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Common variable immunodeficiency (CVID) is an immune defect characterized by hypogammaglobulinemia and impaired development of B cells into plasma cells. As follicular helper T cells (TFH) play a central role in humoral immunity, we examined TFH cells in CVID, and investigated whether an inducible T cell co-stimulator (ICOS) agonist, vopratelimab, could modulate TFH, B cell interactions and enhance immunoglobulin production. CVID subjects had decreased TFH17 and increased TFH1 subsets; this was associated with increased transitional B cells and decreased IgG+ B and IgD-IgM-CD27+ memory B cells. ICOS expression on CVID CD4+ T cells was also decreased. However, ICOS activation of CD4+ T cells by vopratelimab significantly increased total CVID TFH, TFH2, cell numbers, as well as IL-4, IL-10 and IL-21 secretion in vitro. Vopratelimab treatment also increased plasma cells, IgG+ B cells, reduced naïve & transitional B cells and significantly increased IgG1 secretion by CVID B cells. Interestingly, vopratelimab treatment also restored IgA secretion in PBMCs from several CVID patients who had a complete lack of endogenous serum IgA. Our data demonstrate the potential of TFH modulation in restoring TFH and enhancing B cell maturation in CVID. The effects of an ICOS agonist in antibody defects warrants further investigation. This biologic may also be of therapeutic interest in other clinical settings of antibody deficiency.
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Linfócitos B , Imunodeficiência de Variável Comum , Proteína Coestimuladora de Linfócitos T Induzíveis , Células T Auxiliares Foliculares , Humanos , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/tratamento farmacológico , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Células T Auxiliares Foliculares/imunologia , Células T Auxiliares Foliculares/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Imunoglobulina G/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Idoso , Adulto JovemRESUMO
BACKGROUND: Microscopic unilateral laminotomy for bilateral decompression (ULBD) is a minimally invasive technique used in the treatment of lumbar spinal stenosis and could limit spinal instability and be associated with better clinical outcomes. However, there is ongoing debate regarding its utility compared to conventional laminectomy (CL). The primary objective was to collate and describe the current evidence base for ULBD, including perioperative parameters, functional outcomes, and complications. The secondary objective was to identify operative techniques. METHODS: A scoping review was conducted between January 1990 and August 2022 according to the PRISMA extension for scoping reviews (PRISMA-ScR) guidelines. Major databases were searched for full text English articles reporting on outcomes following microscopic unilateral laminotomy in patients with lumbar spinal stenosis. RESULTS: Seventeen articles met the inclusion criteria. Two studies were randomised controlled trials. Two studies were prospective data collection and the rest were retrospective analysis. Three studies compared ULBD with CL. ULBD preserves the osteoligamentous complex and may be associated with shorter operative time, less blood loss, and similar clinical outcomes when compared to CL. CONCLUSION: This review highlights that ULBD aims to minimise disruption to the normal posterior spinal anatomy and may have acceptable clinical outcomes. It also highlights that it is difficult to draw valid conclusions given there are limited data available as most studies identified were retrospective or did not have a comparator group.
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Descompressão Cirúrgica , Estenose Espinal , Humanos , Descompressão Cirúrgica/métodos , Laminectomia/métodos , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Estenose Espinal/cirurgia , Resultado do TratamentoRESUMO
Anaplastic gangliogliomas of the spinal cord are extremely rare with only four cases reported in the literature. Here we present the case of a 22-year-old female who presented acutely with quadraparesis and urinary retention. Radiographic imaging demonstrated an intramedullary lesion within the cervical spine. She underwent a cervical laminectomy and resection of the lesion under neurophysiological monitoring. Post-operatively, she regained some function, but remained paraparetic. Histopathology demonstrated an anaplastic ganglioglioma (WHO Grade 3). She subsequently underwent radiotherapy. Following surgery, she remained stable and had MRC Grade 3 Power in all four limbs. Herein, we describe a previously undescribed case of cervical anaplastic ganglioglioma and review the existing literature.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Ganglioglioma , Neoplasias da Medula Espinal , Feminino , Humanos , Adulto Jovem , Adulto , Ganglioglioma/diagnóstico por imagem , Ganglioglioma/cirurgia , Ganglioglioma/patologia , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias Encefálicas/cirurgia , Radiografia , Imageamento por Ressonância MagnéticaRESUMO
Lumbar vertebral tuberculosis presenting with a focal solitary osteolytic lesion is rare in spinal tuberculosis (TB) and the English literature describing this entity is scant. The differential diagnosis includes primary and secondary malignancies. In this report, we describe a case of 35-year-old woman who presented with low back pain and was found to have a focal L4 vertebral lytic lesion on MRI and CT. Whole body CT was carried out as a potential malignancy staging procedure and demonstrated lung lesions suggestive of TB. Her neurological and general examination were entirely normal. Her blood test was positive for QuantiFERON Gold. She was managed conservatively with anti-TB medications and serial imaging which showed evidence of resolution of the osteolytic lesion. Although it is unusual for TB to present as an isolated osteolytic vertebral body lesion, the possibility should always be considered in the differential diagnosis, along with neoplastic processes. Conservative medical management, in the absence of neurological deficits and deformity, is the main stay of management with a very good outlook.
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Dor Lombar , Tuberculose da Coluna Vertebral , Humanos , Adulto Jovem , Feminino , Adulto , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Região Lombossacral , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologiaRESUMO
OBJECTIVE: To investigate if COVID-19 UK lockdown measures resulted in a delay in the presentation and treatment of patients with cauda equina syndrome (CES). METHODS: This is a multicenter retrospective study of patients with surgically treated CES across 3 time periods: April-May 2020 (first lockdown), August-September 2020 (no-lockdown group), and January-February 2021 (second lockdown). Data regarding duration of symptoms, time from referral to admission, time from admission to surgery, and postoperative outcomes were collected. RESULTS: A total of 56 patients (male: 26, female: 30, mean age: 44.3 years) were included in the study (n = 14, n = 18, and n = 24 in the 3 time periods, respectively). There was no significant difference in duration of symptoms across the time periods (12.6 days vs. 8.2 days vs. 3.8 days) (P = 0.16). Nearly all the patients were admitted within 48 hours of referral (n = 55, 98.2%). The majority of patients were operated on within 48 hours: first lockdown (n = 12, 85.7%), no-lockdown (n = 16, 88.9%), and second lockdown (n = 21, 87.5%). The length of hospital stay was significantly shorter in the second lockdown (3.3 days) versus the other 2 time periods (4.4 days and 6.4 days) (P = 0.02). Thirteen complications were present, with dural tear being the most common (n = 6, 10.7%). Majority reported symptom improvement (n = 53, 94.6%), with a similar number discharged home (n = 54, 96.4%). CONCLUSION: Despite the pandemic, patients with CES were promptly admitted and operated on with good outcomes. Shorter duration of hospital stay could be attributed to adaptation of spinal services.
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COVID-19 , Síndrome da Cauda Equina , Cauda Equina , Humanos , Masculino , Feminino , Adulto , Síndrome da Cauda Equina/epidemiologia , Síndrome da Cauda Equina/cirurgia , Síndrome da Cauda Equina/etiologia , Estudos Retrospectivos , Descompressão Cirúrgica/efeitos adversos , Controle de Doenças Transmissíveis , Reino Unido/epidemiologia , Cauda Equina/cirurgiaRESUMO
PURPOSE: The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors. PATIENTS AND METHODS: In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed. RESULTS: ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was well tolerated; phase I established 0.3 mg/kg every 3 weeks as the vopratelimab RP2D. Vopratelimab resulted in modest objective response rates of 1.4% and with nivolumab of 2.3%. The prospective selection for ICOS+ tumors did not enrich for responses. A vopratelimab-specific peripheral blood pharmacodynamic biomarker, ICOS-high (ICOS-hi) CD4 T cells, was identified in a subset of patients who demonstrated greater clinical benefit versus those with no emergence of these cells [overall survival (OS), P = 0.0025]. A potential genomic predictive biomarker of ICOS-hi CD4 T-cell emergence was identified that demonstrated improvement in clinical outcomes, including OS (P = 0.0062). CONCLUSIONS: Vopratelimab demonstrated a favorable safety profile alone and in combination with nivolumab. Efficacy was observed only in a subset of patients with a vopratelimab-specific pharmacodynamic biomarker. A potential predictive biomarker of response was identified, which is being prospectively evaluated in a randomized phase II non-small cell lung cancer trial. See related commentary by Lee and Fong, p. 3633.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/uso terapêutico , Linfócitos T CD4-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/administração & dosagem , Estudos ProspectivosRESUMO
OBJECTIVE: Benign spinal intradural tumors are rare entities and there have been relatively few case series describing the epidemiology and characteristics of these tumors. Here, we evaluate the presentation, demographics, pathology and outcomes associated with the surgical management of spinal meningioma in our unit over a 6-year period. RESULTS: A total of 68 cases presented to the operating surgeon during a 6-year period. Of these, over 80% (n = 55) were in females. Seventy-nine percent of the meningiomas were observed in the thoracic region (n = 54). Weakness and gait disturbance were the most common presenting complaints. Surgery significantly improved both motor outcome (p < 0.001) and health related qualities of life (SF36, p < 0.01).Seventeen percent of spinal meningioma cases (n = 12) had a preceding cancer diagnosis. Of these 75% (n = 9/12) were attributable to breast cancer. Overall, breast cancer preceded a diagnosis of a spinal meningioma in 16.4% of female cases (9/55). This is higher than expected number of breast cancer based on UK population and those reported in literature for breast cancer and intracranial meningioma. CONCLUSION: Spinal meningioma is disproportionately over-represented in females. Patients present with neurological deficits and surgery improved both neurology and patient reported quality of life. Relative to the known UK prevalence of breast cancer, there is a significantly higher than expected association between spinal meningioma and a preceding history of breast cancer.
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PURPOSE: A dural tear is a common iatrogenic complication of spinal surgery associated with a several post-operative adverse events. Despite their common occurrence, guidelines on how best to repair the defect remain unclear. This study uses five post-operative outcomes to the compare repair methods used to treat 106 dural tears to determine which method is clinically favourable. METHODS: Data were retrospectively collected from Southampton General Hospital's online databases. 106 tears were identified and grouped per repair method. MANOVA was used to compare the following five outcomes: Length of stay, numbers of further admissions or revision surgeries, length of additional admissions, post-operative infection rate and dural tear associated neurological symptoms. Sub-analysis was conducted on patient demographics, primary vs non-primary closure and type of patch. Minimal clinically important difference (MCID) was calculated via the Delphi procedure. RESULTS: Age had a significant impact on patient outcomes and BMI displayed positive correlation with three-fifth of the predefined outcome measures. No significant difference was observed between repair groups; however, primary closure ± a patch achieved an MCID percentage improvement with regards to length of original stay, rate of additional admissions/surgeries and post-operative infection rate. Artificial over autologous patches resulted in shorter hospital stays, fewer readmissions, infections and neurological symptoms. CONCLUSION: This study reports primary closure ± dural patch as the most efficient repair method with regards to the five reported outcomes. This study provides limited evidence in favour of artificial over autologous patches and recommends that dural patches be used in conjunction with primary closure. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
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Dura-Máter , Procedimentos Neurocirúrgicos , Estudos Transversais , Dura-Máter/cirurgia , Humanos , Procedimentos Neurocirúrgicos/efeitos adversos , Reoperação , Estudos RetrospectivosRESUMO
Previous research demonstrated that bacterial and viral vaccines delivered via the nasal route in rainbow trout (Oncorhynchus mykiss) at 7 and 28 days post-vaccination are highly protective (>95% protection). Long-term protection following nasal vaccination in teleosts has not been evaluated. The goal of this study was to assess efficacy and immune responses at 6 months (mo) post-vaccination (mpv), and long-lasting immune responses at 12 mpv of two different vaccines: an inactivated enteric red mouth disease (ERM) Yersinia ruckeri bacterin and a live attenuated infectious hematopoietic necrosis virus (IHNV) vaccine. Juvenile rainbow trout were vaccinated for Y. ruckeri via intraperitoneal (I.P.) and intranasal (I.N.) routes, and for IHNV by intramuscular (I.M.) and I.N. routes, then challenged at 6 mpv. Immune responses were determined at 6 and 12 mpv. ERM vaccine I.P. delivery elicited significantly higher serum IgM-specific titers that remained elevated compared to mock-vaccinated fish at 6 mpv. By 12 mpv, antibody titers to Y. ruckeri were not significantly different across all treatments. Following Y. ruckeri challenge at 6 mpv, a significant difference in cumulative percent mortality (CPM) was found for I.P.-vaccinated fish but not I.N.-vaccinated fish. I.M. and I.N. vaccination with live attenuated IHNV did not result in significant specific serum IgM titers at 6 or 12 mpv. Yet, I.N.-vaccinated fish showed the lowest CPM 6 mpv indicating long-term protection that does not correlate with systemic IgM responses. Repertoire analyses confirmed unique expansions of VH-JH rearrangements in the spleen of rainbow trout 12 mpv that varied with the type of vaccine and route of vaccination. Combined, these data demonstrate that I.N. vaccination with a live attenuated viral vaccine confers long lasting protection, but I.N. ERM vaccination does not and booster before 6 mpv is recommended.
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Doenças dos Peixes , Doenças da Boca , Oncorhynchus mykiss , Yersiniose , Animais , Doenças dos Peixes/prevenção & controle , Necrose , Vacinação , Yersiniose/prevenção & controle , Yersiniose/veterinária , Yersinia ruckeriRESUMO
BACKGROUND: Paraspinal tumors are rare neoplasms arising from neurogenic elements of the posterior mediastinum and surgical resection can be challenging. Here, we demonstrate feasibility and outcomes from the first European case series of combined laminectomy and video-assisted thoracoscopic surgery (VATS) resection of thoracic neurogenic dumbbell tumors. METHODS: A retrospective review of all combined thoracic dumbbell tumor resections performed at our institution between March 2015 to February 2019 was undertaken. Outcomes included operative time, blood loss, length of stay and recurrence rate. Statistical analysis was performed with SPSS statistics (v26). Values are given as mean ± standard deviation and median ± interquartile range. RESULTS: Seven patients were included in the case series and there were no major complications or mortality. Mean tumor size and operative time were 66 (± 35) mm and 171 (± 63) min, respectively. Median blood loss and length of stay were 40 (± 70) ml and four (± 3) days, respectively. One patient required conversion to thoracotomy to remove a tumor of 135 mm in maximal dimension. Histology in all seven cases confirmed schwannoma. There was no disease recurrence at a maximum follow-up of 54 months. CONCLUSIONS: Our experience demonstrates favorable operative times, minimal blood loss and short length of stay when dealing with relatively large tumors compared to previous reports. Thoracotomy may be required for tumors exceeding 90 mm and chest drain removal on the operative day can facilitate early mobility and discharge. We advocate a combined, minimally invasive laminectomy and VATS resection as the gold-standard approach for thoracic neurogenic dumbbell tumors.
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Laminectomia/métodos , Neoplasias do Mediastino/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neurilemoma/cirurgia , Neoplasias Torácicas/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Sports-related injuries are the third commonest cause of spine fractures. Spinal fractures incurred as a result of partaking in sport by their nature are different from those associated with frailty and road traffic accidents. The patient demographics and nature of fractures associated with sports activities are not well documented. We aim to describe the management and outcome of patients with a sports-related spine fracture in a single U.K. major trauma center in a 6-year time period. METHODS: Patients with sports-related spinal fractures were identified from the Trauma Audit and Research Network database at a U.K. major trauma center between January 2011 and December 2016. Patient notes were retrospectively reviewed for demographics, injury severity score, treatment, complications, and outcomes. RESULTS: In the study period, 122 patients were admitted with a sports-related spinal fracture, sustaining a total of 230 fractures. Of these, 48 (20.9%) were in the cervical, 79 (34.3%) in the thoracic, and 103 (44.8%) in the lumbar regions. The sports most commonly associated with spinal fractures were horse riding (n = 55), cycling (n = 36), and boating (n = 10). Of the 230 fractures, 32 (13.9%) were associated with neurologic injury. Forty-five of the 230 fractures (19.6%) were managed surgically, and the remainder were managed conservatively. CONCLUSIONS: Within our population, sports most commonly associated with spinal fractures were horse riding, cycling, and boating. The majority of cases were managed nonoperatively. Further research is required to establish evidence-based guidelines on the management of sports-related spinal fractures.
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Traumatismos em Atletas/complicações , Traumatismos em Atletas/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/patologia , Adulto , Idoso , Traumatismos em Atletas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/terapia , Reino UnidoRESUMO
INTRODUCTION: The acute management of spinal fractures is traditionally split between neurosurgeons and orthopaedic surgeons and the specialities have varying approaches to management. This study investigates differences between neurosurgeons and spinal orthopaedic surgeons in the management of spinal fractures at a single trauma centre in the United Kingdom. METHODS: A retrospective study at a single trauma centre of patients identified using the Trauma Audit and Research Network (TARN). Case notes and radiological investigations were reviewed for demographics, fracture classification, clinical management and outcomes. Polytrauma cases and patients managed by non-neurosurgical/orthopaedic specialties were excluded. RESULTS: A total of 465 patients were included in this study (neurosurgery n = 266, orthopaedics n = 199). There were no significant differences between groups for age, gender, Charlson co-morbidity score or distribution of fractures using the AO spine classification. Patients admitted and managed under the orthopaedic surgeons were more likely to undergo a surgical procedure when compared to those admitted under the neurosurgeons (n = 71; 35.7% vs n = 71; 26.8%, p = 0.042, OR 1.56 95%CI 1.056 to 2.31). The median overall length of stay was 8 days and there was no significant difference between teams; however, the neurosurgical cohort were more likely to be admitted to an intensive care unit (24.3% vs 16.2%, p = 0.04). CONCLUSION: This study is the first in the United Kingdom to compare neurosurgical and orthopaedic teams in their management of spinal fractures. It demonstrates that differences may exist both in operating rates and outcomes.
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Neurocirurgia , Ortopedia , Fraturas da Coluna Vertebral , Humanos , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Reino Unido/epidemiologiaRESUMO
Innate lymphoid cells (ILCs) rapidly undergo expansion in population size and functional maturation in response to cytokines that signal infection, tissue damage, or changes in physiology. Optimal ILC responses are shaped, in part, by the microbiota but the mechanisms remain unclear. We report that short-chain fatty acids (SCFAs), produced by the commensal microbiota from dietary fibers, support optimal expansion of ILCs, including ILC1, ILC2, and ILC3 in the intestines through their G-protein-coupled receptors (GPCRs). While this function is primarily important for intestinal ILC populations, it can also boost ILC responses in other tissues depending on host condition. ILCs express multiple GPCRs that detect SCFAs. Interestingly, we found that the expression of SCFA receptors, such as Ffar2 and Ffar3, by ILCs is induced by SCFAs. GPCR triggering by SCFAs co-stimulates the activation of phosphoinositide 3-kinase (PI3K), Stat3, Stat5, and mammalian target of rapamycin (mTOR), which is important for ILC proliferation. While Ffar2 signaling promotes ILC2 proliferation, SCFAs can suppress ILC2 proliferation through a non-Ffar2-mediated mechanism. In conclusion, our findings indicate that SCFAs, as the major mediator of healthy microbiota and nutritional status, function to maintain optimal numbers of ILCs in peripheral tissues during infection and inflammatory responses.
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Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Linfócitos/imunologia , Microbiota/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
Introduction: Accidents during sporting activities are a common cause of head injury, particularly in children and young adults. Whilst most sporting head injuries are minor, there remains a proportion which is associated with high morbidity and mortality. The epidemiology of sports associated head injuries is variable based on geographical region so the aim of this study was to review the management and outcomes of sporting head injuries managed by a single neurosurgical unit in the South of England.Method: A retrospective review of the Trauma Audit and Research Network database was conducted for all patients admitted to a tertiary neurosurgical centre over a six-year period (January 2011-December 2016). Case notes were reviewed for demographics, mechanism of injury, injury severity score, intensive care admission, surgical interventions and Glasgow Outcome Score at discharge.Results: Seventy-six patients (mean age: 37.6 ± 18.4 years, male gender n = 43; 56.6%) were eligible for inclusion in this series. Horse riding accidents were identified as the most common cause of head injury (n = 31; 40.8%). Fifteen patients (19.7%) in this series had a severe head injury (GCS 3-8 on admission). Twenty-eight (36.8%) patients required admission to an intensive care unit and 26 (34.2%) patients underwent neurosurgical intervention. At discharge, 68 (89.5%) patients had a Glasgow Outcome Score 4-5.Conclusion: The majority of patients with head injuries admitted to a neurosurgical unit can expect a good functional outcome despite the need for intensive care or neurosurgical intervention. The range of sports resulting in head injury is likely influenced by geographic location; however, further national study is required for wider comparison.
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Traumatismos Craniocerebrais , Adulto , Animais , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/cirurgia , Inglaterra/epidemiologia , Escala de Coma de Glasgow , Cabeça , Cavalos , Hospitalização , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Esportes , Adulto JovemRESUMO
The nervous system regulates host immunity in complex ways. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with pathogens; however, OSNs' ability to detect danger and initiate immune responses is unclear. We report that nasal delivery of rhabdoviruses induces apoptosis in crypt OSNs via the interaction of the OSN TrkA receptor with the viral glycoprotein in teleost fish. This signal results in electrical activation of neurons and very rapid proinflammatory responses in the olfactory organ (OO), but dampened inflammation in the olfactory bulb (OB). CD8α+ cells infiltrate the OO within minutes of nasal viral delivery, and TrkA blocking, but not caspase-3 blocking, abrogates this response. Infiltrating CD8α+ cells were TCRαß T cells with a nonconventional phenotype that originated from the microvasculature surrounding the OB and not the periphery. Nasal delivery of viral glycoprotein (G protein) recapitulated the immune responses observed with the whole virus, and antibody blocking of viral G protein abrogated these responses. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviruses. These results indicate a function for OSNs as a first layer of pathogen detection in vertebrates and as orchestrators of nasal-CNS antiviral immune responses.
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Linfócitos T CD8-Positivos/imunologia , Vírus da Necrose Hematopoética Infecciosa/imunologia , Neurônios Receptores Olfatórios/fisiologia , Receptor trkA/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Neurônios Receptores Olfatórios/citologia , Neurônios Receptores Olfatórios/virologia , Oncorhynchus mykissRESUMO
OBJECTIVE: Evaluation of the presentation and outcomes associated with surgical marsupialisation of spinal arachnoid cysts and formulation of a putative hypothesis explaining their pathogenesis. PATIENTS AND METHODS: Cases were identified from electronic and theatre records at a single centre. All patients underwent pre-operative assessment and radiographic evaluation with subsequent spinal multidisciplinary discussion. Following surgery patients were reviewed at 6, 12 weeks, 6-months and beyond. RESULTS: A total of 17 patients with dorsal thoracic arachnoid cysts with a mean age at time of surgery of 58 years with a male to female ratio of 1.8:1 were identified. Paraesthesia (76%), neuropathic pain (76%), weakness (47%) and unsteadiness (53%) were the commonest presenting complaints. Abnormal gait (76%), altered sensation (71%) and weakness (47%) were the most commonly observed signs. Average cyst volume was observed to be 2570â¯mm3 (sd ±1682, range 544 to 7644â¯mm3), spanning a median of 2 thoracic levels, with a resultant reduction of cord volume of 33% (sd 12%). A syrinx was associated with 35% of SAC. All cases underwent marsupialisation of the arachnoid cyst. Six months following surgery all patients experienced improvement in at least of one their presenting symptoms and or clinical signs. Weakness, gait and paraesthesia were most likely to improve following surgery. Only 29% of cases had resolution of neuropathic pain, with 13% of the rest reporting an improvement in the sensitivity component of their pain. Clinical improvements correlated with an average 45% (sd 18%) volume increase in previously compressed cord. CONCLUSION: Intradural arachnoid cysts commonly present with paraesthesia, neuropathic pain and gait disturbance. Marsupialisation of the SAC heralds immediate and long-term improvement in symptoms. Cysts putatively arise within a dissection in the septum posticum and give rise to both dynamic and static compression of cord parenchyma secondary to the complex CSF flow dynamics within the thoracic spine.
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Cistos Aracnóideos/cirurgia , Doenças da Medula Espinal/cirurgia , Adulto , Idoso , Cistos Aracnóideos/diagnóstico , Cistos Aracnóideos/fisiopatologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Cisto Mediastínico/diagnóstico , Cisto Mediastínico/fisiopatologia , Cisto Mediastínico/cirurgia , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Neuralgia/etiologia , Procedimentos Neurocirúrgicos , Parestesia/etiologia , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: Falls from standing are common, particularly amongst the aging population, due to declining mobility, proprioception and vision. They are often complicated by fragility fractures, including vertebral fractures, that are associated with significant morbidity and may represent a pre-terminal condition with high one-year mortality rates. PATIENTS AND METHODS: A retrospective review of the Trauma Audit and Research Network database for a major trauma centre was conducted for all patients admitted between January 2011 and December 2016. Patients with a spinal fracture and a confirmed fall from standing height were eligible for inclusion. Case notes were reviewed for demographics, Injury Severity Score, Charlson co-morbidity score, treatment, complications and outcomes. RESULTS: Of 1408 patients with a spine fracture admitted during the study period, 229 (16.3%) were confirmed to be secondary to a fall from standing height. The average age of this cohort was 76.6 ± 14.5 years and 134 (58.5%) cases were female. The average ISS score was 9.7 ± 5.4. The 229 patients sustained 283 fractures with a distribution of: cervical (n = 140), thoracic (n = 65) and lumbar (n = 78) spine. Fifty-six (24.5%) patients underwent surgical intervention. Forty-three patients (18.7%) died within 6 months of admission and all-cause mortality was significantly higher in patients with increasing age and Charlson co-morbidity score. CONCLUSION: Spinal fractures due to a fall from standing height represent one sixth of the fracture workload of the emergency spinal service at a major trauma centre. Whilst the majority of patients can be managed conservatively there are still considerable implications for hospital bed usage and patient mortality.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Vértebras Cervicais/cirurgia , Traumatismos da Medula Espinal/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/lesões , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos da Medula Espinal/complicações , Fraturas da Coluna Vertebral/epidemiologia , Centros de Traumatologia/estatística & dados numéricosRESUMO
Calcific discitis is a well recognized entity in the paediatric population but more recently has been increasingly reported in adults. It typically involves the lower thoracic vertebrae and is of unknown aetiology. Herniation of the calcified fragment is rare but typically occurs out through the annulus fibrosus into the canal space. Herein we describe the first reported case of calcific discitis involving the lumbar vertebrae with subsequent herniation of the calcified disc into and through the anterior aspect of the L5 vertebra. The patient first presented with a history of right back pain and leg sciatica. Radiographic imaging demonstrated calcification within the L4/5 interspace, which was managed with simple analgesia. She subsequently re-presented 24-months later with worsening sciatica, right leg weakness and faecal incontinence. No evidence of cord or root compression was noted on MRI. However, an abnormality was noted at the anterior body of L5 with evidence of superior endplate depression and marrow signal change. Subsequent radionucleide bone studies confirmed a solitary focus of increased linear activity extending across the width of the L4-L5 interspace. Her symptoms were managed medically. Serial radiographic imaging demonstrated regression of the disc space calcification and healing of the L5 fracture. Despite its sinister presentation this condition was self-limiting. We describe the radiographic evolution of this pathology and postulate a putative hypothesis through which it may have arisen.
Assuntos
Calcinose/complicações , Discite/complicações , Deslocamento do Disco Intervertebral/etiologia , Vértebras Lombares/patologia , Idoso , Dor nas Costas/etiologia , Dor nas Costas/patologia , Calcinose/patologia , Discite/patologia , Feminino , Humanos , Deslocamento do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal , Radiografia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Syringomyelia is a fluid-filled cavitation within the substance of the spinal cord. This condition usually follows a primary pathology that disrupts the normal cerebrospinal fluid circulation or disturbs the microcirculation and cytoarchitecture of the spinal cord parenchyma. However, an etiology of recurrent syringomyelia resulting from an ectopic choroid plexus (CP) has not been discussed. Ectopic CP rests may be found within the central nervous system. Although there has been a single report, describing ectopic intramedullary spinal cord CP, to our knowledge, extra-cranial nonmalignant CP in the central canal of the spinal cord has not been reported. CASE DESCRIPTION: We report CP in the central canal of the spinal cord in a 23-year-old male patient who had developmental delay and diabetes mellitus type I who presented with dissociated sensory changes and muscle wastage predominantly on the right upper and lower limbs. Magnetic resonance imaging demonstrated a multiloculated spinal cord syringomyelia stretching from cervical (C3) to the conus medullaris causing recurrent neurologic deficits. A biopsy of the central canal spinal cord lesion revealed CP. Decompression and syringosubarachnoid shunt insertion stabilized the patient's neurology. CONCLUSIONS: Our illustrative case reveals the presence of CP in the central canal of the spinal cord that may suggest a role in the etiology of recurrent syringomyelia. Although management poses a challenge to neurosurgeons, prompt decompression and shunting of the syringomyelia remains a favorable approach with acceptable outcomes. Further investigation into the pathophysiology of central canal CP ectopic causing recurrent syringomyelia and its correlation with spinal cord development may help future treatments.