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.

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.

Microfluidic extensional flow device to study mass transfer dynamics in the polymer microparticle formation process.

Polymer microparticles are often used to encapsulate drugs for sustained drug-release treatments. One of the ways they are manufactured is by using a solvent extraction process, in which the polymer solution is emulsified into an aqueous bulk phase using a surfactant as a stabilizing agent, followed by the removal of the solvent. The radius of a polymer drop decreases as a function of time until the polymer reaches the gelling point, after which it is separated and dried. Among the various operating parameters, the rate of solvent extraction is a critical step that affects the morphology and porosity, and consequently, the kinetics of drug release. But a fundamental mechanistic understanding of the solvent extraction dynamics as a function of shear is still unexplored. In this study, we have developed an experimental mass transfer model to predict the extraction by using the microfluidic extensional flow device (MEFD) to probe the shear and extraction dynamics at the level of a single drop in a linear extensional flow field. We used a computer-controlled feedback algorithm to manipulate the flow field and hydrodynamically trap a Hele-Shaw drop and observe the extraction process. For the polymer solution, we used a biocompatible polymer, poly-lactic-co-glycolic acid (PLGA) with ethyl acetate (EtOAc) as the solvent. Our experiments were conducted by varying the extensional rate (G) in the channel from ∼0.1 s-1 to ∼10 s-1, and using an analytical solution of the flow field, we captured the dissolution process and measured the change in drop radius (R) with time (t). Interestingly, we initially observed a short-time asymptote R ∼ t, and later the long-time asymptote of R = constant; both trends were physically explained. The transport model developed in this work can be used to predict extraction rates and polymer microparticle composition for any polymer-solvent system. This work is also an important contribution to the literature on convective mass transfer in partially miscible emulsions.

Identification of extracellular matrix proteins in plasma as a potential biomarker for intervertebral disc degeneration.

PURPOSE: Recently, there has been significant focus on extracellular matrix proteolysis due to its importance in the pathological progression of intervertebral disc degeneration (IVDD). The present study investigates the circulating levels of extracellular matrix proteins in the plasma of IVDD and determines their potential relevance as biomarkers in disc degeneration. METHODS: Global proteomic analysis was performed in the plasma samples of 10 healthy volunteers (HV) and 10 diseased subjects (DS) after depletion of highly abundant proteins such as albumin and IgG. RESULTS: We identified 144 and 135 matrix-associated proteins in plasma samples from healthy volunteers (HV) and patients with disc degeneration (DS), respectively. Among these, 49 of the matrix-associated proteins were identical to the proteins found in intervertebral disc (IVD) tissues retrieved from the in-house library. Applying stringent parameters, we selected 28 proteins, with 26 present in DS and 21 in HV. 19 proteins were found common between the groups, two of which-aggrecan (ACAN) and fibulin 1 (FBLN1) - showed statistically significant differences. Specifically, ACAN was up-regulated and FBLN1 was down-regulated in the DS-plasma. In particular, DS-plasma exhibited specific expression of collagen type 2a1 (COL2A1), native to the nucleus pulposus. CONCLUSION: The distinct presence of collagen type 2a1 and the elevated expression of aggrecan in IVDD plasma may serve as the basis for the development of a potential biomarker for monitoring the progression of disc degeneration.

Crimping-induced structural gradients explain the lasting strength of poly l-lactide bioresorbable vascular scaffolds during hydrolysis.

Biodegradable polymers open the way to treatment of heart disease using transient implants (bioresorbable vascular scaffolds, BVSs) that overcome the most serious complication associated with permanent metal stents-late stent thrombosis. Here, we address the long-standing paradox that the clinically approved BVS maintains its radial strength even after 9 mo of hydrolysis, which induces a ∼40% decrease in the poly l-lactide molecular weight (Mn). X-ray microdiffraction evidence of nonuniform hydrolysis in the scaffold reveals that regions subjected to tensile stress during crimping develop a microstructure that provides strength and resists hydrolysis. These beneficial morphological changes occur where they are needed most-where stress is localized when a radial load is placed on the scaffold. We hypothesize that the observed decrease in Mn reflects the majority of the material, which is undeformed during crimping. Thus, the global measures of degradation may be decoupled from the localized, degradation-resistant regions that confer the ability to support the artery for the first several months after implantation.

Triple-negative breast cancer cell line sensitivity to englerin A identifies a new, targetable subtype.

PURPOSE: Triple-negative breast cancers (TNBCs) represent a heterogeneous group of tumors. The lack of targeted therapies combined with the inherently aggressive nature of TNBCs results in a higher relapse rate and poorer overall survival. We evaluated the heterogeneity of TNBC cell lines for TRPC channel expression and sensitivity to cation-disrupting drugs. METHODS: The TRPC1/4/5 agonist englerin A was used to identify a group of TNBC cell lines sensitive to TRPC1/4/5 activation and intracellular cation disruption. Quantitative RT-PCR, the sulforhodamine B assay, pharmacological inhibition, and siRNA-mediated knockdown approaches were employed. Epifluorescence imaging was performed to measure intracellular Ca2+ and Na+ levels. Mitochondrial membrane potential changes were monitored by confocal imaging. RESULTS: BT-549 and Hs578T cells express high levels of TRPC4 and TRPC1/4, respectively, and are exquisitely, 2000- and 430-fold, more sensitive to englerin A than other TNBC cell lines. While englerin A caused a slow Na+ and nominal Ca2+ accumulation in Hs578T cells, it elicited rapid increases in cytosolic Ca2+ levels that triggered mitochondrial depolarization in BT-549 cells. Interestingly, BT-549 and Hs578T cells were also more sensitive to digoxin as compared to other TNBC cell lines. Collectively, these data reveal TRPC1/4 channels as potential biomarkers of TNBC cell lines with dysfunctional mechanisms of cation homeostasis and therefore sensitivity to cardiac glycosides. CONCLUSIONS: The sensitivity of BT-549 and Hs578T cells to englerin A and digoxin suggests a subset of TNBCs are highly susceptible to cation disruption and encourages investigation of TRPC1 and TRPC4 as potential new biomarkers of sensitivity to cardiac glycosides.

Multiplicity of morphologies in poly (l-lactide) bioresorbable vascular scaffolds.

Poly(l-lactide) (PLLA) is the structural material of the first clinically approved bioresorbable vascular scaffold (BVS), a promising alternative to permanent metal stents for treatment of coronary heart disease. BVSs are transient implants that support the occluded artery for 6 mo and are completely resorbed in 2 y. Clinical trials of BVSs report restoration of arterial vasomotion and elimination of serious complications such as late stent thrombosis. It is remarkable that a scaffold made from PLLA, known as a brittle polymer, does not fracture when crimped onto a balloon catheter or during deployment in the artery. We used X-ray microdiffraction to discover how PLLA acquired ductile character and found that the crimping process creates localized regions of extreme anisotropy; PLLA chains in the scaffold change orientation from the hoop direction to the radial direction on micrometer-scale distances. This multiplicity of morphologies in the crimped scaffold works in tandem to enable a low-stress response during deployment, which avoids fracture of the PLLA hoops and leaves them with the strength needed to support the artery. Thus, the transformations of the semicrystalline PLLA microstructure during crimping explain the unexpected strength and ductility of the current BVS and point the way to thinner resorbable scaffolds in the future.

Improved yield of canine islet isolation from deceased donors.

BACKGROUND: Canine diabetes is a strikingly prevalent and growing disease, and yet the standard treatment of a twice-daily insulin injection is both cumbersome to pet owners and only moderately effective. Islet transplantation has been performed with repeated success in canine research models, but has unfortunately not been made available to companion animals. Standard protocols for islet isolation, developed primarily for human islet transplantation, include beating-heart organ donation, vascular perfusion of preservation solutions, specialized equipment. Unfortunately, these processes are prohibitively complex and expensive for veterinary use. The aim of the study was to develop a simplified approach for isolating canine islets that is compatible with the financial and logistical restrictions inherent to veterinary medicine for the purpose of translating islet transplantation to a clinical treatment for canine diabetes. RESULTS: Here, we describe simplified strategies for isolating quality islets from deceased canine donors without vascular preservation and with up to 90 min of cold ischemia time. An average of more than 1500 islet equivalents per kg of donor bodyweight was obtained with a purity of 70% (N = 6 animals). Islets were 95% viable and responsive to glucose stimulation for a week. We found that processing only the body and tail of the pancreas increased isolation efficiency without sacrificing islet total yield. Islet yield per gram of tissue increased from 773 to 1868 islet equivalents when the head of the pancreas was discarded (N = 3/group). CONCLUSIONS: In summary, this study resulted in the development of an efficient and readily accessible method for obtaining viable and functional canine islets from deceased donors. These strategies provide an ethical means for obtaining donor islets.

Long-term cryopreservation of reaggregated pancreatic islets resulting in successful transplantation in rats.

Preservation of pancreatic islets for long-term storage of islets used for transplantation or research has long been a goal. Unfortunately, few studies on long-term islet cryopreservation (1 month and longer) have reported positive outcomes in terms of islet yield, survival and function. In general, single cells have been shown to tolerate the cryopreservation procedure better than tissues/multicellular structures like islets. Thus, we optimized a method to cryopreserve single islet cells and, after thawing, reaggregated them into islet spheroids. Cryopreserved (CP) single human islet cells formed spheroids efficiently within 3-5 days after thawing. Approximately 79% of islet cells were recovered following the single-cell cryopreservation protocol. Viability after long-term cryopreservation (4 weeks or more) was significantly higher in the CP islet cell spheroids (97.4 ± 0.4%) compared to CP native islets (14.6 ± 0.4%). Moreover, CP islet cell spheroids had excellent viability even after weeks in culture (88.5 ± 1.6%). Metabolic activity was 4-5 times higher in CP islet cell spheroids than CP native islets at 24 and 48 h after thawing. Diabetic rats transplanted with CP islet cell spheroids were normoglycemic for 10 months, identical to diabetic rats transplanted with fresh islets. However, the animals receiving fresh islets required a higher volume of transplanted tissue to achieve normoglycemia compared to those transplanted with CP islet cell spheroids. By cryopreserving single cells instead of intact islets, we achieved highly viable and functional islets after thawing that required lower tissue volumes to reverse diabetes in rats.

Double Level Non-Contiguous Traumatic Lumbar Disc Herniation Presenting With Cauda Equina Syndrome: A Case Report and Literature Review.

CASE: A 52-year-old man presented with cauda equina syndrome after a motorcycle accident. Magnetic resonance imaging revealed traumatic disc herniation, at L2-L3 and L5-S1 levels without bony injury. He was managed successfully by wide laminectomy and microdiscectomy at both levels with complete neurological recovery at 2-month follow-up. CONCLUSION: With a reported incidence of 0.4%, traumatic disc herniation in the lumbar region is an uncommon occurrence that may resemble a spinal epidural hematoma in acute trauma. Although MRI may not reliably differentiate spinal epidural hematoma from disc herniation, urgent surgical intervention may be required in profound neurological deficits.

From Modic to Disc Endplate Bone Marrow Complex - The Natural Course and Clinical Implication of Vertebral Endplate Changes.

STUDY DESIGN: Review article. OBJECTIVES: A review of literature on the epidemiology, natural course, pathobiology and clinical implications of vertebral endplate changes. METHODS: A literature search was performed using the Cochrane Database of Systematic Reviews, EMBASE, and PubMed. Studies published over the last 10 years were analysed. The searches were performed using Medical Subject Headings terms, and the subheadings used were "Vertebral endplate changes", "Modic changes", "Disc Endplate Bone Marrow complex". RESULTS: The disc, endplate (EP), and bone marrow region of the spine constitute a unified morphological and functional unit, with isolated degeneration of any one structure being uncommon. Disc degeneration causes endplate defects, which result in direct communication and a constant cross-talk between the disc and the vertebral body. This may result in a persistent inflammatory state of the vertebral bone marrow, serving as a major pain generator. This review article focuses on vertebral endplate changes and how the current understanding has progressed from the Modic classification to the Disc Endplate Bone Marrow complex classification. It provides a clear portrayal of the natural course of these alterations and their clinical implications in low back pain. CONCLUSIONS: In light of the heightened interest and current prominence of vertebral endplate changes within the spine community, we must progress beyond the Modic changes to achieve a comprehensive understanding. The DEBM complex classification will play a major part in disc degeneration research and clinical care, representing a considerable advancement in our understanding of the vertebral endplate changes over the classical Modic changes.

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.

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.

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.

Neuromonitoring Signal Changes in Degenerative Cervical Myelopathy: An Analysis of Risk Factors for Signal Drops During Posterior Cervical Decompression.

OBJECTIVE: To analyze intraoperative neuromonitoring data of patients with degenerative cervical myelopathy undergoing cervical laminectomy and assess the incidence of signal drops and their risk factors. METHODS: This retrospective observational study included patients with degenerative cervical myelopathy who underwent cervical laminectomy with intraoperative neuromonitoring between July 2018 and March 2023. We analyzed the signal changes for any correlation with the type of pathology (ossified posterior longitudinal ligament vs. cervical spondylotic myelopathy [CSM]) and clinical (severity of myelopathy, duration of symptoms) and radiological (length of cord signal changes and K-line) parameters. RESULTS: Of 100 degenerative cervical myelopathy cases, 55 were diagnosed as OPLL and 45 as CSM. Signal drops were recorded in 26 patients-14 persistent drops and 12 transient drops. True positive drops were seen in 4 patients (2 OPLL and 2 CSM), 3 of whom had sustained bimodal drops (both somatosensory evoked potentials and motor evoked potentials). Signal drops were significantly more frequent with OPLL compared with CSM (P < 0.01). Ten of 14 persistent signal drops and 9 of 12 transient drops were seen in patients in OPLL. Continuous OPLL, negative K-line, hill type OPLL, severity of myelopathy, and longer duration of symptoms were risk factors for signal drops. CONCLUSIONS: Patients with cervical OPLL have a higher incidence of false positive and transient signal drops after decompression compared with patients with CSM. Longer duration of symptoms, high-grade myelopathy, continuous OPLL, hill type OPLL, and negative K-line were risk factors for signal drops.

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.

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.

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.

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.

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.