Preoperative Low-Dose Aspirin Exposure and Outcomes After Emergency Neurosurgery for Traumatic Intracranial Hemorrhage in Elderly Patients.

BACKGROUND: Antiplatelet medications are usually discontinued before elective neurosurgery, but this is not an option for emergent neurosurgery. We performed a retrospective cohort study to examine whether preoperative aspirin use was associated with worse outcomes after emergency neurosurgery in elderly patients. METHODS: We analyzed all cases of emergency neurosurgical procedures for traumatic intracranial hemorrhage from 2008 to 2012 at a level 1 trauma center. Demographics, comorbidities, and outcomes were compared for patients ≥65 years by preoperative aspirin exposure. Exclusion criteria were: (1) polytrauma, (2) concomitant use of other preoperative anticoagulants or antiplatelet agents, (3) surgical indication other than subdural, extradural, or intraparenchymal hemorrhage, and (4) repeat neurosurgical procedures within a single admission. Estimated intraoperative blood loss, postprocedural intracranial bleeding requiring reoperation, death in hospital, intensive care unit, and hospital lengths of stay and perioperative blood product transfusion from 48 hours before 48 hours after surgery were the study outcomes. We also examined whether platelet transfusion had an impact on outcomes for patients on aspirin. RESULTS: The cohort included 171 patients. Patients receiving preoperative aspirin (n = 87, 95% taking 81 mg/day) were the same age as patients not receiving aspirin (n = 84; 78.3 ± 7.8 vs 75.9 ± 7.9 years, P > .05), had slightly higher admission Glasgow Coma Scale scores (12.8 ± 3.4 vs 11.4 ± 4, P = .02) and tended to have more coronary artery disease (P< .05). Adjusted for Glasgow Coma Scale and coronary artery disease, patients receiving preoperative aspirin had a higher odds of perioperative platelet transfusion (adjusted odds ratio 9.89, 95% confidence interval, 4.24-26.25). There were no other differences in outcomes between the 2 groups. Preoperative or intraoperative platelet transfusion was not associated with better outcomes among aspirin patients. CONCLUSIONS: In patients age ≥65 years undergoing emergency neurosurgery for traumatic intracranial hemorrhage, preoperative low-dose aspirin treatment was not associated with increased perioperative bleeding, hospital lengths of stay, or in-hospital mortality.

The Feasibility of Using Large-Scale Text Mining to Detect Adverse Childhood Experiences in a VA-Treated Population.

Free text in electronic health records resists large-scale analysis. Text records facts of interest not found in encoded data, and text mining enables their retrieval and quantification. The U.S. Department of Veterans Affairs (VA) clinical data repository affords an opportunity to apply text-mining methodology to study clinical questions in large populations. To assess the feasibility of text mining, investigation of the relationship between exposure to adverse childhood experiences (ACEs) and recorded diagnoses was conducted among all VA-treated Gulf war veterans, utilizing all progress notes recorded from 2000-2011. Text processing extracted ACE exposures recorded among 44.7 million clinical notes belonging to 243,973 veterans. The relationship of ACE exposure to adult illnesses was analyzed using logistic regression. Bias considerations were assessed. ACE score was strongly associated with suicide attempts and serious mental disorders (ORs = 1.84 to 1.97), and less so with behaviorally mediated and somatic conditions (ORs = 1.02 to 1.36) per unit. Bias adjustments did not remove persistent associations between ACE score and most illnesses. Text mining to detect ACE exposure in a large population was feasible. Analysis of the relationship between ACE score and adult health conditions yielded patterns of association consistent with prior research.

Selective peripheral tissue response to high testosterone levels in an infertile woman without virilization signs.

Summary: Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2-3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation. Learning points: Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women. Very high total testosterone levels in women (>2-3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization. In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it. Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25-43% of cases. A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

Ultrasound localization of the sacral plexus using a parasacral approach.

In this report, we describe the feasibility of locating the sacral plexus nerve using a parasacral approach and an ultrasound-guided technique. The parasacral region using a curved probe (2-5 MHz) was scanned in 17 patients in search of the medial border of the ischial bone and the lateral border of the sacrum, which represent the limit of the greater sciatic foramen. In addition, attempts were made to identify the piriformis muscles and the gluteal arteries. The sacral plexus was identified at the level of the sciatic foramen as a round hyperechoic structure. The gluteal arteries were identified in 10 of 17 patients, but we failed to positively identify the piriformis muscle in any patient. To confirm localization of the sacral plexus, an insulated needle attached to a nerve stimulator was advanced and, in each case, a sacral plexus motor response was elicited (plantar flexion-12, dorsal flexion-1, hamstring muscle stimulation-3, gastrocnemius muscle stimulation-1-not recorded) at a current between 0.2 and 0.5 mA. No complications were observed. This report confirms the feasibility of using ultrasound to locate the sacral plexus using a parasacral approach.

Ultrasound-guided paravertebral block using an intercostal approach.

We describe an ultrasound-guided technique of continuous bilateral paravertebral block using an intercostal approach in 12 patients undergoing elective abdominal surgery. Postoperatively, each of the patient's paravertebral catheters was bolused with 10 mL lidocaine (15 mg/mL), and each of the patient's catheters was infused with 0.2% ropivacaine at 10 mL/h. Using a pinprick test, the median number of dermatomes blocked after the initial bolus was 5 (interquartile range, 4-6), and 23 of 24 catheters produced a local anesthetic block. The median verbal pain score on postoperative day 1 was 5.5 (interquartile range, 3.5-6), and median dose of IV hydromorphone consumed during the first 24 h after surgery was 1.9 mg (interquartile range, 0.7-5.05). All catheters were removed within 72 h after surgery.

Rifampicin-induced CYP3A4 activation in CTX patients cannot replace chenodeoxycholic acid treatment.

Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disorder with cholestanol accumulation resulting from mutations in the sterol 27-hydroxylase gene (CYP27A). Conventional treatment includes chenodeoxycholic acid and HMG-CoA reductase inhibitors. Mice with disrupted Cyp27A (Cyp27 KO) do not show elevated cholestanol levels nor develop CTX manifestations. This phenomenon was proposed to be due to murine CYP3A overexpression leading to an alternative pathway for degradation of bile alcohols including cholestanol. Our objective was to examine the influence of CYP3A4 induction on cholestanol elimination in CTX patients. Rifampicin (600 mg/day x 7 days), known to induce the PXR, and thereby to increase CYP3A activity, was used. The degree of CYP3A4 induction was assessed by comparing midazolam pharmacokinetics before and after rifampicin treatment. Cholestanol levels and cholestanol/cholesterol ratios were assayed during the experimental period and compared to a 3 weeks period without treatment. The results show that despite 60% increase in CYP3A4 activity following rifampicin treatment, there is no significant change in cholestanol levels. We conclude that up-regulated expression of CYP3A affects cholestanol elimination in mice differently as compared to its effect in CTX patients. Therefore, CYP3A4 inducers cannot replace chenodeoxycholic acid for the treatment of CTX.

A Risk Calculator Using Preoperative Opioids for Prediction of Total Knee Revision Arthroplasty.

OBJECTIVES: Total knee arthroplasty (TKA) is a procedure to improve quality of life. However, some patients require early total knee revision (TKR). Chronic opioid use before TKA is associated with TKR. No risk calculator including opioid use or other risk factors is currently available for predicting TKR. MATERIALS AND METHODS: We retrospectively analyzed medical records of Veterans Affairs patients who underwent TKA from January 1, 2006 to January 1, 2012. Patients were followed until January 1, 2013. Chronic opioid use was defined as opioid use for ≥3 months preoperatively. A cross-validated Cox proportional hazards model was created to predict TKR before initial TKA. Model performance was evaluated by the mean absolute error at 1 and 5 years. RESULTS: Totally, 32,297 patients were included. A risk calculator was generated with a mean absolute error of 0.1% at 1 year and 3.6% at 5 years. Chronic opioid use was a significant predictor of TKR (hazard ratio [HR], 1.27; 95% confidence interval, 1.13-1.43; P<0.001). Other model variables were age (HR, 0.95; P<0.001), female sex (HR, 0.77; P=0.020), body mass index (HR, 0.99; P=0.022), diabetes (HR, 1.20; P=0.001), chronic kidney disease (HR, 1.48; P<0.001), and nonchronic opioid use (HR, 1.07; P=0.313). DISCUSSION: Preoperative chronic opioid use is a predictor of TKR. Using this association and others, a TKA revision risk calculator was generated at http://www.bit.do/tka.

High-yield isolation, expansion, and differentiation of murine bone marrow-derived mesenchymal stem cells using fibrin microbeads (FMB).

Transplantation of adult mesenchymal stem cells (MSCs) could provide a basis for tissue regeneration. MSCs are typically isolated from bone marrow (BM) based on their preferential adherence to plastic, although with low efficiency in terms of yield and purity. Extensive expansion is needed to reach a significant number of MSCs for any application. Fibrin microbeads (FMB) were designed to attach mesenchymal cells and to provide a matrix for their expansion. The current study was aimed at isolating a high yield of purified BM-derived mouse MSCs based on their preferential adherence and proliferation on FMB in suspension cultures. MSCs could be downloaded to plastics or further expanded on FMB. The yield of MSCs obtained by the FMB isolation technique was about one order of magnitude higher than that achieved by plastic adherence, suggesting that these cells are more abundant than previously reported. FMB-isolated cells were classified as MSCs by their fibroblastic morphology, self-renewal ability, and expression profile of their surface antigens, as examined by flow cytometry and immunostaining. In cell culture, the isolated MSCs could be induced to differentiate into three different mesodermal lineages, as demonstrated by histochemical stains and by RT-PCR analyses of tissue-specific genes. MSCs were also able to differentiate into osteocytes while still cultured on FMB. Our results suggest that FMB might serve as an efficient platform for the isolation, expansion, and differentiation of mouse BM-derived MSCs to be subsequently implanted for tissue regeneration.

Preoperative Opioid Use Is Associated with Early Revision After Total Knee Arthroplasty: A Study of Male Patients Treated in the Veterans Affairs System.

BACKGROUND: Opioid use is endemic in the U.S. and is associated with morbidity and mortality. The impact of long-term opioid use on joint-replacement outcomes remains unknown. We tested the hypothesis that use of opioids is associated with adverse outcomes after total knee arthroplasty (TKA). METHODS: We performed a retrospective analysis of patients who had had TKA within the U.S. Veterans Affairs (VA) system over a 6-year period and had been followed for 1 year postoperatively. The length of time for which an opioid had been prescribed and the morphine equivalent dose were calculated for each patient. Patients for whom opioids had been prescribed for >3 months in the year prior to the TKA were assigned to the long-term opioid group. A natural language processing-based machine-learning classifier was developed to classify revisions due to infectious and non-infectious causes on the basis of the postoperative note. Survival curves for the time to knee revision or manipulation were used to compare the long-term opioid group with the patients who did not take opioids long-term. Hazard and odds ratios for knee revision and manipulation were obtained as well. RESULTS: Of 32,636 patients (94.4% male; mean age [and standard deviation], 64.45 ± 9.41 years) who underwent TKA, 12,772 (39.1%) were in the long-term opioid group and 734 (2.2%) had a revision within a year after the TKA. Chronic kidney disease, diabetes, and long-term opioid use were associated with revision within 1 year-with odds ratios (95% confidence intervals [CIs]) of 1.76 (1.37 to 2.22), 1.11 (0.93 to 1.31), and 1.40 (1.19 to 1.64), respectively-and were also the leading factors associated with a revision at any time after the index TKA-with odds ratios (95% CIs) of 1.61 (1.34 to 1.92), 1.21 (1.08 to 1.36), and 1.28 (1.15 to 1.43), respectively. Long-term opioid use had a hazard ratio of 1.19 (95% CI = 1.10 to 0.24) in the analysis of its relationship with knee revision, but the hazard was not significant in the analysis of its association with knee manipulation. The accuracy of the text classifier was 0.94, with the area under the receiver operating characteristic curve being 0.99. There was no association between long-term use of opioids and the specific cause for knee revision. CONCLUSIONS: Long-term opioid use prior to TKA was associated with an increased risk of knee revision during the first year after TKA among predominantly male patients treated in the VA system. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Intravenous Tissue Plasminogen Activator Administration for Ischemic Stroke 1 Hour After Epidural Catheter Removal: A Case Report.

Anticoagulation after a recent neuraxial procedure poses risk for development of spinal hematoma. Clinical evidence supports prompt IV tissue plasminogen activator administration after onset of ischemic stroke. There is an absence of data regarding emergency fibrinolytic therapy for patients experiencing a stroke with recent neuraxial procedures, resulting in highly disparate, nonevidence-based guidelines. This report describes a patient who developed ischemic stroke when receiving postoperative epidural analgesia. Tissue plasminogen activator was emergently administered 1 hour after epidural catheter removal with a favorable recovery. The patient and his family reviewed the manuscript, and written consent to publish this case report was obtained from the patient.

Isolation and implantation of bone marrow-derived mesenchymal stem cells with fibrin micro beads to repair a critical-size bone defect in mice.

Fibrin microbeads (FMBs) made using thermal treatment of fibrin drops in oil can efficiently isolate mesenchymal stem cells (MSCs) from bone marrow (BM) and other similar sources and culture them continuously in suspension culture. The pure mesenchymal profile of MSCs isolated using FMBs and their differentiation potency to different mesenchymal lineages were previously described in detail. In the current study, MSCs were isolated from the BM of (GFP+) C57/bl mice using FMBs. Addition of pro-osteogenic medium with 10 mM of ss-glycerolphosphate, 50 microg/mL of ascorbic acid, and 10(-8) M of dexamethasone for 1 month resulted in ossified bone-like solid cellular structures, as seen using fluorescence and scanning electron microscopy (SEM). Such spontaneously formed structures were implanted in full-depth approximately 5-mm-diameter drilled defects in the skulls of wild-type c57/bl mice. Two months later, the excised upper parts of the skulls with the defects were viewed using fluorescence microscopy for green fluorescence protein of the cells in the defect and using SEM. They were also scanned using micro-computed tomography to visualize the formation of new hard tissue. Then the samples were processed and sectioned for hematoxylin and eosin staining and immunohistochemistry. Implanted FMBs loaded with (GFP+) MSCs formed partially mature, dense bone-like tissue using a residual moderate inflammatory process containing remnants of FMBs and neo-angiogenesis. The filled defect with bone-like tissue had a Ca/P ratio similar to that of native bone. Limited merging of the implant with the skull indicated that the induced bone regeneration derived from the MSCs that were delivered with the implant. No repair was seen in the control animals without implants or where the defect was filled with FMBs only. Repair scoring (on a 0-5 scale) was found to be 3.38+/-0.35 in the experimental arm, relative to 0 in the controls (p < 0.001).

Chronic administration of ketamine for analgesia.

Use of the dissociative anesthetic ketamine in subanesthetic doses has demonstrated efficacy in neuropathic pain. This article reviews the scientific and clinical literature on ketamine. Mechanisms of both central and peripheral neuropathic pain are described. Studies of ketamine analgesia in postherpetic neuralgia, phantom pain, complex regional pain syndrome and cancer pain are reviewed. A range of administration methods for ketamine including neuroaxial administration are described.

Protein and peptide parenteral controlled delivery.

Protein and peptide delivery has been a challenge due to their limited stability during preparation of formulation, storage and in vitro and in vivo release. These biopolymers have traditionally been administered via intramuscular or subcutaneous routes. Recent efforts have been made to develop formulations for non-invasive routes of administration, including oral, intranasal, transdermal and transmucosal delivery. Despite these efforts, invasive delivery remains the main method of administering peptide and protein drugs. This review focuses on recent developments in injectable, polymeric controlled-release formulations, with an emphasis on hydrogels and particulate systems.