RESUMEN
BACKGROUND: In the treatment of peripheral nerve injuries with nerve defects, second-generation collagen-based conduits, such as Renerve® (Nipro, Osaka, Japan), have shown the potential for promoting nerve regeneration. However, there is concern related to the weak material properties. No previous studies have addressed the strength of the bridging model using collagen conduits. This study aimed to investigate the tensile strength and failure patterns in nerve defect models bridged with Renerve® conduits through biomechanical research. METHODS: Using fresh chicken sciatic nerves, we examined the maximum failure load of four groups: bridging models using Renerve® with one suture (group A), with two sutures (group B), with three sutures (group C), and end-to-end neurorrhaphy models with two sutures (group N). Each group had eight specimens. We also evaluated failure patterns of the specimens. RESULTS: Group N showed a significantly higher maximum failure load (0.96 ± 0.13 N) than groups A (0.23 ± 0.06 N, p < 0.0001), B (0.29 ± 0.05 N, p < 0.0001), and C (0.40 ± 0.10 N, p < 0.0001). Regarding failure patterns, all specimens in group A showed nerve end dislocation from the conduit. Two specimens in group B and three specimens in group C failed due to circumferential cracks in the conduit. Six specimens in group B and five specimens in group C exhibited cutting out of sutures from the conduit. CONCLUSION: This study suggests that the number of sutures in synthetic collagen nerve conduits has little effect on the maximum failure load. To take advantage of its biomaterial benefits, a period of postoperative range of motion restriction may be required.
RESUMEN
Proximal phalanx fractures of the big toe involving angulation or dislocation of the articular surface require repositioning and fixation. We treated a patient with such a fracture using a novel wire-connected external fixator, the ICHI-FIXATOR® system. A 45-year-old male sustained an injury when slipping down the stairs and impacting his left big toe. Plain radiography and computed tomography revealed a proximal phalangeal fracture of the left big toe with dislocation of the articular surface and comminution. The surgical intervention was performed using 1.1-mm diameter C-wires and an external fixator. The patient regained ambulation and resumed work immediately after surgery. Four weeks postoperatively, all wires were removed on an outpatient basis. Eight months postoperatively, the patient experienced no pain during strenuous activities or exercises. This novel wire-connected external fixator provides reliable and secure fixation, facilitating a prompt return to normal daily activities. This technique may be an effective option for managing toe fractures.
RESUMEN
Necrotizing fasciitis is a fatal, soft tissue infection of the skin that requires prompt treatment. Historically, most cases have been attributed to group A beta-hemolytic Streptococcus infection. However, in recent years, other bacteria have been identified as causing necrotizing fasciitis. In the current study, we analyzed cases of necrotizing fasciitis and examined the significant differences in symptoms caused by pathogenic bacteria. We included 79 patients (43 males and 36 females, mean age 65.4 years) diagnosed with necrotizing fasciitis who visited our hospital between April 2004 and July 2023. The patients were classified into five groups based on the identified pathogen: group A beta-hemolytic Streptococcus; group B beta-hemolytic streptococcus; group G beta-hemolytic Streptococcus; mixed infection, including anaerobic bacteria; and Staphylococcus (S) aureus. The clinical characteristics of patients, including treatment duration and laboratory values, were analyzed. Group G beta-hemolytic Streptococcus was more common in older patients (Bonferroni method, p < 0.05). Patients with S. aureus tended to be hyperglycemic (Bonferroni method, p < 0.05), had a higher rate of bacteremia (Fisher's direct probability test, p < 0.05), and had a longer treatment duration than the other examined groups (Bonferroni method, p = 0.0132). Although the five groups did not differ in the mortality rate, overall survival was shorter in the mixed infection group than in the other groups (log-rank test, p < 0.05). The legs were the most common site of infection in the non-mixed infection group; in the mixed infection group, the pubic area was identified as the most common site of infection, accompanied by a poor prognosis. Collectively, these findings suggest that necrotizing fasciitis can be characterized by pathogenic bacteria and that these characteristics may inversely predict the pathogen of origin.
RESUMEN
While lung cancer is the predominant neoplasm causing hemoptysis, rare benign neoplasms can also be associated with hemoptysis. A 60-year-old woman presented with cough and hemoptysis. Chest computed tomography revealed an oval-shaped, well-circumscribed solitary mass (10 cm in size) in the right lower lobe, which had grown rapidly over the past year. The presence of intramass air bubbles and a surrounding halo of ground-glass opacities suggested the hemorrhagic rupture of a circumscribed hematoma into the surrounding lung tissue. Subsequent right lower lobectomy revealed a well-demarcated hematoma; its wall consisted of nonatypical spindle tumor cells, which were histologically diagnosed as meningioma. No meningioma was observed in the central nervous system, leading to the diagnosis of primary pulmonary meningioma. This case highlights PPM as a rare benign tumor (World Health Organization grade 1) capable of rapid development due to intratumoral hemorrhage, presenting with hemoptysis.
RESUMEN
INTRODUCTION: In most previous studies investigating return to preinjury level of sport (RTPS) after anterior cruciate ligament reconstruction (ACLR), whether patients continue aiming for RTPS not only before but also after ACLR was unclear because environmental and social factors were not considered. Herein, we aimed to evaluate factors associated with RTPS among athletes who desired to achieve RTPS even after ACLR, excluding patients who no longer desire this goal owing to environmental and social factors. METHODS: Ninety-two patients who underwent primary double-bundle ACLR with a minimum 2-year follow-up and desired to achieve RTPS before surgery were retrospectively enrolled. Twelve (13%) patients who no longer desired to achieve RTPS after ACLR owing to environmental and social factors were excluded. Sixty-nine patients were included in the final cohort. At the final follow-up, the patients were split into two groups: those who achieved (R group) or did not achieve (N group) RTPS based on patient self-assessment. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm scores were also determined. The anterior tibial translation in the Lachman test and acceleration and external rotational angular velocity (ERAV) in the pivot shift test were measured at the hardware removal operation. RESULTS: Significant differences were observed for preinjury level of sports between the groups (p < 0.05). The rate of RTPS in competitive athletes was lower than that in recreational athletes (20/46: 43% vs. 16/22: 73%; p =.037). Lysholm score, KOOS symptom, pain, and quality of life showed higher values in the R group than in the N group (p < 0.050). Acceleration was significantly lower in the R group than in the N group (p = 0.028). CONCLUSION: Competitive level of sports is a risk factor for failure to achieve RTPS. The postoperative functional outcomes in the group that achieved RTPS showed more favorable results. These results provide important information to enable the surgeons to consider the appropriate surgical plan for competitive athletes who desire to achieve RTPS after ACLR.
RESUMEN
Background: The effect of lymph node dissection (LND) on the efficacy of immune checkpoint inhibitor (ICI) remains unclear. The purpose of this study was to examine the difference in the effect of ICI between patients with non-small cell lung cancer (NSCLC) according to the extent of LND performed in surgery prior to postoperative recurrence. Methods: A total of 134 patients with postoperative recurrence (surgery group, n=26) or unresectable advanced lung cancer (non-surgery group, n=108) who were treated with ICIs between January 2016 and December 2022 were included for analysis. In the surgery group, 16 patients underwent systematic LND, whereas the remaining 10 patients underwent selective LND. Progression-free survival with ICI treatment (ICI-PFS) and overall survival (OS) were compared between the surgery and non-surgery groups and between the systematic and selective LND groups using the inverse probability of treatment weighting (IPTW) method to adjust for patient background characteristics. Results: In the IPTW-adjusted analysis, the 2-year PFS rate with ICI treatment was 31.2% in the surgery group and 27.3% in the non-surgery group (P=0.19); the corresponding 2-year OS rates were 69.6% and 62.2%, respectively (P=0.10). In the surgery group, the 2-year PFS rates under ICI were 20.0% in the systematic LND group and 45.7% in the selective LND group (P=0.03). Conclusions: IPTW-adjusted analysis indicated no difference in prognosis between patients with postoperative recurrence and those with advanced unresectable lung cancer. However, in patients with postoperative recurrence, the extent of LND was a significant predictor of ICI-PFS. These findings suggest that systematic LND may reduce the efficacy of ICI, indicating that preoperative ICI administration may be warranted.
RESUMEN
Bite injuries frequently occur on human hands. Human bite injuries to the hand may lead to an infection because of limited soft tissue protection and wound contamination. However, no studies have reported severe bite injuries on hands treated by flaps. We report a case of an 80-year-old woman diagnosed with a major neurocognitive disorder. The patient accidentally had a self-bite injury accompanied with an open metacarpal fracture. Debridement and fixation of the first metacarpal fracture were performed. Afterward, skin necrosis occurred gradually on the dorsum of the hand. Therefore, a reverse posterior interosseous artery (PIA) flap was used, and the postoperative course was uneventful. Given the high risk of infection, human bite injuries, particularly hand bites, should be treated immediately. Delayed treatment for such injuries may lead to extensive soft tissue defects requiring reconstruction with flaps.
RESUMEN
Background: Postoperative residual rotatory laxity remains despite improvement in surgical techniques for anterior cruciate ligament (ACL) reconstruction (ACLR). Purpose: To evaluate factors associated with residual pivot shift after ACLR by quantitative measurement of the pivot shift before and after surgery. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 97 patients who underwent primary double-bundle ACLR between June 2016 and March 2021 and underwent surgery to remove staples, with at least 12 months of follow-up evaluation, were enrolled. Quantitative measurements were performed under general anesthesia immediately before ACLR (preoperatively), after temporary fixation of the ACL graft (intraoperatively), and immediately before staple removal (postoperatively). The laxity of pivot shift was assessed using inertial sensors to measure acceleration and external rotational angular velocity (ERAV). Descriptive data were assessed for associations with postoperative acceleration and ERAV in a univariate analysis. A multiple linear regression analysis was performed to identify factors associated with postoperative acceleration and ERAV. Results: Anterior tibial translation, acceleration, and ERAV increased from intra- to postoperatively (P < .05). Factors significantly associated with postoperative acceleration were age (ß = -0.238; P = .021), lateral posterior tibial slope (PTS) (ß = 0.194; P = .048), and preoperative acceleration (ß = 0.261; P = .008). Factors significantly affecting postoperative ERAV were age (ß = -0.222; P = .029), ramp lesions (ß = 0.212; P = .027), and preoperative ERAV (ß = 0.323; P = .001). Conclusion: Greater preoperative laxity in the pivot shift was the factor having the most significant association with residual pivot shift after ACLR using quantitative measurements under general anesthesia. Younger age, higher lateral PTS, and concomitant ramp lesions were significant predictors of residual pivot shift. These findings can help pre- and intraoperative decision-making regarding whether an anterolateral structure augmentation should be added.
RESUMEN
Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.
Asunto(s)
Diabetes Insípida Neurogénica , Células Madre Pluripotentes Inducidas , Enfermedades Neurodegenerativas , Humanos , Ratones , Animales , Arginina Vasopresina/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Vasopresinas/farmacología , Vasopresinas/metabolismo , Diabetes Insípida Neurogénica/metabolismo , Neurofisinas/genética , Proteínas Mutantes/metabolismo , MutaciónRESUMEN
PURPOSE: The aim of this study is to assess the dynamics of the tear site of meniscal ramp lesions, particularly considering knee flexion angles, and validate anchor fixation using an all-inside device. METHODS: Eight Thiel-embalmed paired cadaveric knees with their whole bodies were used in this study. The ramp lesions were created arthroscopically, and ramp lesion dynamics were evaluated by gradually extending the knee from 90° of knee flexion. Changes in the gap and step-off (0: no step-off; 1: cross-sectional overlap exists; and 2: tibial articular surface exposed) were evaluated at 90°, 60°, 30°, and 10° of knee flexion. After dynamic evaluation, all-inside repairs of the ramp lesions using all-inside devices were conducted. Dissection was performed to confirm the position of anchor fixation. RESULTS: As the knee was extended, the gap significantly decreased at all knee flexion angles. Similarly, the step-off grade decreased as the knee was extended, and the step-off completely disappeared in all cases when the knee was extended from 30° to 10°. The average knee flexion angle at which the gap and step-off completely disappeared was 22.5°. After suturing the ramp lesion, arthroscopic evaluation showed that the gap had disappeared and the step-off had been repaired in all cases. Anchor fixation locations were not found within the joint but were fixed to the semimembranosus tendon or its surrounding articular capsule. Overall, 31% (5/16) anchors were fixed to the attachment site of the semimembranosus tendon, whereas the remaining were fixed to the articular capsule, located peripherally to the semimembranosus tendon. CONCLUSION: Suturing with an all-inside device for ramp lesions is a good option, and the repair in knee extension was found to be reasonable, considering the dynamics of ramp lesions in this study. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Meniscos Tibiales , Humanos , Estudios Transversales , Meniscos Tibiales/cirugía , Articulación de la Rodilla/cirugía , Rodilla , Cadáver , Lesiones del Ligamento Cruzado Anterior/cirugíaRESUMEN
INTRODUCTION: This retrospective study evaluated the outcomes of variable-angle locking compression plate, mesh plate, or footplate box fixation for posterior acetabular wall fractures. PATIENTS AND METHODS: The study included nine patients with unstable posterior acetabular wall fractures who underwent internal fixation with the "spring-locking plate fixation method" between January 2015 and December 2019. Patient demographics, fracture classifications, surgical details, radiological and clinical evaluations, and complications were collected from electronic medical records. Statistical analyses were performed to assess the relationship between preoperative and postoperative dislocations. RESULTS: The mean age of the patients was 46 years, and the majority were men (88.9%). Fracture types included posterior wall fractures and posterior column plus posterior wall fractures. The mean operative time was 246 min and the mean blood loss was 663 mL. The surgical approaches included the Kocher-Langenbeck, Ganz trochanteric flip, and transtrochanteric approaches. Variable-angle locking compression plate mesh plates and footplate box type implants were used for fixation. The mean preoperative dislocation was 23 mm, which was significantly reduced to 1 mm immediately post-operation and at the final observation. The bone fusion rate was 100% and radiological and clinical evaluations revealed favourable outcomes. Complications were minimal, with mild heterotopic ossification observed in four patients. CONCLUSION: The spring-locking plate fixation method demonstrated satisfactory outcomes for the treatment of posterior acetabular wall fractures. This technique provides rigid fixation. Furthermore, the use of variable-angle locking screws minimizes the risk of intra-articular perforations. Despite limitations such as a small sample size and the absence of a control group, the results suggest that the spring-locking plate fixation method may be valuable in managing these fractures.
Asunto(s)
Fracturas Óseas , Luxaciones Articulares , Masculino , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Mallas Quirúrgicas , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fijación Interna de Fracturas/métodos , Placas Óseas , Resultado del TratamientoRESUMEN
STUDY DESIGN: This experimental study was performed using human ligamentum flavum-derived cells (HFCs). PURPOSE: To investigate the intracellular signaling mechanism of interleukin-6 (IL-6) secretion in transforming growth factor-ß (TGF- ß)-stimulated HFCs. OVERVIEW OF LITERATURE: Lumbar spinal stenosis (LSS) is a prevalent disease among the elderly, characterized by debilitating pain in the lower extremities. Although the number of patients with LSS has increased in recent years, the underlying pathomechanism remains unclear. Clinical examinations typically rely on magnetic resonance imaging to diagnose patients, revealing ligamentum flavum hypertrophy. Some studies have suggested an association between ligamentum flavum hypertrophy and inflammation/fibrosis, and expression of TGF-ß and IL-6 has been observed in surgically obtained ligamentum flavum samples. However, direct evidence linking TGF-ß and IL-6 expression in HFCs is lacking. METHODS: HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-ß and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. RESULTS: TGF-ß administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-ß-induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-ß stimulation. CONCLUSIONS: Our findings indicate that TGF-ß induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6-mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.
RESUMEN
AIMS: In our previously reported randomized controlled trial in patients with noninsulin-treated type 2 diabetes, the use of flash glucose monitoring (FGM) improved glycated hemoglobin (HbA1c), and the improvement was sustained after the cessation of glucose monitoring. In this post-hoc analysis, we examined data from our trial to identify the factors that influenced FGM efficacy. METHODS: We analyzed data for 48 of 49 participants of the FGM group who completed the trial to clarify the changes in various parameters and factors related to HbA1c improvement with the use of FGM. RESULTS: Analyses of the FGM data during the 12-week FGM provision period showed that the weekly mean blood glucose levels considerably decreased as early as at 1 week compared with the baseline values, and this decline continued for 12 weeks. An enhancement in the Diabetes Treatment Satisfaction Questionnaire regarding "willingness to continue the current treatment" score was significantly associated with the improvement in HbA1c at 12 (p = 0.009) and 24 weeks (p = 0.012). CONCLUSIONS: Glycemic control was improved soon after FGM initiation, accompanied by improved satisfaction with continuation of the current treatment in patients with noninsulin-treated type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucemia/análisis , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada , Automonitorización de la Glucosa Sanguínea , Control Glucémico/efectos adversos , Satisfacción del PacienteRESUMEN
Pituitary organoids are promising graft sources for transplantation in treatment of hypopituitarism. Building on development of self-organizing culture to generate pituitary-hypothalamic organoids (PHOs) using human pluripotent stem cells (hPSCs), we established techniques to generate PHOs using feeder-free hPSCs and to purify pituitary cells. The PHOs were uniformly and reliably generated through preconditioning of undifferentiated hPSCs and modulation of Wnt and TGF-ß signaling after differentiation. Cell sorting using EpCAM, a pituitary cell-surface marker, successfully purified pituitary cells, reducing off-target cell numbers. EpCAM-expressing purified pituitary cells reaggregated to form three-dimensional pituitary spheres (3D-pituitaries). These exhibited high adrenocorticotropic hormone (ACTH) secretory capacity and responded to both positive and negative regulators. When transplanted into hypopituitary mice, the 3D-pituitaries engrafted, improved ACTH levels, and responded to in vivo stimuli. This method of generating purified pituitary tissue opens new avenues of research for pituitary regenerative medicine.
Asunto(s)
Hormona Adrenocorticotrópica , Células Madre Pluripotentes , Ratones , Animales , Humanos , Molécula de Adhesión Celular Epitelial , Técnicas de Cultivo de Célula/métodos , Diferenciación CelularRESUMEN
Arginine vasopressin (AVP) is an antidiuretic hormone synthesized principally in the hypothalamic supraoptic and paraventricular nuclei. The immunoglobulin heavy chain binding protein (BiP), one of the most abundant endoplasmic reticulum (ER) chaperones, is highly expressed in AVP neurons, even under basal conditions. Moreover, its expression is upregulated in proportion to the increase in AVP expression under dehydration. These data suggest that AVP neurons are constantly exposed to ER stress. BiP knockdown in AVP neurons induces ER stress and autophagy, resulting in AVP neuronal loss, indicating that BiP is pivotal in maintaining the AVP neuron system. Furthermore, inhibition of autophagy after BiP knockdown exacerbates AVP neuronal loss, suggesting that autophagy induced under ER stress is a protective cellular mechanism by which AVP neurons cope with ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant disorder caused by mutations in the AVP gene. It is characterized by delayed-onset progressive polyuria and eventual AVP neuronal loss. In AVP neurons of FNDI model mice, mutant protein aggregates are confined to a specific compartment of the ER, called the ER-associated compartment (ERAC). The formation of ERACs contributes to maintaining the function of the remaining intact ER, and mutant protein aggregates in ERACs undergo autophagic-lysosomal degradation without isolation or translocation from the ER, representing a novel protein degradation system in the ER.
Asunto(s)
Arginina Vasopresina , Diabetes Insípida Neurogénica , Ratones , Animales , Arginina Vasopresina/genética , Arginina Vasopresina/metabolismo , Agregado de Proteínas , Vasopresinas/metabolismo , Estrés del Retículo Endoplásmico , Neuronas/metabolismoRESUMEN
For the treatment of osteosarcoma, cisplatin (CDDP) can be substituted by carboplatin (CBDCA) to reduce toxicity. We report a single institution experience of CBDCA-based regimen. Two to three cycles of CBDCA + ifosfamide (IFO) therapy (window therapy) were administered as neoadjuvant therapy for osteosarcoma. Depending on the response of window therapy, the subsequent protocols were determined; for good responders, surgery is performed, and postoperative therapies with CBDCA + IFO, adriamycin (ADM) and high-dose methotrexate (MTX) were administered; for stable disease, the postoperative regimens were advanced before surgery, and the remaining amount of postoperative chemotherapy is deduced; for progressive disease, CBDCA-based regimen is changed to CDDP-based regimen. From 2009 to 2019, seven patients were treated with this protocol. During the window therapy, two patients (28.6%) were assessed as good responders and completed the regimen as planned. Four patients (57.1%) had stable disease, and the chemotherapy schedules were modified. One patient (14.2%) with progressive disease was shifted to the CDDP-based regimen. At final follow-up, four patients showed no evidence of disease and three patients died of the disease. Since the efficacy during window therapy was limited, a CBDCA-based regimen in the neoadjuvant setting was considered insufficient for performing adequate surgery.
RESUMEN
Background: This study aimed to investigate the relationship between postoperative clinical results and long-term morphological changes in patients with carpal tunnel syndrome (CTS) as observed on magnetic resonance imaging (MRI) before and after open carpal tunnel release (OCTR). Methods: We retrospectively analysed data for 28 hands that had undergone OCTR with at least 24 months of follow-up data. Two-point discrimination (2PD) test results were examined for the first three fingers, as were the distal motor latency (DML) and sensory conduction velocity (SCV) of the median nerve. We also calculated the cross-sectional area (CSA) of the carpal tunnel and the distance from the median nerve to the volar carpal bone at the hamate and the pisiform levels using MRI images. Variables were compared before and 24 months after OCTR. Results: Significant improvements in all variables were observed, including average 2PD scores (Finger I: 13.1 ± 6.2 vs. 7.7 ± 4.3, p < 0.01, Finger II: 11.9 ± 6.6 vs. 7.0 ± 3.5, p < 0.01, Finger III: 13.6 ± 6.1 vs. 7.8 ± 4.5, p < 0.01), average DML (8.3 ± 3.3 vs. 4.3 ± 0.6 m/s, p < 0.01), average SCV (30.8 ± 11.0 vs. 41.3 ± 5.3 m/s, p < 0.01), CSA of the carpal tunnel (hamate level: 194.9 ± 30.6 vs. 254.2 ± 47.6 mm2, p < 0.01, pisiform level: 244.2 ± 46.5 vs. 274.7 ± 75.1 mm2, p = 0.01) and the distance between the median nerve and volar carpal bone (hamate level: 8.7 ± 1.4 vs. 11.2 ± 1.6 mm, p < 0.01, pisiform level: 11.8 ± 1.7 vs. 13.8 ± 2.5 mm, p < 0.01). Conclusions: Our results demonstrate that OCTR is successful in achieving long-term decompression and recovery of the median nerve in patients with CTS. Level of Evidence: Level III (Therapeutic).
Asunto(s)
Síndrome del Túnel Carpiano , Imagen por Resonancia Magnética , Nervio Mediano , Humanos , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/cirugía , Nervio Mediano/diagnóstico por imagen , Nervio Mediano/cirugía , Estudios Retrospectivos , Muñeca/cirugíaRESUMEN
When damaged, restoring the function of the hypothalamus is currently impossible. It is unclear whether neural stem cells exist in the hypothalamus. Studies have reported that adult rodent tanycytes around the third ventricle function as hypothalamic neural stem cell-like cells. However, it is currently impossible to collect periventricular cells from humans. We attempted to generate hypothalamic neural stem cell-like cells from human embryonic stem cells (ESCs). We focused on retina and anterior neural fold homeobox (RAX) because its expression is gradually restricted to tanycytes during the late embryonic stage. We differentiated RAX::VENUS knockin human ESCs (hESCs) into hypothalamic organoids and sorted RAX+ cells from mature organoids. The isolated RAX+ cells formed neurospheres and exhibited self-renewal and multipotency. Neurogenesis was observed when neurospheres were transplanted into the mouse hypothalamus. We isolated RAX+ hypothalamic neural stem cell-like cells from wild-type human ES organoids. This is the first study to differentiate human hypothalamic neural stem cell-like cells from pluripotent stem cells.
Asunto(s)
Células-Madre Neurales , Células Madre Pluripotentes , Ratones , Animales , Humanos , Diferenciación Celular/fisiología , Neurogénesis/fisiología , Hipotálamo/metabolismoRESUMEN
Arginine vasopressin (AVP) is expressed in both magnocellular (magnAVP) and parvocellular AVP (parvAVP) neurons of the paraventricular nucleus, and AVP colocalizes with corticotropin-releasing hormone (CRH) only in the parvocellular neurons. The immunoglobulin heavy chain binding protein (BiP) is a major endoplasmic reticulum (ER) chaperone which regulates the unfolded protein response under ER stress. We previously demonstrated that knockdown of BiP in magnAVP neurons exacerbated ER stress, which resulted in the autophagy-associated cell death of magnAVP neurons. Using the same approach, in the present study we examined the role of BiP in mouse parvAVP/CRH neurons. Our data demonstrate that BiP is expressed in mouse parvAVP/CRH neurons under nonstress conditions and is upregulated in proportion to the increase in CRH expression after adrenalectomy. For BiP knockdown in parvAVP/CRH neurons, we utilized a viral approach in combination with shRNA interference. Knockdown of BiP expression induced ER stress in parvAVP/CRH neurons, as reflected by the expression of C/EBP homologous protein. Furthermore, BiP knockdown led to the loss of parvAVP/CRH neurons after 4 weeks. In summary, our results demonstrate that BiP plays a pivotal role in parvAVP/CRH neurons, which function as neuroendocrine cells producing a large number of secretory proteins.
Asunto(s)
Arginina Vasopresina , Hormona Liberadora de Corticotropina , Ratones , Animales , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Arginina Vasopresina/metabolismo , Chaperón BiP del Retículo Endoplásmico , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Retículo Endoplásmico/metabolismoRESUMEN
Bone remodeling mediated by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCs) maintains bone structure and function. Excessive OC activation leads to bone-destroying diseases such as osteoporosis and bone erosion of rheumatoid arthritis (RA). Differentiation of OCs from bone marrow cells (BMCs) is regulated by the bone microenvironment. The proinflammatory cytokine interleukin (IL)-1ß reportedly enhances osteoclastogenesis and plays important roles in RA-associated bone loss. The present study investigated the effect of IL-1ß on OC formation via microenvironmental cells. Treating mouse BMCs with IL-1ß in the presence of receptor activator of NF-κB ligand and macrophage colony-stimulating factor increased the number of OCs. Real-time RT-PCR revealed increased expression of the IL-1ß, IL-1RI, and IL-1RII genes in non-OCs compared with OCs. Removing CD45- cells which cannot differentiate into OCs, from mouse BMCs reduced the IL-1ß-mediated enhancement of osteoclastogenesis. IL-1ß treatment upregulated the expression of inducible nitric oxide synthase, insulin-like growth factor 2 (IGF2), and the chemokines stromal cell derived factor 1, C-X3-C motif ligand 1 (CX3CL1), and CXCL7 in non-OCs. Neutralizing antibodies against these chemokines and IGF2 suppressed osteoclastogenesis in the presence of IL-1ß. These results suggest that IL-1ß enhances osteoclastogenesis by upregulating IGF2 and chemokine expression in non-OCs.