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1.
Rheumatol Int ; 44(6): 1077-1087, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581449

RESUMO

Sporadic inclusion body myositis (sIBM) is a subgroup of idiopathic inflammatory myopathies characterised by progressive muscle weakness and skeletal muscle inflammation. Quantitative data on the myofibre morphology in sIBM remains scarce. Further, no previous study has examined fibre type association of satellite cells (SC), myonuclei number, macrophages, capillaries, and myonuclear domain (MD) in sIBM patients. Muscle biopsies from sIBM patients (n = 18) obtained previously (NCT02317094) were included in the analysis for fibre type-specific myofibre cross-sectional area (mCSA), SCs, myonuclei and macrophages, myonuclear domain, and capillarisation. mCSA (p < 0.001), peripheral myonuclei (p < 0.001) and MD (p = 0.005) were higher in association with type 1 (slow-twitch) than type 2 (fast-twitch) fibres. Conversely, quiescent SCs (p < 0.001), centrally placed myonuclei (p = 0.03), M1 macrophages (p < 0.002), M2 macrophages (p = 0.013) and capillaries (p < 0.001) were higher at type 2 fibres compared to type 1 fibres. In contrast, proliferating (Pax7+/Ki67+) SCs (p = 0.68) were similarly associated with each fibre type. Type 2 myofibres of late-phase sIBM patients showed marked signs of muscle atrophy (i.e. reduced mCSA) accompanied by higher numbers of associated quiescent SCs, centrally placed myonuclei, macrophages and capillaries compared to type 1 fibres. In contrast, type 1 fibres were suffering from pathological enlargement with larger MDs as well as fewer nuclei and capillaries per area when compared with type 2 fibres. More research is needed to examine to which extent different therapeutic interventions including targeted exercise might alleviate these fibre type-specific characteristics and countermeasure their consequences in impaired functional performance.


Assuntos
Miosite de Corpos de Inclusão , Regeneração , Humanos , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Macrófagos/patologia , Inflamação/patologia , Biomarcadores/análise , Músculo Esquelético/patologia , Células Satélites de Músculo Esquelético/patologia , Biópsia , Fibras Musculares de Contração Lenta/patologia , Fibras Musculares de Contração Rápida/patologia
2.
Dan Med J ; 71(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314731

RESUMO

INTRODUCTION: We aimed to investigate "pain without loosening" as an indication for knee arthroplasty revisions and to screen for other indications potentially hidden in this category to improve future registration and enhance data quality in the Danish Knee Arthroplasty Register. METHODS: We included 104 patients undergoing revision knee arthroplasty for the indication "pain without loosening" from 1 January 2016 to 31 December 2018 at five Danish centres. Medical records, radiographs and computed tomographies were reviewed. RESULTS: In 103 of 104 cases, we confirmed "pain without loosening" as an indication for revision. We found hidden indications in 44 cases; malposition of components (n = 19), stiffness (n = 13), progression of arthrosis (n = 6), instability (n = 3), liner dislocation (n = 1), residual cement (n = 1) and aseptic loosening (n = 1). The Kellgren-Lawrence arthrosis grades prior to primary knee arthroplasty were 1-2 (31%) and 3-4 (69%). CONCLUSIONS: The indication "pain without loosening" covered patients revised due to pain, but other hidden indications were also present. Stiffness and malposition of components were hidden indications and these are not provided as indication options in the DKR and other registers. The relatively high frequency of arthrosis grade 1-2 prior to primary knee arthroplasty is concerning and may explain the occurrence of knee pain without any other pathology present. FUNDING: The Danish Rheumatism Association, the Region of Southern Denmark, the Research Fund of Region Zeeland and Region of Southern Denmark, and the University of Southern Denmark. TRIAL REGISTRATION: Not relevant.


Assuntos
Artroplastia do Joelho , Osteoartrite , Humanos , Artroplastia do Joelho/efeitos adversos , Reoperação , Falha de Prótese , Dor , Dinamarca/epidemiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-37575962

RESUMO

Radiostereometric analysis (RSA) studies have shown that the continuous migration of tibial components is predictive of aseptic loosening following total knee arthroplasty (TKA). In the present study, we investigated whether accurate sizing and placement of tibial components are related to the degree of implant migration as measured with use of RSA. Methods: A total of 111 patients who underwent TKA surgery with a cementless tibial component were followed for a period of 2 years postoperatively, during which implant migration was assessed with use of RSA. RSA was performed within 7 days postoperatively and after 3, 6, 12, and 24 months. Postoperative radiographs were evaluated for component size and placement in the tibia. The evaluations were performed by experienced knee surgeons who were blinded to the migration data and clinical outcomes. A multivariable linear regression analysis was conducted. Results: Continuous implant migration (i.e., migration occurring between 12 and 24 months postoperatively) had a negative association with tibial component size (coefficient [B], -0.2; 95% confidence interval [CI], -0.33 to -0.08). Subsidence was associated with the absence of posterior cortical bone support (B, -0.7; 95% CI, -1.09 to -0.28), the absence of lateral cortical bone support (B, 0.8; 95% CI, 0.29 to 1.37), frontal-plane varus malalignment (B, 0.6; 95% CI, 0.12 to 1.16), and component undersizing (B, -0.4; 95% CI, -0.06 to -0.68). Posterior tilt was associated only with undersizing (B, 0.6; 95% CI, 0.27 to 1.11). Conclusions: Undersized cementless tibial components are at a higher risk for poor fixation with continuous migration following TKA. Therefore, a higher risk of aseptic loosening should be expected. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

4.
Knee Surg Sports Traumatol Arthrosc ; 31(11): 4766-4772, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37498328

RESUMO

PURPOSE: Does patients revised for unexplained pain after mUKA present the same PROM and satisfaction scores 1-3 years after revision as patients revised for aseptic loosening?". METHODS: 104 patients undergoing revision of mUKA's for the indications unexplained pain and aseptic loosening were included in the period January 1, 2018 to December 31, 2020. from the Danish Knee Arthroplasty Register. 52 patients were revised for unexplained pain and 52 for aseptic loosening. Patient demographics did not differ between the two groups. PROMs [Oxford Knee Score (OKS), EQ-5D-5L, Forgotten Joint Score (FJS)] and questions about satisfaction with the surgery were sent to digitally secured mailboxes. Pearson's Chi-square test and Wilcoxon Rank Sum test were used to test for statistical differences between groups. RESULTS: The median OKS 1-3 years after revision was 26 (IQR 22) for unexplained pain vs 34 (IQR 12) for aseptic loosening, p = 0.033. The median EQ-5D-5L Index after revision was 0.7 (IQR 0.6) for unexplained vs 0.8 (IQR 0.1) for aseptic loosening, p = 0.014. The median FJS after revision was 48 (IQR 10) for unexplained pain vs 52 (IQR 14) for aseptic loosening, p = 0.1. The mean satisfaction with the surgery on a 0-100 scale (100 = not satisfied; 0 = very satisfied) was 55 (IQR 60) for unexplained pain vs 50 (IQR 67) for aseptic loosening, p = 0.087, and patients revised for unexplained pain were less likely to find their knee problem importantly improved (p = 0.032). CONCLUSION: Patients undergoing revision of mUKAs for unexplained pain presented poor postoperative PROM scores, and PROM scores were worse compared to those of patients revised for aseptic loosening. Patients revised for unexplained pain were less likely to find their knee problem importantly improved. This study support the evidence against revisions for unexplained pain. LEVEL OF EVIDENCE: Level III.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Satisfação do Paciente , Reoperação , Dor/cirurgia , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento , Falha de Prótese , Articulação do Joelho/cirurgia
5.
BMC Neurol ; 23(1): 233, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328820

RESUMO

BACKGROUND: Sporadic late onset nemaline myopathy is a rare, progressive muscle disease, presenting in adulthood, mainly affecting proximal limb and bulbar muscles. Muscle biopsies show characteristic nemaline rods. The putative mechanism is considered immune-related. Other manifestations aside from neuromuscular symptoms have not been described previously. CASE PRESENTATION: We present a case with atypical sporadic late onset nemaline myopathy (SLONM) of a non-HIV, non-MGUS subtype, where skin manifestations preceded neuromuscular symptoms, and a residual thymus with the histology of thymic follicular hyperplasia was detected during the diagnostic workup. Thorough dermatological investigations could not explain the skin presentations. Muscle biopsy revealed variation in fiber diameter, ragged-red and COX-negative fibers associated with discrete fibrosis. Electron microscopy detected atrophic muscle fibres with disorganization of the myofibrils, nemaline rods and abnormal mitochondria. Single-fiber EMG suggested signs of a neuromuscular transmission defect, EMG showed signs of myopathy. Analyses of antibodies associated with myasthenia gravis were negative. The patient showed improvement after intravenous immunoglobulin treatment regarding both the skin and the muscle symptoms. CONCLUSIONS: Our case highlights the heterogeneity of SLONM with its varied spectrum of presentation. A unique combination of dermatological symptoms and SLONM could be seen with skin lesions as primary presenting symptoms. An association can be considered between the different manifestations, presumably based on immune etiology, where immunosuppressive therapy has been beneficial.


Assuntos
Miastenia Gravis , Miopatias da Nemalina , Humanos , Miopatias da Nemalina/complicações , Miopatias da Nemalina/tratamento farmacológico , Miopatias da Nemalina/diagnóstico , Imunossupressores , Imunoglobulinas Intravenosas , Músculos/patologia , Miastenia Gravis/complicações , Músculo Esquelético/patologia
6.
J Plast Surg Hand Surg ; 58: 40-47, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37338078

RESUMO

Lymphedema is a common complication following breast cancer treatment with axillary lymphadenectomy and radiotherapy. Currently, there is no curative treatment for this disease, hence there is a need for new therapeutic suggestions. The aim of this study was to investigate the effect of hyaluronidase (HYAL) injections after inducing hindlimb lymphedema in 36 female C57BL/6 mice. HYAL injections were administered every second day for 14 days in three groups: (1) HYAL for 1 week followed by saline for 1 week, (2) HYAL for 2 weeks, and (3) saline injections for 2 weeks. Volume of the lymphedema limb was weekly assessed with micro-computed tomography (µ-CT) scans for a total course of 6 weeks. Lymph vessel morphometry was assessed in the end of the study after staining cross-sections of the hindlimb for anti-LYVE-1 blindly. Lymphatic function was assessed by lymphoscintigraphy to assess lymphatic clearance. There was a significant reduction of the volume of lymphedema in mice treated with HYAL-7 compared with mice treated with HYAL-14 (p < 0.05) and saline (p < 0.05). No differences were detected in lymph vessel morphometry and the lymphoscintigraphy between groups. Short-term treatment with HYAL-7 might be a potential therapeutic suggestion for secondary lymphedema induced in mouse hindlimbs. In the future, clinical studies are needed to investigate the potential of HYAL treatment in human beings.


Assuntos
Hialuronoglucosaminidase , Linfedema , Camundongos , Feminino , Humanos , Animais , Hialuronoglucosaminidase/farmacologia , Hialuronoglucosaminidase/uso terapêutico , Microtomografia por Raio-X/efeitos adversos , Camundongos Endogâmicos C57BL , Linfedema/diagnóstico por imagem , Linfedema/tratamento farmacológico , Linfedema/etiologia , Membro Posterior , Extremidade Inferior , Linfocintigrafia/efeitos adversos , Doença Crônica
8.
Clin Neurophysiol ; 148: 65-75, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36804609

RESUMO

OBJECTIVE: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology. METHODS: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup. RESULTS: Mean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests. CONCLUSIONS: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology. SIGNIFICANCE: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.


Assuntos
COVID-19 , Doenças Musculares , Humanos , Eletromiografia/métodos , Síndrome de COVID-19 Pós-Aguda , Qualidade de Vida , COVID-19/complicações , Músculo Esquelético , Fadiga
9.
Eur J Med Genet ; 66(3): 104706, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36669590

RESUMO

Disease causing variants in the Ryanodine receptor 1 (RYR1) gene are a common cause for congenital myopathy and for malignant hyperthermia susceptibility. We report a 17 year old boy with congenital muscle weakness progressing to a myasthenia like myopathy with muscle weakness, fatigability, ptosis, and ophthalmoplegia. Muscle biopsy showed predominance and atrophy of type 1 fibers. Whole-exome trio sequencing revealed three variants in the RYR1-gene in the patient: c.6721C > T,p.(Arg2241*) and c.2122G > A,p.(Asp708Asn) in cis position, and the c.325C > T,p.(Arg109Trp) variant in trans. Treatment with pyridostigmine improved symptoms. This case supports that a myasthenia like phenotype is part of the phenotypic spectrum of RYR1 related disorders, and that treatment with pyridostigmine can be beneficial for patients with this phenotype.


Assuntos
Doenças Musculares , Brometo de Piridostigmina , Adolescente , Humanos , Masculino , Debilidade Muscular/genética , Músculo Esquelético/patologia , Doenças Musculares/genética , Mutação , Fenótipo , Brometo de Piridostigmina/uso terapêutico , Canal de Liberação de Cálcio do Receptor de Rianodina/genética
10.
J Arthroplasty ; 38(3): 535-540.e3, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36257505

RESUMO

BACKGROUND: It is unknown if patients are relieved of pain after knee arthroplasty revision for unexplained pain. The aim of this cross-sectional case-control study was to compare patient-reported outcome measures (PROMs) and satisfaction 1 to 3 years after revision of total knee arthroplasties (TKAs) for the indications of unexplained pain versus aseptic loosening. METHODS: We included 384 patients undergoing TKA revision for the indications of unexplained pain and aseptic loosening from January 1, 2018 to December 31, 2020 from the Danish Knee Arthroplasty Register. A total of 81 patients were revised for unexplained pain and 303 for aseptic loosening. Questionnaires including PROMs (Oxford Knee Score, EQ-5D-5L, and Forgotten Joint Score) and satisfaction with the surgery on a 0-100 scale (100 = not satisfied; 0 = very satisfied) were sent to digitally secured mailboxes. Time from revision to data collection was a median 3.1 years (range, 1.4-4.4 years). RESULTS: Median Oxford Knee Score was 25 (interquartile range [IQR] 15) versus 31 (IQR 18) 1-3 years after revisions for unexplained pain versus aseptic loosening, P = .009. Median EQ-5D-5L was 0.6 (IQR 0.4) versus 0.8 (IQR 0.3) for unexplained pain versus aseptic loosening, P = .009. Median Forgotten Joint Score was 50 (IQR 7) versus 50 (IQR 16) for unexplained pain versus aseptic loosening, P = .905. Satisfaction was 75 (IQR 38) for unexplained pain and 50 (IQR 73) for aseptic loosening, P < .001. CONCLUSION: Patients undergoing TKA revision for the indication of unexplained pain had worse results on PROMs than those revised for aseptic loosening. Likewise, patients revised for unexplained pain were less satisfied compared to patients revised for aseptic loosening. This information is valuable to both surgeons and patients when candidates for revision surgery are selected, to obtain the best possible outcomes.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Artroplastia do Joelho/métodos , Estudos de Casos e Controles , Estudos Transversais , Satisfação do Paciente , Falha de Prótese , Dor/cirurgia , Reoperação , Inquéritos e Questionários , Medidas de Resultados Relatados pelo Paciente , Prótese do Joelho/efeitos adversos , Articulação do Joelho/cirurgia , Estudos Retrospectivos
12.
Eur J Pediatr Surg ; 32(5): 460-464, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35688448

RESUMO

INTRODUCTION: Treatment for long-gap esophageal atresia (LGEA) aims at achieving primary anastomosis with minimal tension. Previous studies have shown that intramural injections with botulinum toxin type-A (BTX-A) from the adventitial side can increase the elongation of the piglet and rat esophagus before bursting, and that this effect is dose and time dependent. Our aim was to determine if endoscopic injections would be feasible, safe, and with an effect on the mechanical properties of the esophagus. METHODS: Twenty-two male piglets (5.15 kg) were randomized into two groups, one receiving 2 units/kg BTX-A, the other equal volume 0.9% NaCl. On day 3, the esophagus was harvested and tested in a stretch-tension machine to evaluate elongation and maximum load, followed by histological examination. RESULTS: No adverse effects to the procedure were observed. No statistically significant difference in elongation or maximum load before bursting between the treatment and placebo group was found. In histopathological analysis, inflammation and abscess formation were observed with no statistically significant difference between the two groups. CONCLUSION: Endoscopic placement of BTX-A injections in the piglet esophagus was safe and feasible but did not result in any difference in the mechanical properties or histology of the esophagus.


Assuntos
Toxinas Botulínicas Tipo A , Atresia Esofágica , Fármacos Neuromusculares , Animais , Atresia Esofágica/tratamento farmacológico , Atresia Esofágica/cirurgia , Injeções/métodos , Masculino , Solução Salina/uso terapêutico , Suínos , Resultado do Tratamento
13.
Eur J Neurol ; 29(9): 2832-2841, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35661354

RESUMO

BACKGROUND AND PURPOSE: Among post-COVID-19 symptoms, fatigue is reported as one of the most common, even after mild acute infection, and as the cause of fatigue, myopathy diagnosed by electromyography has been proposed in previous reports. This study aimed to explore the histopathological changes in patients with post-COVID-19 fatigue. METHODS: Sixteen patients (mean age = 46 years) with post-COVID-19 complaints of fatigue, myalgia, or weakness persisting for up to 14 months were included. In all patients, quantitative electromyography and muscle biopsies analyzed with light and electron microscopy were taken. RESULTS: Muscle weakness was present in 50% and myopathic electromyography in 75%, and in all patients there were histological changes. Muscle fiber atrophy was found in 38%, and 56% showed indications of fiber regeneration. Mitochondrial changes, comprising loss of cytochrome c oxidase activity, subsarcollemmal accumulation, and/or abnormal cristae, were present in 62%. Inflammation was found in 62%, seen as T lymphocytes and/or muscle fiber human leukocyte antigen ABC expression. In 75%, capillaries were affected, involving basal lamina and cells. In two patients, uncommon amounts of basal lamina were found, not only surrounding muscle fibers but also around nerves and capillaries. CONCLUSIONS: The wide variety of histological changes in this study suggests that skeletal muscles may be a major target of SARS-CoV-2, causing muscular post-COVID-19 symptoms. The mitochondrial changes, inflammation, and capillary injury in muscle biopsies can cause fatigue in part due to reduced energy supply. Because most patients had mild-moderate acute affection, the new variants that might cause less severe acute disease could still have the ability to cause long-term myopathy.


Assuntos
COVID-19 , Doenças Musculares , COVID-19/complicações , Fadiga/complicações , Humanos , Inflamação/patologia , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Doenças Musculares/diagnóstico , SARS-CoV-2
14.
J Arthroplasty ; 37(8): 1618-1625.e3, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35378235

RESUMO

BACKGROUND: It is uncertain if patients undergoing revision knee arthroplasty for "pain without loosening" are relieved of pain. This study aimed to compare pre- and postoperative analgesic consumption by patients undergoing revision for "pain without loosening" versus "aseptic loosening" and to determine predictors for postoperative long-term opioid use. METHODS: A retrospective nationwide study of 1,037 revisions for "pain without loosening" and 2,317 revisions for "aseptic loosening" during 1997-2018 from the Danish Knee Arthroplasty Register was carried out. Analgesic use was defined by prescription reimbursement, and long-term opioid use by prescription reimbursement in 4 consecutive quarters. RESULTS: In the preoperative year, 37% and 29% of patients revised for "pain without loosening" and "aseptic loosening" were opioid users compared to 32% and 30% in the postoperative year. Non-steroidal anti-inflammatory drug (NSAID) use was significantly lower postoperatively for both indications (35% versus 28% for "pain without loosening" and 33% versus 25% for "aseptic loosening"). Use of other analgesics was unchanged. Long-term opioid use increased postoperatively by 4% for patients with "pain without loosening" (P = .029) and by 3% for "aseptic loosening" (P = .003). New long-term opioid users (without preoperative long-term use) were 9% for "pain without loosening" and 8% for "aseptic loosening". Predictors of new long-term opioid use were other opioid-requiring diagnoses or procedures within the first postoperative year, Charlson Comorbidity Index (CCI) ≥3, and preoperative long-term NSAID use. CONCLUSION: The consumption of opioids decreased slightly after knee arthroplasty revision for the indication "pain without loosening", but not for "aseptic loosening". The amount of new long-term opioid users increased for both indications.


Assuntos
Artroplastia do Joelho , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides , Artroplastia do Joelho/métodos , Dinamarca , Humanos , Dor , Falha de Prótese , Reoperação , Estudos Retrospectivos
15.
Cardiovasc Pathol ; 60: 107427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35436604

RESUMO

OBJECTIVES: To investigate Stone Heart Syndrome (SHS) as consequence of prolonged ischemic arrest in an experimental study on pigs in regards to onset of SHS and pathological changes. Outcomes defined as aortic cross clamp (ACC) time until onset of SHS and cellular changes characterized by SHS. METHODS: Eight pigs were included to undergo normothermic cardioplegia induced cardiac arrest ranging from 80 to 240 minutes of ACC. Duration of ACC was defined as time from initiation of aortic cross clamping until cessation. Normothermic, cardioplegic solution administered directly into the arterial system, though in a reduced dose compared to clinical practice. Myocardial contracture evaluated by palpation of the myocardium. Biopsies were collected from the left ventricle just after the induction of cardiac arrest and after reperfusion. Biopsies were evaluated for pathological changes indicative of SHS by electron microscopy. RESULTS: Six pigs completed the full trial, while two were lost to bleeding. Pigs undergoing 80 to 120 minutes of ACC regained heart rhythm either spontaneously or after defibrillation. Pigs undergoing more than 180 minutes of ACC had contracted hearts with no electrocardiographic response indicating the development of SHS. Electron microscopy findings after ACC of 80 to 120 minutes showed no or low degrees of cellular changes, whereas pig hearts with more than 180 minutes of ACC showed severe mitochondrial changes, endothelial damage, and shortening of sarcomeres consistent with SHS. CONCLUSION: Development of SHS in pigs was ACC time dependent and solely avoided when ACC was limited to a maximum of 120 minutes.


Assuntos
Parada Cardíaca Induzida , Isquemia Miocárdica , Animais , Soluções Cardioplégicas/efeitos adversos , Parada Cardíaca/induzido quimicamente , Parada Cardíaca Induzida/efeitos adversos , Isquemia Miocárdica/etiologia , Miocárdio/patologia , Projetos Piloto , Suínos
16.
Leukemia ; 36(5): 1274-1282, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35314777

RESUMO

Relapse remains the main obstacle to curing childhood acute lymphoblastic leukemia (ALL). The aims of this study were to compare incidence of relapse, prognostic factors, and survival after relapse between three consecutive Nordic Society of Pediatric Hematology and Oncology trials. Relapse occurred as a primary event in 638 of 4 458 children (1.0-14.9 years) diagnosed with Ph-negative ALL between 1992 and 2018. The 5-year cumulative incidence of relapse was 17.3% (95% CI 15.4-19.2%) and 16.5% (95% CI 14.3-18.8%) for patients in the ALL1992 and ALL2000 trials, respectively, but decreased to 8.4% (95% CI 7.0-10.1%) for patients in the ALL2008 trial. No changes in duration of first complete remission and site of relapse were observed over time; however, high hyperdiploidy, and t(12;21) decreased in the ALL2008 trial. The 4-year overall survival after relapse was 56.6% (95% CI 52.5-60.5%) and no statistically significant temporal improvements were observed. Age ≥10 years, T-cell immunophenotype, bone-marrow involvement, early and very early relapse, hypodiploidy, and Down syndrome all independently predicted worse outcome after relapse. Improvements in the primary treatment of childhood ALL has resulted in fewer relapses. However, failure to improve outcome of remaining relapses suggests a selection of harder-to-cure relapses and calls for new therapeutic strategies.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Estudos de Coortes , Humanos , Incidência , Lactente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Recidiva , Indução de Remissão , Resultado do Tratamento
17.
J Biomed Mater Res B Appl Biomater ; 110(8): 1862-1875, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35233920

RESUMO

Bioreactors have been used for bone graft engineering in pre-clinical investigations over the past 15 years. The ability of bioreactor-incubated bone marrow nuclear cells (BMNCs) to enhance bone-forming potential varies significantly, and the three-dimensional (3D) distribution of BMNCs within the scaffold is largely unknown. The aims of this study were (1) to investigate the efficacy of a carbonated hydroxyapatite (CHA) with/without BMNCs on spine fusion rate and fusion mass microarchitecture using a highly challenging two-level posterolateral spine fusion without instrumentation; and (2) to evaluate 3D distribution of BMNCs within scaffolds characterized by immunohistochemistry. Fusion rate and fusion mass were quantified by micro-CT, microarchitectural analysis, and histology. While the homogenous 3D distribution of BMNCs was not observed, BMNCs were found to migrate towards a substitute core. In the autograft group, the healing rate was 83.3%, irrespective of the presence of BMNCs. In the CHA group, also 83.3% was fused in the presence of BMNCs, and 66.7% fused without BMNCs. A significant decrease in the fusion mass porosity (p = .001) of the CHA group suggested the deposition of mineralized bone. The autograft group revealed more bone, thicker trabeculae, and better trabecular orientation but less connection compared to the CHA group. Immunohistochemistry confirmed the ability of bioreactors to incubate a large-sized substitute coated with viable BMNCs with the potential for proliferation and differentiation. These findings suggested that a bioreactor-activated substitute is comparable to autograft on spine fusion and that new functional bone regeneration could be achieved by a combination of BMNCs, biomaterials, and bioreactors.


Assuntos
Substitutos Ósseos , Fusão Vertebral , Animais , Reatores Biológicos , Medula Óssea , Células da Medula Óssea , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Transplante Ósseo/métodos , Ovinos , Fusão Vertebral/métodos
18.
J Shoulder Elbow Surg ; 31(7): 1344-1356, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35150831

RESUMO

BACKGROUND: Rotator cuff (RC) tendon tear leads to impaired shoulder function and pain. The supraspinatus (SS) tendon is most often affected, but the biological response of the SS muscle to SS tendon tear is largely unknown. This study aimed to investigate time-dependent muscle inflammation, degeneration, fatty infiltration, and regeneration in experimental SS tear conditions. METHODS: Forty-five C57BL/6 mice were subjected to SS tendon tear and allowed to recover for 1, 3, 5, 7, 14, or 28 days. The extent of muscle damage was examined using histologic, flow cytometric, proteomic, and chemiluminescence analyses. RESULTS: We found that muscle inflammation peaked around day 5 with increased monocyte infiltration and increased cytokine levels in the ipsilateral compared to the contralateral SS muscle. Bioinformatics analysis of proteomics on mice that survived 5 days after RC tendon tear revealed upregulated proteins involved in "neutrophil activation involved in immune response" and "extracellular matrix organization," whereas "skeletal muscle tissue development and contraction" and "respiratory electron transport chain" were among the most downregulated. Histologic analysis of collagen showed increased collagen accumulation and fatty infiltration of the ipsilateral SS over time. Finally, we observed time- and lesion-dependent changes in satellite cell and fibro-adipogenic progenitor populations. CONCLUSION: Altogether, we demonstrate that the SS muscle shows severe signs of acute inflammation, early degeneration, and fatty infiltration, as well as reduced regenerative potential following SS tendon tear.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Tecido Adiposo/patologia , Animais , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Atrofia Muscular/patologia , Proteômica , Manguito Rotador/patologia
20.
Acta Orthop ; 93: 103-110, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34906032

RESUMO

Background and purpose - Patients having a knee arthroplasty revision for the indication "pain without loosening" may have a higher risk of re-revisions than patients revised for other indications. The primary aim of this study was to compare the survival of knee arthroplasties revised for "pain without loosening" compared with "aseptic loosening." The second was to investigate the prosthesis survival rates in 3 surgical subgroups (total knee arthroplasty (TKA)-TKA; partial revision (revision of tibial or femoral component); unicompartmental knee arthroplasty-TKA) and to compare the prosthesis survival rates for 1997-2009 and 2010-2018. Patients and methods - 4,299 revisions were identified in the period 1997-2018 from the Danish Knee Arthroplasty Register. Of these, 1,111 (26%) were performed due to "pain without loosening" without any other indications, 674 (16%) due to "pain without loosening" combined with other indications, and 2,514 (59%) due to "aseptic loosening". Survival analysis was performed by a Cox multivariate analysis and Kaplan-Meier curves were presented. Results - The cumulated proportions of re-revision after 2, 5, and 20 years were 12% (95% CI 10-14), 18% (CI 16-20), and 23% (CI 20-25) for "pain without loosening" versus 11% (CI 9.3-12), 16% (CI 14-17), and 19% (CI 18-21) for "aseptic loosening." There were no statistically significant differences between the 2 indications in repeated analyses for each of the surgical subgroups. The hazard ratio for re-revision comparing "pain without loosening" with "aseptic loosening" was 1.03 (CI 0.87-1.2). The 8-year risk of re-revision for "pain without loosening" was 22% (CI 19-26) versus 22% (CI 20-25) for "aseptic loosening" in the period from 1997-2009, and 18% (CI 15-22) versus 14% (CI 13-16) in the period from 2010-2018. Interpretation - The risk of re-revision was similar for patients having a knee arthroplasty revision for the indication "pain without loosening" compared with "aseptic loosening." However, we observed a slight improvement of prosthesis survival rates after revisions for both indications from 1997-2009 to 2010-2018. We cannot recommend for or against revision in cases with "pain without loosening" based on these data alone.


Assuntos
Artroplastia do Joelho/métodos , Prótese do Joelho , Desenho de Prótese , Falha de Prótese , Reoperação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
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