Risk predictive score and cord morphology classification for intraoperative neuromonitoring alerts in kyphosis surgery.

BACKGROUND: Intraoperative neuromonitoring (IONM) alert is one of the worrying events of kyphosis corrective surgery, which can result in a postoperative neurological deficit. To our knowledge, there is no risk prediction score to predict such events in patients undergoing kyphosis surgery. PURPOSE: To develop a new preoperative MRI-based cord morphology classification (CMC) and risk prediction score for predicting IONM alerts in patients with kyphotic deformity. STUDY DESIGN: Retrospective analysis of prospectively collected data. PATIENT SAMPLE: About 114 patients undergoing surgical correction for kyphotic deformity. OUTCOME MEASURES: Intraoperative neuromonitoring alerts and postoperative neurological status using AIS grading. METHODS: Kyphotic deformity patients undergoing posterior spinal fusion were retrospectively reviewed. Based on the morphology of the spinal cord and surrounding CSF in MRI, there are 5 types of cord. Type 1 (normal cord): circular cord with surrounding visible CSF between the cord and the apex, Type 2 (flattened cord): cord with <50% distortion at the apex with obliteration of the anterior CSF; Type 3 (deformed cord): cord with >50% distortion at the apex with complete obliteration of the surrounding CSF; Type 4 (stretched cord): the cord is stretched and atrophied over the apex of the curve. Type 5 (translated cord): horizontal translation of the cord at the apex with buckling collapse of the vertebral column. Preoperative radiographs were used to measure the preoperative sagittal cobbs angle, sagittal deformity angular ratio (S-DAR), sagittal vertical axis (SVA), apex of the curve, and type of kyphosis. Clinical data like the duration of symptoms, clinical signs of myelopathy, neurological status (AIS grade), grade of myelopathy using the mJOA score, and type of osteotomy were documented. Multivariate logistic regression was used to determine the risk factors for IONM alerts and the risk prediction score was developed which was validated with new cohort of 30 patients. RESULTS: A total of 114 patients met the inclusion criteria. IONM alerts were documented in 33 patients (28.9%), with full recovery of the signal in 25 patients and a postoperative deficit in 8 patients. Rate of IONM alerts was significantly higher in Type 5 (66%), followed by Type 4 (50%), Type 3 (21.1%), Type 2 (11.1%), and Type 1 (11.1%) (p-value<.001). Based on multiple logistic regression, 7 factors, namely preoperative neurological status, mJOA score≤6, presence of signs of myelopathy, apex of the curve above T5, preoperative sagittal cobbs, S-DAR, and MRI-based CMC, were identified as risk predictors. The value for the risk factors varies from 0 to 4, and the maximum total risk score was 13. The cut-off value of 6 had good sensitivity (84.9%) and specificity (77.8%) indicating a high risk for IONM alerts. The AUC of the predictive model was 0.92, indicating excellent discriminative ability. CONCLUSION: We developed and validated a risk predictive score that identifies patients at risk of IONM alerts during kyphosis surgery. Identification of such high-risk patients (risk score≥6) helps in proper evaluation and preoperative counselling and helps in providing a proper evidence-based reference for treatment strategies.

Does the gut microbiome influence disc health and disease? The interplay between dysbiosis, pathobionts, and disc inflammation: a pilot study.

BACKGROUND CONTEXT: Gut microbiome alterations resulting in inflammatory responses have been implicated in many distant effects on different organs. However, its influence on disc health is still not fully investigated. PURPOSE: Our objective was to document the gut biome in healthy volunteers and patients with disc degeneration and to understand the role of gut dysbiosis on human disc health. STUDY DESIGN: Experimental case-control study. PATIENT SAMPLE: We included 40 patients with disc degeneration (DG) and 20 healthy volunteers (HV). HV comprised of age groups 30 to 60 years with no known record of back pain and no clinical comorbidities, with normal MRI. Diseased group (DG) were patients in the same age group undergoing surgery for disc disease (disc herniation-25; discogenic stenosis-15) and without instability (with Modic-20; and non-Modic-20). OUTCOME MEASURES: N/A. METHODS: We analyzed 16S V3-V4 rDNA gut metagenome from 20 healthy volunteers (HV) and compared the top signature genera from 40 patients with disc degeneration (DG) across Modic and non-Modic groups. Norgen Stool DNA Kit was used for DNA extraction from ∼200 mg of each faecal sample collected using the Norgen Stool Collection Kit.16S V3-V4 rDNA amplicons were generated with universal bacterial primers 341F and 806R and amplified with Q5 High-Fidelity DNA Polymerase. Libraries were sequenced with 250×2 PE to an average of 0.1 million raw reads per sample (Illumina Novaseq 6000). Demultiplexed raw data was assessed with FastQC, and adapter trimmed reads >Q30 reads were processed in the QIME2 pipeline. Serum C-reactive protein (CRP) was measured by the immunoturbimetry method and Fatty acid-binding protein 5 (FABP5) was measured in albumin-globulin-depleted plasma through global proteome analysis. RESULTS: We observed significant gut dysbiosis between HV and DG and also between the Modic and non-Modic groups. In the Modic group, commensals Bifidobacterium and Ruminococcus were significantly depleted, while pathobionts Streptococcus, Prevotella, and Butryvibrio were enriched. Firmicutes/Bacteroidetes ratio was decreased in DG (Modic-0.62, non-Modic-0.43) compared to HV (0.70). Bacteria-producing beneficial short-chain fatty acids were also depleted in DG. Elevated serum CRP and increased FABP5 were observed in DG. CONCLUSION: The study revealed gut dysbiosis, an altered Firmicutes/Bacteroidetes ratio, reduced SCFA-producing bacteria, and increased systemic and local inflammation in association with disc disease, especially in Modic changes. The findings have considerable importance for our understanding and prevention of disc degeneration.

Efficacy and Safety of Ultrasound Guided Inter-semispinal Plane Block for Postoperative Analgesia in Posterior Cervical Laminectomy - A Prospective Randomised Controlled Study.

STUDY DESIGN: Prospective, randomized controlled study. OBJECTIVE: To assess the safety and efficacy of an ultrasound-guided ISP block for postoperative analgesia in posterior cervical laminectomy. METHODS: 88 patients requiring posterior cervical laminectomy were randomized into two groups, those who underwent ISP block with multimodal analgesia (ISPB group) and those with only multimodal analgesia (control group). Demographic details, intraoperative parameters (blood loss, duration of surgery, perioperative total opioid consumption, muscle relaxants used), and postoperative parameters (numeric rating scale, satisfaction score, mobilization time, and complications) were recorded. RESULTS: The total opioid consumption (128.41 + 39.65vs 284.09 + 140.92mcg; P < .001), muscle relaxant usage (46.14 + 6.18 mg vs 59.32 + 3.97 mg; P < .001), surgical duration (128.61 + 26.08/160.23 + 30.99mins; P < .01), and intra-operative blood loss (233.18 + 66.08 mL vs 409.77 + 115.41 mL; P < .01) were significantly less in the ISPB group compared to the control. In the postoperative period, the control group's pain score was significantly higher (P < .001) in the initial 48 hours. The Modified Observer Alertness/Sedation Score (MOASS) score and satisfaction scores were significantly better in the ISPB compared to the control (P < .001). The mean time required to ambulate was statistically less in ISPB (4.30 + 1.64hours) when compared to controls (9.48 + 3.07hours) (P < .001). CONCLUSION: In patients undergoing posterior cervical laminectomy, ISP block is a safe and effective technique with better outcomes than standard multi-modal analgesia alone, in terms of reduced intra-operative opioid requirements and blood loss, better postoperative analgesia, and early mobilization.

Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

Does Magnetic Resonance Imaging Predict Neurological Deficit in Patients with Traumatic Lower Lumbar Fractures?

STUDY DESIGN: A retrospective cohort study. PURPOSE: This study aimed to understand the role of magnetic resonance imaging (MRI) in predicting neurological deficits in traumatic lower lumbar fractures (LLFs; L3-L5). OVERVIEW OF LITERATURE: Despite studies on the radiological risk factors for neurological deficits in thoracolumbar fractures, very few have focused on LLFs. Moreover, the potential utility of MRI in LLFs has not been evaluated. METHODS: In total, 108 patients who underwent surgery for traumatic LLFs between January 2010 and January 2020 were reviewed to obtain their demographic details, injury level, and neurology status at the time of presentation (American Spinal Injury Association [ASIA] grade). Preoperative computed tomography scans were used to measure parameters such as anterior vertebral body height, posterior vertebral body height, loss of vertebral body height, local kyphosis, retropulsion of fracture fragment, interpedicular distance, canal compromise, sagittal transverse ratio, and presence of vertical lamina fracture. MRI was used to measure the canal encroachment ratio (CER), cross-sectional area of the thecal sac (CSAT), and presence of an epidural hematoma. RESULTS: Of the 108 patients, 9 (8.3%) had ASIA A, 4 (3.7%) had ASIA B, 17 (15.7%) had ASIA C, 21 (19.4%) had ASIA D, and 57 (52.9%) had ASIA E neurology upon admission. The Thoracolumbar Injury Classification and Severity score (p =0.000), CER (p =0.050), and CSAT (p =0.019) were found to be independently associated with neurological deficits on the multivariate analysis. The receiver operating characteristic curves showed that only CER (area under the curve [AUC], 0.926; 95% confidence interval [CI], 0.860-0.968) and CSAT (AUC, 0.963; 95% CI, 0.908-0.990) had good discriminatory ability, with the optimal cutoff of 50% and 65.3 mm2, respectively. CONCLUSIONS: Based on the results, the optimal cutoff values of CER >50% and CSAT >65.3 mm2 can predict the incidence of neurological deficits in LLFs.

ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum.

Intracellular Mg2+ (iMg2+) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg2+ transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major iMg2+ compartment refilled by a largely uncharacterized ER-localized protein, TMEM94. Conventional and AlphaFold2 predictions suggest that ERMA (TMEM94) is a multi-pass transmembrane protein with large cytosolic headpiece actuator, nucleotide, and phosphorylation domains, analogous to P-type ATPases. However, ERMA uniquely combines a P-type ATPase domain and a GMN motif for ERMg2+ uptake. Experiments reveal that a tyrosine residue is crucial for Mg2+ binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg2+ ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca2+ cycling in mouse Erma+/- cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of ERMg2+ uptake in eukaryotes.

Comparison Between Relative Efficacy of Erector Spinae Plane Block and Caudal Epidural Block for Postoperative Analgesia in Lumbar Fusion Surgery- A Prospective Randomized Controlled Study.

STUDY DESIGN: Prospective, randomized controlled double-blinded study. OBJECTIVE: To compare the relative efficacy of ultrasound-guided ESPB and CEB for postoperative analgesia after a single-level lumbar fusion surgery and compared it with conventional multimodal analgesia. METHODS: 81 patients requiring single-level lumbar fusion surgery were randomly allocated into 3 groups (ESPB group, CEB group, and the control group). Demographic and surgical data (blood loss, duration of surgery, perioperative total opioid consumption, muscle relaxants used) were assessed. Postoperatively, the surgical site pain, alertness scale, satisfaction score, time to mobilization, and complications were recorded. RESULTS: The total opioid consumption in the first 24 hours was significantly lower in both the block groups than in the control group (103.70 ± 13.34 vs 105 ± 16.01 vs 142.59 ± 40.91mcg; P < .001). The total muscle relaxant consumption was also significantly less in block groups compared to controls (50.93 ± 1.98 vs 52.04 ± 3.47 vs 55.00 ± 5.29 mg; P < .001). The intraoperative blood loss was significantly less in both the block group (327.78 ± 40.03 mL, 380.74 ± 77.80 mL) than the control group (498.89 ± 71.22 mL) (P < .001). Among the block groups, the immediate postoperative pain relief was better in the CEB group, however, the ESPB group had a longer duration of postoperative pain relief. CONCLUSION: Both ESPB and CEB produce adequate postoperative analgesia after lumbar fusion however the duration of action was significantly longer in the ESPB group with relatively shorter surgical time and lesser blood loss compared to the CEB group.

Active tuberculosis of spine: Current updates.

Background: Spinal tuberculosis (TB) is the most common extrapulmonary form of tuberculosis. In both developing and developed countries, TB has been on the rising trend due to factors such as increasing HIV coinfection, multidrug resistance of the organism, and global migration. Spinal TB, which most often affects the lower thoracic and thoracolumbar area, accounts for 50% of all musculoskeletal tuberculosis. Methods: Using the Cochrane Database of Systematic Reviews, EMBASE, and PubMed, a systematic computerized literature search was performed. Analyses of studies published within the past 10 years were conducted. The searches were performed using Medical Subject Headings terms, with "spinal tuberculosis," "diagnosis," "epidemiology," and "etiology","management," "surgery," and "therapy" as subheadings. Results: Progressive collapse, kyphosis, and neurological deficiency are hallmarks of the disease because of its destructive effect on the intervertebral disc and adjacent vertebral bodies. The condition may be identified using laboratory testing and distinctive imaging features, but the gold standard for diagnosis is tissue diagnosis using cultures, histology, and polymerase chain reaction. Uncomplicated spinal TB is today a medical condition that can be adequately treated by multidrug ambulatory chemotherapy. Surgery is reserved for individuals who have instability, neurological impairment, and deformity correction. Debridement, deformity correction, and stable fusion are the cornerstones of surgical treatment. Conclusions: Clinical results for the treatment of spinal TB are generally satisfactory when the disease is identified and treated early. However, the major health issue and the biggest obstacle in achieving the goals of the "End TB strategy" is the recent rise in the emergence of drug resistance. Hence strict vigilance and patient perseverance in the completion of the treatment is the main need of the hour.

Ralstonia mannitolilytica as a rare cause of spondylodiscitis following endoscopic lumbar discectomy- A report of two cases.

Ralstonia mannitolilytica is a low-virulence, gram-negative bacillus which causes opportunistic infections in immunosuppressed patients. Postoperative spondylodiscitis by R. mannitolilytica has not been reported so far. We report the management of two cases of postoperative spondylodiscitis caused by Ralstonia mannitolilytica presenting to our center within a span of one month following endoscopic lumbar discectomy at a different center. They were managed successfully by surgical debridement and appropriate antibiotics. In these two cases of R.mannitolilytica spondylodiscitis, prompt detection, and intensive treatment resulted in satisfactory outcomes in terms of fulfilling the purpose of the original surgery.

Propensity matched outcome analysis following microdiscectomy versus interlaminar endoscopic discectomy for L5-S1 disc herniation.

Purpose: The main purpose of the study is to perform a propensity-matched functional outcome analysis following microdiscectomy (MD) versus interlaminar endoscopic lumbar discectomy (IELD) for L5-S1 disc herniation. Although many studies have compared endoscopic lumbar discectomy and microdiscectomy, few have compared the outcomes of microdiscectomy (MD) and interlaminar endoscopic discectomy (IELD) at the L5-S1 level. Methods: This is a propensity-matched analysis of 100 patients (50 MD patients, 50 IELD patients) based on baseline covariates with a minimum of one-year follow-up. Patient-reported outcome measures were obtained from EMR during follow-up visits. Back pain and sciatic pain were assessed by the Visual Analogue Scale (VAS-B and VAS-L). Functional outcome was assessed using Oswestry Disability Index (ODI) Score and 12-item Short Form Survey (SF-12) score. Data were obtained at baseline (pre-op) and at 0, 1, 3, and 12 months post-operatively. Results: Mean operative time was significantly lower (p < 0.001) in the IELD group (44 min) compared to the MD group (59 min). Mean VAS-B at the immediate and 1-month postoperative period was significantly (p < 0.001) lower in the IELD group (0.36, 0.24) when compared with the MD group (1.74, 1.16). There was no significant difference between IELD and MD groups with regard to improvement in sciatic pain (VAS-L). ODI scores at 1 month and 3 months post-operative period were significantly (p < 0.001) lower in the IELD group (30.1, 23.2) when compared with the MD group (41, 27.5). However, there was no significant difference between the two groups with regards to VAS-B, ODI, and SF-12 at 1-year follow-up. Conclusion: Our findings indicate that the IELD group achieved better immediate and early postoperative outcomes despite no significant difference at one-year follow-up.

Giant Anomalous Cervical Spinous Process Causing Dynamic Cord Compression: An Unusual Cause for Myelopathy: A Case Report.

CASE: A 47-year-old male patient presented with progressively worsening gait instability caused by a giant anomalous, free-floating C5 spinous process resulting in dynamic cord compression and myelopathy. The patient was successfully managed with a C5 laminectomy and total excision of the anomalous spinous process with a good functional outcome at the final follow-up. CONCLUSION: Anomalies of the posterior arch of the subaxial cervical spine are relatively uncommon and asymptomatic. This case is being reported for its rarity and to highlight the role of dynamic imaging in patients presenting with congenital anomalies of the cervical spine presenting with compressive myelopathy.

Preoperative pain sensitivity predicts postoperative pain severity and analgesics requirement in lumbar fusion surgery - a prospective observational study.

BACKGROUND CONTENT: The goal of postoperative pain management is to facilitate the patient's return to normal activity and decrease the detrimental effects of acute postsurgical pain. In order to provide more tailored and successful pain treatment, it is necessary to identify individuals who are at a high risk of experiencing severe postoperative pain. The most precise way to assess pain sensitivity is by determining the pressure pain threshold and heat pain threshold by objective methods using a digital algometer and neurotouch respectively. PURPOSE: The primary aim of the study is to assess the preoperative pain threshold and its influence on postoperative pain severity and analgesics requirements in patients undergoing lumbar fusion surgeries. STUDY DESIGN: Prospective, observational study. PATIENT SAMPLE: Sixty patients requiring a single-level lumbar fusion surgery. OUTCOME MEASURES: Postoperative pain intensity and the amount of postoperative analgesics consumption. METHODS: In our patients, preoperative pain sensitivity was assessed by pressure pain threshold measurements with the help of a digital algometer, and heat pain threshold using a neurotouch instrument. In addition, pain sensitivity questionnaires (PSQ) were used in all our patients to determine pain sensitivity. Preoperative psychosocial and functional assessments were performed by Hospital anxiety-depression scores (HADS), and Oswestry disability index (ODI) respectively. Preoperative visual analog scale (VAS) score was determined at three instances of needle prick (phlebotomy, glucometer blood sugar, and intradermal antibiotic test dose) and during the range of movements of the lumbar spine region. Postoperative VAS score and postoperative breakthrough analgesic requirements were recorded in all of these patients from day 0 to day 3. RESULTS: The average age of the patients was 51.11±13.467 years and 70% were females. Females had lower mean algometry values (72.14±7.56) compared to males (77.34±6.33). Patients with higher HADS (p<.0016), higher PSQ (p<.001), higher ODI scores(p<.001), and female gender significantly correlated with a lower algometer average indicating high pain sensitivity. Patients with lower preoperative VAS scores and with higher neurotouch scores showed lower postoperative VAS scores at different time periods. Preoperative VAS scores, algometer average scores, neurotouch scores, and HADS scores were considered as independent variables (predictors) for postoperative VAS at 6 hours period. By the multivariate analysis, factors like preoperative VAS scores, algometer average scores, and HADS scores were statistically significant (p<.05). There was a significant correlation between algometer average scores (p<.001) with the breakthrough analgesics. CONCLUSION: Preoperative assessment of pain sensitivity can predict postoperative analgesic requirements and aid in recovery. Patients with a lower pain threshold should be counseled preoperatively and also receive a better titration of analgesics perioperatively.

Perioperative analgesic efficacy and safety of erector spinae plane block in posterior cervical spine surgery-a double blinded, randomized controlled study.

BACKGROUND CONTENT: Posterior cervical spine surgery (PCSS) are typically open surgeries and entail significant postoperative pain. Current perioperative pain management in PCSS is reliant on multimodal analgesia. While perioperative epidural anesthetic infusion can be used in lumbar surgeries, this is not an option in the cervical spine. Pre-emptive regional analgesia through erector spinae plane block (ESPB) has shown significant perioperative analgesic benefits in lumbar spine surgeries. There are no such clinical studies in PCSS. PURPOSE: To assess the safety and efficacy of ultrasound-guided ESPB for perioperative analgesia in PCSS. STUDY DESIGN: Prospective, randomized controlled, double-blinded study. PATIENT SAMPLE: Eighty-six patients requiring sub-axial PCSS with or without instrumentation were randomized into two groups, those who underwent ESPB with multimodal analgesia (case) and those with only multimodal analgesia (control). OUTCOME MEASURES: Demographic and surgical data (blood loss, duration of surgery, perioperative total opioid consumption, muscle relaxants used) were assessed. Postoperatively, the surgical site pain, alertness scale, satisfaction score, time to mobilization and complications were recorded. METHODS: After anesthesia and prone position, case patients received ultrasound-guided ESPB at the T1 level using 15 ml of 0.25% bupivacaine and 8 mg Dexamethasone bilaterally while the control patients received only standard postoperative multimodal analgesia. RESULTS: There were 43 patients in each group; the two groups were identical in demographic and surgical profile. The intraoperative opioid consumption (119.53±40.35 vs. 308.6±189.78; p<.001) in mcg), muscle relaxant usage (50.00±0.00 mg vs. 59.53±3.75 mg, p<.001), surgical duration (124.77±26.63/ 156.74±37.01 min; p<.01) and intraoperative blood loss (310.47±130.73 ml vs. 429.77±148.50 ml; p<.05) were significantly less in the ESPB group. In the postoperative period, the control group's pain score was significantly higher (p<.001). The Modified Observer Alertness/Sedation Score (MOASS) score and satisfaction scores also showed significant differences between the case and control groups (p<.001). The mean time required to ambulate (sitting/walking) was statistically less in cases (15.81±6.15/20.72±4.02 h) when compared to controls (16.86±6.18/ 23.05±8.88 h; p<.001). CONCLUSION: In patients undergoing PCSS, ESPB is a safe and effective technique with better outcomes than standard multimodal analgesia alone, in terms of reduced intraoperative opioid requirements and blood loss, better postoperative analgesia and early mobilization.

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression.

BACKGROUND: Protection of islets without systemic immunosuppression has been a long-sought goal in the islet transplant field. We conducted a pilot biocompatibility/safety study in healthy dogs followed by a dose-finding efficacy study in diabetic dogs using polyethylene glycol diacrylate (PEGDA) microencapsulated allogeneic canine islets. METHODS: Prior to the transplants, characterization of the canine islets included the calculations determining the average cell number/islet equivalent. Following measurements of purity, insulin secretion, and insulin, DNA and ATP content, the islets were encapsulated and transplanted interperitoneally into dogs via a catheter, which predominantly attached to the omentum. In the healthy dogs, half of the microspheres injected contained canine islets, the other half of the omentum received empty PEGDA microspheres. RESULTS: In the biocompatibility study, healthy dogs received increasing doses of cells up to 1.7 M cells/kg body weight, yet no hypoglycemic events were recorded and the dogs presented with no adverse events. At necropsy the microspheres were identified and described as clear with attachment to the omentum. Several of the blood chemistry values that were abnormal prior to the transplants normalized after the transplant. The same observation was made for the diabetic dogs that received higher doses of canine islets. In all diabetic dogs, the insulin required to attempt to control blood glucose was cut by 50-100% after the transplant, down to no required insulin for the course of the 60-day study. The dogs had no adverse events and behavioral monitoring suggested normal activity after recovery from the transplant. CONCLUSIONS AND IMPLICATIONS: The study provides evidence that PEGDA microencapsulated canine islets reversed the signs of diabetes without immunosuppression and led to states of insulin-independence or significantly lowered insulin requirements in the recipients.

A Mechanistic Based Analysis of Clinicoradiological and Functional Outcome in C7-T1 Translational Injury.

OBJECTIVES: C7-T1 translational injuries are relatively rare, unstable, and usually associated with neurological impairment. We aim to analyze the C7-T1 translational injury based on Allen and Ferguson's classification and to highlight the clinicoradiologic and neurologic outcomes in these patients. METHODS: Patients with C7-T1 translational injury were retrospectively analyzed and demographic data, mechanism, mode of injury, surgery details, and associated injuries were obtained. The initial neurologic status was recorded as American Spinal Injury Association (ASIA) grade. All the injuries were classified as per Allen and Ferguson classification and stage 4 compressive extension (CE) injury was further classified into stage 4a and stage 4b according to Rebich et al. RESULTS: Among 44 patients, the most common mechanism of injury was CE injury seen in 27 patients (61.4%) followed by distractive flexion (DF) in 16 patients (36.4%) and compressive flexion in 1 patient (2.2%). Neurologic deficit was noted in 14 of 27 patients (51.85%) with CE injury, which was less compared to 12 of 16 patients (75%) with DF injury. However, there was no significant difference in terms of neurologic recovery. One patient with standalone anterior fixation had implant loosening and underwent additional posterior fixation. CONCLUSIONS: We present the largest series of C7-T1 translational injuries in the literature to our best knowledge. CE injury is nearly 2 times more common than DF injury and is associated with a lower incidence of neurologic deficit and easier fracture reduction techniques. Staging the injury severity aids in better planning in terms of surgical approach and levels of fixation.

Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity.

Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to "scaffold" regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS2) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. The in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo. Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BRS and expand the range of lesions that can be treated using transient implants. STATEMENT OF SIGNIFICANCE: Bioresorbable Scaffolds (BRSs) support regeneration of arteries without permanent mechanical constraint. Poly-L-lactide (PLLA) is the structural material of the first approved BRS for coronary heart disease (ABSORB BVS), withdrawn due to adverse events in years 1-3. Here, we examine tungsten disulfide (WS2) nanotubes (WSNT) in PLA to address two contributors to early complications: (1) reinforce PLLA (enable thinner BRS), and (2) increase radiopacity (provide intraoperative visibility). For BRS, it is significant that WSNT disperse, remain dispersed, reduce friction and improve mechanical properties without additional chemicals or surface modifications. Like WS2 nanospheres, bare WSNT and PLA-WSNT nanocomposites show low cytotoxicity in vitro. PLA-WSNT show enhanced flow-induced crystallization relative to PLA, motivating future study of the processing behavior and strength of these materials.

Spinal Hypertrophic Pachymeningitis Causing Thoracic Myelopathy in a Patient of Takayasu Arteritis: A Case Report.

CASE: A 52-year-old man presented with thoracic myelopathy, and his magnetic resonance imaging (MRI) was suggestive of T1-T4 hypertrophic-pachymeningitis. Incidentally, circumferential thickening of the infra-renal abdominal aorta and right common iliac artery was seen, which along with the findings in a contrast computed tomography was consistent with Takayasu arteritis (TA). The patient underwent T1-T4 laminectomy, thinning of dura, biopsy, and steroid therapy. At the 1-year follow-up, he was asymptomatic and MRI revealed resolution of the lesion. CONCLUSION: This is the first report describing an association between TA and hypertrophic spinal pachymeningitis, emphasizing the unusual neurological manifestation of myelopathy and complete resolution of symptoms with timely and appropriate intervention.

A Versatile Microencapsulation Platform for Hyaluronic Acid and Polyethylene Glycol.

Cell microencapsulation is a rapidly expanding field with broad potential for stem cell therapies and tissue engineering research. Traditional alginate microspheres suffer from poor biocompatibility, and microencapsulation of more advanced hydrogels is challenging due to their slower gelation rates. We have developed a novel, noncytotoxic, nonemulsion-based method to produce hydrogel microspheres compatible with a wide variety of materials, called core-shell spherification (CSS). Fabrication of microspheres by CSS derived from two slow-hardening hydrogels, hyaluronic acid (HA) and polyethylene glycol diacrylate (PEGDA), was characterized. HA microspheres were manufactured with two different crosslinking methods: thiolation and methacrylation. Microspheres of methacrylated HA (MeHA) had the greatest swelling ratio, the largest average diameter, and the lowest diffusion barrier. In contrast, PEGDA microspheres had the smallest diameters, the lowest swelling ratio, and the highest diffusion barrier, while microspheres of thiolated HA had characteristics that were in between the other two groups. To test the ability of the hydrogels to protect cells, while promoting function, diabetic NOD mice received intraperitoneal injections of PEGDA or MeHA microencapsulated canine islets. PEGDA microspheres reversed diabetes for the length of the study (up to 16 weeks). In contrast, islets encapsulated in MeHA microspheres at the same dose restored normoglycemia, but only transiently (3-4 weeks). Nonencapsulated canine islet transplanted at the same dose did not restore normoglycemia for any length of time. In conclusion, CSS provides a nontoxic microencapsulation procedure compatible with various hydrogel types.

Lactate Elicits ER-Mitochondrial Mg2+ Dynamics to Integrate Cellular Metabolism.

Mg2+ is the most abundant divalent cation in metazoans and an essential cofactor for ATP, nucleic acids, and countless metabolic enzymes. To understand how the spatio-temporal dynamics of intracellular Mg2+ (iMg2+) are integrated into cellular signaling, we implemented a comprehensive screen to discover regulators of iMg2+ dynamics. Lactate emerged as an activator of rapid release of Mg2+ from endoplasmic reticulum (ER) stores, which facilitates mitochondrial Mg2+ (mMg2+) uptake in multiple cell types. We demonstrate that this process is remarkably temperature sensitive and mediated through intracellular but not extracellular signals. The ER-mitochondrial Mg2+ dynamics is selectively stimulated by L-lactate. Further, we show that lactate-mediated mMg2+ entry is facilitated by Mrs2, and point mutations in the intermembrane space loop limits mMg2+ uptake. Intriguingly, suppression of mMg2+ surge alleviates inflammation-induced multi-organ failure. Together, these findings reveal that lactate mobilizes iMg2+ and links the mMg2+ transport machinery with major metabolic feedback circuits and mitochondrial bioenergetics.