RESUMEN
Lipid alterations in the brain are well-documented in disease and aging, but our understanding of their pathogenic implications remains incomplete. Recent technological advances in assessing lipid profiles have enabled us to intricately examine the spatiotemporal variations in lipid compositions within the complex brain characterized by diverse cell types and intricate neural networks. In this study, we coupled time-of-flight secondary ion mass spectrometry (ToF-SIMS) to an amyotrophic lateral sclerosis (ALS) Drosophila model, for the first time, to elucidate changes in the lipid landscape and investigate their potential role in the disease process, serving as a methodological and analytical complement to our prior approach that utilized matrix-assisted laser desorption/ionization mass spectrometry. The expansion of G4C2 repeats in the C9orf72 gene is the most prevalent genetic factor in ALS. Our findings indicate that expressing these repeats in fly brains elevates the levels of fatty acids, diacylglycerols, and ceramides during the early stages (day 5) of disease progression, preceding motor dysfunction. Using RNAi-based genetic screening targeting lipid regulators, we found that reducing fatty acid transport protein 1 (FATP1) and Acyl-CoA-binding protein (ACBP) alleviates the retinal degeneration caused by G4C2 repeat expression and also markedly restores the G4C2-dependent alterations in lipid profiles. Significantly, the expression of FATP1 and ACBP is upregulated in G4C2-expressing flies, suggesting their contribution to lipid dysregulation. Collectively, our novel use of ToF-SIMS with the ALS Drosophila model, alongside methodological and analytical improvements, successfully identifies crucial lipids and related genetic factors in ALS pathogenesis.
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Esclerosis Amiotrófica Lateral , Animales , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/metabolismo , Drosophila , Espectrometría de Masa de Ion Secundario , LípidosRESUMEN
The purpose of this study was to determine the ratio of sagittal length to coronal length of the distal tibia for predicting the sagittal length of the distal tibia. A total of 202 ankles were measured based on CT imaging availability. We measured the coronal length (Width, W) parallel to the Chaput tubercle from CT scans. Sagittal length was divided into 3 points (Diameter D1, D2, D3) in the axial plane on the same level. The relationship between coronal length and each sagittal length was determined through correlation analysis. A prediction model was then developed using multiple regression. We also analyzed the quality of the prediction model and validated the prediction model with a validation cohort. Each sagittal length (D1, D2, D3) and coronal length had a significant positive correlation (p < .01). In the prediction model, sex, height, and W were significantly associated with D1, D2, and D3 (p < .05). Prediction models were made for each sagittal length (D1, D2, D3). Concordance correlation coefficient (CCC) values of prediction models for D1, D2, and D3 were 0.78, 0.72, and 0.72 for the derivation cohort and 0.69, 0.63, and 0.61 for the validation cohort, respectively. Accuracies of models as ± 2SD for D1, D2, and D3 were 93.9%, 94.9%, and 94.9%, respectively. This study predicted the sagittal length of the distal tibia for preoperative planning by measuring the coronal length of the distal tibia. Prediction of the sagittal length of the distal tibia can help foot and ankle surgeons fixate screws stably to prevent iatrogenic injury of posterior structures of the distal tibia.
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Tibia , Tomografía Computarizada por Rayos X , Humanos , Tibia/diagnóstico por imagen , Tibia/cirugía , Tobillo , Articulación del TobilloRESUMEN
OBJECTIVE: This study aimed to propose treatment protocol and identify patterns of tillaux fractures using three-dimensional (3D) computed tomography (CT) analysis and to describe an effective reduction technique. METHODS: Forty-two juvenile patients with tillaux fractures were evaluated with 3D-CT scan for fracture displacement pattern and received surgical treatment. Tillaux fragment was reduced by pushing the superomedial quadrant part of the fragment slightly downward towards the ankle joint from anterolateral to posteromedial through 5-mm skin incisions with mosquito forceps. A 4.0 cannulated screw was subsequently inserted from the anterolateral to the posteromedial side parallel to the ankle joint. We analysed the distance and direction of fracture displacement with 3D-CT before the surgery. Pre-operative and post-operative plain radiographs were evaluated. RESULTS: Pre-operative 3D-CT analysis revealed a common fracture pattern, varus tilt, and external rotation of fragment. We achieved satisfactory reduction with residual fracture gaps less than 2 mm in 42 cases. Two cases had a 13-mm anterior gap that was reduced by mini-open reduction because of periosteal impingement. No significant clinical complications were found. CONCLUSION: The closed reduction technique developed based on the fracture pattern identified by 3D-CT anatomical analysis is safe and effective in treating tillaux fractures.
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Fijación Interna de Fracturas , Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Humanos , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Niño , Adolescente , Tornillos Óseos , Reducción Cerrada/métodos , Fracturas de Tobillo/cirugía , Fracturas de Tobillo/diagnóstico por imagen , Cuidados Preoperatorios/métodosRESUMEN
BACKGROUND: Gastric adenomas can be successfully treated with endoscopic resection, including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The aim of this study was to evaluate and compare the efficacy of ESD and EMR with circumferential precutting (EMR-P) in the treatment of small gastric adenomas. METHODS: This study included 1014 gastric adenomas ≤ 15 mm in diameter treated with ESD or EMR-P from 2012 to 2019, retrospectively. Propensity score matching between the ESD and EMR-P groups (1:1 to 3:1) was performed according to age, sex, tumor size, tumor location (upper, middle, and lower thirds), morphology, and preprocedural histology. The procedure time and the rates of en bloc resection, complete resection, adverse events, and local recurrence were compared between the two groups. RESULTS: After propensity score matching, 478 lesions (ESD: 295, EMR-P: 183) were analyzed. The rates of en bloc resection (94.9% vs. 93.4%, p = 0.498), complete resection (93.6% vs. 90.2%, p = 0.177), bleeding (8.1% vs. 3.8%, p = 0.063), and local recurrence (0.0% vs. 1.4%, p = 0.185) did not significantly differ between the two groups. The procedure time was significantly longer for ESD than for EMR-P (p < 0.001). In the EMR-P group, the complete resection rate was significantly lower in the upper third than in the middle and lower thirds (p < 0.001). CONCLUSION: EMR-P is as effective as ESD for the treatment of small gastric adenomas. However, the efficacy of EMR-P is lower for gastric adenomas in the proximal stomach.
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Adenoma , Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Adenoma/patología , Adenoma/cirugía , Pólipos Adenomatosos , Resección Endoscópica de la Mucosa/métodos , Humanos , Mucosa Intestinal/cirugía , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
After selection in the thymus, the post-thymic T cell compartments comprise heterogenous subsets of naive and memory T cells that make continuous T cell receptor (TCR) contact with self-ligands bound to major histocompatibility complex (MHC) molecules. T cell recognition of self-MHC ligands elicits covert TCR signaling and is particularly important for controlling survival of naive T cells. Such tonic TCR signaling is tightly controlled and maintains the cells in a quiescent state to avoid autoimmunity. Here, we review how naive and memory T cells are differentially tuned and wired for TCR sensitivity to self and foreign ligands.
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Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Animales , Antígenos CD5/metabolismo , Diferenciación Celular/inmunología , Antígenos de Histocompatibilidad/inmunología , Antígenos de Histocompatibilidad/metabolismo , Humanos , Activación de Linfocitos/inmunología , Receptores de Antígenos de Linfocitos T/genética , Subgrupos de Linfocitos T/citología , Timocitos/citología , Timocitos/inmunología , Timocitos/metabolismoRESUMEN
BACKGROUND: Caregivers of patients who wear conventional diapers are required to check for voiding every hour because prolonged wearing of wet diapers causes health problems including diaper dermatitis and urinary tract infections. However, frequent checking is labor intensive and disturbs patients' and caregivers' sleep. Furthermore, assessing patients' urine output with diapers in an acute care setting is difficult. Recently, a smart diaper system with wetness detection technology was developed to solve these issues. OBJECTIVE: We aimed to evaluate the applicability of the smart diaper system for urinary detection, its accuracy in measuring voiding volume, and its effect on incontinence-associated dermatitis (IAD) occurrence in an acute care hospital. METHODS: This prospective, observational, single-arm pilot study was conducted at a single tertiary hospital. We recruited 35 participants aged ≥50 years who were wearing diapers due to incontinence between August and November 2020. When the smart diaper becomes wet, the smart diaper system notifies the caregiver to change the diaper and measures voiding volume automatically. Caregivers were instructed to record the weight of wet diapers on frequency volume charts (FVCs). We determined the voiding detection rate of the smart diaper system and compared the urine volume as automatically calculated by the smart diaper system with the volume recorded on FVCs. Agreement between the two measurements was estimated using a Bland-Altman plot. We also checked for the occurrence or aggravation of IAD and bed sores. RESULTS: A total of 30 participants completed the protocol and 390 episodes of urination were recorded. There were 108 records (27.7%) on both the FVCs and the smart diaper system, 258 (66.2%) on the FVCs alone, 18 (4.6%) on the smart diaper system alone, and 6 (1.5%) on the FVCs with sensing device lost. The detection rate of the smart diaper system was 32.8% (126/384). When analyzing records concurrently listed in both the FVCs and the smart diaper system, linear regression showed a strong correlation between the two measurements (R2=0.88, P<.001). The Bland-Altman assessment showed good agreement between the two measurements, with a mean difference of -4.2 mL and 95% limits of agreement of -96.7 mL and 88.3 mL. New occurrence and aggravation of IAD and bed sores were not observed. Bed sores improved in one participant. CONCLUSIONS: The smart diaper system showed acceptable accuracy for measuring urine volume and it could replace conventional FVCs in acute setting hospitals. Furthermore, the smart diaper system has the potential advantage of preventing IAD development and bed sore worsening. However, the detection rate of the smart diaper system was lower than expected. Detection rate polarization among participants was observed, and improvements in the user interface and convenience are needed for older individuals who are unfamiliar with the smart diaper system.
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Teléfono Inteligente , Micción , Hospitales , Humanos , Proyectos Piloto , Estudios ProspectivosRESUMEN
OBJECTIVE: to present a new and easy classification of atlanto-axial rotatory fixation (AARF) and to investigate the efficiency of conservative treatment of AARF. BACKGROUND: Although there is a precise definition and diagnostic classification of AARF, there is still significant difficulty in measuring the atlas and axis angles because all of the atlas or axis cannot be seen in a certain 2-dimensional computed tomogram image. In addition, some recent case reports showed that long-term conservative treatment can reduce pediatric AARFs, even that are severe or chronic. METHODS: Fifty-one children with AARF were analyzed retrospectively with new 3-dimensional computed tomogram (3DCT)-based AARF classification; the mean age was 72.7 ± 35.2 months (19-139 months). In the new AARF classification, type 1 was defined as that when the C1C2 angle is not 0° on midline and type 2 as that when the C1C2 angle is 0° on the midline. RESULTS: All 7 children with AARF type 1 were treated successfully only with Halter tractions. Twenty among 44 children with type 2 did not show any difference in improvement compared with not-treated 24 children with type 2. CONCLUSION: The first new AARF classification based on 3DCT appears to be easy to use and even the most severe children with AARF may be managed only with conservative treatment such as long-term Halter traction.
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Articulación Atlantoaxoidea , Luxaciones Articulares , Tortícolis , Articulación Atlantoaxoidea/diagnóstico por imagen , Niño , Preescolar , Tratamiento Conservador , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The extraesophageal manifestations of gastroesophageal reflux disease (GERD) are more difficult to manage than the typical symptoms. The efficacy of high-dose and standard-dose proton pump inhibitors against these atypical symptoms is not yet established. METHODS: In this single center, randomized, open-label study, patients with GERD received rabeprazole for 8 weeks, either 20 mg once daily (standard-dose group) or 20 mg twice daily (high-dose group). Patients were assessed before treatment and at weeks 4 and 8 with a 5-graded scale questionnaire consisting of 2 typical symptoms (heartburn and acid regurgitation) and 8 atypical symptoms (chest pain, cough, globus, wheezing, laryngopharyngitis, hoarseness, belching, and dysphagia). Sufficient improvement of reflux symptoms was defined as ≥50% reduction from the initial questionnaire score. RESULTS: Final analyses included 35 patients in the standard-dose group and 38 patients in the high-dose group. The rate of sufficient improvement for typical symptoms was significantly higher in the high-dose group than in the standard-dose group (100.0% vs. 84.0%, P = 0.040). For atypical symptoms, the rate of sufficient improvement tended to be higher in the high-dose group than in the standard-dose group (82.4% vs. 63.0%, P = 0.087). Scores of typical and some atypical symptoms (cough and globus) improved after treatment, with significant inter-group differences in time-course changes. CONCLUSIONS: High-dose rabeprazole is more effective for relieving typical GERD symptoms and some atypical symptoms such as cough and globus than a standard-dose regimen. TRIAL REGISTRATION: This research was enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health ( ClinicalTrials.gov Protocol Registration and Results system ID: NCT04001400 ). This study was registered on June 26, 2019 - Retrospectively registered.
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Reflujo Gastroesofágico , Inhibidores de la Bomba de Protones , Reflujo Gastroesofágico/tratamiento farmacológico , Pirosis/tratamiento farmacológico , Pirosis/etiología , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Rabeprazol , Resultado del TratamientoRESUMEN
PURPOSE: This study aimed to (1) quantitatively analyze the fibular footprints of the lateral collateral ligament (LCL) and popliteofibular ligament (PFL) and (2) evaluate whether a fibular tunnel can restore the LCL and PFL fibular footprints simultaneously without modification in anatomic posterolateral corner reconstruction of the knee. METHODS: In 20 cadaveric knees, anatomic characteristics, such as diameter, location and relationship with anatomic landmarks, of the LCL and PFL footprints were analyzed. Subsequently, a fibular tunnel that connected the LCL and PFL footprint centers was created with 1.5 mm drill bit, and tunnel depth, which is defined as the distance between the tunnel and the nearest cortex, was evaluated. An additional tunnel from the anteroinferior border of the LCL footprint to the posteroinferior border of the PFL footprint was created, and its tunnel depth was evaluated as well and compared with that of the original tunnel. RESULTS: The LCL footprint was longitudinally ovoid (8.4 ± 1.0 × 13 ± 1.0 mm), and its inferior margin corresponded well with the lateral apex of the fibula (distance, 1.0 ± 0.7 mm). The PFL footprint was round (9.7 ± 1.3 × 9.0 ± 1.1 mm), and its center was very close to the tip of the fibular styloid process (1.2 ± 0.8 mm). The tunnel depth of the original fibular tunnel was 1.8 ± 0.7 mm, and it was very shallow for tunnel reaming. On the contrary, the tunnel depth of the modified fibular tunnel (6.4 ± 1.1 mm) was significantly higher than that of the original tunnel (P < 0.05), and it was relatively safe for tunnel reaming. CONCLUSIONS: A single fibular tunnel cannot reproduce the LCL and PFL footprint centers simultaneously because the trajectory is too close to the cortex. A modified fibular tunnel, using the margins of the footprints, is recommended to avoid cortical blowout. CLINICAL RELEVANCE: A modified fibular tunnel that covers only portions of the LCL and PFL footprints, from the anteroinferior LCL footprint to the posteroinferior PFL footprint, is less likely to blow out the lateral fibula than is a similar tunnel using the anatomic footprint centers.
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Puntos Anatómicos de Referencia , Peroné/cirugía , Traumatismos de la Rodilla/cirugía , Articulación de la Rodilla/cirugía , Ligamentos Articulares/cirugía , Procedimientos Ortopédicos/métodos , Procedimientos de Cirugía Plástica/métodos , Anciano , Cadáver , Femenino , Humanos , Traumatismos de la Rodilla/diagnóstico , Ligamentos Articulares/lesiones , MasculinoRESUMEN
BACKGROUND: Ankle sprains are one of the most common musculoskeletal injuries. To guide management decisions, a clear insight into the relevant subgroups of patients with a potentially better or worse prognosis is important. This study aimed to evaluate injury severity, using ultrasonography (US), as a prognostic factor of acute ankle sprain and other possible factors including age, sex, body mass index (BMI), level of job activity, and level of sports activity. MATERIALS AND METHODS: We retrospectively reviewed 28 patients with acute ankle sprain who reported at initial examination with an acutely twisted ankle. All patients had received a standard physical examination, radiography and standard ultrasound, to diagnose specific ligament injuries and their ankle sprain had been treated using standard conservative management. Various data including age, sex, BMI, level of sports activity, level of daily job activity, and final functional score (Foot and Ankle Outcome Scores, FAOS) were obtained. Mean comparison and correlations were used to assess risk factors. Risk factors associated with functional outcomes were evaluated using a multiple linear regression test. RESULTS: At final follow-up as 1 year after injury, FAOS differed significantly for injury severity, age, and BMI. There were no significant differences in sex, job activity, and exercise levels. The factor most affecting FAOS for both pain (FAOS-Pain) and symptoms (FAOS-Sx) was the number of completely torn ligaments. Age was the most important factor affecting the FAOS-Daily Living Activity (ADL). BMI was the most important factor for sports activity level (FAOS-Sports). Age and the number of completely torn ligaments were both important to FAOS-Sports and quality of life (FAOS-QOL). CONCLUSION: The severity of injury, defined using US, was a prognostic factor for long-term outcome following acute ankle sprain. Therefore, US imaging of acute ankle ligament injury may be important to predict prognosis of acute ankle sprain.
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Traumatismos del Tobillo/diagnóstico por imagen , Ligamentos Articulares/diagnóstico por imagen , Ligamentos Articulares/lesiones , Esguinces y Distensiones/diagnóstico por imagen , Ultrasonografía , Actividades Cotidianas , Adulto , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios RetrospectivosRESUMEN
T cell receptor (TCR) contact with self ligands keeps T cells alive and is shown here to cause naive CD8(+), but not CD4(+), T cells to be hypersensitive to certain gamma(c) cytokines, notably interleukin (IL)-2, IL-15, and IL-7. Hypersensitivity of CD8(+) T cells to IL-2 was dependent on a low-level TCR signal, associated with high expression of CD5 and GM1, a marker for lipid rafts, and was abolished by disruption of lipid rafts. By contrast, CD4(+) T cells expressed low amounts of GM1 and were unresponsive to IL-2. Physiologically, sensitivity to IL-7 and IL-15 maintains survival of resting CD8(+) T cells, whereas sensitivity to IL-2 may be irrelevant for normal homeostasis but crucial for the immune response. Thus, TCR contact with antigen upregulates GM1 and amplifies responsiveness of naive CD8(+) T cells to IL-2, thereby making the cells highly sensitive to exogenous IL-2 from CD4(+) T helper cells.
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Linfocitos T CD8-positivos/metabolismo , Citocinas/metabolismo , Glicoesfingolípidos/biosíntesis , Microdominios de Membrana/metabolismo , Subgrupos de Linfocitos T/metabolismo , Animales , Autoantígenos/inmunología , Autoantígenos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Supervivencia Celular/inmunología , Células Cultivadas , Citocinas/inmunología , Glicoesfingolípidos/genética , Glicoesfingolípidos/inmunología , Antígenos de Histocompatibilidad/metabolismo , Homeostasis , Subunidad gamma Común de Receptores de Interleucina/metabolismo , Ratones , Ratones Endogámicos C57BL , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Unión Proteica/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patologíaRESUMEN
BACKGROUND: Peripheral arterial disease (PAD) is known as the greatest risk factor affecting the amputation of diabetic foot. Thus, it is crucial to understand the epidemiology of PAD associated with diabetic foot and the relationship between PTA and amputation in predicting prognosis. However, no such multi-year data are available in Korea. Thus, the purpose of this study was to investigate trends of amputation involving diabetic foot based on vascular interventions for PAD in Korea. METHODS: This study was conducted using six-year data obtained from Health Insurance Review and Assessment Service from January 1, 2011 to December 31, 2016. Our study included data pertaining to diabetic foot, PAD, and vascular intervention codes (percutaneous transluminal angioplasty [PTA, M6597], percutaneous intravascular installation of stent-graft [PIISG, M6605], and percutaneous intravascular atherectomy [PIA, M6620]). We analyzed the number of vascular interventions and minor and major amputations each year. The relationship between annual amputation and vascular intervention was analyzed using χ² test. RESULTS: The overall number of vascular interventions increased from 253 (PTA, 111; PIISG, 140; and PIA, 2) in 2011 to 1,230 (PTA, 745; PIISG, 470; and PIA, 15) in 2016. During the same period, the number of minor amputations increased from 2,534 to 3,319 while major amputations decreased from 980 to 956. The proportion of minor amputations among patients who underwent vascular intervention was significantly increased from 19.34% in 2011 to 21.45% in 2016 while the proportion of major amputations among these patients was significantly reduced from 9.88% to 4.27%. In addition, the association between vascular intervention and amputation increased from 0.56 (spearman correlation coefficient) in 2011 to 0.62 in 2016. CONCLUSION: In diabetic foot patients, increase in vascular intervention resulted in a change in amputation pattern, showing statistically significant correlation.
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Amputación Quirúrgica/tendencias , Pie Diabético/patología , Extremidad Inferior/cirugía , Enfermedad Arterial Periférica/diagnóstico , Angioplastia , Aterectomía , Bases de Datos Factuales , Pie Diabético/complicaciones , Pie Diabético/cirugía , Humanos , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/terapia , República de CoreaRESUMEN
The purpose of the present study was to compare the outcomes of patients with Achilles tendon rupture treated with minimally invasive repair and early functional rehabilitation with the outcomes of similar patients treated with cast immobilization. After undergoing minimally invasive surgery, a below-knee splint with the foot in 30° of plantarflexion was applied to each patient for the first week. Patients were then assigned to a cast immobilization group (IG; nâ¯=â¯25) or a functional group (FG; nâ¯=â¯16). Data were collected during outpatient checks at 6 weeks, 3 months, 6 months, and 1 year. Outcomes of interest included range of motion (ROM), heel height, calf circumference, pain and functional score, return to work and light sports activity, and complications. The time interval for return to work in the FG was faster than that in the IG (pâ¯=â¯.026). There was no clinically important difference between the 2 groups with regard to heel height, ROM, return to sports, calf circumference, visual analog scale, American Orthopaedic Foot and Ankle Society score, or Achilles tendon Total Rupture Score at every outpatient check except ROM difference at 6 weeks and heel height at 3 months. Rerupture occurred in 2 patients (1 [4%] in the IG and 1 [6.25%] in the FG). Early functional rehabilitation seemed to be as safe as traditional postoperative immobilization with a similar functional result and complications, but it was advantageous for the early phase of rehabilitation only.
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Tendón Calcáneo/lesiones , Inmovilización , Procedimientos Quirúrgicos Mínimamente Invasivos , Modalidades de Fisioterapia , Traumatismos de los Tendones/cirugía , Tendón Calcáneo/cirugía , Adulto , Moldes Quirúrgicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Recuperación de la Función , Recurrencia , Estudios Retrospectivos , Rotura/cirugía , Traumatismos de los Tendones/rehabilitación , Traumatismos de los Tendones/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
γδ T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing γδ T (γδT-17) and IFN-γ-producing γδ T (γδT-IFNγ) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional γδ T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like γδT-17 and γδT-IFNγ cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional γδ T cells, but they do not monopolize the same cytokine. γδT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. γδT-IFNγ cells instead depend heavily on IL-15. They display traits analogous to memory CD8(+) T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional γδ T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive αß T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that γδ T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes.
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Homeostasis/inmunología , Inmunidad Innata/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T/inmunología , Traslado Adoptivo , Animales , Citocinas/inmunología , Citometría de Flujo , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-17/biosíntesis , Interleucina-17/inmunología , Ratones , Ratones Endogámicos C57BL , Receptores de Antígenos de Linfocitos T gamma-deltaRESUMEN
We analyzed patterns of care and outcomes for patients with primary central nervous system lymphoma (PCNSL) in this multi-institutional retrospective study. Between January 2000 and December 2011, 220 patients with PCNSL received radiotherapy (RT). Among these patients, 26 patients received RT alone; 179 patients were treated with chemotherapy and radiotherapy; the rest of the patients (N = 15) initially underwent chemotherapy alone, then received RT as a salvage treatment. Most of the patients (N = 188) received methotrexate-based chemotherapy. The median follow up duration was 38 months (range 3-179 months). The median RT dose and whole brain RT (WBRT) dose were 45.0 Gy (range 20.0-59.4) and 30.6 Gy (range 18.0-45.0), respectively. Seventy-seven (35%) patients received WBRT alone, and 143 patients (65%) underwent WBRT plus boost RT. Total RT dose and WBRT dose decreased during the study period. The median survival was 64 months and actuarial 5-year overall survival was 51.4%. In multivariate analysis, age (P < 0.001), ECOG performance status (P = 0.036), deep structure involvement (P = 0.011) and treatment response (P = 0.001) were significant prognosticators. RT combined with chemotherapy is effective modality for treatment of PCNSL. The survival outcome improved in spite of total radiation dose and whole brain RT (WBRT) dose having been decreased over the study period, indicating that low-dose WBRT could be effective.
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Neoplasias del Sistema Nervioso Central/radioterapia , Linfoma/radioterapia , Neoplasias del Sistema Nervioso Central/diagnóstico , Terapia Combinada/efectos adversos , Terapia Combinada/tendencias , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Linfoma/diagnóstico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia/efectos adversos , Radioterapia/tendencias , Dosificación Radioterapéutica , República de Corea , Estudios Retrospectivos , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/tendencias , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess the incidence of abnormal internal rotation of the talus in the axial plane in patients with varus ankle osteoarthritis, and to determine whether this incidence differs from the severity of varus ankle osteoarthritis (moderate versus severe). MATERIALS AND METHODS: We retrospectively evaluated weight-bearing computed tomography (CT) and plain radiographs of 52 ankles with no abnormalities (control group) and 96 ankles with varus osteoarthritis (varus-OA group), which were further stratified into a moderate-OA subgroup (50 ankles) and a severe-OA subgroup (46 ankles). A new radiographic parameter on weight-bearing CT, the talus rotation ratio, was used to assess the rotation of the talus in the axial plane. The normal range of the talus rotation ratio was defined as the 95% prediction interval for talus rotation ratio values in the control group. Abnormal internal rotation of the talus was defined for talus rotation ratio values above the normal range. We determined the incidence of abnormal internal rotation of the talus in the varus-OA group, moderate-OA subgroup, and severe-OA subgroup. RESULTS: In the varus-OA group, the incidence of abnormal internal rotation of the talus was 45% (43 ankles), which corresponded to an incidence of 32% (16 ankles) in the moderate-OA subgroup and 59% (27 ankles) in the severe-OA subgroup (p = 0.013). CONCLUSION: Our study demonstrates that abnormal internal rotation of the talus occurs in patients with varus ankle osteoarthritis, and is more frequently noted in severe than in moderate varus ankle osteoarthritis.
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Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/fisiopatología , Osteoartritis/diagnóstico por imagen , Osteoartritis/fisiopatología , Astrágalo/diagnóstico por imagen , Astrágalo/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Soporte de Peso/fisiología , Adolescente , Adulto , Anciano , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rotación , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To investigate whether microfracture with a cannulated hollow awl can yield more patent marrow channels and allow greater mobilization of the reparable cells to the defect compared to the conventional awl with blunt end in human knee joints. METHODS: Patients who were planned for 1-stage bilateral total knee arthroplasty due to degenerative osteoarthritis with well-preserved lateral femoral condylar cartilage were retrospectively included. A 10-mm × 20-mm, rectangular, full-thickness chondral defect was made on the lateral femoral condyle on each knee joint. The 6-holed microfracture procedure, each at 9 mm depth and 3 mm separation of perforations, was followed using a hollow awl in one knee and using a conventional awl in the other knee, respectively. The bleeding through the microfracture holes was observed and collected using an absorbable gelatin sponge and was analyzed microscopically by colony forming unit-fibroblast assays and automated cell counting method. The representative 3 bony samples of the distal lateral femoral condyles obtained were also scanned with micro-computed tomography (micro-CT) for morphometric analysis (percent bone volume, trabecular separation, and total porosity) of subchondral bone microarchitecture of the microfracture holes. RESULTS: Twenty-two patients were enrolled, and the mean age was 70.8 ± 6.1 (58-83) years. Compared with the conventional awl group, the hollow awl group had a significantly greater amount of bleeding (1.8 ± 0.2 g vs 1.1 ± 0.1 g; P < .001) and a greater number of mesenchymal stem cells in the blood clot (21,474.0 ± 3,911.1 vs 13,329.7 ± 3,311.0; P = .004). The hollow awl group also showed overall more patent marrow channels around the adjacent subchondral bone of the microfracture hole, with greater trabecular separation on micro-CT analysis (P < .001). CONCLUSIONS: Compared to the conventional awl, microfracture with a cannulated hollow awl can yield more patent marrow channels at the adjacent subchondral bone of the microfracture hole and result in greater mobilization of the reparable cells to the defect in human knee joints. LEVEL OF EVIDENCE: Level III, therapeutic case control.
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Artroplastia Subcondral/métodos , Médula Ósea/cirugía , Cartílago Articular/cirugía , Articulación de la Rodilla/cirugía , Células Madre Mesenquimatosas/citología , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla , Estudios de Casos y Controles , Ensayo de Unidades Formadoras de Colonias , Femenino , Fémur/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Microtomografía por Rayos XRESUMEN
BACKGROUND: Pediatric patients with olecranon fractures are uncommon. The tension band suture technique was introduced to reduce the burden of implant removal and other complications. However, to our knowledge, early range of motion (ROM) exercise has not been introduced in this population of patients. Double Vicryl loops and knots with 2 cross-pins are used to maintain the benefits of the tension band suture technique and to enhance fixation tensile strength. We believe that early ROM exercises could be achieved without nonunion or fixation failure. METHODS: Twelve pediatric patients with olecranon fractures were treated with tension band suture with double loops and knots between 2004 and 2015. Vicryl No. 1 was used for wiring. ROM exercises were initiated 1 week postoperatively with a customized functional brace. Early functional outcomes were evaluated by the Mayo Elbow Performance Score at every visit after 8 weeks postoperatively. RESULTS: Nine boys and 3 girls (average age, 10.6 years; range, 5 years 7 months-16 years 2 months) were included in the study. Initial displacement and angulation of the fractures were 5 mm (2-7 mm) and 12° (4°-25°), respectively. Two cases had radial neck fractures of the ipsilateral elbow. All patients had a perfect Mayo Elbow Performance Score after 8 weeks postoperatively. Pin removals were performed at 13.1 weeks. No complications, including growth arrest, were observed. DISCUSSION/CONCLUSION: Tension band suture with double loops and knots, combined with early ROM exercise, may be a complete alternative to tension band wiring.
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Terapia por Ejercicio , Fijación Interna de Fracturas/rehabilitación , Olécranon/lesiones , Técnicas de Sutura/rehabilitación , Fracturas del Cúbito/rehabilitación , Fracturas del Cúbito/cirugía , Adolescente , Niño , Preescolar , Femenino , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Olécranon/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Resistencia a la Tracción , Resultado del Tratamiento , Fracturas del Cúbito/fisiopatologíaRESUMEN
PURPOSE: Clinicians frequently diagnose chronic ankle instability using the manual anterior drawer test and stress radiography. However, both examinations can yield incorrect results and do not reveal the extent of ankle instability. Stress ultrasound has been reported to be a new diagnostic tool for the diagnosis of chronic ankle instability. The purpose of this study was to assess the diagnostic value of stress ultrasound for chronic ankle instability compared to the manual anterior drawer test, stress radiography, magnetic resonance imaging (MRI), and arthroscopy. METHODS: Twenty-eight consecutive patients who underwent ankle arthroscopy and subsequent modified Broström repair for treatment of chronic ankle instability were included. The arthroscopic findings were used as the reference standard. A standardized physical examination (manual anterior drawer test), stress radiography, MRI, and stress ultrasound were performed to assess the anterior talofibular ligament (ATFL) prior to operation. Ultrasound images were taken in the resting position and the maximal anterior drawer position. RESULTS: Grade 3 lateral instability was verified arthroscopically in all 28 cases with a clinical diagnosis (100%). Twenty-two cases showed grade III instability on the manual anterior drawer test (78.6%). Twenty-four cases displayed anterior translation exceeding 5 mm on stress radiography (86%), and talar tilt angle exceeded 15° in three cases (11 %). Nineteen cases displayed a partial chronic tear (change in thickness or signal intensity), and nine cases displayed complete tear on MRI (100%). Lax and wavy ATFL was evident on stress ultrasound in all cases (100 %). The mean value of the ATFL length was 2.8 ± 0.3 cm for the stressed condition and 2.1 ± 0.2 cm for the resting condition (p < 0.001). CONCLUSION: Stress ultrasound may be useful for the diagnosis of chronic ankle instability in addition to the manual anterior drawer test and stress radiography. LEVEL OF EVIDENCE: III.
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Articulación del Tobillo/diagnóstico por imagen , Inestabilidad de la Articulación/diagnóstico por imagen , Adolescente , Adulto , Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Artroscopía , Enfermedad Crónica , Femenino , Humanos , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen Físico , Radiografía , Estudios Retrospectivos , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Tibial fractures are the most common long bone fracture and are often associated with severe soft tissue and bone defects. The objectives of our study were to describe the management and clinical results of patients with extra-articular open tibial fractures and to identify factors associated with a poor functional outcome. METHODS: This study included 82 adults available for follow-up for over 1 year after surgery. According to the AO Foundation/Orthopedic Trauma Association fracture classification, 26 fractures were type 41 A, 34 were type 42, and 22 were type 43 A. In accordance with the Gustilo-Anderson classification system, 31 were type I, 19 were type II, and 32 were type III. Initial nerve injury was confirmed in 18 cases. RESULTS: Definitive fixation occurred at a mean of 6.73 days (range, 0-16 days) after the injury. Soft tissue reconstruction was as follows: primary closure with debridement, 50 patients; split-thickness skin graft, 5; perforator based rotational flaps, 10; and free flaps, 17. Complications occurred in 29 cases (35.4%): superficial infection, 5 patients; deep infection, 3; primary suture site skin necrosis, 7; partial flap necrosis, 4; malalignment, 7; joint stiffness, 2; and hardware breakage, 1. Thirty additional operations (36.6%) were performed during the hospital stay. Mean bone union time was 20.4 weeks (range, 13-63 weeks) and the mean Lower Extremity Functional Scale score (LEFS) was 70.93 (range, 36-79). Multiple linear regression analysis indicated that skin defect size (p = 0.002), and occurrence of complications (p < 0.001) correlated with the LEFS score. CONCLUSION: Functional outcome after treatment of extra-articular open tibial fractures was influenced by the skin defect size and the presence of any complications. This suggests that good clinical results can be expected if complications are prevented through proper reduction, firm fixation, early soft tissue reconstruction, and early rehabilitation.