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BACKGROUND/AIM: Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers. PATIENTS AND METHODS: Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE. RESULTS: There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision. CONCLUSION: A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary.
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Encaminhamento e Consulta , Sarcoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Sarcoma/cirurgia , Sarcoma/patologia , Idoso , Japão , Adulto , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologia , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.
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Biomarcadores Tumorais , Neoplasias Ósseas , Metilação de DNA , Metilases de Modificação do DNA , Enzimas Reparadoras do DNA , Osteossarcoma , Regiões Promotoras Genéticas , Temozolomida , Proteínas Supressoras de Tumor , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Temozolomida/uso terapêutico , Feminino , Masculino , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/mortalidade , Adolescente , Adulto Jovem , Estudos Retrospectivos , Criança , Prognóstico , Antineoplásicos Alquilantes/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Type 2 diabetes (T2D) is a significant global health challenge. Physicians need to assess whether future glycemic control will be poor on the current trajectory of usual care and usual-care treatment intensifications so that they can consider taking extra treatment measures to prevent poor outcomes. Predicting poor glycemic control from trends in hemoglobin A1c (HbA1c) levels is difficult due to the influence of seasonal fluctuations and other factors. OBJECTIVE: We sought to develop a model that accurately predicts poor glycemic control among patients with T2D receiving usual care. METHODS: Our machine learning model predicts poor glycemic control (HbA1c≥8%) using the transformer architecture, incorporating an attention mechanism to process irregularly spaced HbA1c time series and quantify temporal relationships of past HbA1c levels at each time point. We assessed the model using HbA1c levels from 7787 patients with T2D seeing specialist physicians at the University of Tokyo Hospital. The training data include instances of poor glycemic control occurring during usual care with usual-care treatment intensifications. We compared prediction accuracy, assessed with the area under the receiver operating characteristic curve, the area under the precision-recall curve, and the accuracy rate, to that of LightGBM. RESULTS: The area under the receiver operating characteristic curve, the area under the precision-recall curve, and the accuracy rate (95% confidence limits) of the proposed model were 0.925 (95% CI 0.923-0.928), 0.864 (95% CI 0.852-0.875), and 0.864 (95% CI 0.86-0.869), respectively. The proposed model achieved high prediction accuracy comparable to or surpassing LightGBM's performance. The model prioritized the most recent HbA1c levels for predictions. Older HbA1c levels in patients with poor glycemic control were slightly more influential in predictions compared to patients with good glycemic control. CONCLUSIONS: The proposed model accurately predicts poor glycemic control for patients with T2D receiving usual care, including patients receiving usual-care treatment intensifications, allowing physicians to identify cases warranting extraordinary treatment intensifications. If used by a nonspecialist, the model's indication of likely future poor glycemic control may warrant a referral to a specialist. Future efforts could incorporate diverse and large-scale clinical data for improved accuracy.
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There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.
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BACKGROUND: Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues, occurring in hemodialysis patients. Calcium phosphate crystals are mainly composed of hydroxyapatite, which is highly infiltrative to tissues, thus making complete resection difficult. An adjuvant method to remove or resolve the residual crystals during the operation is necessary. CASE SUMMARY: A bicarbonate Ringer's solution with bicarbonate ions (28 mEq/L) was used as the adjuvant. After resecting calcium phosphate deposits of tumoral calcinosis as much as possible, while filling with the solution, residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field. A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders, bilateral hip joints, and the right foot. A shoulder lesion was resected, but the calcification remained and early re-deposition was observed. Considering the difficulty of a complete rection, we devised a bicarbonate dissolution method and excised the foot lesion. After resection of the calcified material, the residual calcified material was washed away with bicarbonate Ringer's solution. CONCLUSION: The bicarbonate dissolution method is a new, simple, and effective treatment for tumoral calcinosis in hemodialysis patients.
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The control of the selectivity is a central issue in the total synthesis of complex natural products. In this paper, we report the total synthesis of (±)-keramaphidin B and (±)-ingenamine. The key reaction is a DMAP-catalyzed Diels-Alder reaction in which the regioselectivity is completely controlled by dynamic crystallization. Our synthesis successfully demonstrates that dynamic crystallization can be an alternative when the selectivity is not controlled by either kinetic or thermodynamic approaches in solution.
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INTRODUCTION: Recycled bone autografts prepared using extracorporeal irradiation (ECIR) or liquid nitrogen freezing (LNF) methods have been used for the reconstruction of skeletal elements after wide resection of sarcomas involving bone tissues. Few reports include long-term follow-up data for histological analyses of recycled autografts, particularly in the case of ECIR autografts. MATERIALS: A total of 34 malignant bone and soft tissue tumors were resected and reconstructed using 11 ECIR- and 23 LNF-recycled autografts; the mean postoperative follow-ups were 14 and 8 years, respectively. ECIR was used for either osteosarcomas or Ewing sarcomas, whereas in addition to these tumors LNF was used for chondrosarcomas and soft tissue sarcomas involving bone tissues. Recycled bone was implanted as total bone, osteoarticular, or intercalary grafts, with or without prosthesis or vascularized fibular grafts. RESULTS: The 10-year graft survival rate was similar between groups, 81.8% using ECIR and 70.2% using LNF. There were no autograft-related tumor recurrences in either group. Graft survival was unrelated to type of graft or additional procedures. Complication rates tended to be higher using ECIR (64%) compared with LNF (52%) and the infection rate was significantly higher with ECIR (27%) versus LNF (0%). At the final assessment, plain radiographs revealed original recycled bone was present in 7 of 11 ECIR cases and in zero cases treated with LNF autografts, indicating that recycled bone treated with LNF autografts was remodeled into new bone. Histological examination of ECIR-treated bones revealed a delayed and incomplete endochondral ossification process, necrosis and empty lacunae. Conversely, LNF autografts showed remodeled bones with normal trabecular structures. CONCLUSIONS: ECIR and LNF treatment of autografts provided adequate tumor control with acceptable clinical results as a reconstruction method.
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Neoplasias Ósseas , Transplante Ósseo , Nitrogênio , Humanos , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/patologia , Transplante Ósseo/métodos , Masculino , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Criança , Adulto Jovem , Condrossarcoma/cirurgia , Condrossarcoma/radioterapia , Condrossarcoma/patologia , Osteossarcoma/cirurgia , Osteossarcoma/patologia , Osteossarcoma/radioterapia , Sobrevivência de Enxerto , Seguimentos , Sarcoma de Ewing/cirurgia , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/patologia , Autoenxertos , Sarcoma/cirurgia , Sarcoma/radioterapia , Sarcoma/patologia , Congelamento , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologiaRESUMO
Osteosarcoma is a highly invasive primary bone tumor that predominantly occurs in childhood and adolescence. The Stryker Growing Prosthesis provides a means of reconstructing large bone defects resulting from bone resection in skeletally immature patients. This device can be expanded as the patient grows. The possible length of extension depends on the length of the prosthesis. Because further expansion was not possible, by turning the adjustable part of the extension back to zero and adding a new permanent extension allow the prosthesis to be further adjusted as growth ensues. Using this method/device only, a separate endoprosthesis was required to be attached onto the extension. Therefore, the applicable cases are limited, because of the fact that extensive resection usually means total femoral replacement is best indicated. However, this method is still useful for reducing the number of revision surgeries in such cases. This reduces costs and increases savings for insurers/countries.
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BACKGROUND: The use of Bio 3D nerve conduits is a promising approach for peripheral nerve reconstruction. This study aimed to assess their safety in three patients with peripheral nerve defects in their hands. METHODS: We describe a single institution, non-blinded, non-randomised control trial conducted at Kyoto University Hospital. Eligibility criteria included severed peripheral nerve injuries or a defect in the region distal to the wrist joint not caused by a congenital anomaly; a defect with a length of ≤20 mm in a nerve with a diameter ≤2 mm; failed results of sensory functional tests; ability to register in the protocol within 6 months from the day of injury; refusal of artificial nerve or autologous nerve transplantation; age 20-60 years; and willingness to participate and provide informed written consent. Six weeks before transplantation, skin was harvested, dermal fibroblasts were isolated and expanded, and Bio 3D nerve conduits were created using a Bio 3D printer. Bio 3D nerve conduits were transplanted into the patients' nerve defects. The safety of Bio 3D nerve conduits in patients with a peripheral nerve injury in the distal part of the wrist joint were assessed over a 48-week period after transplantation. RESULTS: No adverse events related to the use of Bio 3D nerve conduits were observed in any patient, and all three patients completed the trial. CONCLUSIONS: Bio 3D nerve conduits were successfully used for clinical nerve reconstruction without adverse events and are a possible treatment option for peripheral nerve injuries.
Physical injuries often result in damage to nerves, for example, in the hands. Replacement of the nerve with nerves removed from elsewhere in the patient's body is often the suggested treatment when the nerve is unable to repair itself. As an alternative to remove healthy nerve from elsewhere in the body, we used an adapted printer to create an artificial nerve equivalent from skin cells obtained from the patient's skin. We reconstructed the nerves of three individual with nerve defects in their hands, and we found that the function of the nerve improved, and the people did not experience negative consequences. This approach could be used widely to repair damaged nerves.
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Background: Rotation flaps are arcuate repairs that redistribute tension vectors and recruit adjacent and/or distant tissue laxity. The incision curve could be a logarithmic spiral curve to reduce the length of an incision. We propose a rotation flap-the golden ratio flap-designed using a golden rectangle. Methods: The flap incision is an arc though the major square which is beside the minor square of a golden rectangle. The defect is attached to the line of another minor square and diagonal to the major square. The bottom line runs from the incision end to the tangent point of the circle or the oval, and the perpendicular height line runs from the bottom line to the cross point of the flap incision. These parameters were analyzed retrospectively for four superficial sarcomas that were treated using a rotation flap with an incision approximating the logarithmic spiral curve. Results: The ratio of height to bottom of the golden ratio flap design was highly similar to the preoperative flap design in the four cases assessed. With the new design, the ratio of bottom to the defect diameter (minor axis in the oval defect) was 1.3, and for the height, it was 1.4. Conclusions: The golden ratio flap, designed using the golden rectangle, is reproducible. The parameters of height and bottom approximate the flap shape, or the length and width, respectively. For clinical applications, step-by-step guidance for drawing the new flap are also proposed.
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BACKGROUND: Flap reconstruction after resection of a superficial malignant soft tissue tumor extends the surgical field and is an indicator for potential recurrence sites. AIM: To describe a grading system for surgical field extension of soft tissue sarcomas. METHODS: Grading system: CD-grading is a description system consisting of C and D values in the surgical field extension, which are related to the compartmental position of the flap beyond the nearby large joint and deeper extension for the pedicle, respectively. C1/D1 are positive values and C0/D0 are negative. With a known location, 1/0 values can be "p" (proximal), "d" (distal), and "b" (in the tumor bed), and the description method is as follows: flap type, CxDx [x = 0, 1, p, d or b]. RESULTS: Four representative patients with subcutaneous sarcomas who underwent reconstruction using fasciocutaneous flaps are presented. The cases involved a distal upper arm (elbow) synovial sarcoma reconstructed using a pedicled latissimus dorsi (pedicled flap: CpDp); a distal upper arm (elbow) pleomorphic rhabdomyosarcoma reconstructed using a transpositional flap from the forearm (transpositional flap: CdD0); an undifferentiated pleomorphic sarcoma in the buttocks reconstructed using a transpositional flap (transpositional flap: C0D0); and a myxofibrosarcoma in the buttocks reconstructed using a propeller flap from the thigh (pedicled flap: CdDd). CONCLUSION: The reconstruction method is chosen by the surgeon based on size, location, and other tumor characteristics; however, the final surgical field cannot be determined based on preoperative images alone. CD-grading is a description system consisting of C and D values in the surgical field extension that are related to the compartmental position of the flap beyond the nearby large joint and deeper extension for the pedicle, respectively. The CD-grading system gives a new perspective to the flap reconstruction classification. The CD-grading system also provides important information for follow-up imaging of a possible recurrence.
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BACKGROUNDS: Few paediatric and perinatal quality indicators (QIs) have been developed in the Japanese setting, and the quality of care is not assured or validated. The aim of this study was to develop QIs in paediatric and perinatal care in Japan using an administrative database and confirm the feasibility and applicability of the indicators using a single-site practice test. METHODS: We used a RAND-modified Delphi method that integrates evidence review with expert consensus development. QI candidates were generated from clinical practice guidelines (CPGs) available in English or Japanese and existing QIs in nine selected paediatric or perinatal conditions. Consensus building was based on independent panel ratings. The performance of QIs was retrospectively assessed using data from an administrative database at the National Children's Hospital. Data between April 2018 and March 2019 were used, while data between April 2019 and March 2021 were also used for selected condition, considering the small number of patients. Each QI was calculated as follows: number of times the indicator was met/number of participants×100. RESULTS: From the literature review conducted between 2010 and 2020, 124 CPGs and 193 existing indicators were identified to generate QI candidates. Through the consensus-building process, 133 QI candidates were assessed and 79 QIs were accepted. The practice test revealed wide variations in the process-level performance of QIs in four categories: patient safety: median 43.9% (IQR 16.7%-85.6%), general paediatrics: median 98.8% (IQR 84.2%-100%), advanced paediatrics: median 94.4% (IQR 46.0%-100%) and advanced obstetrics: median 80.3% (IQR 59.6%-100%). CONCLUSIONS: We established 79 QIs for paediatric and perinatal care in Japan using an administrative database that can be applied to hospitals nationwide. The practice test confirmed the measurability of the developed QIs. Benchmarking these QIs will be an attractive approach to improving the quality of care.
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Assistência Perinatal , Indicadores de Qualidade em Assistência à Saúde , Feminino , Gravidez , Recém-Nascido , Humanos , Criança , Japão , Técnica Delphi , Estudos RetrospectivosRESUMO
Introduction: Mohs paste has a zinc chloride component and the ability to coagulate tissue. Mohs chemosurgery or surgery is a method by which coagulated tissue is removed and can be repeated until the tumor disappears. The palliative purpose of Mohs chemosurgery or surgery is to control bleeding or exudate from a malignancy with a skin ulcer. In the current report, a single application of Mohs paste as a pre-operative treatment for a superficial sarcoma with a skin ulcer prevented intra-operative bleeding. Case Report: Two metastatic sarcomas are described: one in the scalp originating from a rectoperineal dedifferentiated liposarcoma and one in the elbow originating from a humeral telangiectatic osteosarcoma. Mohs paste treatment was performed the day before surgical resection. The Mohs paste procedure successfully prevented intra-operative bleeding from the tumor, leading to easy removal of the tumors with appropriate tumor-free margins. Conclusion: Preoperative Mohs paste treatment is a simple and reliable method. Intra-operative neoplastic bleeding may contaminate the tumor cells within the surgical field; thus the prevention of bleeding with Mohs paste treatment may lead to a decrease in the tumor recurrence rate.
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Objective: Lipomas are common, benign tumors usually located in the subcutaneous tissue. The "one-inch method" is a minimally invasive technique for resecting large subcutaneous lipomas through a one-inch incision after blunt dissection of the lipoma from its peripheral retaining ligaments. The limitations of this method are currently unclear. Materials and methods: We assessed twenty-five patients with large lipomas, defined as a tumor diameter greater than 5 cm. The location of the lipoma was at the shoulder in fifteen patients, the extremity in six patients, and the torso in four patients. Results: The mean operative time for all lesions was 28.3 minutes, with a mean time of 25.9 minutes for lipomas at the shoulder, 21.8 minutes for the extremities, and 47.0 minutes for the torso. We classified patients into three groups according to operative time: the short group (10-29 min), middle group (30-49 min), and long group (50-70 min). For lipomas of the shoulder, there were eleven patients (73%) in the short group, three patients (20%) in the middle group, and one patient (7%) in the long group. For lipomas of the extremity, the groups contained five patients (83%), one patient (17%), and no patients (0%), respectively. For lipomas of the torso, the groups contained one patient (25%), no patients (0%), and three patients (75%), respectively. Conclusions: Lipomas of the torso require a longer operative time than those of the shoulder or extremity; this difference could be due to the number of retaining ligaments present, which is reportedly higher in the back than in the anterior or side body. Lipomas of the back are less amenable to the one-inch method, and posterior shoulder lipomas may take more time than those at other parts of the shoulder or at the extremities.
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Purpose: Tenosynovial giant cell tumors (TSGCTs) are benign but aggressive lesions, and the treatment is resection. A low to intermediate signal intensity on both T1- and T2-weighted images of magnetic resonance imaging (MRI) is characteristic, which is similar to the signal intensity of muscle, and therefore can be challenging for lesion detection. T2-star (T2*)-weighted MR images reflect paramagnetic deoxyhemoglobin, methemoglobin, or hemosiderin. Methods: In 23 TSGCT patients (6 male and 17 females), the T2*MRI findings were analyzed. The tumor locations involved 10 large joints including nine knees and one ankle, 10 small joints including six fingers and four toes, as well as three wrists/hands. Results: Ten diffuse and 13 localized tumors were predominantly located in the large joints and small joints, respectively. The T2*-weighted images indicated three signal patterns of low, iso and high signal intensity compared to muscle. Low-, iso- and high-signal intensities were seen in 22 (96 %), 23 (100 %) and 12 (52 %) of the locations, respectively. To distinguish TSGCTs from the surrounding tissue, the low intensity T2*-weighted images and low to intermediate intensity T1-weighted images when compared to muscle and fluid, respectively were useful for the large joints. Low to intermediate intensity on T1- or T2-weighted images was useful to distinguish TSGCTs from subcutaneous tissue in the small joints. Conclusions: MRI using T2*-, as well as T1- and T2-weighted images, may be useful to detect lesions and assess the extent of TSGCTs in a tissue-specific manner, which is important for surgical planning.
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Arthroscopic partial trapeziectomy with suture-button suspensionplasty was developed for the surgical treatment of thumb carpometacarpal arthritis. However, the relationship between clinical results and radiographic evidence is unclear. Methods: The authors retrospectively reviewed 33 consecutive patients who underwent arthroscopic partial trapeziectomy with suture-button suspensionplasty for thumb carpometacarpal arthritis between 2016 and 2021. Clinical and radiographic outcomes were recorded, and the correlations between them were evaluated. Results: The average patient age at surgery was 69 years. Patient radiologic evidence was Eaton stage â ¡ in three thumbs, â ¢ in 25 thumbs, and â £ in five thumbs. The average trapezial space ratio (TSR) was 0.36 immediately after the operation but declined to 0.32 after 6 months. In contrast, the average joint subluxation was reduced to 0.005 immediately after the operation compared with 0.28 before, and was maintained at 0.04 at final follow-up. A statically significant correlation was detected between grip strength and TSR (P = 0.03), and between pinch strength and TSR (P = 0.02). A significant correlation was detected between TSR and trapezium height (P = 0.0215), which remained after partial trapeziectomy. No correlation was detected between rope position and other clinical or radiographic scores. Conclusions: Suture-button can have an effect on the medialization of the first metacarpal base. Excessive trapeziectomy can result in functional deficiency of the thumb through metacarpal subsidence, which potentially causes loss of grip and pinch strength.
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Giant cell tumors of bone (GCTBs) are locally aggressive tumors with the histological features of giant cells and stromal cells. Denosumab is a human monoclonal antibody that binds to the cytokine receptor activator of nuclear factor-kappa B ligand (RANKL). RANKL inhibition blocks tumor-induced osteoclastogenesis, and survival, and is used to treat unresectable GCTBs. Denosumab treatment induces osteogenic differentiation of GCTB cells. In this study, the expression of RANKL, special AT-rich sequence-binding protein 2 (SATB2, a marker of osteoblast differentiation), and sclerostin/SOST (a marker of mature osteocytes) was analyzed before and after treatment with denosumab in six cases of GCTB. Denosumab therapy was administered a mean of five times over a mean 93.5-day period. Before denosumab treatment, RANKL expression was observed in one of six cases. After denosumab therapy, spindle-like cells devoid of giant cell aggregation were RANKL-positive in four of six cases. Bone matrix-embedded osteocyte markers were observed, although RANKL was not expressed. Osteocyte-like cells were confirmed to have mutations, as identified using mutation-specific antibodies. Our study results suggest that treatment of GCTBs with denosumab results in osteoblast-osteocyte differentiation. Denosumab played a role in the suppression of tumor activity via inhibition of the RANK-RANKL pathway, which triggers osteoclast precursors to differentiate into osteoclasts.
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Conservadores da Densidade Óssea , Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Humanos , Denosumab/farmacologia , Osteócitos/metabolismo , Tumor de Células Gigantes do Osso/genética , Tumor de Células Gigantes do Osso/metabolismo , Tumor de Células Gigantes do Osso/patologia , Osteogênese , NF-kappa B , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Conservadores da Densidade Óssea/farmacologia , Ligante RANK/metabolismo , Diferenciação CelularRESUMO
Reconstruction with a pedicled latissimus dorsi flap is used for a large defect after resection of soft tissue sarcoma of the shoulder. Primary donor site closure is sometimes difficult and a skin graft is necessary, possibly delaying postoperative chemotherapy. Combined latissimus dorsi and scapular flaps are used for free flaps in head and neck reconstruction. Myxofibrosarcoma resection in the shoulder of a 76-year-old man resulted in a 16 cm diameter skin resection. The defect was reconstructed with a scapular flap (width = 5 cm) for the distal defect and a pedicled latissimus dorsi muscle flap (flap size, 10 × 7 cm) for the proximal defect. Primary closure of the donor site in the latissimus dorsi flap was easy. By adding a scapular flap to the latissimus dorsi flap, the latissimus dorsi flap area can be reduced, making it easy for primary suture and contributing to less invasive surgery.