Intravitreal topotecan for vitreous seeds in retinoblastoma: A long-term review of 91 eyes.

OBJECTIVE: To study the long-term safety and efficacy of intravitreal topotecan (IVT) against vitreous seeds in eyes with retinoblastoma and risk factors for their recurrence. DESIGN: Retrospective, non-comparative, interventional study. SUBJECTS: 91 eyes of 90 patients with retinoblastoma treated between January 2013 to April 2019. INTERVENTION: Patients with recurrent or refractory vitreous seeds following completion of intravenous or intra-arterial chemotherapy were treated with IVT (30µg/0.15ml) by the safety enhanced technique. The injection was repeated every 4 weeks till the regression of seeds. Patients with a minimum follow up of 12 months were included in the analysis. MAIN OUTCOME MEASURES: Primary outcome measures were vitreous seed regression, and eye salvage. Secondary outcomes were risk factors for vitreous seed recurrence following treatment with IVT, vision salvage and complications of IVT. RESULTS: The median age of the patients was 18 months, majority having group D (58, 64%) and group E (26, 29%) retinoblastoma. Vitreous seeds were refractory in 46 (51%) and recurrent in 45 (49%) eyes. A total of 317 IVT injections were given, median being 3. The median number of IVT injections required were 2.5 for dust, 3 for sphere and 5 for cloud morphology. Recurrence of vitreous seeds following IVT was seen in 17 eyes (19%) at a mean follow up of 7.9 months. At a mean follow up 34 months, vitreous seed regression was achieved in 88 (97%) eyes and eye salvage in 77 (85%) eyes. Older age (p=0.018) and recurrence of retinal tumor (15/17 eyes) (p<0.01) significantly increased the risk of vitreous seed recurrence. Cataract was the most common complication seen in 17 (9%) eyes. CONCLUSION: Intravitreal topotecan at a 3-4-weekly regimen is effective against both refractory and recurrent vitreous seeds. The vitreous seed morphology corresponds to the number of injections required for regression. Increasing age and recurrence of retinal tumor increase the risk of vitreous seed recurrence following treatment with IVT.

A Whole-Spine Magnetic Resonance Imaging-Based Cross-Sectional Study of the Clinicoradiological Association of Lumbosacral Transitional Vertebra with Degenerative Disc Disease, End Plate Degeneration, Low Back Pain, and Facet Tropism.

OBJECTIVE: To understand lumbosacral transitional vertebra (LSTV)-associated degenerative pathologies and their correlation to low back pain and radicular pain. METHODS: Whole-spine magnetic resonance imaging was evaluated for disc degeneration using Pfirrmann grading, end plate changes using total end plate score (TEPS), and facet tropism in patients with low back pain and radicular pain, and their association with LSTV was analyzed. RESULTS: In group 1, LSTV was seen in 15% of patients with 83% of these patients having sacralization. Disc degeneration was seen in 58%, 51%, and 63% of patients at levels C, B, and A, respectively; patients with sacralization had significant degeneration at all 3 levels. Similarly, the total end plate score and facet tropism were significantly higher in patients with sacralization. Facet tropism was observed in 31%, 40%, and 35% of patients with no -LSTV, patients with sacralization, and patients with lumbarization, respectively. In group 2, LSTV was seen in 17% of patients with sacralization accounting for 82%. Disc degeneration was seen in 44%, 36%, and 54% patients at levels C, B, and A, respectively. No significant difference was observed in the mean total end plate score between groups. Facet tropism was identified in 89% and 81% of patients with sacralization and patients with lumbarization, respectively, compared with only 19% of patients with no LSTV. CONCLUSIONS: Patients with low back pain had a higher incidence of sacralization with corresponding disc degeneration, facet tropism ,and end plate changes. In patients with radicular pain, lumbarization was associated only with facet tropism. These findings may aid clinicians in prognostication and patient counseling.

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

PURPOSE: To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). METHODS: A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). RESULTS: Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). CONCLUSION: Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.

Innovative blood transfusion strategies to address global blood deserts: a consensus statement from the Blood Delivery via Emerging Strategies for Emergency Remote Transfusion (Blood DESERT) Coalition.

In rural settings worldwide, many people live in effective blood deserts without access to any blood transfusion. The traditional system of blood banking is logistically complex and expensive for many resource-restricted settings and demands innovative and multidisciplinary solutions. 17 international experts in medicine, industry, and policy participated in an exploratory process with a 2-day hybrid seminar centred on three promising innovative strategies for blood transfusions in blood deserts: civilian walking blood banks, intraoperative autotransfusion, and drone-based blood delivery. Participant working groups conducted literature reviews and interviews to develop three white papers focused on the current state and knowledge gaps of each innovation. Seminar discussion focused on defining blood deserts and developing innovation-specific implementation agendas with key research and policy priorities for future work. Moving forward, advocates should prioritise the identification of blood deserts and address the context-specific challenges for these innovations to alleviate the ongoing crisis in blood deserts.

The disc-endplate-bone-marrow complex classification: progress in our understanding of Modic vertebral endplate changes and their clinical relevance.

BACKGROUND CONTEXT: The disc, endplate (EP), and bone marrow region of the spine form a single anatomical and functional interdependent unit; isolated degeneration of any one structure is rare. Modic changes (MC), however, are restricted to the subchondral bone alone and based on only T1 and T2 sequences of MRI. This results in poor reliability in differentiating fat from edema and hence may give a false impression of disease inactivity. PURPOSE: To study the changes in disc, endplate, and bone marrow as a whole in degeneration and propose a classification based on the activity status of this complex with the addition of STIR MRI sequences. STUDY DESIGN: Observational cohort. PATIENT SAMPLE: Patients with isolated brain, cervical, or thoracic spine injury and patients with low back pain (LBP) who underwent MRI formed the control and study groups, respectively. OUTCOME MEASURES: Demographic data, the prevalence of MC and disc-endplate-bone marrow classification (DEBC) changes, EPs undergoing reclassification based on DEBC, and comparison of the prevalence of MC, DEBC, H+modifier and DEBC with H+concordance between control and LBP group. The study determined the risk of LBP patients undergoing surgery as well as the incidence of postoperative infection based on DEBC changes. Significance was calculated by binomial test and chi-square test with the effect size of 0.3 to 0.5. Prevalence and association of outcome were calculated by Altman's odds ratio with the 95% CI and the scoring of z statistics. Logistic expression was plotted for independent variables associated with each class of both Modic and DEBC against dependent variables surgery and nonsurgery. METHODS: Lumbar segments in both groups were assessed for MC types. The DEBC classification was developed with the addition of STIR images and studying the interdependent complex as a whole: type-A: acute inflammation; type-B: chronic persistence; type-C: latent and type-D: inactive. Modifier H+ was added if there was disc herniation. The classification was compared with MC and correlated to clinical outcomes. RESULTS: A total of 3,560 EPs of 445 controls and 8,680 EPs in 1,085 patients with LBP were assessed. Four nonMC, 560 MC-II, and 22 MC-III EPs were found to have previously undetected edema in STIR (n=542) or hyperintensity in discs (n=44) needing reclassification. The formerly undescribed type-B of DEBC, representing a chronic persistent activity state was the most common (51.8%) type. The difference between the control and LBP of H+(12% vs 28.8%) and its co-occurrence with DEBC type 1.1% vs 23.3%) was significant (p<.0001). The odds ratio for the need for surgery was highest (OR=5.2) when H+ and DEBC type change co-occurred. Postoperative deep infection (as determined by CDC criteria) was 0.47% in nonDEBC, compared with 2.4% in patients with DEBC (p=.002), with maximum occurrence in type-B. CONCLUSION: Classification based on the classic MC was found to need a reclassification in 586 EPs showing the shortcomings of results of previous studies. Considering the DEBC allowed better classification and better predictability for the need for surgical intervention and incidence of postoperative infection rate than MC.

SECONDARY SALVAGE INTRAVENOUS CHEMOTHERAPY FOR REFRACTORY/RECURRENT RETINOBLASTOMA: A Study of 41 Eyes.

PURPOSE: To determine the efficacy of secondary salvage intravenous chemotherapy (IVC) for refractory/recurrent retinoblastoma. METHODS: Retrospective, nonrandomized interventional case series of 41 eyes of 33 patients with recurrent retinoblastoma. RESULTS: Of the 33 patients, mean age at the time of commencement of salvage IVC was 5 years (median, 5 years; range, 2-8 years). At presentation, recurrent retinoblastoma in 41 eyes of 33 patients was classified by the International Classification of Retinoblastoma as Group B (n = 7; 17%), Group C (n = 3; 7%), Group D (n = 16; 39%), and Group E (n = 15; 37%). All patients received 6 cycles of IVC as primary treatment. The indication for secondary salvage IVC with focal treatment included recurrent solid tumor (n = 36; 88%), subretinal seeds (n = 22; 54%), or persistent solid tumor (n = 2; 5%). Mean number of cycles of salvage IVC were 8 (median, 6; range, 6-18). Over a mean follow-up period of 43 months (median, 43 months; range, 12-96 months) after completion of salvage IVC, globe salvage was achieved in 22 (54%) eyes, 1 (3%) patient had histopathology-proven bone metastasis, and 1 (3%) patient died because of presumed metastasis. CONCLUSION: Secondary salvage IVC with appropriate focal treatment allows globe salvage in 54% eyes with refractory/recurrent retinoblastoma and thus serves as an alternative to intraarterial chemotherapy or enucleation.

Metastatic retinoblastoma at presentation: Clinical presentation, treatment, and outcomes.

The aim of this study was to retrospectively determine clinical features, treatment outcomes, and overall survival in four patients with metastatic retinoblastoma at presentation. The mean age at diagnosis was 63 months (range: 24-108 months). Three patients had overt orbital disease of at least one eye and one patient had microscopic orbital disease with scleral infiltration on histopathology. Metastatic sites included regional lymph nodes (RLN) (n = 4), bone marrow (BM) (n = 2), and cerebrospinal fluid (CSF) (n = 1). The most common sites of RLN were ipsilateral preauricular nodes (two patients) and contralateral parotid gland involvement (one patient). The treatment administered included primary enucleation (n = 1), high-dose intravenous chemotherapy (n = 4), secondary enucleation (n = 2), orbital external beam radiotherapy (n = 3), and intrathecal chemotherapy (n = 1). High-risk features included massive choroidal and microscopic scleral infiltration in the eye that underwent primary enucleation. At a mean follow-up of 33 months (range, 4-68 months), one patient with CSF involvement deceased in 4 months. The remaining three patients were alive and disease-free at the last mean follow-up period of 43 months (range, 18-68 months). The results of our study showed that RLN and BM metastasis respond well to treatment while CSF metastasis is associated with poor prognosis.

Vancomycin Flushing Syndrome After the Use of Vancomycin-Impregnated Bone Graft During Spine Surgery: A Case Report.

CASE: Intrawound vancomycin in spine surgery is a common clinical practice. We report a case of a 14-year-old adolescent girl undergoing surgery for scoliosis correction who developed features of vancomycin flushing syndrome after the use of vancomycin-impregnated bone graft. After resuscitation, she was extubated and had an uneventful postoperative recovery. At 1-year follow-up, she is back to her routine without any sequelae of the intraoperative event. CONCLUSION: The use of intrawound vancomycin can result in life-threatening reactions. With the increase in its use, the anesthetist and the surgeon must be aware of such complications.

Plaque brachytherapy - Radiating positivity.

Background: Plaque brachytherapy is an evolving, yet effective globe and vision-sparing modality for the treatment of intraocular tumors by transscleral irradiation of the tumor base with a radioactive implant. The American Brachytherapy Society (ABS) along with the collaboration of the international multicenter Ophthalmic Oncology Task Force (OOTF) was assembled to reach a consensus regarding establishing practice guidelines and setting standards of care for intraocular tumors. The advent of plaque brachytherapy has revolutionized the outcomes of intraocular tumors, thus ensuring globe salvage, reducing morbidity and mortality, and avoiding cosmetic disfigurement. A well-planned dosimetry for plaque brachytherapy results in achieving local tumor control and excellent prognosis. Purpose: This technique provides the advantage of focal radiation, thus eliminating the damage to the adjacent structures, minimal periorbital tissue damage, absence of cosmetic disfigurement owing to lack of retarded bone growth as seen in external beam radiotherapy. Thus, it reduces the risk of metastasis, and with the recent advances, it provides a shorter duration of treatment. Synopsis: : In this video, we shall display the concept of plaque brachytherapy, the various types of plaques available, different radiations sources, planning dosimetry and calculations, target disease spectrum, surgical placement, and post-radiation outcomes in terms of local tumor control and prognosis. Highlights: This video highlights the history, basic principles and techniques of plaque brachytherapy and provides an understanding of its applications in the world of ocular oncology. Video link: https://youtu.be/7PX0mDQETRY.

Brachytherapy training in India: Results from the GEC-ESTRO-India survey.

INTRODUCTION: Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. METHODS AND MATERIALS: An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1-5 Likert-type scale. Descriptive statistics were used to describe proportions. RESULTS: One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). CONCLUSION: This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT.

Hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated patients with exacerbation of COPD: results from the HOPE COPD Study.

Background: Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. Methods: This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. Results: 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). Conclusions: COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation.

Validation of Blood Pressure Devices as per 2020 World Health Organization Technical Specifications: A Scoping Review of Global Literature.

BACKGROUND: To identify and summarize the global research literature on validation of automated noninvasive blood pressure measurement devices (BPMDs) with upper arm cuff, develop a repository of validated BPMDs in compliance with the 2020 World Health Organization technical specifications, and identify challenges and gaps in evidence base on validated BPMDs. METHODS: A scoping review was conducted. Primary research validating BPMDs complying with the 2020 World Health Organization technical specifications (ie, semiautomated/automated noninvasive devices with upper arm cuff), published in English between January 2000 and December 2021, was included. We searched MEDLINE, Web of Science, Scopus, EMBASE, CINAHL, CENTRAL, ProQuest and the dabl website. RESULTS: We included 269 studies validating 251 BPMDs across 89 manufacturers. Omron (29%), Microlife (10%), and A&D Company (8%) were the top 3 manufacturers. The 3 most frequently used validation protocols were the European Society of Hypertension-international protocol 2002 (27%), European Society of Hypertension-international protocol 2010 (25%), and modified British Hypertension Society protocol 1993 (16%), respectively. Nearly 45% of the validated BPMDs were intended for use in clinical settings, 38% were for home or self-measurement use, and 48% were for general adults. Most studies reported that BPMDs passed the validation criteria. There was inadequate reporting across studies, especially pertaining to validation settings. CONCLUSIONS: Most BPMDs fulfilled the validation criteria. However, there are considerable gaps in BPMD research in terms of geographical representation, including specific target populations and diseases/conditions, and a range of arm circumferences. Additionally, a potential strategy is required to accelerate the adoption of the Association for the Advancement of Medical Instrumentation (AAMI)/European Society of Hypertension/International Organization for Standardization Universal Standard (International Organization for Standardization 81060-2:2018) for BPMD validation.

ISSLS PRIZE in basic science 2023: Lactate in lumbar discs-metabolic waste or energy biofuel? Insights from in vivo MRS and T2r analysis following exercise and nimodipine in healthy volunteers.

PURPOSE: To quantitatively assess the dynamic changes of Lactate in lumbar discs under different physiological conditions using MRS and T2r. METHODS: In step1, MRS and T2r sequences were standardized in 10 volunteers. Step2, analysed effects of high cellular demand. 66 discs of 20 volunteers with no back pain were evaluated pre-exercise (EX-0), immediately after targeted short-time low back exercises (EX-1) and 60 min after (EX-2). In Step 3, to study effects of high glucose and oxygen concentration, 50 lumbar discs in 10 volunteers were analysed before (D0) and after 10 days intake of the calcium channel blocker, nimodipine (D1). RESULTS: Lactate showed a distinctly different response to exercise in that Grade 1 discs with a significant decrease in EX-1 and a trend for normalization in Ex-2. In contrast, Pfirrmann grade 2 and 3 and discs above 40 years showed a higher lactate relative to proteoglycan in EX-0, an increase in lactate EX-1 and mild dip in Ex-2. Similarly, following nimodipine, grade 1 discs showed an increase in lactate which was absent in grade 2 and 3 discs. In contrast, exercise and Nimodipine had no significant change in T2r values and MRS spectrum of proteoglycan, N-acetyl aspartate, carbohydrate, choline, creatine, and glutathione across age groups and Pfirrmann grades. CONCLUSION: MRS documented changes in lactate response to cellular demand which suggested a 'Lactate Symbiotic metabolic Pathway'. The differences in lactate response preceded changes in Proteoglycan/hydration and thus could be a dynamic radiological biomarker of early degeneration.

Surgical Approach to Cervical Fractures in Ankylosing Spondylitis Patients: Rationale and Surgical Strategy.

BACKGROUND: Current literature lacks objective criteria to determine surgical management in patients with ankylosing spondylitis who sustain cervical fractures. The purpose of our study was to analyze the determinants for stratifying surgical approach, evaluate the outcome in patients, and postulate a management strategy. METHODS: This was a retrospective study of patients with ankylosing spondylitis who underwent surgery for cervical spine injury with a minimum follow-up of 2 years. Neurological recovery, fracture pattern including translation and angulation, surgical duration, blood loss, and postoperative complications were recorded, and a comparative analysis of these factors with anterior, posterior, and combined surgical approaches was performed. RESULTS: The study included 43 men with a mean age of 57 years; 49% underwent anterior-only stabilization, 16% underwent posterior-only stabilization, and 35% underwent combined anteroposterior stabilization. Mean operative time was significantly lower in anterior-only (81.4 minutes; P < 0.05) and posterior-only (124 minutes; P < 0.05) approaches compared with combined approach (266.6 minutes). Mean blood loss was significantly lower in anterior-only (87.5 mL, P < 0.05) approach compared with posterior-only (714.7 mL) and combined (912.7 mL) approaches. Mean translation was 1.8 mm, 1.7 mm, and 3.7 mm in anterior, posterior, and combined approaches (P < 0.05), respectively. CONCLUSIONS: Our study provides insights into management of cervical spine fractures in ankylosing spondylitis patients. A fracture displacement ≤2 mm may be successfully managed by an anterior approach, while the posterior approach may be beneficial in similar fractures warranting instrumentation extending to the thoracic spine. All other fractures warrant a combined surgical approach.

RETINOBLASTOMA ASSOCIATED WITH TOTAL EXUDATIVE RETINAL DETACHMENT: Treatment and Outcomes.

PURPOSE: To study the clinical presentation, treatment, and outcomes of eyes presenting with retinoblastoma and total retinal detachment. METHODS: A retrospective study of 50 eyes in 43 patients. RESULTS: The mean age at presentation was 15 months (median, 9 months). Retinoblastoma-associated total retinal detachment was unilateral (n = 36; 84%) or bilateral (n = 7; 16%). The mean tumor basal diameter was 17 mm (median, 18 mm), and the mean tumor thickness was 13 mm (median, 12 mm). Associated features included subretinal seeds (n = 26; 52%), vitreous seeds (n = 13; 26%), and subretinal exudation (n = 4; 8%). Based on eighth edition of American Joint Committee on Cancer classification, the tumors were classified as cT2a (n = 19; 38%), cT2b (n = 28; 56%), or cT3c (n = 3; 6%). Primary treatment included intravenous (n = 48; 96%) or intraarterial chemotherapy (n = 2; 4%). Over a mean follow-up period of 30 months (median, 29 months; range, 7-62 months), retinal detachment resolved in 41 eyes (82%), tumor recurrence was noted in 39 eyes (78%), globe salvage was achieved in 35 eyes (70%), and one patient (2%) died due to metastasis. CONCLUSION: Relatively high tumor recurrence rate is noted in retinoblastoma presenting with total retinal detachment. With appropriate treatment, 70% of the globes can be salvaged.

Hippocampal subfields, daily stressors, and resting cortisol in individuals at clinical high-risk for psychosis.

INTRODUCTION: The hippocampus, comprised of functionally distinct subfields, both regulates stress and is affected by it during psychosis pathogenesis. Hippocampal abnormalities are evident across psychosis spectrum and are associated with aberrant cortisol levels and greater environmental stressors exposure. These associations, particularly at the subfield-level, are poorly understood in individuals at clinical high-risk (CHR) for psychosis. This represents a significant literature gap given this critical pathogenetic period is characterized by an interplay between environmental stressors and biological susceptibility. METHODS: A total of 121 participants including 51 CHR (mean age=18.61) and 70 healthy controls (HC; mean age=18.3) were enrolled in the study. Participants completed a structural scan, salivary cortisol assays, and a self-report measure assessing distress from daily stressors exposure (DSI). Hippocampal subfield segmentation was conducted using Freesurfer. RESULTS: Smaller hippocampal subfields were associated with greater stress levels. Greater DSI was associated with lower volumes in CA1 (r = -0.38) and CA2/3 (r = -0.29), but not in CA4/DG (r = -0.28), presubiculum (r = -0.09), or subiculum (r = -0.17). Higher resting cortisol was associated with lower volumes in presubiculum (r = -0.4) but not subiculum (r = -0.22), CA1 (r = 0.08), CA2/3 (r = 0.1), or CA4/DG (r = -0.005). Regressions indicated effects for CA1 and DSI (ß = 0.57, p = .03) and presubiculum and cortisol (ß = 0.61, p = .02) are specific to CHR participants relative to HCs. CONCLUSIONS: The findings provided insights into links between stress and brain vulnerability during psychosis-risk period. Regional differences highlighted potentially different mechanisms by which stress impacts specific subfields. Presubiculum may be more susceptible to the impact of early stress on HPA-axis and cornu amonis to acute stressors.

In Vertebral Hemangiomas with Neurological Deficit, Is a Less Extensive Approach Adequate.

STUDY DESIGN: This was a retrospective study. PURPOSE: To analyze the surgical and neurological outcomes following surgical decompression in patients with aggressive vertebral hemangioma (AVH) presenting with neurological deficit and to determine whether a less extensive approach is appropriate. OVERVIEW OF LITERATURE: AVHs are a rare subset of benign vascular tumors frequently presenting with neurological deficit because of spinal cord compression. Though the results of surgical management have improved over time, there is a lack of consensus on the ideal management in this group of patients. METHODS: Twenty-one patients who underwent surgery for AVH between 2009 and 2018 were analyzed. Demographic and clinical details of patients were retrieved from hospital information system. Imaging information (i.e., radiography, computed tomography, magnetic resonance imaging) of all patients was accessed and analyzed in picture archiving and communication system. Tumor staging was performed using Enneking and Weinstein-Boriani-Biagini classifications and Spinal Instability Neoplastic Score. At followup, neurological and radiological evaluations were performed. RESULTS: Twenty-one patients (13 [61.9%] females and 8 [38.1%] males) were included with a mean age of 44.29 years (range, 14-72 years). All patients in the study had neurological deficit. Back pain was present in 80.9% of patients. Mean duration of symptoms was 4.6 months (range, 1 day to 10 months). Most common lesion location was thoracic spine (n=12), followed by thoracolumbar (D11- L2; n=7) and lumbar (n=2) regions. Ten patients had multiple level lesions. All patients underwent preoperative embolization. Nine patients underwent intralesional spondylectomy with reconstruction; another nine patients underwent stabilization, decompression, and vertebroplasty; three patients underwent decompression and stabilization. Neurology improved in all patients, and only one case of recurrence was noted in a mean follow-up of 55.78±25 months (range, 24-96 months). CONCLUSIONS: In AVH, good clinical and neurological outcomes with low recurrence rates can be achieved using less extensive procedures, such as posterior instrumented decompression with vertebroplasty and intralesional tumor resection.

Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs.

STUDY DESIGN: Profiling proteins expressed in the nucleus pulposus (NP) of intervertebral discs (IVDs) in five different biological states. PURPOSE: To evaluate the molecular complexity of the collagen (COL) framework and its role in the health and disease of human IVDs. OVERVIEW OF LITERATURE: Changes in COL composition have been linked to degenerative disk disease (DDD). Despite the fact that humans have 28 different types of COLs, most of the literature focuses solely on COL-1 and COL-2. This study used high-end proteomic technology to examine the entire COL composition of the human IVD across fetal (developmental-FD), normal (healthy-ND), scoliotic (early degeneration-SD), herniated (degenerate-DH), and degenerated (DD) disk phenotypes. METHODS: Forty NP tissues were snap-frozen in liquid nitrogen (-196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). RESULTS: Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan-collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. CONCLUSIONS: COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

Bacteria in human lumbar discs - subclinical infection or contamination? Metabolomic evidence for colonization, multiplication, and cell-cell cross-talk of bacteria.

BACKGROUND CONTEXT: The accumulating evidence associating sub-clinical infection with disc degeneration (DD) and the controversy of contamination versus infection mandates a further understanding of the microbial activity in the disc and host-microbiome interaction. PURPOSE: To utilize a novel approach of metabolomics to probe the presence of bacterial metabolites involved in colonization, survival, and replication in human lumbar intervertebral discs (LIVD). STUDY DESIGN: An observational case-control study. PATIENT SAMPLE: Nucleus pulposus from the LIVD of three brain-dead voluntary organ donors (MRI normal and classified as controls) and of three patients undergoing surgery for disc degeneration (DD) (cases) were utilized. METHODS: Untargeted metabolite profiling was carried out in six discs (3-controls and 3-cases) after extraction using methanol: acetonitrile: water (2:2:1) solvent system and acquired through HPLC-MS/MS platform using C18 reversed-phase column. From the total IVD metabolome, microbial metabolites were filtered by mapping against HMDB, ChEBI, SigMol, Siderophore database, ecdmb database, and PaMet databases. The biological functions of the metabolites were then studied by MSEA pipeline from Metaboanalyst, and the enrichment ratio, p-value, and Variably Importance Projection scores of the metabolites were calculated. Degeneration responsive changes in the abundance of the microbial metabolites were calculated based on the peak intensities between the control and cases. RESULTS: Mass spectrometry identified a total of 17601 and 15003 metabolites, respectively, in the control and degenerated discs. Preliminary mapping of the above metabolites against HMDB indicated the multiple sources, and of these, 64 metabolites were of microbial origin, accounting for 1.6% of the total IVD metabolome. Principle Component Analysis and Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA) showed distinct clustered patterns between control and disc degene`ration, indicating a strong variation in concentration, peak, and spectral values of the 64 metabolites between controls and cases. After the exclusion of metabolites that were also associated with humans, drugs, and food, 39 metabolites specific to bacteria were isolated. Nine were primary metabolites related to bacterial growth and survival, and the remaining 30 were secondary metabolites related to different environmental stress response activities. The three significant pathways (p<.001) which were predominant in the bacterial metabolites were autoinducer-2 biosynthesis, peptidoglycan biosynthesis, and chorismate pathway. In addition, a significant fold change of >1.0 was found for nine metabolites which included (S)-14-Methyilhexadecanoic acid related to P. acnes, 9-OxoODE, and 13-OxoODE related to gut flora, vibriobactin - a siderophore, tuberculosinol and iso-tuberculosinol, virulence factors of M. tuberculosis. There was also upregulation of Autoinducer- 2, an important "Quorum sensing molecule" involved in bacterial cross-talk. CONCLUSION: We identified several bacterial-specific metabolites participating in bacterial growth, survival, and cross-talk pathways. These were found in both groups but up-regulated in degenerated discs. The presence of Quorum sensing molecules and cell-cell interactions provides firm proof of colonization and growth. These findings indicate that the bacterial presence may not be mere contamination but could be colonization with a possible role in infection-mediated inflammation in DD. CLINICAL SIGNIFICANCE: Proof of subclinical infection as an initiator of DD and documentation of exact germ and drug sensitivity will change the way millions of patients with non-specific low back pain (NSLBP) are treated across the world.