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The microbiome dictates the response to cancer immunotherapy efficacy. However, the mechanisms of how the microbiota impacts therapy efficacy remain poorly understood. In a recent issue of Nature Immunology, Sharma and colleagues elucidate a multifaceted, macrophage-driven mechanism exerted by a specific strain of fermented food commensal plantarum strain IMB19, LpIMB19. LpIMB19 activates tumor macrophages, resulting in the enhancement of cytotoxic cluster differentiation 8 (CD8) T cells. LpIMB19 administration led to an expansion of tumor-infiltrating CD8 T cells and improved the efficacy of anti-PD-L1 therapy. Rhamnose-rich heteropolysaccharide, a strain-specific cell wall component, was identified as the primary effector molecule of LplMB19. Toll-like receptor 2 signaling and the ability of macrophages to sequester iron were both critical for rhamnose-rich heteropolysaccharide-mediated macrophage activation upstream of the CD8 T-cell effector response and contributed to tumor cell apoptosis through iron deprivation. These findings reveal a well-defined mechanism connecting diet and health outcomes, suggesting that diet-derived commensals may warrant further investigation. Additionally, this work emphasizes the importance of strain-specific differences in studying microbiome-cancer interactions and the concept of "nutritional immunity" to enhance microbe-triggered antitumor immunity.
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Microambiente Tumoral , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Humanos , Animales , Hierro/metabolismo , Linfocitos T CD8-positivos/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Neoplasias/inmunología , Neoplasias/microbiología , Neoplasias/patología , Lactobacillus plantarum , Ratones , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/efectos de los fármacos , DietaRESUMEN
Background: Spinal cord injuries (SCI) often result in cardiovascular issues, increasing the risk of stroke and cognitive deficits. Objectives: This study assessed cerebrovascular reactivity (CVR) using functional magnetic resonance imaging (fMRI) during a hypercapnic challenge in SCI participants compared to noninjured controls. Methods: Fourteen participants were analyzed (n = 8 with SCI [unless otherwise noted], median age = 44 years; n = 6 controls, median age = 33 years). CVR was calculated through fMRI signal changes. Results: The results showed a longer CVR component (tau) in the grey matter of SCI participants (n = 7) compared to controls (median difference = 3.0 s; p < .05). Time since injury (TSI) correlated negatively with steady-state CVR in the grey matter and brainstem of SCI participants (RS = -0.81, p = .014; RS = -0.84, p = .009, respectively). Lower steady-state CVR in the brainstem of the SCI group (n = 7) correlated with lower diastolic blood pressure (RS = 0.76, p = .046). Higher frequency of hypotensive episodes (n = 7) was linked to lower CVR outcomes in the grey matter (RS = -0.86, p = .014) and brainstem (RS = -0.89, p = .007). Conclusion: Preliminary findings suggest a difference in the dynamic CVR component, tau, between the SCI and noninjured control groups, potentially explaining the higher cerebrovascular health burden in SCI individuals. Exploratory associations indicate that longer TSI, lower diastolic blood pressure, and more hypotensive episodes may lead to poorer CVR outcomes. However, further research is necessary to establish causality and support these observations.
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Circulación Cerebrovascular , Imagen por Resonancia Magnética , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Masculino , Adulto , Femenino , Persona de Mediana Edad , Circulación Cerebrovascular/fisiología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiopatología , Tronco Encefálico/fisiopatología , Tronco Encefálico/diagnóstico por imagenRESUMEN
OBJECTIVE: Individuals with spinal cord injury (SCI) report using cannabis to self-manage chronic pain and spasticity. However, its safety and efficacy are not well understood. As more women with SCI are pursuing motherhood, clinicians must consider the possibility of maternal cannabis use and its impact on fetal development. Moreover, due to the lack of current evidence for cannabis, it is important to characterize the perceptions and knowledge of physicians towards both recreational and synthetic cannabinoids. DESIGN: Two anonymous surveys (10-items each) were conducted. SETTING AND PARTICIPANTS: Women with SCI (n = 20) completed an anonymous, online survey regarding cannabis use. Physicians at a Canadian SCI rehabilitation center (n = 15) completed a survey on their knowledge of recreational and synthetic cannabinoids among individuals with SCI. OUTCOME MEASURES: Survey 1 evaluated cannabis use patterns and perceptions before/after SCI in women, including during pregnancy and breastfeeding. The aim of Survey 2 was to understand the perception and current knowledge of physicians regarding recreational cannabis and synthetic cannabinoid use by patients with SCI. RESULTS: At the time of survey, 7 women with SCI reported use of cannabis, only 4 of them used prior to injury. Managing tone/spasticity (n = 5) was the major reported benefit of cannabis use. Women used cannabis during pregnancy and/or breastfeeding as a sleep aid or relief for morning sickness (n = 1 pregnancy, n = 1 breastfeeding, n = 1 both). The most-reported challenge with cannabis use was difficulty obtaining consistent, desirable effects (n = 5). Almost all physicians (n = 13) described their knowledge on recreational cannabis products as "none, very little or poor", with greater overall comfort and knowledge of synthetic cannabinoids. CONCLUSION: Due to the reported use of cannabis during pregnancy/breastfeeding and current impoverishment of physicians' knowledge (particularly regarding recreational cannabis products), it is imperative to further investigate the safety and efficacy of cannabis use in women with SCI.
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Cannabinoides , Cannabis , Médicos , Traumatismos de la Médula Espinal , Humanos , Femenino , Estudios Transversales , Canadá , Encuestas Epidemiológicas , Espasticidad MuscularRESUMEN
The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). Twelve participants (four females, eight males; median age 42 years) completed this study and underwent urodynamics, 24-h ambulatory blood pressure monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. Compared with baseline, fesoterodine improved lower urinary tract (LUT) function, that is, increased cystometric capacity (205 vs. 475 mL, p = 0.002) and decreased maximum detrusor pressure (44 vs. 12 cm H2O, p = 0.009). NDO was eliminated in seven (58%) participants. Severity of AD events during urodynamics (40 vs. 27 mm Hg, p = 0.08) and 24-h ABPM (59 vs. 36 mm Hg, p = 0.05) were both reduced, yielding a large effect size (r = -0.58). AD Frequency (14 vs. 3, p = 0.004) during 24-h ABPM was significantly reduced. Urinary incontinence-related QoL improved (68 vs. 82, p = 0.02), however, cognitive (p = 0.2) and bowel function (p = 0.4) did not change significantly. In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.
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Disreflexia Autónoma , Traumatismos de la Médula Espinal , Vejiga Urinaria Hiperactiva , Incontinencia Urinaria , Masculino , Femenino , Humanos , Adulto , Disreflexia Autónoma/tratamiento farmacológico , Disreflexia Autónoma/etiología , Calidad de Vida , Estudios Prospectivos , Monitoreo Ambulatorio de la Presión Arterial , Traumatismos de la Médula Espinal/complicaciones , Incontinencia Urinaria/tratamiento farmacológico , Incontinencia Urinaria/etiología , Vejiga Urinaria , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/etiología , Resultado del TratamientoRESUMEN
The BCG (Bacille Calmette-Guérin) vaccine, introduced 100 years ago for tuberculosis prevention, has emerging therapeutic off-target benefits for autoimmunity. In randomized controlled trials, BCG vaccinations were shown to gradually improve two autoimmune conditions, type 1 diabetes (T1D) and multiple sclerosis. Here, we investigate the mechanisms behind the autoimmune benefits and test the hypothesis that this microbe synergy could be due to an impact on the host T cell receptor (TCR) and TCR signal strength. We show a quantitative TCR defect in T1D subjects consisting of a marked reduction in receptor density on T cells due to hypermethylation of TCR-related genes. BCG corrects this defect gradually over 3 years by demethylating hypermethylated sites on members of the TCR gene family. The TCR sequence is not modified through recombination, ruling out a qualitative defect. These findings support an underlying density defect in the TCR affecting TCR signal strength in T1D.
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Cervical spinal cord injury (SCI) leads to autonomic cardiovascular dysfunction that underlies the three- to fourfold elevated risk of cardiovascular disease in this population. Reduced common carotid artery (CCA) dilatory responsiveness during the cold-pressor test (CPT) is associated with greater cardiovascular disease risk and progression. The cardiovascular and CCA responses to the CPT may provide insight into cardiovascular autonomic dysfunction and cardiovascular disease risk in individuals with cervical SCI. Here, we used CPT to perturb the autonomic nervous system in 14 individuals with cervical SCI and 12 uninjured controls, while measuring cardiovascular responses and CCA diameter. The CCA diameter responses were 55% impaired in those with SCI compared with uninjured controls (P = 0.019). The CCA flow, velocity, and shear response to CPT were reduced in SCI by 100% (P < 0.001), 113% (P = 0.001), and 125% (P = 0.002), respectively. The association between mean arterial pressure and CCA dilation observed in uninjured individuals (r = 0.54, P = 0.004) was absent in the SCI group (r = 0.22, P = 0.217). Steady-state systolic blood pressure (P = 0.020), heart rate (P = 0.003), and cardiac contractility (P < 0.001) were reduced in those with cervical SCI, whereas total peripheral resistance was increased compared with uninjured controls (P = 0.042). Relative cerebral blood velocity responses to CPT were increased in the SCI group and reduced in controls (middle cerebral artery, P = 0.010; posterior cerebral artery, P = 0.026). The CCA and cardiovascular responsiveness to CPT are impaired in those with cervical SCI.NEW & NOTEWORTHY This is the first study demonstrating that CCA responses during CPT are suppressed in SCI. Specifically, CCA diameter, flow, velocity, and shear rate were reduced. The relationship between changes in MAP and CCA dilatation in response to CPT was absent in individuals with SCI, despite similar cardiovascular activation between SCI and uninjured controls. These findings support the notion of elevated cardiovascular disease risk in SCI and that the cardiovascular responses to environmental stimuli are impaired.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedades Cardiovasculares , Médula Cervical , Traumatismos de la Médula Espinal , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Arteria Carótida Común , Arterias Carótidas , Arteria Cerebral Media , Traumatismos de la Médula Espinal/complicacionesRESUMEN
STUDY DESIGN: Narrative review. OBJECTIVES: To evaluate the availability and quality of breastfeeding guidelines for women with spinal cord injury (SCI). SETTING: International Collaboration on Repair Discoveries (ICORD), Department of Medicine, Vancouver, BC. METHODS: An environmental scan restricted to English language literature was performed to identify existing postpartum and breastfeeding guidelines. Guidelines were evaluated using a structured, validated tool (AGREE II) by 13 appraisers [medical/research experts (n = 10) and those with lived experience (n = 3)] from Vancouver and two international sites. Seven guidelines were evaluated across Domain 1 of the AGREE II tool to determine if they were applicable to mothers with SCI/physical disabilities. Domains 2 to 7 were evaluated if the guideline made mention of the SCI population. RESULTS: Of the seven guidelines evaluated, only one mentioned SCI (Postpartum Care in SCI from BC Women's Hospital). Other guidelines were excluded from further evaluation as they did not address the issue of breastfeeding in women with SCI. The overall scaled score for this guideline was 34.5%. There was significant variability between domains but no AGREE II domain scored greater than 50%, indicating substantial limitations. CONCLUSIONS: Current breastfeeding guidelines are not targeted to persons with SCI. The one guideline that made mention of women with SCI had significant global deficits. This highlights the importance of developing guidelines for health care providers focused specifically on women with SCI to support and optimize breastfeeding in this unique population for the benefit of mother and infant across the lifespan.
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Personas con Discapacidad , Traumatismos de la Médula Espinal , Lactancia Materna , Femenino , Personal de Salud , HumanosRESUMEN
Individuals with cervical spinal cord injury (SCI) are at an increased risk for cardiovascular disease. Exercise is well-established for preventing cardiovascular disease; however, there are limited straightforward and safe exercise approaches for increasing the activity of the cardiorespiratory system after cervical SCI. The objective of this study was to investigate the cardiorespiratory response to passive leg cycling in people with cervical SCI. Beat-by-beat blood pressure, heart rate, and cerebral blood flow were measured before and throughout 10 minutes of cycling in 11 people with SCI. Femoral artery flow-mediated dilation was also assessed before and immediately after passive cycling. Safety was monitored throughout all study visits. Passive cycling elevated systolic blood pressure (5 ± 2 mm Hg), mean arterial pressure (5 ± 3 mm Hg), stroke volume (2.4 ± 0.8 mL), heart rate (2 ± 1 beats/min) and cardiac output (0.3 ± 0.07 L/min; all p < 0.05). Minute ventilation (0.67 ± 0.23 L/min), tidal volume (70 ± 30 mL) and end-tidal PO2 (2.6 ± 1.23 mm Hg) also increased (all p < 0.05). Endothelial function was improved immediately after exercise (1.62 ± 0.13%, p < 0.01). Passive cycling resulted in an incidence of autonomic dysreflexia. Therefore, passive leg cycling increased the activity of the cardiorespiratory system and improved endothelial function, indicating it may be a beneficial exercise intervention for the cardiovascular and respiratory systems in people with cervical SCI. Novelty: Passive leg cycling increases the activity of the cardiorespiratory system and improves markers of cardiovascular health in cervical SCI. Passive leg cycling exercise is an effective, low-cost, practical, alternative exercise modality for people with cervical SCI.
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Pierna , Traumatismos de la Médula Espinal , Ciclismo , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Cuadriplejía , Traumatismos de la Médula Espinal/complicacionesRESUMEN
Objective: To examine the prevalence of postpartum depression (PPD) and postpartum anxiety (PPA) in mothers with spinal cord injury (SCI).Design: Retrospective, cross-sectional study.Setting: Online multi-national study.Participants: We surveyed an international sample of 102 women who gave birth following cervical SCI (C1-C8, n = 30), upper thoracic SCI (T1-T6, n = 12) or lower level SCI (T7 & below, n = 60). Participants were primarily from Canada and Sweden, and mean age at childbirth was 30 ± 6 years.Outcome Measures: Subscales from the Pregnancy Risk Assessment Monitoring System (PRAMS) were used to measure PPD (PRAMS-3D) and PPA (PRAMS-2A).Results: PPD and PPA were most prevalent in women with cervical SCI, followed by upper thoracic SCI then lower SCI. Self-reported PPD was more prevalent than clinically diagnosed PPD in women with cervical SCI (P = 0.03) and upper thoracic SCI (P = 0.03). With cervical SCI, 75% of women diagnosed with MDD before pregnancy scored >9 on the PRAMS PPD subscale, indicating clinically relevant PPD. However, only 10% were diagnosed with PPD. Of women with lower SCI diagnosed with MDD before pregnancy, 25% had a clinically relevant score for self-reported PPD; 7% were diagnosed.Conclusions: This is currently the largest study examining PPD and PPA after SCI. Clinicians should be aware that mothers with SCI (particularly high-level SCI) may have increased risk of PPD and PPA. PPD is poorly understood in women with SCI and may even be underdiagnosed. SCI-related risk factors for PPD and PPA should be explored.
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Depresión Posparto , Traumatismos de la Médula Espinal , Ansiedad/epidemiología , Ansiedad/etiología , Estudios Transversales , Depresión Posparto/epidemiología , Depresión Posparto/etiología , Femenino , Humanos , Embarazo , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiologíaRESUMEN
CONTEXT: Individuals with spinal cord injury (SCI) suffering from autonomic dysreflexia (AD) due to neurogenic detrusor overactivity (NDO) can effectively be treated with intradetrusor onabotulinumtoxinA. We present a complex case to highlight the treatment's potential limitations to ameliorate AD and improve lower urinary tract (LUT) function in this population. FINDINGS: A 46-year old man, who was relying on an indwelling urethral catheter for bladder emptying due to severely impaired hand function following a SCI (C5, AIS B) sustained 30 years ago, underwent intradetrusor onabotulinumtoxinA injections for treatment of refractory NDO and associated AD. Although LUT function slightly improved (i.e. cystometric capacity increased while detrusor pressure was reduced), severe bladder-related AD persisted post-treatment. CONCLUSIONS: This case raises awareness of serious considerations when treating NDO-related AD in individuals with longstanding neurogenic LUT dysfunction and compromised dexterity following SCI. Given the limited improvement in LUT function and persisting bladder-related AD following treatment, urinary diversion as advocated in the wider literature should be considered to protect an individual's urinary tract from further deterioration and thus eliminate bladder-related AD consequences long-term. Early treatment and management of NDO and AD is crucial to minimize complications associated with these two major health risks in this population.
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Traumatismos de la Médula Espinal , Vejiga Urinaria Neurogénica , Sueños , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de la Médula Espinal/complicaciones , Vejiga Urinaria Neurogénica/complicaciones , Vejiga Urinaria Neurogénica/tratamiento farmacológico , UrodinámicaRESUMEN
BACKGROUND: People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. OBJECTIVES: We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. METHODS: PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. RESULTS: 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. CONCLUSION: Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.
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Traumatismos de la Médula Espinal , Adolescente , Adulto , Anciano , Analgésicos/uso terapéutico , Cannabinoides/uso terapéutico , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológico , Resultado del Tratamiento , Adulto JovenRESUMEN
Individuals living with chronic spinal cord injury (SCI) often exhibit impairments in cognitive function, which impede their rehabilitation and transition into the community. Although a number of clinical studies have demonstrated the impact of impaired cardiovascular control on cognitive impairment, the mechanistic understanding of this deleterious relationship is still lacking. The present study investigates whether chronic disruption of cardiovascular control following experimental SCI results in cerebrovascular decline and vascular cognitive impairment. Fourteen weeks following a high thoracic SCI (at the third thoracic segment), rats were subjected to a battery of in vivo and in vitro physiological assessments, cognitive-behavioral tests, and immunohistochemical approaches to investigate changes in cerebrovascular structure and function in the middle cerebral artery (MCA). We show that in the MCA of rats with SCI, there is a 55% (SCI vs. control: 13.4 ± 1.9% vs. 29.63 ± 2.8%, respectively) reduction in the maximal vasodilator response to carbachol, which is associated with reduced expression of endothelial marker cluster of differentiation 31 (CD31) and transient receptor potential cation channel 4 (TRPV 4) channels. Compared with controls, MCAs in rats with SCI were found to have 50% (SCI vs. control: 1.5 ± 0.2 vs. 1 ± 0.1 a.u., respectively) more collagen 1 in the media of vascular wall and 37% (SCI vs. control: 30.5 ± 2.9% vs. 42.0 ± 4.0%, respectively) less distensibility at physiological intraluminal pressure. Further, the cerebral blood flow (CBF) in the hippocampus was reduced by 32% in the SCI group (SCI vs. control: 44.3 ± 4.5 mL/100 g/min vs. 65.0 ± 7.2 mL/100 g/min, respectively) in association with impairment of short-term memory based on a novel object recognition test. There were no changes in the sympathetic innervation of the vasculature and passive structure in the SCI group. Chronic experimental SCI is associated with structural alterations and endothelial dysfunction in cerebral arteries that likely contribute to significantly reduced CBF and vascular cognitive impairment.
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Circulación Cerebrovascular/fisiología , Disfunción Cognitiva/fisiopatología , Endotelio Vascular/fisiología , Arteria Cerebral Media/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Vértebras Torácicas/lesiones , Animales , Circulación Cerebrovascular/efectos de los fármacos , Agonistas Colinérgicos/farmacología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/efectos de los fármacos , Masculino , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/efectos de los fármacos , Ratas , Ratas Wistar , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico por imagen , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
OBJECTIVE: To determine the population-level odds of individuals with spinal cord injury (SCI) experiencing fatigue and sleep apnea, to elucidate relationships with level and severity of injury, and to examine associations with abnormal cerebrovascular responsiveness. METHODS: We used population-level data, meta-analyses, and primary physiologic assessments to provide a large-scale integrated assessment of sleep-related complications after SCI. Population-level and meta-analyses included more than 60,000 able-bodied individuals and more than 1,800 individuals with SCI. Physiologic assessments were completed on a homogenous sample of individuals with cervical SCI and matched controls. We examined the prevalence of (1) self-reported chronic fatigue, (2) clinically identified sleep apnea, and 3) cerebrovascular responsiveness to changing CO2. RESULTS: Logistic regression revealed a 7-fold elevated odds of chronic fatigue after SCI (odds ratio [OR] 7.9, 95% confidence interval [CI] 3.5-16.2), and that fatigue and trouble sleeping are correlated with the level and severity of injury. We further show that those with SCI experience elevated risk of clinically defined sleep-disordered breathing in more than 600 individuals with SCI (pooled OR 3.1, 95% CI 1.3-7.5). We confirmed that individuals with SCI experience a high rate of clinically defined sleep apnea using primary polysomnography assessments. We then provide evidence using syndromic analysis that sleep-disordered breathing is a factor strongly associated with impaired cerebrovascular responsiveness to CO2 in patients with SCI. CONCLUSIONS: Individuals with SCI have an increased prevalence of sleep-disordered breathing, which may partially underpin their increased risk of stroke. There is thus a need to integrate sleep-related breathing examinations into routine care for individuals with SCI.
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Síndromes de la Apnea del Sueño/epidemiología , Traumatismos de la Médula Espinal/complicaciones , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Síndromes de la Apnea del Sueño/etiologíaRESUMEN
STUDY DESIGN: Experimental study. OBJECTIVES: Compromised cerebrovascular function likely contributes to elevated neurological risk in spinal cord injury (SCI). Passive heating offers many cardiovascular and neurological health benefits; therefore, we aimed to determine the effects of an acute bout of heating on cerebrovascular function in chronic SCI. METHODS: Persons with cervical SCI (n = 15) and uninjured controls (CON; n = 15) completed 60 min of lower limb hot water immersion (40 °C). Assessments of middle cerebral (MCA) and posterior cerebral artery (PCA) velocities, pulsatilities, and neurovascular coupling (NVC) were performed using transcranial Doppler ultrasound. Duplex ultrasonography was used to index cerebral blood flow via the internal carotid artery (ICA), and carotid-femoral pulse-wave velocity (PWV) was measured using tonometry. The NVC response was quantified as the peak hyperemic value during 30-s cycles of visual stimulation. RESULTS: Mean arterial pressure changed differentially with heating [mean (standard deviation); SCI: +6(14) mmHg, CON: -8(12) mmHg; P = 0.01]. There were no differences in any intracranial artery measures (all P > 0.05), except for small (~10%) increases in MCA conductance in CON after heating vs. SCI (interaction P = 0.006). Resting ICA flow was greater in SCI vs. CON (P = 0.03) but did not change with heating in either group (interaction P = 0.34). There were also no between-group differences in the NVC response (ΔPCA conductance) pre- [SCI: 29(19)% vs. CON: 30(9)%] or post-heating [SCI 30(9)% vs. 25(9)%; interaction P = 0.22]. CONCLUSIONS: Mild acute heating does not impair or improve cerebrovascular function in SCI or CON. Thus, further study of the effects of chronic heating interventions are warranted.
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Circulación Cerebrovascular/fisiología , Vértebras Cervicales/diagnóstico por imagen , Hipertermia Inducida/métodos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/fisiopatología , Adulto , Vértebras Cervicales/lesiones , Femenino , Humanos , Hipertermia Inducida/tendencias , Masculino , Persona de Mediana Edad , Traumatismos de la Médula Espinal/terapiaRESUMEN
INTRODUCTION: Although lactation dysfunction and breastfeeding difficulties after spinal cord injury have been previously reported, there is still a lack of research on the specific challenges and aspects that require more support. This unique case of a mother with C6 tetraplegia details her breastfeeding experience before and after spinal cord injury. MAIN ISSUE: A 23-year-old woman with a 20-month-old daughter sustained a motor and sensory complete traumatic spinal cord injury in a motor-vehicle crash while she was 6 months pregnant with her second child. This resulted in complete absence of sensory function below the level of injury (including the breast) and limited hand function. In comparison with her breastfeeding experience before injury, after injury she experienced decreased milk production, absence of the milk ejection reflex, and impaired ability to pick up, hold, and position her infant. MANAGEMENT: Care aides and family members assisted this mother with picking up, positioning, and latching her infant. She also utilized alternative breastfeeding positions, nursing pillows, and wedges. Domperidone was suggested by her physiatrist to increase milk production but ultimately was not used as there were no concerns with her infant's growth or development. CONCLUSION: Breastfeeding as a recently injured mother while undergoing intensive post-injury rehabilitation was challenging. Her second child developed well and was breastfed for 3 months compared to her first child (9 months). Breastfeeding was possible for this mother after spinal cord injury, in part due to previous experience successfully breastfeeding her first child, assistance from care personnel, and nursing aids.
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Lactancia Materna , Atención Perinatal , Complicaciones del Embarazo , Cuadriplejía , Traumatismos de la Médula Espinal , Vértebras Cervicales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Adulto JovenRESUMEN
Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b-) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (-93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.
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Selectina E/sangre , Endotelio Vascular/fisiopatología , Respuesta al Choque Térmico , Traumatismos de la Médula Espinal/fisiopatología , Adulto , Arterias/diagnóstico por imagen , Biomarcadores/sangre , Vértebras Cervicales/lesiones , Endotelio Vascular/diagnóstico por imagen , Femenino , Hemorreología , Humanos , Hipertermia Inducida , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
The capacity of the cerebrovasculature to buffer changes in blood pressure (BP) likely plays an important role in the prevention of stroke, which is three- to fourfold more common after spinal cord injury (SCI). Although the directional relationship between BP and cerebral blood flow (CBF) has traditionally been thought to travel solely from BP to CBF, a Cushing-like mechanism functioning in the inverse direction, in which changes in CBF influence BP, has recently been revealed using Granger causality analysis. Although both CBF buffering of BP and the Cushing-like mechanism are influenced by the sympathetic nervous system, we do not understand the impact of disruption of descending sympathetic pathways within the spinal cord, caused by cervical SCI on these regulatory systems. We hypothesized that people with cervical SCI would have greater BP to CBF transmission, as well as a reduced Cushing-like mechanism. The directional relationships between mean arterial BP (MAP; Finometer® PRO) and middle cerebral artery blood velocity (MCAv; transcranial Doppler) were assessed at rest in 14 cervical SCI subjects and 16 uninjured individuals using Granger causality analysis, while also accounting for end-tidal CO2 tension. Those with SCI exhibited 66% increased forward MAPâMCAv information transmission as compared with the uninjured group (p = 0.0003), indicating reduced cerebrovascular buffering of BP, and did not have a predominant backward Cushing-like MCAvâMAP phenotype. These results indicate that both forward and backward communication between BP and CBF are influenced by SCI, which may be associated with impaired cerebrovascular BP buffering after SCI as well as widespread BP instability.
Asunto(s)
Presión Sanguínea/fisiología , Circulación Cerebrovascular/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Lactation dysfunction following spinal cord injury has been noted in the literature. However, researchers have often grouped together all women of physical disability or do not account for injury level. The extent of lactation dysfunction and influence of spinal cord injury on breastfeeding ability and behavior is not well understood. Research aim: This study aimed to identify major barriers to lactation and breastfeeding related to spinal cord injury, specifically comparing high- and low-level injuries. METHODS: A retrospective cross-sectional survey design was used. Two online questionnaires were developed and completed by women ( N = 52) who chose to breastfeed with spinal cord injury, primarily in Canada and Sweden. RESULTS: The first questionnaire was completed by 52 women with spinal cord injury; 38 of the original 52 participants completed the second questionnaire. Of the 52 women, 28 (53.8%) had high-level spinal cord injury (at or above T6) and 24 (46.1%) had low-level injury (below T6). On the second questionnaire, 14 (77.8%) women with high-level injury reported insufficient milk production or ejection. Only 35% of women ( n = 7) with low-level injury reported the same. Autonomic dysreflexia was experienced by 38.9% of women ( n = 7) with high-level injury. Exclusive breastfeeding duration was significantly shorter ( p < .05) in the high-level injury group (3.3 months) compared with women with low-level injury (6.5 months). CONCLUSION: These results further support the notion that spinal cord injury (particularly at or above T6) disrupts lactation and is associated with shorter breastfeeding duration. Autonomic dysreflexia should be addressed in prospective mothers with high-level spinal cord injury.
Asunto(s)
Lactancia Materna/métodos , Traumatismos de la Médula Espinal/complicaciones , Adulto , Anciano , Lactancia Materna/psicología , Colombia Británica , Distribución de Chi-Cuadrado , Estudios Transversales , Técnica Delphi , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Traumatismos de la Médula Espinal/clasificación , Traumatismos de la Médula Espinal/psicología , Estadísticas no Paramétricas , Encuestas y Cuestionarios , SueciaRESUMEN
The capacity of the cerebrovasculature to buffer changes in blood pressure (BP) is crucial to prevent stroke, the incidence of which is three- to fourfold elevated after spinal cord injury (SCI). Disruption of descending sympathetic pathways within the spinal cord due to cervical SCI may result in impaired cerebrovascular buffering. Only linear analyses of cerebrovascular buffering of BP, such as transfer function, have been used in SCI research. This approach does not account for inherent nonlinearity and nonstationarity components of cerebrovascular regulation, often depends on perturbations of BP to increase the statistical power, and does not account for the influence of arterial CO2 tension. Here, we used a nonlinear and nonstationary analysis approach termed wavelet decomposition analysis (WDA), which recently identified novel sympathetic influences on cerebrovascular buffering of BP occurring in the ultra-low-frequency range (ULF; 0.02-0.03Hz). WDA does not require BP perturbations and can account for influences of CO2 tension. Supine resting beat-by-beat BP (Finometer), middle cerebral artery blood velocity (transcranial Doppler), and end-tidal CO2 tension were recorded in cervical SCI ( n = 14) and uninjured ( n = 16) individuals. WDA revealed that cerebral blood flow more closely follows changes in BP in the ULF range ( P = 0.0021, Cohen's d = 0.89), which may be interpreted as an impairment in cerebrovascular buffering of BP. This persisted after accounting for CO2. Transfer function metrics were not different in the ULF range, but phase was reduced at 0.07-0.2 Hz ( P = 0.03, Cohen's d = 0.31). Sympathetically mediated cerebrovascular buffering of BP is impaired after SCI, and WDA is a powerful strategy for evaluating cerebrovascular buffering in clinical populations.
Asunto(s)
Presión Arterial , Arteria Braquial/fisiopatología , Circulación Cerebrovascular , Arteria Cerebral Media/fisiopatología , Modelos Cardiovasculares , Traumatismos de la Médula Espinal/fisiopatología , Ultrasonografía Doppler Transcraneal/métodos , Análisis de Ondículas , Adaptación Fisiológica , Adulto , Velocidad del Flujo Sanguíneo , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/inervación , Valor Predictivo de las Pruebas , Traumatismos de la Médula Espinal/diagnóstico , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Regaining control of autonomic functions such as those of the cardiovascular system, lower urinary tract and bowel, rank among the most important health priorities for individuals living with spinal cord injury (SCI). Recently our research provided evidence that epidural spinal cord stimulation (ESCS) could acutely modulate autonomic circuits responsible for cardiovascular function after SCI. This finding raised the question of whether ESCS can be used to modulate autonomic circuits involved in lower urinary tract and bowel control after SCI. We present the case of a 32-year-old man with a chronic motor-complete SCI (American Spinal injury Association Impairment Scale B) at the 5th cervical spinal segment. He sustained his injury during a diving accident in 2012. He was suffering from neurogenic lower urinary tract and bowel dysfunction. Epidural stimulation of the lumbosacral spinal cord immediately modulated both functions without negatively affecting the cardiovascular system. Specifically, the individual's bowel function was assessed using different pre-set configurations and stimulation parameters in a randomized order. Compared to the individual's conventional bowel management approach, ESCS significantly reduced the time needed for bowel management (p = 0.039). Furthermore, depending on electrode configuration and stimulation parameters (i.e., amplitude, frequency, and pulse width), ESCS modulated detrusor pressure and external anal sphincter/pelvic floor muscle tone to various degrees during urodynamic investigation. Although, ESCS is currently being explored primarily for restoring ambulation, our data suggest that application of this neuroprosthetic intervention may provide benefit to lower urinary tract and bowel function in individuals with SCI. To fully capitalize on the potential of improving lower urinary tract and bowel function, further research is needed to better understand the neuronal pathways and identify optimal stimulation configurations and parameters.