RESUMEN
Endochondral ossification contributes to longitudinal skeletal growth. Osteoblasts, which are bone-forming cells, appear close to terminally differentiated hypertrophic chondrocytes during endochondral ossification. We established mice with conditional knockout (cKO) of Smad4, an essential co-activator for transforming growth factor ß family signaling. The mice showed a marked increase in bone volume in the metaphysis as a result of increased bone formation by osteoblasts, in which ß-catenin, an effector of canonical Wnt signaling, accumulated. We identified Wnt7b as a factor with increased expression in growth plate cartilage in Smad4 cKO mice. Wnt7b mRNA was expressed in differentiated chondrocytes and suppressed by BMP4 stimulation. Ablation of Wnt7b blunted the increase in bone in adult Smad4 cKO mice and reduced skeletal growth in juvenile mice. Overall, we conclude that Wnt7b is a crucial factor secreted from hypertrophic chondrocytes to initiate endochondral ossification. These results suggest that Smad4-dependent BMP signaling regulates the Wnt7b-ß-catenin axis during endochondral ossification.
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Condrocitos , Osteogénesis , Animales , Ratones , beta Catenina/metabolismo , Huesos , Cartílago/metabolismo , Diferenciación Celular/genética , Condrocitos/metabolismo , Osteogénesis/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMEN
PURPOSE: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. METHOD: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients' airways was evaluated preoperatively and postoperatively in intensive-care units. RESULTS: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. CONCLUSIONS: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes.
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Donadores Vivos , Trasplante de Pulmón , Adulto , Humanos , Pulmón/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
OBJECTIVES: To validate and establish targets for the physician-based clinical scale for foot surgery in rheumatoid arthritis (RA) patients based on patient-reported outcomes from a multicenter prospective cohort. METHODS: We collected data on demographics, values from the RA foot and ankle scale by the Japanese Society for Surgery of the Foot (JSSF-RA), and patient-reported outcomes (PROs) including the Health Assessment Questionnaire Disability Index (HAQ-DI) before (baseline) and 6 and 12 months after joint surgery. Target values for JSSF-RA were determined according to the lower limit of the 95% CI of JSSF-RA in patients with HAQ-DI ≤0.5 after adjusting for age and sex. We used multiple linear regression analysis to examine potential predictors of JSSF-RA target achievement at baseline. RESULTS: Cross-sectional analysis was conducted on data from 417 cases. The JSSF-RA target for foot and ankle surgery was set at 74 according to the JSSF-RA value corresponding to HAQ-DI ≤0.5 (mean 77.6, 95% CI: 74.3-80.9). Longitudinal analysis of patients who underwent foot surgery (N = 59) determined target cut-off values of 1.188 and 65 for HAQ-DI and JSSF-RA at baseline, respectively, as being predictive for achieving JSSF-RA ≥74 after surgery. CONCLUSIONS: A JSSF-RA value of 74 represents an important target for patients with RA who have undergone foot surgery. In order to achieve this target, the timing of the surgery should be considered in the treatment of established RA patients.
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Articulación del Tobillo/cirugía , Artritis Reumatoide/cirugía , Evaluación de la Discapacidad , Pie/cirugía , Medición de Resultados Informados por el Paciente , Complicaciones Posoperatorias/epidemiología , Anciano , Articulación del Tobillo/patología , Artritis Reumatoide/patología , Estudios de Cohortes , Estudios Transversales , Femenino , Pie/patología , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO2 /FiO2 in the intensive-care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.
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Hipertensión Pulmonar , Trasplante de Pulmón , Síndrome de Circulación Fetal Persistente , Adulto , Niño , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/cirugía , Recién Nacido , Donadores Vivos , Trasplante de Pulmón/efectos adversos , Masculino , Recurrencia Local de NeoplasiaRESUMEN
OBJECTIVES: Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs. METHODS: SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22 HKDMs were examined after stimulation with tumour necrosis factor α (TNF-α) in RASFs and OASFs. RESULTS: The gene expression of the 12 HKMTs, including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4, DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36, H3K79, or H4K20 was higher after TNFα stimulation in RASFs vs. OASFs. The gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFα stimulation in RASFs vs. OASFs. CONCLUSIONS: The study findings suggest that the HKM-modifying enzymes are involved in the alteration of HKM, which results in changes in the gene expression of RASFs.
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Artritis Reumatoide/enzimología , Fibroblastos/enzimología , Histona Demetilasas/genética , N-Metiltransferasa de Histona-Lisina/genética , Transcriptoma , Humanos , Membrana Sinovial/citología , Membrana Sinovial/enzimologíaRESUMEN
OBJECTIVE: To explore the characteristics of functional impairment in patients with established rheumatoid arthritis (RA) based on the range of motion (ROM) of joints in a prospective observational study of RA patients undergoing joint surgery. METHODS: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of each joint and disability in the eight HAQ-DI categories were determined using receiver operating characteristic (ROC) and logistic regression analyses. ROM cut-off values of each joint for the absence of disability in each HAQ-DI category were determined using ROC curves. RESULTS: A total of 460 patients were enrolled and analyzed in this study. Based on ROC analysis, the ROM of each joint was significantly associated with disability in each category. After adjusting for disease activity, age, and sex, shoulder abduction had the highest independent impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion-extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR: 3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)]. CONCLUSIONS: Limited ROM of multiple joints was significantly associated with functional impairment in patients with long-standing RA. Motion in daily activity involves multiple joints, and at least two joints were independently involved in disability.
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Artritis Reumatoide/cirugía , Artroplastia de Reemplazo/efectos adversos , Complicaciones Posoperatorias/patología , Rango del Movimiento Articular , Actividades Cotidianas , Anciano , Artritis Reumatoide/patología , Femenino , Humanos , Articulaciones/fisiopatología , Articulaciones/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: Complete circumferential osseous extension in the acetabular rim has been reported to occur in the deep hip with pincer impingement. However, this phenomenon occasionally is observed in dysplastic hips without pincer impingement, and the degree to which this finding might or might not be associated with hip pain, and how often it occurs bilaterally among patients, are not well characterized. QUESTIONS/PURPOSES: (1) To determine the proportion of patients with complete circumferential osseous extension in the acetabular rim using three-dimensional (3-D) CT in patients with and without hip pain who had CT scans obtained for various reasons. (2) To elucidate how often this complete circumferential osseous extension occurred bilaterally among those patients. (3) To investigate the relationship between the proportions of patients with complete circumferential osseous extension observed on CT scans among three different acetabular coverage groups: dysplasia, normal, and overcoverage. (4) To determine how often the finding of hip pain was associated with complete circumferential osseous extension. PATIENTS AND METHODS: Between September 2011 to July 2016, we evaluated 3788 patients with pelvic complaints such as hip, groin, thigh, buttock, or sacroiliac joint pain. We obtained consent from 26% (992 of 3788) of them, and obtained 3-D CT scans as part of that evaluation. For the current retrospective study, we excluded patients younger than 20 years or 80 years or older (181 patients), patients who had previous hip surgery (185 patients), patients with severe osteoarthritis with Tönnis Grades 2 or 3 (301 patients), and patients who could not have an accurate lateral center-edge (LCE) angle measured owing to poor-quality radiographs (24 patients), leaving 301 patients (602 hips) for this analysis. In this study population, patients reported pain in 131 hips (22%), defined as all types of hip pain except for trauma, including activity pain, pain with sports, pain on motion, and impingement pain; the others did not report hip pain. The mean age of the patients was 56 ± 16 years, and the mean LCE angle was 26° ± 8° (range, -9° to 47°). We first determined the proportion of patients with complete circumferential osseous extension in the acetabular rim using 3-D CT for those with and without hip pain who had CT obtained for various reasons. We next elucidated how often this complete circumferential osseous extension occurred bilaterally among the patients, and finally we investigated the relationship between the proportion of patients with complete circumferential osseous extension observed on CT scans among the three groups: dysplasia (defined as LCE angles of 22° or smaller), normal, and overcoverage (defined as LCE angles of 34° or larger) groups. We finally determined how often the finding was associated with hip pain attributable to complete circumferential osseous extension. RESULTS: The proportion of patients with complete circumferential osseous extension was 6% (18 of 301 patients). Eighty-nine percent (16 of 18) of the patients had bilateral complete circumferential osseous extension. There were no differences in the proportions of patients with complete circumferential osseous extension among the three groups: 5.3% (odds ratio [OR], 1.02; 95% CI, 0.45-2.31; p = 0.97), 5.3%, and 7.4% (OR, 0.70; 95% CI, 0.28-1.73; p = 0.44) in the dysplasia, normal, and overcoverage groups, respectively, with the numbers available. Eighteen percent (six of 34) of the hips with complete circumferential osseous extension had pain. CONCLUSIONS: Complete circumferential osseous extension in the acetabular rim is relatively uncommon. When it occurs, it usually is bilateral, it occurs regardless of acetabular coverage, and it is associated with pain in a minority of patients. LEVEL OF EVIDENCE: Level III, prognostic study.
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Acetábulo/patología , Artralgia/patología , Luxación de la Cadera/patología , Articulación de la Cadera/patología , Acetábulo/diagnóstico por imagen , Adulto , Anciano , Artralgia/diagnóstico por imagen , Artralgia/etiología , Femenino , Luxación de la Cadera/complicaciones , Luxación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/diagnóstico por imagen , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
Daily and weekly administration of teriparatide (PTH1-34) reduces the risk of osteoporotic bone fractures. However, their effects on markers of bone formation and bone resorption differ. These results indicate that the dosing frequency of teriparatide may affect bone metabolism and bone structure, with different effects on bone strength. In the present study, to evaluate the dose-related effects of a low administration frequency of teriparatide on bone status, we investigated the effects of three-times-weekly administration of teriparatide (1.1, 5.6, or 28.2 µg/kg) for 12 months on bone parameters, including bone metabolism markers, bone mineral density (BMD), micro-computed tomography, and bone strength, using 6-month-old ovariectomized (OVX) rats. Three-times-weekly administration of teriparatide dose-dependently increased the BMD of the lumbar vertebra and femur in OVX rats, and increased serum osteocalcin (a marker of bone formation), but not type I collagen C-telopeptide (a marker of bone resorption). The trabecular number and thickness increased in the vertebrae and femur, as in prior reports of daily teriparatide administration in OVX rats. Cortical thickness increased only toward the endocortical side of the femur, unlike with daily administration. Bone strength of the vertebrae and proximal and shaft of the femur was correlated with the changes in BMD and bone structure. These results demonstrate the effects of low frequency, intermittent administration of teriparatide on the biomechanical, and microstructural properties of bone in OVX rats.
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Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Teriparatido/farmacología , Animales , Modelos Animales de Enfermedad , Femenino , Análisis de Elementos Finitos , Humanos , Ovariectomía , Ratas , Ratas Sprague-Dawley , Columna Vertebral/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
BACKGROUND: Although little is known, a limited number of three-dimensional computed tomography (CT) images of the pelvis present focal concavity of posterior superior acetabulum. The purpose of the present study was to investigate this morphologic deformity and its relation with dysplasia and retroversion in adults who were expected to have the original morphology of the acetabulum after growth. METHODS: Consecutive adult patients with hip pain who visited our hospital and had three-dimensional pelvic CT images were retrospectively analyzed after approval of the institutional review board; exclusion criterions included diseases, injuries and operations that affect the morphology of the hip including radiographic osteoarthritis Tönnis grades 2 and 3. Focal concavity of posterior superior acetabulum was evaluated by three-dimensional CT image. Acetabular dysplasia was determined by lateral center edge (LCE) angle <25°, Tönnis angle >10°, and anterior center edge (ACE) angle <25° on standing hip radiographs. Acetabular version angle was measured at the one-fourth cranial level of axial CT image. A subgroup analysis included only younger adult patients up to 50 years. RESULTS: The subjects analyzed were 46 men (92 hips) and 54 women (108 hips) with a median age of 57.5 (21-79) and 51.0 (26-77) years, respectively. Focal concavity of posterior superior acetabulum was observed in 13 hips; 7 patients had unilaterally, while 3 patients showed bilaterally. Among these hips, pain was observed in 8 hips but 4 hips (2 patients) were associated with injuries. This morphologic abnormality was not associated with acetabular dysplasia determined by LCE angle <25°, Tönnis angle >10° or ACE angle <25°. Of note, no acetabulum with the deformity plus dysplasia was retroverted. These findings were confirmed in a subgroup analysis including 22 men (44 hips) and 27 women (54 hips) with a median age of 31.0 (21-50) and 41.0 (26-50) years, respectively. CONCLUSIONS: Focal concavity of posterior superior acetabulum could be a rare morphologic abnormality of acetabular formation independent of lateral or anterior dysplasia or retroversion.
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Acetábulo/anomalías , Retroversión Ósea , Acetábulo/diagnóstico por imagen , Adulto , Anciano , Femenino , Luxación de la Cadera/etiología , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: This study aimed to evaluate the clinical safety and wear-resistance of the novel highly cross-linked polyethylene (HXLPE) acetabular liner with surface grafting of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) at 3 years after total hip replacement (THR). METHODS: Eighty consecutive patients underwent cementless THR using a 26-mm diameter cobalt-chromium-molybdenum alloy femoral head and a PMPC-grafted HXLPE liner for the bearing couplings. We evaluated the clinical and radiographic outcomes of 76 patients at 3 years after the index surgery. RESULTS: The clinical results at 3 years were equivalent to a Harris hip score of 95.6 points. No adverse events were associated with the implanted PMPC-grafted HXLPE liner, and no periprosthetic osteolysis was detected. The mean femoral head penetration rate was 0.002 mm/year, representing marked reduction compared with other HXLPE liners. CONCLUSIONS: A PMPC-grafted HXLPE liner is a safe option in THR and probably reduces the generation of wear particles.
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Artroplastia de Reemplazo de Cadera , Necrosis de la Cabeza Femoral/cirugía , Articulación de la Cadera/cirugía , Prótesis de Cadera , Osteoartritis de la Cadera/cirugía , Fosforilcolina/análogos & derivados , Ácidos Polimetacrílicos , Adulto , Anciano , Femenino , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Articulación de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/diagnóstico por imagen , Estudios Prospectivos , Radiografía , Resultado del TratamientoRESUMEN
OBJECTIVE: To clarify the obstacles preventing the implementation of the treat-to-target (T2T) strategy for rheumatoid arthritis (RA) in clinical practice. METHODS: A total of 301 rheumatologists in Japan completed a questionnaire. In the first section, participants were indirectly questioned on the implementation of basic components of T2T, and in the second section, participants were directly questioned on their level of agreement and application. RESULTS: Although nearly all participants set treatment targets for the majority of RA patients with moderate to high disease activity, the proportion who set clinical remission as their target was 59%, with only 45% of these using composite measures. The proportion of participants who monitored X-rays and Health Assessment Questionnaires for all their patients was 44% and 14%, respectively. The proportion of participants who did not discuss treatment strategies was 44%, with approximately half of these reasoning that this was due to a proportion of patients having a lack of understanding of the treatment strategy or inability to make decisions. When participants were directly questioned, there was a high level of agreement with the T2T recommendations. CONCLUSION: Although there was a high level of agreement with the T2T recommendations, major obstacles preventing its full implementation still remain.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Pautas de la Práctica en Medicina , Inducción de Remisión/métodos , Humanos , Japón , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Accumulating evidence indicates that epigenetic aberrations have a role in the pathogenesis of rheumatoid arthritis (RA). However, reports on histone modifications are as yet quite limited in RA. Interleukin (IL)-6 is an inflammatory cytokine which is known to be involved in the pathogenesis of RA. Here we report the role of histone modifications in elevated IL-6 production in RA synovial fibroblasts (SFs). The level of histone H3 acetylation (H3ac) in the IL-6 promoter was significantly higher in RASFs than osteoarthritis (OA) SFs. This suggests that chromatin structure is in an open or loose state in the IL-6 promoter in RASFs. Furthermore, curcumin, a histone acetyltransferase (HAT) inhibitor, significantly reduced the level of H3ac in the IL-6 promoter, as well as IL-6 mRNA expression and IL-6 protein secretion by RASFs. Taken together, it is suggested that hyperacetylation of histone H3 in the IL-6 promoter induces the increase in IL-6 production by RASFs and thereby participates in the pathogenesis of RA.
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Artritis Reumatoide/genética , Artritis Reumatoide/patología , Fibroblastos/patología , Histonas/metabolismo , Interleucina-6/genética , Regiones Promotoras Genéticas , Acetilación/efectos de los fármacos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Células Cultivadas , Curcumina/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Epigénesis Genética , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Histona Acetiltransferasas/antagonistas & inhibidores , Histona Acetiltransferasas/metabolismo , Histonas/genética , Humanos , Interleucina-6/análisis , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/genética , Membrana Sinovial/citologíaRESUMEN
OBJECTIVES: Thoracoscopic sympathectomy is an effective treatment for palmar hyperhidrosis. However, compensatory hyperhidrosis occurs frequently as a postoperative complication of the procedure. The goal of this study was to elucidate the clinical significance of thoracoscopic sympathectomy using our surgical procedure. METHODS: Consecutive 151 patients who underwent thoracoscopic sympathectomy for palmar hyperhidrosis were studied. In addition, to investigate patients' satisfaction and long-term quality of life, 111 patients were asked to complete a mailing questionnaire survey, and 84 responded (response rate of 75.7%). RESULTS: All of the 151 patients reported a reduction in palmar sweating during the immediate postoperative period. None of the patients had pneumothorax, hemothorax, Horner's syndrome, or worsening of bradycardia. Based on the questionnaire, the surgical success rate was 98.8%. None of the patients had a recurrence of palmar hyperhidrosis during the long-term postoperative period. However, compensatory hyperhidrosis was reported in 82 patients (97.6%). In total, 94.0% of patients had high levels of postoperative satisfaction. CONCLUSIONS: Thoracoscopic sympathectomy is an effective surgical treatment for palmar hyperhidrosis. By contrast, the careful preoperative explanation of compensatory hyperhidrosis is considered to be very important.
RESUMEN
In the realm of obstetric care, discerning the subtle signs of primary hyperparathyroidism (PHPT) amidst common pregnancy symptoms remains a formidable challenge. Our exploration into a case of gestational hypercalcemia peels back the layers of this complexity, revealing the clinical conundrum posed by overlapping gastrointestinal manifestations. The journey from diagnosis through surgical intervention to the resolution of symptoms underscores the importance of vigilance for PHPT in pregnant patients. This case further prompts consideration of gamma-aminobutyric acid (GABA) as a potential piece in the puzzle of persistent symptoms post-calcium normalization, inviting a broader dialogue on the intricacies of parathyroid pathology in pregnancy.
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BACKGROUND: We have shown the efficacy of CD26/dipeptidyl peptidase 4 (CD26/DPP-4) inhibitors, antidiabetic agents, in allograft protection after experimental lung transplantation (LTx). We aimed to elucidate whether CD26/DPP-4 inhibitors effectively improve postoperative outcomes after clinical LTx. METHODS: We retrospectively reviewed the records of patients undergoing LTx at our institution between 2010 and 2021 and extracted records of patients with diabetes mellitus (DM) at 6 months post-LTx. The patient characteristics and postoperative outcomes were analyzed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Hazard ratios were estimated by Cox regression after propensity score weighting, using CD26/DPP-4 inhibitor treatment up to 6 months post-LTx as the exposure variable. We evaluated CLAD samples pathologically, including for CD26/DPP-4 immunohistochemistry. RESULTS: Of 102 LTx patients with DM, 29 and 73 were treated with and without CD26/DPP-4 inhibitors, respectively. Based on propensity score adjustment using standardized mortality ratio weighting, the 5-year OS rates were 77.0% and 44.3%, and the 5-year CLAD-free survival rates 77.8% and 49.1%, in patients treated with and without CD26/DPP-4 inhibitors, respectively. The hazard ratio for CD26/DPP-4 inhibitor use was 0.34 (95% confidence interval (CI) 0.14-0.82, p = 0.017) for OS and 0.47 (95% CI 0.22-1.01, p = 0.054) for CLAD-free survival. We detected CD26/DPP-4 expression in the CLAD grafts of patients without CD26/DPP-4 inhibitors. CONCLUSIONS: Analysis using propensity score weighting showed that CD26/DPP-4 inhibitors positively affected the postoperative prognosis of LTx patients with DM.
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Inhibidores de la Dipeptidil-Peptidasa IV , Trasplante de Pulmón , Humanos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Dipeptidil Peptidasa 4/metabolismo , Estudios Retrospectivos , Trasplante de Pulmón/efectos adversos , Trasplante HomólogoRESUMEN
BACKGROUND: The physiological function of p38α, which is an isoform of p38 MAPK, has been investigated previously in several studies using pharmacological inhibitors. However, the results regarding whether p38α promotes or inhibits nerve regeneration in vivo have been controversial. METHODS: We generated novel p38α mutant mice (sem mice) with a point mutation in the region encoding the p38α substrate-docking-site, which serves as a limited loss-of-function model of p38α. In the present study, we utilized sem mice and wild-type littermates (wt mice) to investigate the physiological role of p38α in nerve regeneration following crush injuries. RESULTS: At four weeks after crush injury, the average axon diameter and the average axon area in sem mice were significantly smaller than those in wt mice. The average myelin sheath thickness in sem mice was reduced compared to wt mice, but no significant difference was observed in the G-ratio between the two groups. The sciatic functional index value demonstrated that functional nerve recovery in sem mice following crush injury was delayed, which is consistent with the histological findings. To investigate the underlying mechanisms of these findings, we examined inflammatory responses of the sciatic nerve by immunohistochemistry and western blotting. At an early phase following crush injury, sem mice showed remarkably lower expression of inflammatory cytokines, such as TNF-α and IL-1ß, than wt mice. The expression of Caspase-3 and Tenascin-C were also lower in sem mice. Conversely, at a late phase of the response, sem mice showed considerably higher expression of TNF-α and of IL-1ß with lower expression of S-100 than wt mice. CONCLUSIONS: This is the first study of the physiological role of p38 MAPK in nerve regeneration that does not rely on the use of pharmacological inhibitors. Our results indicate that p38α insufficiency may cause an inflammatory disorder, resulting in a delay of histological and functional nerve recovery following crush injury. We conclude that p38 MAPK has an important physiological role in nerve regeneration and may be important for controlling both initiation of inflammation and recovery from nerve injury.
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Compresión Nerviosa , Regeneración Nerviosa/fisiología , Recuperación de la Función/fisiología , Nervio Ciático/fisiología , Neuropatía Ciática/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Compresión Nerviosa/métodos , Neuropatía Ciática/patologíaRESUMEN
To control particle-induced osteolysis in total hip replacement (THR), we developed a new technique to graft poly(2-methacryloyloxyethyl phosphorylcholine) onto the surface of polyethylene liners. A prospective cohort study was conducted to investigate the clinical safety of this novel bearing surface. Between April 2007 and September 2008, we recruited a prospective consecutive series of 80 patients in five participating hospitals. These patients received a cementless THR; a 26-mm-diameter cobalt-chromium-molybdenum alloy ball and a poly(2-methacryloyloxyethyl phosphorylcholine)-grafted cross-linked polyethylene liner were used for the bearing couplings. These individuals were followed a year postoperatively. An evaluation of clinical performance was conducted through an assessment of hip joint function based on the evaluation chart authorized by the Japanese Orthopaedic Association. No patients were lost to follow-up. No adverse events were found to be correlated with the implanted liners. The average hip joint function score improved from 43.2 preoperatively to 91.7 postoperatively at 1 year. There was no implant migration nor periprosthetic osteolysis detected on radiographic analysis. On the basis of our results, we conclude that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted cross-linked polyethylene liners are a safe implant option for hip replacement surgery for short-term clinical use.
Asunto(s)
Artroplastia de Reemplazo de Cadera/instrumentación , Prótesis de Cadera , Metacrilatos , Fosforilcolina/análogos & derivados , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polietilenos , Ácidos Polimetacrílicos , Complicaciones Posoperatorias , Estudios Prospectivos , Diseño de Prótesis , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this study was to evaluate the effects of screw position and compaction of the bone tunnel on the strength of the flexor tendon graft after fixation using interference screws. METHODS: Forty fresh-frozen porcine tibias were used for this study. The digital flexor tendons were folded into a quadrupled graft measuring 9 mm in diameter. In the extraction-drilling group, tibial bone tunnels were drilled with a conventional cannulated 9-mm drill bit in a single step. In the compaction-drilling group, bone tunnels were drilled using a cannulated 7-mm drill bit and were expanded to a final diameter of 9 mm in 0.5-mm increments by placement of dilators with increasing diameter. The grafts were fixed using 9 × 30-mm titanium screws in central and eccentric positions. Specimens underwent a cyclic-loading test, and the surviving specimens were then loaded until failure. RESULTS: Graft displacement after 1,500 loading cycles occurred significantly more often in the extraction-drilling group with eccentric screw placement than in the groups of extraction-drilling (P < .05) and compaction-drilling (P < .01) with central screw placement. There were no statistically significant differences for the maximum screw insertion torque, maximum load at failure, or stiffness among the 4 groups. One strand of the quadrupled tendon grafts showed partial injury during screw insertion in 3 (30%) and 4 (40%) of 10 specimens of the extraction-drilling and compaction-drilling groups with central screw placement, respectively. CONCLUSIONS: Central screw placement significantly decreased the displacement of the tendon graft in comparison with eccentric screw placement in the extraction-drilling condition. Compaction of the bone tunnel walls by serial dilation in a central screw position did not increase the strength of interference screw fixation of a soft tissue graft. CLINICAL RELEVANCE: When using the extraction method and fixing the graft in an eccentric position, it is advisable to provide additional fixation outside the tunnel to prevent slippage of the graft.
Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior/instrumentación , Reconstrucción del Ligamento Cruzado Anterior/métodos , Tendones/fisiopatología , Tendones/trasplante , Trasplantes/fisiopatología , Animales , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior , Fenómenos Biomecánicos , Tornillos Óseos , Técnicas In Vitro , Porcinos , Tibia/cirugíaRESUMEN
OBJECTIVES: Clodronate-liposome is used for depleting mononuclear phagocytes associated with ischemia-reperfusion injury. We hypothesized that administration of clodronate-liposome into the perfusate during ex vivo lung perfusion could reduce mononuclear phagocytes and attenuate ischemia-reperfusion injury. METHODS: First, the number of mononuclear phagocytes in flushed grafts (minimum cold ischemic time, 6-hour cold ischemic time, 15-hour cold ischemic time, and 18-hour cold ischemic time; n = 6 each) was determined using flow cytometry. Second, grafts (15-hour cold ischemic time) were allocated to control or clodronate (n = 5 each). In the clodronate group, clodronate-liposome is administered into the perfusate. After 4 hours of ex vivo lung perfusion, the number of mononuclear phagocytes in the perfusate and lung tissues was measured. Third, grafts (15-hour cold ischemic time) were allocated to control or clodronate (n = 6 each). After 4 hours of ex vivo lung perfusion, the left lungs were transplanted and reperfused for 2 hours. Lung function was evaluated, and samples were analyzed. RESULTS: First, mononuclear phagocytes remain in flushed grafts after prolonged cold ischemia. Second, the number of mononuclear phagocytes in lung tissues after ex vivo lung perfusion was significantly reduced in the clodronate group (P = .008). Third, lung compliance and vascular resistance during ex vivo lung perfusion were significantly improved in the clodronate group (P < .001 for both). Blood oxygenation and pulmonary edema were significantly improved in the clodronate group after 2 hours of reperfusion (P = .015 and P = .026, respectively). Histological findings showed reduced lung injury in the clodronate group (P = .013). CONCLUSIONS: Administration of clodronate-liposome into the perfusate during ex vivo lung perfusion resulted in a significant reduction of mononuclear phagocytes in donor lungs, leading to attenuation of ischemia-reperfusion injury.
Asunto(s)
Trasplante de Pulmón , Daño por Reperfusión , Humanos , Ácido Clodrónico , Liposomas , Trasplante de Pulmón/métodos , Pulmón , Daño por Reperfusión/patología , Reperfusión/métodos , Fagocitos/patología , Perfusión/métodosRESUMEN
Background: Patients with bilateral lower limb deep venous thrombosis (DVT) have a higher risk of pulmonary thromboembolism (PTE) and mortality than patients with unilateral lower limb DVT. Preoperative dilatation of the soleal vein (SV) diameter is a predictor of postoperative DVT. The purpose of this study is to investigate the cutoff value for SV diameter as a risk factor for VTE development. Materials and methods: The authors examined 274 patients with unilateral THA who met the inclusion criteria in a retrospective study. The mean age of the patients was 65.7±11.2 years, with 70 males and 204 females. Bilateral lower limb vein ultrasonography was performed preoperatively and ~1 week after THA. The frequency and localization of DVT were investigated in postoperative ultrasonography. The patients were divided into three groups: no DVT (non-DVT), unilateral lower limb DVT (Uni-DVT), and bilateral lower limb DVT (Bi-DVT). The three groups were compared in terms of preoperative venous vessel maximum diameter. Results: There were 62 patients (22.6%) who had postoperative DVT. There are no symptomatic PTE patients. DVT was found in 44 patients (16.0%) of the Uni-DVT group and 18 patients (6.6%) of the Bi-DVT group. The SV maximum diameter was 6.41±1.79 mm in the non-DVT group, 7.06±2.13 mm in the Uni-DVT group, and 8.06±2.26 mm in the Bi-DVT group, with a significant difference (P=0.001) between the non-DVT and Bi-DVT groups. In the Bi-DVT group, the cutoff value for preoperative SV maximum diameter was 6.75 mm (95% CI: 0.625-0.831; P=0.001; sensitivity, 77.8%; specificity, 60.4%; area under the curve, 0.728). Conclusions: In THA, preoperative ultrasonography with a maximum SV diameter of 6.75 mm or greater was the risk of bilateral DVT leading to fatal PTE is increased.