RESUMEN
Retinal ganglion cells (RGCs) are the sole output neurons that transmit visual information from the retina to the brain. Diverse insults and pathological states cause degeneration of RGC somas and axons leading to irreversible vision loss. A fundamental question is whether manipulation of a key regulator of RGC survival can protect RGCs from diverse insults and pathological states, and ultimately preserve vision. Here, we report that CaMKII-CREB signaling is compromised after excitotoxic injury to RGC somas or optic nerve injury to RGC axons, and reactivation of this pathway robustly protects RGCs from both injuries. CaMKII activity also promotes RGC survival in the normal retina. Further, reactivation of CaMKII protects RGCs in two glaucoma models where RGCs degenerate from elevated intraocular pressure or genetic deficiency. Last, CaMKII reactivation protects long-distance RGC axon projections in vivo and preserves visual function, from the retina to the visual cortex, and visually guided behavior.
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Citoprotección , Células Ganglionares de la Retina/patología , Visión Ocular , Animales , Axones/efectos de los fármacos , Axones/patología , Encéfalo/patología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Dependovirus/metabolismo , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Glaucoma/genética , Glaucoma/patología , Ratones Endogámicos C57BL , Neurotoxinas/toxicidad , Traumatismos del Nervio Óptico/patología , Transducción de SeñalRESUMEN
Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.
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Células Asesinas Naturales/fisiología , Proteínas Asociadas a Matriz Nuclear/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Traumatismos de los Nervios Periféricos/metabolismo , Animales , Axones , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Células Asesinas Naturales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Regeneración Nerviosa , Neuronas/citología , Neuronas Aferentes/inmunología , Neuronas Aferentes/metabolismo , Proteínas Asociadas a Matriz Nuclear/fisiología , Proteínas de Transporte Nucleocitoplasmático/fisiología , Dolor , Traumatismos de los Nervios Periféricos/inmunología , Enfermedades del Sistema Nervioso Periférico , Nervio Ciático , Células Receptoras Sensoriales/metabolismoRESUMEN
Axon regeneration is an energy-demanding process that requires active mitochondrial transport. In contrast to the central nervous system (CNS), axonal mitochondrial transport in regenerating axons of the peripheral nervous system (PNS) increases within hours and sustains for weeks after injury. Yet, little is known about targeting mitochondria in nervous system repair. Here, we report the induction of sustained axon regeneration, neural activities in the superior colliculus (SC), and visual function recovery after optic nerve crush (ONC) by M1, a small molecule that promotes mitochondrial fusion and transport. We demonstrated that M1 enhanced mitochondrial dynamics in cultured neurons and accelerated in vivo axon regeneration in the PNS. Ex vivo time-lapse imaging and kymograph analysis showed that M1 greatly increased mitochondrial length, axonal mitochondrial motility, and transport velocity in peripheral axons of the sciatic nerves. Following ONC, M1 increased the number of axons regenerating through the optic chiasm into multiple subcortical areas and promoted the recovery of local field potentials in the SC after optogenetic stimulation of retinal ganglion cells, resulting in complete recovery of the pupillary light reflex, and restoration of the response to looming visual stimuli was detected. M1 increased the gene expression of mitochondrial fusion proteins and major axonal transport machinery in both the PNS and CNS neurons without inducing inflammatory responses. The knockdown of two key mitochondrial genes, Opa1 or Mfn2, abolished the growth-promoting effects of M1 after ONC, suggesting that maintaining a highly dynamic mitochondrial population in axons is required for successful CNS axon regeneration.
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Axones , Traumatismos del Nervio Óptico , Humanos , Axones/metabolismo , Proteínas Mitocondriales/metabolismo , Compresión Nerviosa , Regeneración Nerviosa/fisiología , Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/genética , Traumatismos del Nervio Óptico/metabolismo , Células Ganglionares de la Retina/fisiología , Nervio Ciático/metabolismo , Bibliotecas de Moléculas PequeñasRESUMEN
The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development of therapeutic strategies. Circular RNAs (circRNAs) are important regulators in many biological and pathological processes. Herein, we performed circRNA microarrays to identify dysregulated circRNAs following optic nerve crush (ONC). The results showed that 221 circRNAs were differentially expressed between ONC retinas and normal retinas. Notably, the levels of circular RNA-Dcaf6 (cDcaf6) expression in aqueous humor of glaucoma patients were higher than that in cataract patients. cDcaf6 silencing could reduce oxidative stress-induced RGC apoptosis in vitro and alleviate retinal neurodegeneration in vivo as shown by increased neuronal nuclei antigen (NeuN, neuronal bodies) and beta-III-tubulin (TUBB3, neuronal filaments) staining and reduced glial fibrillary acidic protein (GFAP, activated glial cells) and vimentin (activated glial cells) staining. Collectively, this study identifies a promising target for treating retinal neurodegeneration.
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Traumatismos del Nervio Óptico , ARN Circular , Animales , Humanos , Modelos Animales de Enfermedad , Nervio Óptico/metabolismo , Nervio Óptico/patología , Traumatismos del Nervio Óptico/genética , Traumatismos del Nervio Óptico/tratamiento farmacológico , Traumatismos del Nervio Óptico/metabolismo , Retina , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , ARN Circular/genética , ARN Circular/metabolismoRESUMEN
DYT-TOR1A (DYT1) dystonia, characterized by reduced penetrance and suspected environmental triggers, is explored using a "second hit" DYT-TOR1A rat model. We aim to investigate the biological mechanisms driving the conversion into a dystonic phenotype, focusing on the striatum's role in dystonia pathophysiology. Sciatic nerve crush injury was induced in ∆ETorA rats, lacking spontaneous motor abnormalities, and wild-type (wt) rats. Twelve weeks post-injury, unbiased RNA-sequencing was performed on the striatum to identify differentially expressed genes (DEGs) and pathways. Fenofibrate, a PPARα agonist, was introduced to assess its effects on gene expression. 18F-FDG autoradiography explored metabolic alterations in brain networks. Low transcriptomic variability existed between naïve wt and ∆ETorA rats (17 DEGs). Sciatic nerve injury significantly impacted ∆ETorA rats (1009 DEGs) compared to wt rats (216 DEGs). Pathway analyses revealed disruptions in energy metabolism, specifically in fatty acid ß-oxidation and glucose metabolism. Fenofibrate induced gene expression changes in wt rats but failed in ∆ETorA rats. Fenofibrate increased dystonia-like movements in wt rats but reduced them in ∆ETorA rats. 18F-FDG autoradiography indicated modified glucose metabolism in motor and somatosensory cortices and striatum in both ∆ETorA and wt rats post-injury. Our findings highlight perturbed energy metabolism pathways in DYT-TOR1A dystonia, emphasizing compromised PPARα agonist efficacy in the striatum. Furthermore, we identify impaired glucose metabolism in the brain network, suggesting a potential shift in energy substrate utilization in dystonic DYT-TOR1A rats. These results contribute to understanding the pathophysiology and potential therapeutic targets for DYT-TOR1A dystonia.
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Distonía , Trastornos Distónicos , Fenofibrato , Ratas , Animales , Distonía/genética , Distonía/metabolismo , Roedores/metabolismo , Fluorodesoxiglucosa F18 , PPAR alfa/metabolismo , Trastornos Distónicos/genética , Encéfalo/metabolismo , Metabolismo Energético , GlucosaRESUMEN
Optic neuropathies, such as glaucoma, are due to progressive retinal ganglion cells (RGCs) degeneration, result in irreversible vision loss. The promising RGCs replacement therapy for restoring vision are impeded by insufficient RGC-like cells sources. The present work was enriched one new type RGC-like cells using two surface markers CD184 and CD171 from human induced pluripotent stem cells (hiPSCs) by FACS sorting firstly. These new kind cells have well proliferation ability and possessed passage tolerance in vitro 2D or 3D spheroids culture, which kept expressing Pax6, Brn3b and ßIII-Tubulin and so on. The transplanted CD184+CD171+ RGC-like cells could survive and integrate into the normal and optic nerve crush (ONC) mice retina, especially they were more inclined to across the optic nerve head and extend to the damaged optic nerve. These data support the feasible application for cell replacement therapy in RGC degenerative diseases, as well as help to develop new commercial cells sorting reagents and establish good manufacturing practice (GMP) grade RGC-like donor cells for further clinical application.
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Células Madre Pluripotentes Inducidas , Traumatismos del Nervio Óptico , Ratones , Animales , Humanos , Retina , Células Ganglionares de la Retina , Nervio Óptico , Organoides , Modelos Animales de Enfermedad , Compresión NerviosaRESUMEN
BACKGROUND: The preservation of retinal ganglion cells (RGCs) and the facilitation of axon regeneration are crucial considerations in the management of various vision-threatening disorders. Therefore, we investigate the efficacy of interleukin-4 (IL-4), a potential therapeutic agent, in promoting neuroprotection and axon regeneration of retinal ganglion cells (RGCs) as identified through whole transcriptome sequencing in an in vitro axon growth model. METHODS: A low concentration of staurosporine (STS) was employed to induce in vitro axon growth. Whole transcriptome sequencing was utilized to identify key target factors involved in the molecular mechanism underlying axon growth. The efficacy of recombinant IL-4 protein on promoting RGC axon growth was validated through in vitro experiments. The protective effect of recombinant IL-4 protein on somas of RGCs was assessed using RBPMS-specific immunofluorescent staining in mouse models with optic nerve crush (ONC) and N-methyl-D-aspartic acid (NMDA) injury. The protective effect on RGC axons was evaluated by anterograde labeling of cholera toxin subunit B (CTB), while the promotion of RGC axon regeneration was assessed through both anterograde labeling of CTB and immunofluorescent staining for growth associated protein-43 (GAP43). RESULTS: Whole-transcriptome sequencing of staurosporine-treated 661 W cells revealed a significant upregulation in intracellular IL-4 transcription levels during the process of axon regeneration. In vitro experiments demonstrated that recombinant IL-4 protein effectively stimulated axon outgrowth. Subsequent immunostaining with RBPMS revealed a significantly higher survival rate of RGCs in the rIL-4 group compared to the vehicle group in both NMDA and ONC injury models. Axonal tracing with CTB confirmed that recombinant IL-4 protein preserved long-distance projection of RGC axons, and there was a notably higher number of surviving axons in the rIL-4 group compared to the vehicle group following NMDA-induced injury. Moreover, intravitreal delivery of recombinant IL-4 protein substantially facilitated RGC axon regeneration after ONC injury. CONCLUSION: The recombinant IL-4 protein exhibits the potential to enhance the survival rate of RGCs, protect RGC axons against NMDA-induced injury, and facilitate axon regeneration following ONC. This study provides an experimental foundation for further investigation and development of therapeutic agents aimed at protecting the optic nerve and promoting axon regeneration.
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Axones , Interleucina-4 , Regeneración Nerviosa , Células Ganglionares de la Retina , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Animales , Interleucina-4/farmacología , Axones/efectos de los fármacos , Axones/metabolismo , Regeneración Nerviosa/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Traumatismos del Nervio Óptico/patología , Traumatismos del Nervio Óptico/tratamiento farmacológico , N-Metilaspartato/farmacología , Estaurosporina/farmacología , Fármacos Neuroprotectores/farmacología , Proteínas Recombinantes/farmacologíaRESUMEN
BACKGROUND: Among the two stent strategies, contemporary evidence favors double kissing crush technique (DKC) for complex unprotected distal left main bifurcation (UdLMB) lesions. However one of the major challenges to these lesions is side branch (SB) restenosis. AIMS: Our aim was to identify optical coherence tomographic (OCT) characteristics that may predict SB restenosis (SBR) after UdLMB angioplasty using DKC technique. METHODS: This was a single-center, retrospective study that included 60 patients with complex UdLMB disease, who underwent OCT-guided angioplasty using DKC technique. Angiographic follow-up was performed in all patients at 1 year to identify patients with SBR. Patients with SBR group were compared with patients without SBR (NSBR group) for OCT parameters during index procedure. RESULTS: Twelve (20%) patients developed SBR at 1-year follow-up. The SBR group had longer SB lesion (18.8 ± 3.2 vs. 15.3 ± 3.7 mm, p = 0.004) and neo-metallic carinal length (2.1 vs. 0.1 mm, p < 0.001) when compared to the NSBR group. Longer neo-metallic carinal length was associated with the absence of the dumbbell sign, presence of hanging stent struts across the SB ostium on OCT of final MB pullback. On multivariate regression analysis, SB distal reference diameter (DRD) and SB stent expansion were identified as independent predictors of SBR with SB-DRD of ≤2.8 mm (area under curve-0.73, sensitivity-83.3%, and specificity-62.5%) and SB stent expansion of ≤89% (area under curve-0.88, sensitivity-83.3%, and specificity- 81.2%) as the best cut off values to predict SBR. CONCLUSIONS: SB DRD and SB stent expansion are the OCT predictors of future SBR after UdLMB angioplasty using DKC technique.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Enfermedades de las Válvulas Cardíacas , Humanos , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/métodos , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/cirugía , Stents , Constricción Patológica , Angiografía Coronaria/métodosRESUMEN
BACKGROUND: Two earthquakes on 6 February 2023 destroyed 10 cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: Web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were recorded. RESULTS: A total of 903 injured children (median age 11.62 years) were evaluated. Mean TUR was 13 h (interquartile range 32.5, max 240 h). Thirty-one of 32 patients with a TUR of >120 h survived. The patient who was rescued after 10 days survived. Two-thirds of the patients were given 50 mEq/L sodium bicarbonate in 0.45% sodium chloride solution on admission day. Fifty-eight percent of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% at 3000-4000 mL/m2 BSA and only 2% at >4000 mL/m2 BSA. A total of 425 patients had surgeries, and 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively. Crush-AKI developed in 314 patients (36% of all patients). In all, 189 patients were dialyzed. Age >15 years, creatine phosphokinase (CK) ≥20 950 U/L, TUR ≥10 h and the first-day IVF volume <3000-4000 mL/m2 BSA were associated with Crush-AKI development. Twenty-two deaths were recorded, 20 of 22 occurring in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: These are the most extensive pediatric kidney disaster data obtained after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also associated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.
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Lesión Renal Aguda , Síndrome de Aplastamiento , Terremotos , Humanos , Niño , Femenino , Masculino , Adolescente , Síndrome de Aplastamiento/terapia , Síndrome de Aplastamiento/complicaciones , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Preescolar , Pronóstico , Tasa de Supervivencia , Estudios de Seguimiento , Diálisis Renal , Desastres , Lactante , Estudios RetrospectivosRESUMEN
The association between sleep and pain has been investigated widely. However, inconsistent results from animal studies compared with human data show the need for a validated animal model in the sleep-pain association field. Our study aims to validate common neuropathic pain models as a tool for evaluating the sleep-pain association. Electrodes electroencephalogram (EEG) and electromyogram (EMG) were surgically implanted to measure sleep. The von Frey test was used to measure pain sensitivity. Following the baseline data acquisition, two pain-modelling procedures were performed: sciatic nerve crush injury (SCI) and common peroneal nerve ligation (CPL). Post-injury measurements were performed on days 1, 5, 10, and 15 post-surgery. The results presented decreased paw withdrawal thresholds and reduced NREM sleep duration in both models on the first post-surgery day. In the SCI model, NREM sleep duration was negatively correlated with paw withdrawal thresholds (p = 0.0466), but not in the CPL model. Wake alpha and theta EEG powers were also correlated with the pain threshold. The results confirm that the SCI model shows disturbed sleep patterns associated with increased pain sensitivity, suggesting it is a reliable tool for investigating sleep disturbances associated with neuropathic pain.
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Hyperbaric oxygen therapy (HBOT) has been used as an adjuvant treatment for crush injury because it can improve tissue hypoxia and stimulate wound healing. However, the actual role of HBOT in crush hand injury is still unknown. This study is to assess the efficacy of HBOT for crush hand patients, as well as the impact of HBOT initiation timing. Between 2018 and 2021, 72 patients with crush hand injury were retrospectively reviewed. The patients were divided into the HBOT and control group, and each group had 36 patients. The average session of HBOT was 18.2 (5-32 sessions) per patient, and no patient had a complication related to the treatment. The two groups had similar demographics, but HBOT group had larger injured area (73.6 ± 51.0 vs. 48.2 ± 45.5 cm2 , p = 0.03). To better control the confounding factors, we performed the subgroup analysis with cut-off injured area of 50 cm2 . In the patients with smaller injured area (â¦50 cm2 ), the HBOT group had shorter wound healing time (29.9 ± 12.9 vs. 41.0 ± 18.9 days, p = 0.03). The early HBOT group (first session ≤72 h post-operatively) had shorter hospital stay (8.1 ± 6.4 vs. 15.5 ± 11.4 days, p = 0.04), faster wound healing (28.7 ± 17.8 vs. 41.1 ± 18.1 days, p = 0.08) and less operations (1.54 ± 0.78 vs. 2.41 ± 1.62, p = 0.06) although the latter two didn't achieve statistical significance. HBOT is safe and effective in improving wound healing of hand crush injury. Early intervention of HBOT may be more beneficial. Future research is required to provide more evidence.
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Lesiones por Aplastamiento , Traumatismos de la Mano , Oxigenoterapia Hiperbárica , Humanos , Cicatrización de Heridas , Estudios Retrospectivos , Traumatismos de la Mano/terapia , Lesiones por Aplastamiento/terapiaRESUMEN
BACKGROUND: On February 6th, 2023, two consecutive earthquakes struck southeastern Türkiye with magnitudes of 7.7 and 7.6, respectively. This study aimed to analyze the clinical and laboratory findings, as well as management of pediatric victims with Crush Syndrome (CS) and Acute Kidney Injury (AKI). METHODS: The study included pediatric earthquake victims who were presented to Mersin University Hospital. Clinical and laboratory characteristics of the patients were collected retrospectively. RESULTS: Among 649 patients, Crush injury (CI), CS and AKI was observed in 157, 59, and 17 patients, respectively. White blood cell count (12,870 [IQR: 9910-18700] vs. 10,545 [IQR: 8355-14057] /µL, P < 0.001), C-reactive protein (51.27 [IQR: 14.80-88.78] vs. 4.59 [1.04-18.25] mg/L, P < 0.001) and myoglobin levels (443.00 [IQR: 198.5-1759.35] vs. 17 [11.8-30.43] ng/ml) were higher in patients with CS, while their sodium (IQR: 134 [131-137] vs. 136 [134-138] mEq/L, P < 0.001) levels were lower compared to non-CS patients. An increase in myoglobin levels was identified as an independent risk factor for developing CS (OR = 1.017 [1.006-1.027]). Intravenous fluid replacement was administered to the patients with CS at a dose of 4000 cc/m2/day. Hypokalemia was observed in 51.9% of the CS patients on the third day. All patients with AKI showed improvement and no deaths were reported. CONCLUSIONS: Hyponatremia and increase in inflammation markers associated with CS may be observed. An increase in myoglobin levels was identified as a risk factor for CS. Hypokalemia may be seen as a complication of vigorous fluid therapy during hospitalization.
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Lesión Renal Aguda , Síndrome de Aplastamiento , Terremotos , Humanos , Síndrome de Aplastamiento/sangre , Síndrome de Aplastamiento/terapia , Síndrome de Aplastamiento/complicaciones , Niño , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Adolescente , Proteína C-Reactiva/análisis , Mioglobina/sangre , LactanteRESUMEN
OBJECTIVE: >50,000 people died in the February 2023 earthquakes in Türkiye. The aim of this study was to identify the factors affecting mortality rates of the trauma patients who were presented to the emergency department (ED) after the earthquake and provide suggestions for better preparedness strategies for future natural disasters. METHODS: This retrospective, cross-sectional study encompassed data from 955 trauma patients out of 3072 patients aged 18 years and above who sought assistance in the ED. Patients were divided into two groups: the survivor group and the exitus group. Age, gender, the city where patients came from, type of presentation, injured organ systems and mechanisms of injury, laboratory findings, the diagnoses in the ED, time spent in the ED, surgical intervention, and hemodialysis sessions were analyzed. The characteristics of those who could not be identified at the presentation to the ED were subjected to additional analysis. RESULTS: Out of 955 patients, 75.9% had extremity injuries, with crushing injuries (23.6%) being predominant. There were no significant differences in age or gender between the survivor and exitus groups (p = 0.776, p = 0.522), nor in the province of admission (p = 0.249). Clinical factors indicated that the exitus group were more likely to lack identification documents (29.6%), have spent longer trapped under debris, and have a higher frequency of ambulance transportation. Injuries such as chest and abdominal trauma, specific injury types, and amputation or open wounds were notably more frequent in the exitus group. Diagnoses revealed that metabolic causes were more common in exitus group (p < 0.001). While no significant difference existed in the need for emergency surgical intervention (p = 0.939), a higher frequency of emergency hemodialysis was observed among exitus group (p = 0.001). Laboratory findings indicated higher levels of various markers and lower calcium, base excess, and pH levels among those in the exitus group. CONCLUSION: In the aftermath of a devastating earthquake, this study underscores the formidable challenges faced by healthcare systems during natural disasters. To prepare for future disasters, healthcare systems must enhance resilience, develop rapid identification techniques, and adopt a holistic patient care approach.
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Síndrome de Aplastamiento , Terremotos , Humanos , Estudios Retrospectivos , Estudios Transversales , Turquía , Síndrome de Aplastamiento/epidemiologíaRESUMEN
PURPOSE: This study had two main goals: to determine which rhabdomyolysis patients need haemodialysis; and to highlight the significance of blood gas parameters, particularly base excess, as predictors of the need for haemodialysis. METHOD: A total of 270 patients were included in this multicentre, retrospective study. Among the patients who were transferred in from the earthquake region and developed rhabdomyolysis, those with creatine kinase (CK) values >1000 U/L were included in our study. The need for renal replacement in these patients was determined via laboratory tests, urine output monitoring and clinical follow-up. FINDINGS: A total of 270 patients were included in our study. Univariate and multivariate regression analyses of laboratory parameters were performed to identify predictors of HD treatment. According to the univariate regression analysis, BE, HCO3, creatinine, CK, lactate, alanine transaminase (ALT) and aspartate transaminase (AST) levels were found to be significantly associated with receiving HD treatment. According to multivariate regression analysis, only BE (p = 0.003) was found to be a significant predictor of HD treatment. ROC analysis revealed that the optimal cutoff value for BE was -2.6; at this value, the sensitivity and specificity of BE for predicting HD treatment were 89% and 77.1%, respectively (AUC: 0.912; 95% CI: 0.872-0.943; p < 0.001). CONCLUSION: Base excess is an effective predictor of the need for haemodialysis in patients with crush-related injuries that cause rhabdomyolysis and in patients who develop acute renal failure due to elevated CK.
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BACKGROUND: Double crush syndrome (DCS) is characterized by multiple compression sites along a single peripheral nerve. It commonly presents with persistent distal symptoms despite surgical treatment for cervical radiculopathy. Management typically involves nerve release of the most symptomatic site. However, due to overlapping symptoms with cervical radiculopathy, patients may undergo cervical surgery prior to DCS diagnosis. Due to its rarity and frequent misdiagnosis, the authors aim to utilize a large national database to investigate the incidence and associations of DCS. METHODS: The Pearldiver database was utilized to identify patients undergoing cervical surgery for the management of cervical radiculopathy. Patients were stratified into three cohorts based on their clinical course before and after cervical surgery. The primary outcome was the prevalence of DCS, and secondary outcomes included an evaluation of predictive factors for each Group, using a significance level of P < 0.05. RESULTS: Among 195,271 patients undergoing cervical surgery for cervical radiculomyelopathy, 97.95% were appropriately managed, 1.42% had potentially mids-diagnosed DCS, and 0.63% were treatment-resistant. Diabetes and obesity were significant predictors of potentially misdiagnosed DCS (P < 0.05). CONCLUSION: This study presents data indicating that 1.42% of patients who receive cervical surgery may have underlying DCS and potentially benefit from nerve release prior to undergoing surgery. A concurrent diagnosis of diabetes and obesity may predict an underlying DCS.
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Vértebras Cervicales , Síndrome de Aplastamiento , Bases de Datos Factuales , Radiculopatía , Humanos , Femenino , Persona de Mediana Edad , Incidencia , Radiculopatía/cirugía , Radiculopatía/epidemiología , Vértebras Cervicales/cirugía , Síndrome de Aplastamiento/epidemiología , Síndrome de Aplastamiento/cirugía , Masculino , Anciano , AdultoRESUMEN
BACKGROUND: This study aimed to evaluate the long-term outcomes of double kissing crush stenting (DKC) and mini-culotte technique (MCT) in patients with complex bifurcation lesions. METHODS: This retrospective study enrolled 236 patients who underwent percutaneous coronary intervention (PCI) for complex coronary bifurcation disease between January 2014 and November 2022. The primary endpoint was target lesion failure (TLF), defined as the combination of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (TLR). The secondary endpoint was major cardiovascular and cerebral events (MACCE) including all-cause death, MI, TLR, stroke, or stent thrombosis. The regression models were adjusted by applying the inverse probability weighted (IPW) approach to reduce treatment selection bias. RESULTS: The initial management strategy was DKC in 154 (65.3%) patients and MCT in 82 (34.7%) patients (male: 194 [82.2%], mean age: 60.85⯱ 10.86 years). The SYNTAX scores were similar in both groups. The rates of long-term TLF and MACCE rates were 17.4% and 20%, respectively. The rate of TLF (26.8% vs. 12.3%, pâ¯= 0.005) was higher in patients treated with MCT than those treated with the DKC technique, mainly driven by more frequent TLR (15.9% vs. 7.1%, pâ¯= 0.035). The long-term TLF and MACCE rates were notably lower in the DKC group compared to the others: adjusted hazard ratio (HR; IPW): 0.407, pâ¯= 0.009 for TLF, and adjusted HR(IPW): 0.391 [95% CI: 0.209-0.730], pâ¯= 0.003 for MACCE. CONCLUSION: At long-term follow-up, the rates of TLF and MACCE were 17.4% and 20%, respectively. However, long-term TLF was significantly higher in patients treated with MCT than those treated with the DKC technique, primarily due to a more frequent occurrence of clinically driven TLR.
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BACKGROUND: Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. METHODS: The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. RESULTS: In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. CONCLUSION: Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.
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Síndrome de Aplastamiento , Síndromes de Compresión del Nervio Cubital , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Aplastamiento/cirugía , Síndrome de Aplastamiento/diagnóstico , Síndrome de Aplastamiento/complicaciones , Síndrome de Aplastamiento/fisiopatología , Codo/inervación , Codo/cirugía , Electromiografía , Conducción Nerviosa/fisiología , Resultado del Tratamiento , Nervio Cubital/cirugía , Nervio Cubital/fisiopatología , Síndromes de Compresión del Nervio Cubital/cirugía , Síndromes de Compresión del Nervio Cubital/diagnóstico , Síndromes de Compresión del Nervio Cubital/etiología , Síndromes de Compresión del Nervio Cubital/fisiopatología , Muñeca/inervaciónRESUMEN
BACKGROUND: It is unclear how exposure to and perception of community trauma creates a mental health burden. This study aimed to examine the psychological distress trends among community residents in acute stress reaction, acute stress disorder, and post-traumatic stress disorder phases following the Seoul Halloween crowd crush. METHODS: A three-wave repeated cross-sectional survey was conducted with participants after the incident. Analysis of covariance (ANCOVA) with post hoc Bonferroni test was adopted to examine temporal changes in psychological distress and psychological outcomes resulting from media impacts. A two-way ANCOVA was adopted to examine the interaction effects of time and relevance to victims on psychological distress. RESULTS: A total of 807, 1,703, and 2,220 individuals participated in the three waves. Anxiety (estimated mean [standard error of the mean]: 2.28 [0.03] vs. 2.12 [0.02] vs. 2.03 [0.02]; P < 0.001), depression (2.22 [0.03] vs. 2.01 [0.02] vs. 1.90 [0.02]; P < 0.001), and anger (2.70 [0.03] vs. 2.66 [0.02] vs. 2.49 [0.02]; P < 0.001) gradually improved. However, sense of safety initially worsened and did not recover well (2.96 [0.03] vs. 2.75 [0.02] vs. 2.77 [0.02]; P < 0.001). The interaction effect of time and relevance to the victim were significant in depression (P for interaction = 0.049), anger (P for interaction = 0.016), and sense of safety (P for interaction = 0.004). Among participants unrelated to the victim, those exposed to graphics exhibited higher levels of anxiety (2.09 [0.02] vs. 1.87 [0.07]; P = 0.002), depression (1.99 [0.02] vs. 1.83 [0.07]; P = 0.020), and anger (2.71 [0.03] vs. 2.47 [0.08]; P = 0.003) at W2 and higher anger (2.49 [0.02] vs. 2.31 [0.06]; P = 0.005) at W3. CONCLUSION: Community residents indirectly exposed to trauma also experienced psychological distress in the early stages after the incident. A significant impact of media which might have served as a conduit for unfiltered graphics and rumors was also indicated.
Asunto(s)
Ansiedad , Depresión , Trastornos por Estrés Postraumático , Humanos , Masculino , Femenino , Estudios Transversales , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/epidemiología , Adulto , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Persona de Mediana Edad , Distrés Psicológico , Encuestas y Cuestionarios , Seúl/epidemiología , Medios de Comunicación de Masas , Ira , Trastornos de Estrés Traumático Agudo/psicología , Adulto Joven , Anciano , Exposición a los MediosRESUMEN
Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) and their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play a pivotal role in glaucoma onset and progression. For example, it is known that excitotoxicity, immunological alterations, ischemia, and oxidative stress contribute to the neurodegeneration in glaucoma disease. To study these effects and to discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various glaucoma animal models beyond an elevated IOP. We introduce genetically modified mice, e.g., the optineurin E50K knock-in or the glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting the glutamate analogue N-methyl-D-aspartate intravitreally, which leads to rapid RGC degeneration. To explore the contribution of the immune system, the experimental autoimmune glaucoma model can serve as a useful tool. Here, immunization with antigens led to glaucoma-like damage. The ischemic mechanism can be mimicked by inducing a high IOP for a certain amount of time in rodents, followed by reperfusion. Thereby, damage to the retina and the optic nerve occurs rapidly after ischemia/reperfusion. Lastly, we discuss the importance of optic nerve crush models as model systems for normal-tension glaucoma. In summary, various glaucoma models beyond IOP increase can be utilized.
Asunto(s)
Glaucoma , Animales , Ratones , Ojo , Ácido Glutámico , Modelos Animales , IsquemiaRESUMEN
Evoked motor responses (distal muscle responses) to a specific nerve stimulation are considered an endpoint. Often in crush injuries of the upper limb below the level of the elbow, the distal muscle responses are irrelevant. We report 14 cases of crush injuries of the upper limb that underwent an amputation below the level of the elbow. A parasagittal ultrasound-guided infraclavicular block without neurostimulation was administered in all patients. A reliable local anesthetic (LA) spread either in the perineural or perivascular area is considered adequate. Adequate intraoperative anesthesia and postoperative analgesia were achieved with the deposition of LA beneath the axillary artery.