression was found to be decreased among limb ALS patients as compared to bulbar onset ALS. Further, the count of CCR2+ PBMCs and CCR2 mRNA transcript in PBMCs was significantly lower in severe and moderate ALS as compared to ALS patients with mild impairments. CONCLUSIONS: Downregulation of PBMCs CCR2 may indicate its etio-pathological relevance in ALS pathogenesis. Reduced PBMCs CCR2 may result in decreased infiltration of leukocytes at the site of degeneration as a compensatory response to ALS. CCR2 levels measurements in hematopoietic stem cells and estimation of comparative PBMCs count among ALS, disease controls and normal controls can unveil its direct neuroprotective role. However, the conclusions are restricted by the absence of neurological/non-neurological disease controls in the study

Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral sclerosis patients

<p>Abstract</p> <p>Background</p> <p>We have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset.</p> <p>Methods</p> <p>VEGF-A and CCL2 mRNA levels were measured in peripheral blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50). Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.</p> <p>Results</p> <p>VEGF-A and CCL2 mRNA levels were found to be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs from definite ALS revealed higher VEGF-A mRNA expression as compared to probable and possible ALS. CCL2 mRNA levels were found to be unaltered when definite, probable and possible ALS were compared. PBMCs from patients with respiratory dysfunction showed much higher VEGF-A and CCL2 elevation when compared to patients without respiratory dysfunction. No association of smoking, alcohol and meat consumption with VEGF-A and CCL2 was observed after analyzing the data with univariate and multivariate analysis.</p> <p>Conclusion</p> <p>VEGF-A and CCL2 mRNA upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological association with ALS pathogenesis. The cross-cultural and cross-ethnic investigations of these molecules could determine if they have any role in enhancing the mean survival time unique to Indian ALS patients.</p

Is There a Patient Profile That Characterizes a Patient With Adult Spinal Deformity as a Candidate for Minimally Invasive Surgery?

Study designRetrospective review.ObjectivesThe goal of this study was to evaluate the baseline characteristics of patients chosen to undergo traditional open versus minimally invasive surgery (MIS) for adult spinal deformity (ASD).MethodsA multicenter review of 2 databases including ASD patients treated with surgery. Inclusion criteria were age &gt;45 years, Cobb angle minimum of 20°, and minimum 2-year follow-up. Preoperative radiographic parameters and disability outcome measures were reviewed.ResultsA total of 350 patients were identified: 173 OPEN patients and 177 MIS. OPEN patients were significantly younger than MIS patients (61.5 years vs 63.74 years, P = .013). The OPEN group had significantly more females (87% vs 76%, P = .006), but both groups had similar body mass index. Preoperative lumbar Cobb was significantly higher for the OPEN group (34.2°) than for the MIS group (26.0°, P &lt; .001). The mean preoperative Oswestry Disability Index was significantly higher in the MIS group (44.8 in OPEN patients and 49.8 in MIS patients, P &lt; .011). The preoperative Numerical Rating Scale value for back pain was 7.2 in the OPEN group and 6.8 in the MIS group preoperatively, P = .100.ConclusionsPatients chosen for MIS for ASD are slightly older and have smaller coronal deformities than those chosen for open techniques, but they did not have a substantially lesser degree of sagittal malalignment. MIS surgery was most frequently utilized for patients with an sagittal vertical axis under 6 cm and a baseline pelvic incidence and lumbar lordosis mismatch under 30°

Early and Late Reoperation Rates With Various MIS Techniques for Adult Spinal Deformity Correction.

Study designA multicenter retrospective review of an adult spinal deformity database.ObjectiveWe aimed to characterize reoperation rates and etiologies of adult spinal deformity surgery with circumferential minimally invasive surgery (cMIS) and hybrid (HYB) techniques.MethodsInclusion criteria were age ≥18 years, and one of the following: coronal Cobb &gt;20°, sagittal vertical axis &gt;5 cm, pelvic tilt &gt;20°, and pelvic incidence-lumbar lordosis &gt;10°. Patients with either cMIS or HYB surgery, ≥3 spinal levels treated with 2-year minimum follow-up were included.ResultsA total of 133 patients met inclusion for this study (65 HYB and 68 cMIS). Junctional failure (13.8%) was the most common reason for reoperation in the HYB group, while fixation failure was the most common reason in the cMIS group (14.7%). There was a higher incidence of proximal junctional failure (PJF) than distal junctional failure (DJF) within HYB (12.3% vs 3.1%), but no significant differences in PJF or DJF rates when compared to cMIS. Early (&lt;30 days) reoperations were less common (cMIS = 1.5%; HYB = 6.1%) than late (&gt;30 days) reoperations (cMIS = 26.5%; HYB = 27.7%), but early reoperations were more common in the HYB group after propensity matching, largely due to infection rates (10.8% vs 0%, P = .04).ConclusionsAdult spinal deformity correction with cMIS and HYB techniques result in overall reoperation rates of 27.9% and 33.8%, respectively, at minimum 2-year follow-up. Junctional failures are more common after HYB approaches, while pseudarthrosis/fixation failures happen more often with cMIS techniques. Early reoperations were less common than later returns to the operating room in both groups, but cMIS demonstrated less risk of infection and early reoperation when compared with the HYB group

Treatment of the Fractional Curve of Adult Scoliosis With Circumferential Minimally Invasive Surgery Versus Traditional, Open Surgery: An Analysis of Surgical Outcomes.

Study Design:Retrospective, multicenter review of adult scoliosis patients with minimum 2-year follow-up. Objective:Because the fractional curve (FC) of adult scoliosis can cause radiculopathy, we evaluated patients treated with either circumferential minimally invasive surgery (cMIS) or open surgery. Methods:A multicenter retrospective adult deformity review was performed. Patients included: age &gt;18 years with FC &gt;10°, ≥3 levels of instrumentation, 2-year follow-up, and one of the following: coronal Cobb angle (CCA) &gt; 20°, pelvic incidence and lumbar lordosis (PI-LL) &gt; 10°, pelvic tilt (PT) &gt; 20°, and sagittal vertical axis (SVA) &gt; 5 cm. Results:The FC was treated in 118 patients, 79 open and 39 cMIS. The FCs had similar coronal Cobb angles preoperative (17° cMIS, 19.6° open) and postoperative (7° cMIS, 8.1° open), but open had more levels treated (12.1 vs 5.7). cMIS patients had greater reduction in VAS leg (6.4 to 1.8) than open (4.3 to 2.5). With propensity matching 40 patients for levels treated (cMIS: 6.6 levels, N = 20; open: 7.3 levels, N = 20), both groups had similar FC correction (18° in both preoperative, 6.9° in cMIS and 8.5° postoperative). Open had more posterior decompressions (80% vs 22.2%, P &lt; .001). Both groups had similar preoperative (Visual Analogue Scale [VAS] leg 6.1 cMIS and 5.4 open) and postoperative (VAS leg 1.6 cMIS and 3.1 open) leg pain. All cMIS patients had interbody grafts; 35% of open did. There was no difference in change of primary CCA, PI-LL, LL, Oswestry Disability Index, or VAS Back. Conclusion:Patients' FCs treated with cMIS had comparable reduction of leg pain compared with those treated with open surgery, despite significantly fewer cMIS patients undergoing direct decompression

Hypoxia in CNS Pathologies: Emerging Role of miRNA-Based Neurotherapeutics and Yoga Based Alternative Therapies

Cellular respiration is a vital process for the existence of life. Any condition that results in deprivation of oxygen (also termed as hypoxia) may eventually lead to deleterious effects on the functioning of tissues. Brain being the highest consumer of oxygen is prone to increased risk of hypoxia-induced neurological insults. This in turn has been associated with many diseases of central nervous system (CNS) such as stroke, Alzheimer's, encephalopathy etc. Although several studies have investigated the pathophysiological mechanisms underlying ischemic/hypoxic CNS diseases, the knowledge about protective therapeutic strategies to ameliorate the affected neuronal cells is meager. This has augmented the need to improve our understanding of the hypoxic and ischemic events occurring in the brain and identify novel and alternate treatment modalities for such insults. MicroRNA (miRNAs), small non-coding RNA molecules, have recently emerged as potential neuroprotective agents as well as targets, under hypoxic conditions. These 18–22 nucleotide long RNA molecules are profusely present in brain and other organs and function as gene regulators by cleaving and silencing the gene expression. In brain, these are known to be involved in neuronal differentiation and plasticity. Therefore, targeting miRNA expression represents a novel therapeutic approach to intercede against hypoxic and ischemic brain injury. In the first part of this review, we will discuss the neurophysiological changes caused as a result of hypoxia, followed by the contribution of hypoxia in the neurodegenerative diseases. Secondly, we will provide recent updates and insights into the roles of miRNA in the regulation of genes in oxygen and glucose deprived brain in association with circadian rhythms and how these can be targeted as neuroprotective agents for CNS injuries. Finally, we will emphasize on alternate breathing or yogic interventions to overcome the hypoxia associated anomalies that could ultimately lead to improvement in cerebral perfusion

Regional variability in use of a novel assessment of thoracolumbar spine fractures: United States versus international surgeons

<p>Abstract</p> <p>Background</p> <p>Considerable variability exists in clinical approaches to thoracolumbar fractures. Controversy in evaluation and nomenclature contribute to this confusion, with significant differences found between physicians, between different specialties, and in different geographic regions. A new classification system for thoracolumbar injuries, the Thoracolumbar Injury Severity Score (TLISS), was recently described by Vaccaro. No assessment of regional differences has been described. We report regional variability in use of the TLISS system between United States and non-US surgeons.</p> <p>Methods</p> <p>Twenty-eight spine surgeons (8 neurosurgeons and 20 orthopedic surgeons) reviewed 56 clinical thoracolumbar injury case histories, which included pertinent imaging studies. Cases were classified and scored using the TLISS system. After a three month period, the case histories were re-ordered and the physicians repeated the exercise; 22 physicians completed both surveys and were used to assess intra-rater reliability. The reliability and treatment validity of the TLISS was assessed. Surgeons were grouped into US (n = 15) and non-US (n = 13) cohorts. Inter-rater (both within and between different geographic groups) and intra-rater reliability was assessed by percent agreement, Cohen's kappa, kappa with linear weighting, and Spearman's rank-order correlation.</p> <p>Conclusion</p> <p>Non-US surgeons were found to have greater inter-rater reliability in injury mechanism, while agreement on neurological status and posterior ligamentous complex integrity tended to be higher among US surgeons. Inter-rater agreement on management was moderate, although it tended to be higher in US-surgeons. Inter-rater agreement between US and non-US surgeons was similar to within group inter-rater agreement for all categories. While intra-rater agreement for mechanism tended to be higher among US surgeons, intra-rater reliability for neurological status and PLC was slightly higher among non-US surgeons. Intra-rater reliability for management was substantial in both US and non-US surgeons. The TLISS incorporates generally accepted features of spinal injury assessment into a simple patient evaluation tool. The management recommendation of the treatment algorithm component of the TLISS shows good inter-rater and substantial intra-rater reliability in both non-US and US based spine surgeons. The TLISS may improve communication between health providers and may contribute to more efficient management of thoracolumbar injuries.</p

CEACAM6 is upregulated by <i>Helicobacter pylori</i> CagA and is a biomarker for early gastric cancer

Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach

Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.

Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study integrating measurement of markers of systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics at paired time points to profile the bioactivity of metformin in primary breast cancer. We show metformin reduces the levels of mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumors. Two tumor groups are identified with distinct metabolic responses, an OXPHOS transcriptional response (OTR) group for which there is an increase in OXPHOS gene transcription and an FDG response group with increased 18-FDG uptake. Increase in proliferation, as measured by a validated proliferation signature, suggested that patients in the OTR group were resistant to metformin treatment. We conclude that mitochondrial response to metformin in primary breast cancer may define anti-tumor effect