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BACKGROUND: A systematic review and meta-analysis of flow-diverter stents (FDSs) for the treatment of middle cerebral artery (MCA) aneurysms reported concerns about ischemic complications during treatment. The authors report on the intraoperative and postoperative complications of unruptured MCA aneurysms and their control strategies at their hospital, with detailed information on the aneurysms and a review of the previous literature. OBSERVATIONS: Intraoperative and perioperative in-stent thrombus occlusion occurred in 3 (37.5%) of the 8 patients evaluated. In cases with in-stent thrombus formation, rapid administration of 10 mg argatroban led to improvement in blood flow, as seen on angiography. Only 1 patient (12.5%) had a symptomatic stroke postoperatively. This patient was admitted for rehabilitation and drug therapy but was discharged from the hospital 10 days postoperatively with a modified Rankin Scale (mRS) score of 1. The patient had an mRS score of 0 at 90 days after surgery and at the last observation. LESSONS: Ischemic complications require attention during FDS treatment for MCA aneurysms. The use of argatroban in cases of in-stent thrombosis may contribute to a good neurological prognosis. https://thejns.org/doi/10.3171/CASE24237.
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We aimed to evaluate the materials based on 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate tri-n-butylborane (Super-bond [SB]) and nano hydroxyapatite (naHAp) for the repair of perforation at pulp chamber floor (PPF) in vitro and in vivo models. SB and naHAp were mixed in the mass ratio of 10% or 30% to produce naHAp/SB. Human periodontal ligament stem cells (HPDLSCs) were cultured on resin discs of SB or naHAp/SB to analyze the effects of naHAp/SB on cell adhesion, proliferation, and cementoblastic differentiation. A rat PPF model was treated with SB or naHAp/SB to examine the effects of naHAp/SB on the healing of defected cementum and periodontal ligament (PDL) at the site of PPF. HPDLSCs were spindle-shaped and adhered to all resin discs. Changing the resin from SB to naHAp/SB did not significantly alter cell proliferation. Both 10% and 30% naHAp/SB were more effective than SB in promoting cementoblastic differentiation of HPDLSCs. In the rat PPF model, 30% naHAp/SB was more effective than SB in promoting the formation Sharpey's fiber-like structures with expression of the PDL-related marker and cementum-like structures with expression of cementum-related markers. In conclusion, 30% naHAp/SB can be the new restorative material for PPF because it exhibited the abilities of adhering to dentin and healing of defected periodontal tissue.
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Compuestos de Boro , Durapatita , Metacrilatos , Ligamento Periodontal , Animales , Ratas , Humanos , Durapatita/química , Durapatita/farmacología , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/citología , Ligamento Periodontal/metabolismo , Compuestos de Boro/farmacología , Compuestos de Boro/química , Metacrilatos/química , Metacrilatos/farmacología , Diferenciación Celular/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Masculino , Proliferación Celular/efectos de los fármacos , Cavidad Pulpar/metabolismo , Cavidad Pulpar/efectos de los fármacos , Células Madre/efectos de los fármacos , Células Madre/citología , Células Madre/metabolismo , Células Cultivadas , Ratas Sprague-Dawley , Metilmetacrilatos/química , Metilmetacrilatos/farmacología , Adhesión Celular/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVES: Geographical limitations in remote island medical facilities result in excessive wastage of blood products. To address this, we explored the feasibility of a novel blood rotation system, which enables the return and redelivery of blood products to/from the blood bank while ensuring the management of product quality, including temperature control. This study aimed to enhance the supply of blood products to these facilities. MATERIALS AND METHODS: The Japan Red Cross Nagasaki Blood Center, Nagasaki Goto Chuoh Hospital (NGCH) and Nagasaki University Hospital collaborated to coordinate the transport and supply of red blood cell (RBC) products. Type O, RhD-positive, irradiated RBC products were stored at a precise 4.0 ± 2.0°C in an active transport refrigerator (ATR). After transport from the Japan Red Cross Nagasaki Blood Center to NGCH, RBC products were held for 1 week in the ATR, and unused products were returned. Eligible returned products were reissued to the Nagasaki University Hospital. RESULTS: All the returned RBC products met the redelivery criteria. Among the 103 redelivered RBC preparations, 101 bags (98.1%) were successfully used. NGCH utilized 597 RBC products and discarded 80 samples. The ATR supplied 107 type O RBC bags without any wastage. The overall wastage rate was 10.2% during the study period compared with 24.2% in the same period in the previous year. CONCLUSION: This innovative supply and operation system ensures a consistent and secure RBC product supply to remote islands while maximizing blood product use.
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Estudios de Factibilidad , Humanos , Conservación de la Sangre/métodos , Eritrocitos , Bancos de Sangre , Japón , Islas , Transfusión de EritrocitosRESUMEN
Introduction There is no methodology to predict aneurysm occlusion using residual volume after flow diverter stent treatment. We retrospectively examined whether residual aneurysm volume at 6 months postoperatively can predict the degree of aneurysm obliteration at 1 year after flow diverter stent treatment. Materials and Methods This single institution study included 101 consecutive patients who underwent flow diverter stent treatment for unruptured cerebral aneurysm. Based on pre-treatment aneurysm volume, the percentage residual volume was calculated 6 months postoperatively. The volume of the aneurysm was determined using the volume calculation function of the cerebral angiography equipment. 1 year postoperatively, patients were classified into two groups: the good obliteration group (GG; O'KellyMarotta [OKM] grading scale: C and D) and the poor obliteration group (PG; OKM: A and B). Statistical analysis was performed to determine if there was a difference in residual aneurysm volume percentage at 6 months postoperatively between the two groups. Results A total of 20 patients were studied: 6 in the GG and 14 in the PG. Mean residual aneurysm volume at 6 months postoperatively in the GG was 33.1% (±34.7), while that in the PG was 80.6% (±24.8) (P=0.018). A residual aneurysm volume of ≥35.2% at 6 months postoperatively was significantly associated with poor aneurysm obliteration at 1 year postoperatively (AUC=0.88, P=0.008). Conclusions Residual aneurysm volume percentage at 6 months after flow diverter stent treatment might be able to predict the likelihood of aneurysm occlusion at 1 year postoperatively.
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This study aimed at examining the effect of continued use of home health care resources on end-of-life care at home in older patients with cancer. This retrospective cohort study was conducted using medical and long-term care claims data of 6435 older patients with cancer who died between April 2016 and March 2019 in Fukuoka Prefecture. The main explanatory variables were enhanced home care support clinics and hospitals (HCSCs), enhanced HCSCs with beds, conventional HCSCs, other HCSCs, and home visit nursing care. The covariates were sex, age, required level of care, and the Charlson Comorbidity Index. A logistic regression model was used. The results of the multilevel logistic regression analysis showed that the following were significantly associated with end-of-life care at home: use of enhanced HCSCs with beds (odds ratio, OR: 8.66; 95% confidence interval, CI: [4.31-17.40]), conventional HCSCs (OR: 5.78; 95% CI: [1.86-17.94]), enhanced HCSCs (OR: 4.44; 95% CI: [1.47-13.42]), home-visit nursing care (OR: 1.86; 95% CI: [1.42-2.44]), and a severe need for care (OR: 3.89; 95% CI: [2.92-5.18]). The results suggest that the continued use of home health care resources in older patients with cancer who require out-of-hospital care may lead to increased end-of-life care at home. Particularly, use of enhanced HCSCs with beds is most strongly associated with end-of-life care at home.
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Servicios de Atención de Salud a Domicilio , Neoplasias , Cuidado Terminal , Humanos , Anciano , Japón , Estudios Retrospectivos , Cuidado Terminal/métodos , Neoplasias/terapiaRESUMEN
OBJECTIVES: This study aimed to evaluate the impact of the policy to reduce the reimbursement fee for percutaneous endoscopic gastrostomy (PEG) on the number of PEG procedures performed among older adults with dementia. STUDY DESIGN: Interrupted time series (ITS). METHODS: We used the monthly aggregated data of the number of PEG procedures in older adults with dementia (both broad and narrow definitions), between 2012 and 2018, from the claims data in Fukuoka Prefecture, Japan. A single ITS design was used to estimate changes in the outcome following each intervention (i.e., first, second, and third interventions performed in 2014, 2015, and 2016, respectively). A controlled ITS design was applied to estimate the effects after the sequence of interventions (pre-intervention: 2012-2014; post-intervention: 2016-2018). The control group comprised patients with malignant head and neck tumors who underwent PEG procedures outside the scope of this policy restriction. RESULTS: The number of PEG procedures decreased significantly only in the month wherein the third intervention was introduced (broad definition: IRR = 0.11, CI = 0.03-0.49; narrow definition: IRR = 0.15, CI = 0.03-0.75). No significant difference was observed between the treatment and control groups during the post-intervention phase. CONCLUSIONS: The impact of fee-revision policy for PEG on the decrease in PEG procedures among older adults with dementia is remarkably minimal. It is difficult to reduce unnecessary PEG procedures by relying on this financial incentive alone. Policy decision-makers should consider methods to prevent inappropriate use of artificial nutrition for older adults at their end-of-life stage by reforming the health delivery system.
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Demencia , Gastrostomía , Humanos , Anciano , Gastrostomía/métodos , Nutrición Enteral/métodos , Japón , Demencia/terapia , Análisis de Series de Tiempo Interrumpido , Estudios RetrospectivosRESUMEN
Mucopolysaccharidosis II (MPS II) is an X-linked, recessive, inborn metabolic disorder caused by defects in iduronate-2-sulfatase (IDS). The age at onset, disease severity, and rate of progression vary significantly among patients. This disease is classified into severe or mild forms depending on neurological symptom involvement. The severe form is associated with progressive cognitive decline while the mild form is predominantly associated with somatic features. Newborn screening (NBS) for MPS II has been performed since December 2016, mainly in Kyushu, Japan, where 197,700 newborns were screened using a fluorescence enzyme activity assay of dried blood spots. We diagnosed one newborn with MPS II with lower IDS activity, elevated urinary glycosaminoglycans, and a novel variant of the IDS gene. In the future, NBS for MPS II is expected to be performed in many regions of Japan and will contribute to the detection of more patients with MPS II, which is crucial to the early treatment of the disorder.
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Background: A carotid web is a shelf-like structure on the posterior wall of the origin of the internal carotid artery, and it is believed to cause cerebral infarction due to thrombus formed by turbulent flow with stagnation of blood flow. Recently, it has been suggested that recurrent cerebral infarction cannot be prevented in patients with a symptomatic carotid web by conventional medical management alone. However, there is still no consensus on the treatment of carotid webs. Carotid artery stenting (CAS) with the CASPER stent (Microvention, Terumo, Tustin, CA, USA) was performed in six consecutive patients with symptomatic carotid webs, and the results are reported along with a review of the literature. Methods: Six consecutive patients with a diagnosis of internal carotid artery stenosis due to a carotid web on magnetic resonance imaging and digital subtraction angiography (DSA) were included in this study. All patients underwent dual antiplatelet therapy approximately 10 days before surgery and after 6 months, and then, a CASPER stent was implanted under general anesthesia. All patients were evaluated postoperatively by DSA 6 months after treatment. Results: In all patients, no in-stent stenosis was seen 6 months after the operation, and no symptomatic cerebral infarction occurred within 1 year after the procedure. Conclusions: CASPER stent implantation may be effective for treating carotid webs.
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Background: Persistent primitive hypoglossal artery (PPHA) is a rare residual arterial anastomosis. We placed a CASPER stent using Spider FX as an embolic protection device (EPD) in a patient with internal carotid artery (ICA) stenosis and PPHA. There are no reports of carotid artery stenting (CAS) using a CASPER stent for ICA stenosis with PPHA. We report the EPD strategy used in this case and the usefulness and precautions of CASPER stent insertion for cervical ICA stenosis in association with PPHA. Methods: A 9Fr sheath was placed in the right femoral artery and a 9Fr Branchor balloon guide catheter was guided to the common carotid artery. A Spider FX was placed proximal to the bifurcation of the ICA and the PPHA. A 10 mm × 20 mm CASPER stent was deployed at the site of the stricture with no postoperative ischemic complications. Results: There was no intra-stent occlusion, stenosis, or plaque protrusion immediately after surgery, and no postoperative ischemic complications were observed. Conclusion: CASPER stent deployment with the Spider FX in the ICA and PPHA bifurcation can be considered to be an effective treatment method for ICA stenosis associated with PPHA. However, care should be taken in selecting the appropriate EPDs and stents depending on the location of the stenosis and bifurcation of the PPHA.
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Citrin deficiency is an autosomal recessive disorder caused by a defect of citrin resulting from mutations in the SLC25A13 gene. Intrahepatic cholestasis and various metabolic abnormalities, including hypoglycemia, galactosemia, citrullinemia, and hyperammonemia may be present in neonates or infants in the "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD) form of the disease. Because at present, newborn screening (NBS) for citrin deficiency using citrulline levels in dried blood spots (DBS) can only detect some of the patients, we tried to develop a new evaluation system to more reliably detect newborns with citrin deficiency utilizing parameters already in place in present NBS methods. To achieve this goal, we re-analyzed NBS profiles of amino acids and acylcarnitines in 96 NICCD patients, who were diagnosed through selective screening or positive family history. Hereby, we identified the combined evaluation of arginine (Arg), citrulline (Cit), isoleucine+leucine (Ile + Leu), tyrosine (Tyr), free carnitine (C0) / glutarylcarnitine (C5-DC) ratio in DBS as potentially sensitive to diagnose citrin deficiency in pre-symptomatic newborns. In particular, a scoring system using threshold levels for Arg (≥9 µmol/L), Cit (≥ 39 µmol/L), Ile + Leu (≥ 99 µmol/L), Tyr (≥ 96 µmol/L) and C0/C5-DC ratio (≥327) was significantly effective to detect newborns who later developed NICCD, and could thus be implemented in existing NBS programs at no extra analytical costs whenever citrin deficiency is considered to become a novel target disease.
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OBJECTIVE: This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder. METHODS: Radiographs and clinical information from 115 Japanese patients (female/male: 81/34, mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored. RESULTS: Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying anti-rheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. CONCLUSION: Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.
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BACKGROUND: Reconstruction after periacetabular bone tumor resection involves important tradeoffs; large bone grafts or endoprostheses are reported to offer fair walking function in general but can be technically demanding and carry a high risk of severe complications. Conversely, hip transposition avoids implant-related risks, but stability and functional return may be less consistent. Fewer studies are available on hip transposition, which is also appealing in more resource-constrained environments, and little is known about the time course from surgery to functional return after hip transposition. QUESTIONS/PURPOSES: (1) What is the time course of recovery of walking function after hip transposition, especially in the first 6 months? (2) What factors are associated with a greater likelihood of early functional recovery? (3) Is early (2-month) functional recovery associated with a greater likelihood of walking ability and higher Musculoskeletal Tumor Society (MSTS) scores? METHODS: Between 2009 and 2019, six tertiary care centers in Japan treated 48 patients with internal hemipelvectomy for malignant tumors. During that time, the preferred reconstructive approach was hip transposition, and 92% (44 of 48) of our patients were treated with this procedure. Among them, 86% (38 of 44) had follow-up of at least 6 months, had no local recurrence during that time, and were included in our retrospective study. We chose 6 months as the minimum follow-up duration because the endpoints in this study pertained to early recovery rather than reconstructive durability. Hip transposition involved moving the proximal end of the femur (femoral head, resection end of the trochanteric area, and spacers such as prostheses) upward to the underside of the resected ilium or the lateral side of the sacrum if sacroiliac joint resection was performed. The end of the proximal femur was stabilized to the remaining ilium or sacrum using polyethylene tape, polyethylene terephthalate mesh, an iliotibial tract graft, or an external fixator, according to the surgeon's preference. The median age at surgery was 46 years (range 9 to 76 years), there were 23 women and 15 men, and the median follow-up duration was 17 months (range 6 to 110 months). The postoperative time course of functional recovery was assessed with a record review, the timing of functional milestones was identified (wheelchair, walker, bilateral crutches, single crutch or cane, and walking without an aid), and the MSTS score at the final follow-up was assessed. Additionally, demographic and surgical factors were reviewed, and their association with short-term functional recovery and the final functional outcome was analyzed. RESULTS: Patients started using a walker at median postoperative day (POD) 20 (IQR 14 to 36) and with bilateral crutches at median POD 35 (IQR 20 to 57). At POD 60, which was the approximate median date of discharge, 76% (29 of 38) of patients were able to walk using bilateral crutches (the early recovery group) and 24% (nine of 38) of patients were not able to do so (the delayed recovery group). No baseline factors were different between the two groups. The early recovery group had a higher median MSTS score than the delayed recovery group: 57% (range 17% to 90%) versus 45% (13% to 57%) (p = 0.047). Moreover, more patients acquired better function (a single crutch or cane or more) in the early recovery group, with a median of 5 months (95% CI 4 to 11) than did those in the delayed recovery group (median not reached) (p = 0.0006). The HR was 15.2 (95% CI 2.5 to 93). Forty-two percent (16 of 38) underwent additional surgery for wound management. CONCLUSION: It took patients a fair amount of time to recover walking function after hip transposition, and patients who could not walk on bilateral crutches at POD 60 seemed less likely to regain walking function and were likely to have lower MSTS scores thereafter. Wound-related complications were frequent. This method may be a realistic alternative for younger patients who have the strength for a long rehabilitation period or those who want to minimize prosthesis-related complications. Future studies with more patients are necessary to understand the risk factors associated with delayed recovery.Level of Evidence Level III, therapeutic study.
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Artroplastia de Reemplazo de Cadera , Neoplasias Óseas , Masculino , Humanos , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Óseas/patología , Artroplastia de Reemplazo de Cadera/efectos adversos , CaminataRESUMEN
We describe a three-step, simple binostril approach to endoscopic endonasal transsphenoidal surgery in cases of sellar/parasellar lesions. In the first step, the mucosa of the lower third of the ethmoid bulla on the outside was coagulated with monopolar microdissection needle and opened to create space on the outside of the middle turbinate. The middle turbinate was moved outward using this space, and the natural ostium of the sphenoid sinus could be confirmed easily. In the second step, a less than 10 mm incision was made from the right natural ostium of the sphenoid sinus to the right nasal septal mucosa. The anterior wall of the sphenoid sinus was removed to free the sphenoid sinus. In the third step, the instrument was inserted through the left nostril using a hole connected to the natural ostium of the sphenoid sinus to reach the sellar floor via both nostrils. It took longer for the trainee than for the instructor to reach the sellar floor in the first four cases. However, there was no significant difference in the approach time after the fifth case. Approach-related postoperative complications were observed in 52 cases of sellar/parasellar lesions performed. This approach was considered to provide sufficient space and was simple and less burdensome to the patient.
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Endoscopía , Neoplasias Hipofisarias , Humanos , Endoscopía/efectos adversos , Cavidad Nasal/patología , Cavidad Nasal/cirugía , Cornetes Nasales , Seno Esfenoidal/cirugía , Seno Esfenoidal/patología , Complicaciones Posoperatorias/etiología , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patologíaRESUMEN
Background: There is no established adequate treatment for thrombosed aneurysm of the basilar artery with obstructive hydrocephalus. We conducted coil embolization and peritoneal shunting followed by placement of a stent expected to exert flow diversion (FD) effects to treat 2 patients with giant thrombosed aneurysms of the basilar artery with associated obstructive hydrocephalus, with good results. Methods: From April 2019 to March 2021, consecutive two cases of symptomatic hydrocephalus due to giant thrombosed aneurysms in the posterior cranial fossa at our hospital were treated. At first, coil embolization was performed to prevent aneurysm rupture. After coil embolization, ventriculoperitoneal shunting was performed. Finally, stent-assisted coil embolization was performed with flow re-direction endoluminal device (FRED) or low-profile visualized intraluminal support device (LVIS) stent. Results: Both patients were discharged after recovering well, with no postoperative hemorrhagic or ischemic complications. Conclusion: Staged surgery using a FRED for flow diverter or an LVIS stent expected to have FD effects may offer an effective treatment option.
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Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDAC. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval : 30.9-61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were two CR and five partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AE) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥3 AE emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AE were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat could be a new therapeutic option in patients with R/R PTCL (clinicaltrials gov. Identifier: NCT02953652).
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Linfoma de Células T Periférico , Neutropenia , Trombocitopenia , Humanos , Inhibidores de Histona Desacetilasas/efectos adversos , Recurrencia Local de Neoplasia/patología , Benzamidas/uso terapéutico , Neutropenia/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
The aim of this study is to clarify the biological functions of decorin (DCN) in the healing and regeneration of wounded periodontal tissue. We investigated the expression pattern of DCN during the healing of wounded periodontal tissue in rats by immunohistochemistry and the effects of DCN on the osteoblastic differentiation of human periodontal ligament (PDL) stem cells (HPDLSCs) and preosteoblasts by Alizarin red S staining, quantitative reverse transcription-polymerase chain reactions, and western blotting. The expression of DCN was increased around the wounded PDL tissue on day 5 after surgery compared with the nonwounded PDL tissue, whereas its expression was not changed in the osteoblastic layer around the wounded alveolar bone. Furthermore, DCN promoted the osteoblastic differentiation of HPDLSCs, but it did not affect the osteoblastic differentiation of preosteoblasts. ERK1/2 phosphorylation was upregulated during the DCN-induced osteoblastic differentiation of HPDLSCs. DCN did not affect proliferation, migration, or the PDL-related gene expression of HPDLSCs. In conclusion, this study demonstrates that DCN has a role in the healing of wounded periodontal tissue. Furthermore, DCN secreted from PDL cells may contribute to bone healing by upregulating osteoblastic differentiation through ERK1/2 signaling in HPDLSCs, indicating a therapeutic effect of DCN in periodontal tissue regeneration.
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Ligamento Periodontal , Células Madre , Humanos , Ratas , Animales , Células Cultivadas , Diferenciación Celular , Transducción de Señal , Osteogénesis , Proliferación CelularRESUMEN
In cases in which dental pulp tissue is accidentally exposed, direct pulp capping is often performed to induce reparative dentin formation. Although macrophages are essential for the inflammatory response and tissue repair, the emergence pattern and the role of macrophages in dental pulp tissue have not been clarified. Here, we investigated the emergence of M1/M2 macrophages in dental pulp tissue after a direct pulp capping and the effects of M2 macrophages on odontoblastic differentiation of the dental pulp stem cell (DPSC) clones. The emergence of macrophages in dental pulp tissue was investigated using a rat direct pulp capping model. Alizarin Red S staining and quantitative RT-PCR was performed to examine the effect of M2 macrophages on the mineralization and odontoblastic differentiation of DPSC clones. Immunohistochemical staining revealed that M1 macrophages were detected in dental pulp tissue after treatment and increased in number at three days after treatment. However, M2 macrophages gradually increased in number in dental pulp tissue after treatment, with the highest level recorded at seven days post-operation. Additionally, conditioned medium from M2 macrophages induced odontoblast-like differentiation of DPSC clones. These results suggest that macrophages play a role in the inflammatory response and reparative dentin formation after dental pulp exposure.
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Periodontal ligament stem cells (PDLSCs) play central roles in periodontal ligament (PDL) tissue homeostasis, repair, and regeneration. Previously, we established a protocol to differentiate human-induced pluripotent stem cell-derived neural crest-like cells (iNCs) into PDLSC-like cells (iPDLSCs) using human PDL cell-derived extracellular matrix (ECM). However, it remained unclear what factors principally regulate the differentiation of iNCs into iPDLSCs. In this study, we aimed to identify the transcription factor regulating production of human PDL cell-derived ECM, which is responsible for the generation of iPDLSCs. We cultured iNCs on ECMs of two human PDL cell lines (HPDLC-3S and HPDLC-3U) and of human dermal fibroblasts (HDF). iNCs cultured on HPDLC-3U demonstrated higher iPDLSC-associated gene expression and mesenchymal differentiation capacity than cells cultured on HDF or HPDLC-3S. The transcription factor PAX9 was highly expressed in HPDLC-3U compared with HDF and HPDLC-3S. iNCs cultured on siPAX9-transfected HPDLC-3U displayed downregulation of iPDLSC-associated marker expression and adipocytic differentiation capacity relative to controls. Our findings suggest that PAX9 is one of the transcription factors regulating ECM production in human PDL cells, which is responsible for the differentiation of iNCs into iPDLSCs.
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Donor lymphocyte infusion (DLI) is a therapeutic modality for relapsed hematological malignancies after allogeneic hematopoietic stem cell transplantation. We retrospectively analyzed non-infectious pulmonary complications (non-IPCs) following DLI therapy in 41 post-transplant patients with hematological malignancies, and found that 7 developed post-DLI non-IPCs. The 6-year cumulative incidence of non-IPCs was 18.0%. In these patients, non-IPCs were classified into three subtypes: acute respiratory distress syndrome (ARDS), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans syndrome (BOS). The median intervals from the last date of DLI to the development of ARDS and BOS were 12 days (range, 12-14) and 9.4 months (range, 2.6-61.8), respectively; the intervals between DLI and the development of NSIP were 3.5 and 24.7 in 2 patients. Regarding the status of GVHD before the diagnosis with ARDS, 2 out of 3 patients showed the progression of acute GVHD following DLI therapy. One out of 2 patients with NSIP and all 3 patients with BO had chronic GVHD symptoms prior to the development of non-IPCs. In our cohort, 1 patient died of the progression of NSIP. In conclusion, the present study showed the clinical features of non-IPCs following DLI, suggesting the importance of careful follow-ups for non-IPCs in post-DLI patients.