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1.
BMJ Paediatr Open ; 8(1)2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242630

RESUMO

OBJECTIVE: Describe families' experiences of interventions to improve continence in children and young people with neurodisability, and health professionals' and school and social care staff's perspectives regarding factors affecting intervention use. DESIGN: Four online surveys were developed and advertised to parent carers, young people with neurodisability, health professionals and school and social care staff, via societies, charities, professional contacts, schools, local authorities, and national parent carer and family forums, who shared invitations with their networks. Survey questions explored: difficulties helping children and young people use interventions; acceptability of interventions and waiting times; ease of use and availability of interventions, and facilitators and barriers to improving continence. RESULTS: 1028 parent carers, 26 young people, 352 health professionals and 202 school and social care staff registered to participate. Completed surveys were received from 579 (56.3%) parent carers, 20 (77%) young people, 193 (54.8%) health professionals, and 119 (58.9%) school and social care staff. Common parent carer-reported difficulties in using interventions to help their children and young people to learn to use the toilet included their child's lack of understanding about what was required (reported by 337 of 556 (60.6%) parent carers who completed question) and their child's lack of willingness (343 of 556, 61.7%). Almost all (142 of 156, 91%) health professionals reported lack of funding and resources as barriers to provision of continence services. Many young people (14 of 19, 74%) were unhappy using toilet facilities while out and about. CONCLUSIONS: Perceptions that children lack understanding and willingness, and inadequate facilities impact the implementation of toileting interventions for children and young people with neurodisability. Greater understanding is needed for children to learn developmentally appropriate toileting skills. Further research is recommended around availability and acceptability of interventions to ensure quality of life is unaffected.


Assuntos
Pais , Qualidade de Vida , Criança , Humanos , Adolescente , Pessoal de Saúde , Apoio Social , Cuidadores
2.
Pediatr Blood Cancer ; 70(4): e30195, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36642970

RESUMO

BACKGROUND/OBJECTIVES: Radiotherapy is an effective palliative treatment in advanced cancer. Shorter palliative treatment courses are recommended for adults, though pediatric data addressing treatment efficacy and toxicity according to radiation therapy (RT) dose and fractionation are limited. DESIGN/METHODS: Total 213 patients aged 21 years or younger receiving 422 palliative radiotherapy treatment courses from 2003 to 2016 were included. Symptom response and treatment-associated toxicity were recorded and analyzed in relationship to demographic and treatment variables. RESULTS: Common diagnoses included sarcoma (32.5%), neuroblastoma (24.9%), leukemia/lymphoma (14.9%), and central nervous system tumors (10.9%). The most common indication for treatment was pain (46.7%). Patients received a median of 10 fractions, 2.5 Gy dose per fraction, and 21 Gy total dose. Number of RT fractions was five or less in 166 (39.3%), six to 10 fractions in 117 (27.2%), and 10 or more fractions in 139 (32.9%) of courses. Complete or partial pain relief was achieved in 85% (151 of 178 evaluable patients), including 77.8% receiving five or less fractions and 89.6% receiving more than five fractions. Highest toxicity was grade 1 in 159 (38.9%), grade 2 in 26 (6.4%), and grade 3 in two (0.5%) treatments. On multivariable analysis, RT delivered 30 or more days from death (OR 12.13, 95% CI: 2.13-69.2, p = .005) and no adjuvant chemotherapy (OR 0.14, 95% CI: 0.03-0.54, p = .005) were significantly associated with pain response, and five or less fractions were significantly associated with lower toxicity (OR 0.24, 95% CI: 0.06-0.97, p = .045). CONCLUSIONS: Palliative RT courses of five or less fractions result in high rates of pain control and are associated with low toxicity in pediatric patients with cancer.


Assuntos
Neoplasias , Cuidados Paliativos , Adulto , Humanos , Criança , Fracionamento da Dose de Radiação , Resultado do Tratamento , Dor , Radioterapia
3.
Vasc Endovascular Surg ; 56(1): 29-32, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34601982

RESUMO

Introduction: Completion imaging following carotid endarterectomy (CEA) remains controversial. We present our experience performing routine completion arteriography (CA). Methods: A retrospective review of our prospectively maintained institutional database was performed for patients undergoing isolated CEA. Results: 1439 isolated CEAs with CA were performed on 1297 patients. CEA was for asymptomatic lesions in 70% (1003) of cases. There were no complications related to arteriography. An abnormal arteriogram documented significant abnormalities in the internal carotid artery (ICA) and prompted revision in 1.7% (24/1439) of cases: 20 unsatisfactory distal endpoints of the endarterectomy (12 residual stenoses, 7 intimal flaps, and 1 dissection), 3 kinks or stenoses within the body of the patch, and 1 thrombus. Of the 20 distal endpoint lesions, stent deployment was used in 17 cases and patch revision in 3 cases. The other 4 cases were treated by patch angioplasty (3) or thrombectomy (1). None suffered a perioperative stroke. The overall 30-day stroke, death, and combined stroke/death rate for the 1439 patients in our series was 1.5% (22), .5% (7), and 1.9% (27), respectively. The combined stroke/death rate for asymptomatic lesions was 1.1% (11/1003) and for symptomatic lesions was 2.5% (11/436). Of the 22 strokes in the entire series (all with normal CA), 15 were non-hemorrhagic strokes ipsilateral to the CEA; 14 were confirmed to have widely patent endarterectomy sites by CT-A (13) or re-exploration and repeat arteriography (1). The occluded site was re-explored and underwent thrombectomy, but no technical problems were identified. The remaining strokes were hemorrhagic (4 reperfusion syndrome and 1 surgical site bleeding) or contralateral to the CEA (2). Conclusion: Although not all patients in this series who underwent intraoperative revision due to abnormal CA might have suffered a stroke, performing this simple and safe study may have halved our overall perioperative stroke rate from 3.2% to 1.5%.


Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Acidente Vascular Cerebral , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
4.
Health Technol Assess ; 25(73): 1-258, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34866570

RESUMO

BACKGROUND: Children and young people with neurodisability often need help to achieve socially acceptable bladder and bowel control. Approaches vary depending on whether or not the impairment results from spinal cord pathology that impairs motor control and sensation of the bladder and bowel. Currently, there is uncertainty about which interventions are effective. OBJECTIVE: The objective was to summarise the available evidence on and current practice for improving continence in children and young people with neurodisability. DESIGN: A systematic review of the effectiveness, cost-effectiveness and factors that modify intervention implementation, alongside a cross-sectional, online survey of current practice with health professionals, parent carers, school and care staff and young people with neurodisability. RESULTS: Twelve databases were searched in the review, resulting in 5756 references; 71 studies (72 papers) were included in the analyses. Most of the evidence was for children with spinal cord pathology, which involved evaluations of pharmacological approaches and surgical techniques, whereas the evidence pertaining to those with non-spinal-cord-related pathology tended to be for behavioural interventions. The methodological quality of studies was rated as being moderate to poor. There were three robust qualitative studies about the experience of continence among children with spinal cord pathology. We found substantial heterogeneity across the interventions that we evaluated in terms of quality, study design and outcomes measured. No economic studies were found. The results were synthesised narratively and reported in text and tables. We did not find any eligible studies evaluating interventions using toilet and clothing adaptations in the review, although the survey highlighted that these types of interventions are frequently used and considered. In total, 949 people responded to the survey: 202 health professionals, 605 parent carers, 122 school and social care staff, and 20 young people. The survey results illustrated the different roles that professionals have in improving continence, highlighting the importance of a multidisciplinary approach to supporting children and young people and their families. Clinicians employ a range of assessments and interventions to improve continence or independent toileting, depending on the needs of the child. LIMITATIONS: Quantitative studies in the review were not methodologically robust. The survey had a risk of response bias. CONCLUSIONS: Our research found a dearth of good-quality evidence for many of the interventions currently in use, and no evidence of experiences of implementing interventions for children with non-spinal-cord-related pathology. There was also no evidence of cost-effectiveness of any of the interventions. FUTURE WORK: There is a need to involve young people and families in the design of high-quality evaluative research for interventions that aim to improve continence. This is especially the case for children with autism and learning disability, who have been neglected in previous evaluative and qualitative research. We recommend better training for health, education and care professionals about toileting, informed by evidence and the lived experiences of children and their families. We recommend a joined-up multidisciplinary and holistic approach to improving continence to maximise independence, dignity and comfort. It is vital that children and young people with neurodisability have early access to regular, integrated assessment of their bladder and bowel health, and are fully supported with appropriate personalised treatment. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018100572. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 73. See the NIHR Journals Library website for further project information.


Learning to go to the toilet is an important skill. Becoming continent involves knowing when you need to go, holding on until you find the right place, going to the toilet, cleaning and getting dressed again. Many children and young people with special educational needs or disability can learn to become clean and dry, sometimes with help or equipment. Advice is not consistent about the best ways to assess and treat continence problems for children and young people with neurodisability. This research aimed to find out how families and professionals measure and improve continence, and if there was evidence about which treatments are useful. We brought together the results of studies that have tested ways of assessing and improving toilet training for children and young people with special educational needs or disability. We carried out four online surveys with health professionals, education and care staff, parent carers, and disabled young people. We brought together and explained the findings from the surveys and the studies with help from parent carers and professionals. Approaches to improving continence vary depending on whether or not the child or young person's nerves and muscles that control their bladder and bowel work properly. Children and young people with conditions affecting the nerves and muscles of their bladder and bowel are often helped by medical or surgical treatments. Children and young people with conditions such as learning disability or autism may benefit from behavioural therapies to help them learn to use the toilet. There is poor evidence for how well treatments work and whether or not they are value for money. More and better research is needed to make sure that children and young people are able to be clean and dry without pads, maximising their independence, dignity and comfort. This also requires an adequate number of fully accessible toilets in the community.


Assuntos
Pais , Avaliação da Tecnologia Biomédica , Adolescente , Criança , Análise Custo-Benefício , Estudos Transversais , Humanos , Inquéritos e Questionários
5.
Vasc Endovascular Surg ; 55(7): 684-688, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34008440

RESUMO

OBJECTIVES: Pancreaticoduodenal artery aneurysms (PDAAs) are rare and have a high propensity for rupture. Historically, management of PDAAs included surgical reconstruction but has evolved with advances in endovascular therapy. We report our experience with management of PDAAs during the last 30 years. METHODS: We retrospectively reviewed our prospectively maintained registry between January 1, 1992 - March 30, 2020. RESULTS: We identified 8 patients with PDAAs: 4 with associated celiac artery occlusive disease and 4 without identifiable etiologies. Four patients were treated with surgical resection of the PDAAs: 2 intact aneurysms underwent concomitant revascularization (superior mesenteric artery-to-hepatic artery Dacron bypass; supra celiac aorta-to-hepatic artery Dacron bypass) and 2 (1 intact, 1 rupture) underwent ligation alone. Four patients were treated with coil embolization of the PDAA: 2 with concomitant stent-graft exclusion of the aneurysm (1 non-rupture, 1 rupture) and 2 without adjunctive measures (intact). There were no deaths nor any significant procedure-related morbidity. CONCLUSION: Our large single-center experience shows that PDAAs can be successfully treated by open or endovascular intervention with selective revascularization.


Assuntos
Aneurisma/terapia , Implante de Prótese Vascular , Duodeno/irrigação sanguínea , Embolização Terapêutica , Pâncreas/irrigação sanguínea , Adulto , Idoso , Aneurisma/diagnóstico por imagem , Aneurisma/fisiopatologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Bases de Dados Factuais , Feminino , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Philadelphia , Polietilenotereftalatos , Desenho de Prótese , Estudos Retrospectivos , Stents , Resultado do Tratamento , Adulto Jovem
6.
Vasc Endovascular Surg ; 55(6): 541-543, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33813957

RESUMO

OBJECTIVE: The Society for Vascular Surgery stated there are a lack of studies describing long-term surveillance for aortobifemoral (AoBF) bypasses. Our goal was to investigate the value of DU studies as a surveillance tool for AoBF bypasses. METHODS: We retrospectively identified patients in our prospectively maintained database who underwent AoBF bypasses between 1995-2018. Surveillance was performed routinely with DU post-operatively, every 6 months for 1 year, and then annually. We considered "abnormal" DU findings to include peri-graft fluid, pseudoaneurysm or, peak systolic velocities (PSVs) > 350 cm/sec or PSV ratio > 3.5 anywhere from the proximal aortic to distal femoral anastomosis. If abnormalities were identified patients underwent intervention or shorter surveillance intervals. RESULTS: Of 153 AoBF bypasses, 60 patients with 120 graft limbs fulfilled our post-operative surveillance protocol with a mean follow-up of 4.0 years (0.5-24 years). "Normal" DU surveillance studies were documented throughout follow-up in 112 (93%) limbs. Of these, 2 (1.7%) developed acute limb occlusion. Eight (6.7%) limbs had "abnormal" DU findings: 5 failing grafts with focal elevated PSVs, 2 with peri-graft fluid leading to a diagnosis of an infected graft, and 1 with a pseudoaneurysm (PSA). Contrast arteriography or CT-angiography confirmed > 75% diameter stenosis, fluid or PSA in all 8 limbs. Graft revision (5 endovascular, 2 surgical) was performed in 7 of the 8 limbs initially or after 2 successive "abnormal" DU studies within 6 weeks of each other; 1 patient refused intervention. Without surveillance, urgent or emergent treatment might have proved necessary in 7.5% (7 + 2 = 9/120) of cases instead of only 1.7% (2/120) of cases. CONCLUSION: Vascular surgeons should adopt DU as a useful surveillance tool to identify AoBF bypasses that are failing or have other problems not identified clinically. Persistence of "abnormal" DU findings should prompt operative or endovascular intervention.


Assuntos
Aorta/cirurgia , Implante de Prótese Vascular/efeitos adversos , Artéria Femoral/cirurgia , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Falha de Prótese , Ultrassonografia Doppler Dupla , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Bases de Dados Factuais , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Valor Preditivo dos Testes , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
7.
Cancer ; 126(1): 37-45, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532544

RESUMO

BACKGROUND: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database. METHODS: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM). RESULTS: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups. CONCLUSIONS: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório , Tratamento Farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/efeitos dos fármacos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/efeitos da radiação , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Perioperatório , Período Pré-Operatório , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
8.
Hematol Oncol Clin North Am ; 34(1): 205-227, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31739945

RESUMO

Although the use of ionizing radiation in malignant conditions has been well established, its application in benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, in instances where the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the current use of radiation therapy in some of the more common benign conditions.


Assuntos
Malformações Arteriovenosas/radioterapia , Contratura de Dupuytren/radioterapia , Fibromatose Agressiva/radioterapia , Oftalmopatia de Graves/radioterapia , Ginecomastia/radioterapia , Histiocitose/radioterapia , Ossificação Heterotópica/radioterapia , Humanos , Masculino
9.
Hematol Oncol Clin North Am ; 34(1): 229-251, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31739946

RESUMO

Although the use of ionizing radiation on malignant conditions has been well established, its application on benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, when the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the present use of radiation therapy for some of the most common benign conditions.


Assuntos
Túnica Conjuntiva/anormalidades , Queloide/radioterapia , Degeneração Macular/radioterapia , Pseudotumor Orbitário/radioterapia , Induração Peniana/radioterapia , Pterígio/radioterapia , Neuralgia do Trigêmeo/radioterapia , Humanos , Masculino
10.
Ann Vasc Surg ; 63: 269-274, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31626930

RESUMO

BACKGROUND: Noninvasive diagnostic testing may be beneficial to identify stenotic (failing) stents placed for occlusive lower extremity peripheral arterial disease (LEPAD), especially if subsequent intervention proves useful in maintaining prolonged stent patency. We previously documented the benefit of surveillance duplex ultrasound (DU) for peripheral covered stents (stent grafts). The purpose of this study was to evaluate whether DU can reliably diagnose failing bare metal stents placed in iliac, femoral, and popliteal arteries for LEPAD. METHODS: Between January 1, 2013, and December 31, 2016, 172 stents were placed for LEPAD in 119 arterial segments (1.4 stents/stenotic artery) in 110 patients who underwent one or more DU surveillance study documenting stent patency. Poststent DU surveillance was performed in our Intersocietal Accreditation Commission accredited noninvasive vascular lab at 1 week and then every 6 months. DU measured peak systolic velocities (PSVs) and ratio of adjacent PSVs (Vr) every 2.0 cm within the stent(s) and adjacent arteries. We retrospectively classified the following factors as "abnormal DU findings": focal PSVs >300 cm/s, uniform PSVs <45 cm/s, and Vr > 3.0. RESULTS: During average follow-up of 22 months (range, 1 week-48 months), all three of these DU criteria were "normal" in 62 (52%) of the 119 stented segments. Of the other 57 (48%) stented arterial segments that had one or more abnormal DU findings, 40 underwent prophylactic intervention, 12 patients did not undergo intervention and subsequently occluded (5 patient refusal, 4 surgeon-decision, 3 shortened surveillance interval), and 5 remained patent after mean follow-up of 7.2 months. Of the 12 arterial segments that occluded, 6 patients chose not to have further intervention, 4 failed additional endovascular intervention and required an arterial bypass, and 2 required amputation. Therefore, of the 17 stented arterial segments with one or more abnormal DU findings that did not undergo intervention, 12 (70%) went on to occlude versus 2 of 62 (3%) with normal DU findings demonstrating an odds ratio of 72.0 (95% CI 12.5-415.6, P < 0.0001). Of these 12 stented arterial segments with abnormal DU findings that occluded, 7 had uniform low PSVs alone, 3 had both abnormal PSV and Vr's, and 2 had abnormal Vr's alone. CONCLUSIONS: DU surveillance can predict LEPAD stent occlusion. While PSV >300 cm/sec alone is not a statistically significant predictor of stent failure, Vr > 3.0, and most importantly, uniform PSVs <45 cm/s throughout the stent were statistically reliable markers for predicting stent thrombosis, while the absence of any of these abnormalities strongly predicted stent patency.


Assuntos
Procedimentos Endovasculares/instrumentação , Artéria Femoral/diagnóstico por imagem , Artéria Ilíaca/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Artéria Poplítea/diagnóstico por imagem , Stents , Ultrassonografia Doppler Dupla , Velocidade do Fluxo Sanguíneo , Procedimentos Endovasculares/efeitos adversos , Artéria Femoral/fisiopatologia , Humanos , Artéria Ilíaca/fisiopatologia , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Grau de Desobstrução Vascular
11.
Cardiovasc Res ; 116(6): 1161-1174, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566215

RESUMO

AIMS: The chemotherapy drug doxorubicin (Dox) is commonly used for treating a variety of human cancers; however, it is highly cardiotoxic and induces heart failure. We previously reported that the Bcl-2 mitochondrial death protein Bcl-2/19kDa interaction protein 3 (Bnip3), is critical for provoking mitochondrial perturbations and necrotic cell death in response to Dox; however, the underlying mechanisms had not been elucidated. Herein, we investigated mechanism that drives Bnip3 gene activation and downstream effectors of Bnip3-mediated mitochondrial perturbations and cell death in cardiac myocytes treated with Dox. METHODS AND RESULTS: Nuclear factor-κB (NF-κB) signalling, which transcriptionally silences Bnip3 activation under basal states in cardiac myocytes was dramatically reduced following Dox treatment. This was accompanied by Bnip3 gene activation, mitochondrial injury including calcium influx, permeability transition pore (mPTP) opening, loss of nuclear high mobility group protein 1, reactive oxygen species production, and cell death. Interestingly, impaired NF-κB signalling in cells treated with Dox was accompanied by protein complexes between Bnip3 and cyclophilin D (CypD). Notably, Bnip3-mediated mPTP opening was suppressed by inhibition of CypD-demonstrating that CypD functionally operates downstream of Bnip3. Moreover, restoring IKKß-NF-κB activity in cardiac myocytes treated with Dox suppressed Bnip3 expression, mitochondrial perturbations, and necrotic cell death. CONCLUSIONS: The findings of the present study reveal a novel signalling pathway that functionally couples NF-κB and Dox cardiomyopathy to a mechanism that is mutually dependent upon and obligatorily linked to the transcriptional control of Bnip3. Our findings further demonstrate that mitochondrial injury and necrotic cell death induced by Bnip3 is contingent upon CypD. Hence, maintaining NF-κB signalling may prove beneficial in reducing mitochondrial dysfunction and heart failure in cancer patients undergoing Dox chemotherapy.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Cardiomiopatias/induzido quimicamente , Doxorrubicina/toxicidade , Mitocôndrias Cardíacas/efeitos dos fármacos , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , NF-kappa B/metabolismo , Peptidil-Prolil Isomerase F/metabolismo , Animais , Cardiomiopatias/enzimologia , Cardiomiopatias/genética , Cardiomiopatias/patologia , Cardiotoxicidade , Células Cultivadas , Peptidil-Prolil Isomerase F/genética , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , NF-kappa B/genética , Necrose , Ratos Sprague-Dawley , Transdução de Sinais
12.
Pediatr Blood Cancer ; 67(1): e28027, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571408

RESUMO

BACKGROUND: Radiotherapy boost to the entire posterior fossa (PF) is standard of care for high-risk (H-R) medulloblastoma patients; the utility of tumor bed (TB)-only boost is unclear. The purpose of this study was to examine the impact of PF versus TB boost volume on tumor control and survival in the H-R medulloblastoma population. METHODS: Single-institution records for patients with H-R medulloblastoma were reviewed. The median craniospinal irradiation dose was 36 Gy (range, 23.4-45 Gy), and boost doses to either PF or TB were 54 to 55.8 Gy. PF (local) failures were scored as in-field, marginal (between 80% and 95% isodose lines), or distant. Kaplan-Meier methods and Cox proportional hazards were used to assess the impact of radiation boost technique on local control (LC) and survival endpoints. RESULTS: Thirty-two patients with H-R medulloblastoma were treated between 1990 and 2015, with a median follow-up length of 5.12 years. Twenty-two patients received PF boost, and 10 received TB boost. Patient and disease characteristic were comparable between groups. A total of 11 PF failures occurred, including 3 isolated LFs (2 in the PF and 1 in the TB group). Most PF failures were in-field: three of four in the TB group and six of seven in the PF group; the remainder were marginal failures. TB boost was not associated with inferior LC (hazard ratio [HR] 0.86, log-rank P = 0.81) or overall survival (HR 1.40, P = 0.56) compared with PF boost. CONCLUSION: Reduced-volume radiotherapy boost to the TB does not appear to compromise LC or survival in patients with H-R medulloblastoma; it may reduce the risk of ototoxicity.


Assuntos
Neoplasias Cerebelares/mortalidade , Radiação Cranioespinal/mortalidade , Meduloblastoma/mortalidade , Carga Tumoral , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meduloblastoma/patologia , Meduloblastoma/radioterapia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
13.
J Vasc Surg ; 71(5): 1653-1661, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31708303

RESUMO

OBJECTIVE: With rising health care spending in the United States, the Centers for Medicare and Medicaid Services (CMS) in recent years attempted to use reimbursement rates to influence use of less expensive care sites for covered patients, such as ambulatory surgery centers (ASCs) and office-based laboratories (OBLs), in lieu of hospital service sites. It has been suggested that cost savings have not been realized because of more procedures being performed by physicians with ownership interests in nonhospital facilities. CMS adopted massive reimbursement changes for 2019 OBL and ASC-based procedures, which reduced dialysis access angioplasty reimbursement in the ASC setting by 50%, whereas facility reimbursement for stenting increased by 33% above prior levels. The clinical utility of adjunctive stenting in treating dialysis access stenosis remains controversial and highly discretionary. As a vascular group performing such procedures in both a hospital and nonhospital facility in which we have equity interest, we reviewed our use of stents in dialysis access procedures both in the hospital and in the ASC/OBL to determine whether site of service affected stent use. METHODS: A retrospective review of a prospectively maintained database was performed from 2014 to 2018. All patients undergoing dialysis access angiography with angioplasty and adjunctive stent placement at our OBL (later ASC) and our primary hospital were included in the study. RESULTS: There were 961 angioplasty or stent procedures performed for dialysis accesses between the two sites, 564 (58.7%) in the hospital setting and 397 (41.3%) at the OBL/ASC. There was a significant difference in race and age between the two sites, with younger, minority patients more frequently being treated in the hospital and older, white patients more likely to be treated in the ambulatory setting; 153 (27.1%) underwent adjunctive stent placement in the hospital and 127 (32.0%) in the ambulatory setting (P = .09). CONCLUSIONS: Whereas financial incentives have not yet had an appreciable influence on stent use for dialysis access within previous reimbursement paradigms, the dramatic changes recently adopted by CMS may well alter this dynamic and could lead to substantially higher overall costs without proven clinical advantage. Interventionalists may be incentivized to add stents when performing balloon angioplasty in ASCs. With high failure and reintervention rates and increasingly expensive adjuncts (drug-coated balloons and stents, covered stents), the cost implications of attempts to incentivize interventionalists toward a specific type of procedure or site of care are substantial, and unintended negative consequences are likely to occur.


Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Diálise Renal , Stents , Idoso , Instituições de Assistência Ambulatorial/economia , Angioplastia com Balão/economia , Derivação Arteriovenosa Cirúrgica/economia , Centers for Medicare and Medicaid Services, U.S. , Feminino , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Mecanismo de Reembolso , Estudos Retrospectivos , Stents/economia , Estados Unidos
14.
J Vasc Surg Venous Lymphat Disord ; 7(6): 839-844, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31471278

RESUMO

OBJECTIVE: Traditional management of venous thoracic outlet syndrome (VTOS) has involved catheter-directed thrombolysis (CDT) followed by transaxillary or paraclavicular (PC) first rib resection. More recently, we have adopted an infraclavicular (IC) approach for first rib resection and five other strategies to treat these patients. We report our evolving experience with the treatment of acute VTOS. METHODS: We reviewed our prospectively maintained database to identify patients treated for VTOS. Our strategy includes CDT with pharmacomechanical thrombectomy, IC first rib resection during the same hospitalization, and subclavian vein angioplasty immediately after rib resection. Postoperatively, a sequential compression device was applied to the affected arm and low-dose heparin given through the ipsilateral venous sheath. Antiplatelet therapy was given for 6 weeks and anticoagulation for 6 months. Our strategy evolved from a PC to an IC approach, given that the added morbidity of the supraclavicular approach to allow excision of the posterior portion of the rib may add no benefit with VTOS compared with arterial or neurogenic thoracic outlet syndrome. RESULTS: There were 51 patients who underwent first rib resection for VTOS, 11 (22%) through a PC approach and 40 (78%) through an IC approach. The average age was 36 years (range, 16-63 years), and the majority were female (36 [71%]) and involved the right subclavian vein (36 [71%]). All patients underwent preoperative CDT, 40 (78%) at our hospital and 11 (22%) elsewhere. Fifty patients (98%) underwent subclavian vein angioplasty after rib resection. A bare-metal stent was placed in two (4%) patients for persistent stenosis. Average length of stay was 3.7 (±2.1) days. Average operative time was 2.2 hours (range, 1.5-3.0 hours) when the IC approach was used vs 3.5 hours (range, 2.5-4.5 hours) for the PC approach (P < .0001). Of the entire group, one (2.6%) patient required reoperation for wound hematoma and six (12%) patients underwent repeated endovascular intervention for recurrent vein stenosis during follow-up (average, 38 months; range, 1-240 months). Primary and assisted primary patency rates at 3 years were 78% and 100%, respectively. There were no significant differences in patency rates or complications between the IC and PC approaches. CONCLUSIONS: Our transition to an IC approach demonstrated low perioperative morbidity and excellent subclavian vein patency rates with shorter operative times compared with a PC approach. Our practice has evolved to include IC first rib resection followed by concomitant postoperative venous balloon angioplasty.


Assuntos
Anticoagulantes/administração & dosagem , Osteotomia , Inibidores da Agregação Plaquetária/administração & dosagem , Costelas/cirurgia , Síndrome do Desfiladeiro Torácico/terapia , Trombectomia , Terapia Trombolítica , Adolescente , Adulto , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Anticoagulantes/efeitos adversos , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Stents , Síndrome do Desfiladeiro Torácico/diagnóstico por imagem , Síndrome do Desfiladeiro Torácico/fisiopatologia , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Adulto Jovem
15.
J Vasc Surg Cases Innov Tech ; 5(3): 365-368, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31440715

RESUMO

A 37-year-old asymptomatic man presented with incidentally identified intra-abdominal venous aneurysms. Workup, which included venography, demonstrated an absent segment of the inferior vena cava between the inferior right and superior left renal vein, resulting in a 4.4-cm right renal vein aneurysm, dilated common iliac veins, and left external iliac vein aneurysm. Collateralization was robust. Given the limited natural history data and complexities of open reconstruction, we opted to observe this asymptomatic patient with serial imaging, which demonstrated no interval change. We present our case and a review of the literature pertaining to intra-abdominal venous aneurysms.

16.
Vasc Endovascular Surg ; 53(7): 589-592, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31248350

RESUMO

Anomalous connections between the anterior and posterior cranial circulation are rare embryologic entities. A persistent hypoglossal artery has a reported incidence of 0.03% to 0.09% and has been linked to intracranial aneurysms, atherosclerosis, and posterior circulation ischemia. Identification of this anomaly is essential prior to carotid artery revascularization given the technical challenges and added risks with intervention. We report a case of an 80-year-old female with progression of carotid stenosis in the setting of a persistent hypoglossal artery. We provide a review of the literature and discuss the technical challenges of carotid revascularization in this patient.


Assuntos
Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Malformações Arteriovenosas Intracranianas/complicações , Idoso de 80 Anos ou mais , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/fisiopatologia , Resultado do Tratamento , Grau de Desobstrução Vascular
17.
J Vasc Surg ; 69(4): 1129-1136, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30292617

RESUMO

OBJECTIVE: Prosthetic arterial graft infections (PAGIs) in the groin pose significant challenges in terms of revascularization options and risk of limb loss as well as associated morbidities. Although obturator canal bypass (OCB) has been suggested for revascularization of the extremity in these cases, moderate success rates and technical challenges have limited widespread use. Our study analyzed lateral femoral bypass (LFB) as an alternative approach for the treatment of groin PAGIs. METHODS: This is a retrospective review of a prospectively maintained database of patients who underwent LFB for groin PAGIs at a single center from 2000 to 2017. Patients' data including demographics, comorbidities, perioperative complications, graft patency, and need for reintervention were used. Patients were observed after LFB with duplex ultrasound surveillance in an accredited noninvasive vascular laboratory every 3 months during the first year, followed by every 6 months for the second year and yearly thereafter. After isolation of the infected wound with sterile dressings, remote proximal and distal arterial exposure incisions were made. LFBs were tunneled under the inguinal ligament and lateral to the infected wound from an uninvolved inflow artery or bypass graft to an uninvolved outflow vessel. RESULTS: A total of 19 LFBs were performed in 16 patients (mean age, 69 ± 12.6 years). Three LFBs were performed urgently for acute bleeding. Choice of conduit included 6 (31.6%) autogenous vein grafts, 10 (52.6%) cadaveric grafts, 2 (10.5%) rifampin-soaked Dacron grafts, and 1 (5.3%) polytetrafluoroethylene graft. Average follow-up was 33 months (range, 0-103 months). Major adverse events occurring within 30 days of the operation included one (5.3%) death and one (5.3%) graft excision for pseudoaneurysm. Primary patency and primary assisted patency at 12 and 24 months were 73% and 83%, respectively. One patient required an amputation 17 months after surgery after failure of repeated revascularization attempts. Overall limb salvage was 93.8% during this follow-up period. CONCLUSIONS: In this series, LFB for management of groin PAGIs demonstrated higher patency and limb salvage rates compared with previous reports of OCB. Diligent postoperative duplex ultrasound surveillance is critical to the achievement of limb salvage and maintenance of graft patency. These results suggest that LFB, which is technically less complex than OCB, should be considered the first choice for revascularization in select cases of PAGIs involving the groin.


Assuntos
Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Prótese Vascular/efeitos adversos , Artéria Femoral/cirurgia , Virilha/irrigação sanguínea , Infecções Relacionadas à Prótese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Bases de Dados Factuais , Feminino , Artéria Femoral/fisiopatologia , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/fisiopatologia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
18.
Ann Vasc Surg ; 56: 81-86, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30347242

RESUMO

BACKGROUND: A percutaneous brachial artery (BA) approach is a suitable or even favorable alternative to femoral artery access when performing certain endovascular interventions. However, this approach may have a higher complication rate compared to femoral artery access. We analyzed our results using percutaneous BA approach for noncardiac endovascular interventions. METHODS: Between January 1, 2003 and December 31, 2017, BA access was used in 157 cases performed on 136 patients. The procedures included 102 (65%) therapeutic interventions and 55 (35%) diagnostic studies. The vessels studied or treated included lower extremity arteries (48), the aorta and iliac arteries (45), mesenteric arteries (45), failing arterial revascularizations (24), renal arteries (9), subclavian arteries (8), carotid arteries (2), and visceral aneurysms (2), or in conjunction with endovascular aneurysm repair (EVAR), fenestrated EVAR, or thoracic EVAR (8). More than 1 vessel was studied or treated in 34 cases. Sheath sizes included 5F in 38 (24%) cases, 6F in 93 (59%) cases, and 7F in 26 (17%) cases. Percutaneous puncture was utilized in 142 (90.4%) cases and planned surgical exposure with primary closure of the BA in 15 (9.6%) cases (10, 7F; 4, 6F; 1, 5F). Manual compression was used for hemostasis at the conclusion of all percutaneous cases. RESULTS: There were 2 (1.3%; 2/157 cases) deaths in the perioperative period, one due to myocardial infarction and the other from mesenteric ischemia. Access site complications occurred in 10.6% (15/142) of percutaneous cases, which required open surgical repair for bleeding (8) and BA thrombosis (7). There was an increased risk of complications with increasing sheath size in the percutaneous approach: 5.4% (2/37), 12.4% (11/89), and 12.5% (2/16) for 5F, 6F, and 7F sheaths, respectively (P = 0.49). None of the 15 patients who underwent surgical treatment suffered long-term vascular or neuropathic complications. CONCLUSIONS: In our experience, percutaneous BA access was associated with a 10% complication rate with an increased risk of complications associated with increasing sheath size. There was approximately the same incidence of bleeding as thrombosis. For patients who require 6 or 7F sheaths via a BA approach, we recommend more liberal use of open surgical exposure and primary BA repair.


Assuntos
Artéria Braquial , Cateterismo Periférico/métodos , Procedimentos Endovasculares/métodos , Doenças Vasculares/cirurgia , Idoso , Artéria Braquial/diagnóstico por imagem , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/mortalidade , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Punções , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/mortalidade
20.
Surg Oncol ; 27(4): A3-A8, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30237037

RESUMO

BACKGROUND: Scalp angiosarcomas (SA) are rare, representing <1% of soft tissue sarcomas. The optimal management of these tumors is unknown, with management based on small case series. We sought to assess the impact of different therapies on overall survival (OS), the practice patterns nationally, and identify factors associated with OS for non-metastatic scalp angiosarcomas. METHODS: A prospectively maintained database was used to identify non-metastatic scalp angiosarcomas who received some form of definitive therapy. Logistics regression, Kaplan-Meier, and Cox proportional-hazard models were utilized. RESULTS: A total of 589 patients met study entry criteria with a median follow-up of 4.2 years. The majority (482 patients, 81.8%) had upfront definitive resection and an additional 317 patients (65.8%) received postoperative radiation. Of the 107 patients who didn't have surgery, the majority (65 patients, 60.7%) received definitive radiation and 42 patients (39.3%) received radiation and chemotherapy. One-year and five-year survival estimates for patients not receiving definitive surgery were 68.0% (95%CI: 57.5-76.4) and 18.0% (95%CI: 10.2-27.5) respectively compared to 78.2% (95%CI: 74.0-81.9) and 34.1% (95%CI: 28.9-39.3) for patients receiving definitive surgery (p < 0.01). On multivariable analysis, age ≥65 years, tumor size ≥5 cm, and not receiving definitive surgery was associated with worse OS. CONCLUSIONS: The majority of patients with non-metastatic scalp angiosarcomas had upfront definitive surgery, with a subsequent improvement in OS, including when accounting for other patient and tumor factors. Postoperative radiation was frequently given. Our large series confirmed age and tumor size as prognostic factors for this rare disease.


Assuntos
Hemangiossarcoma/mortalidade , Complicações Pós-Operatórias/mortalidade , Couro Cabeludo , Neoplasias Cutâneas/mortalidade , Idoso , Feminino , Seguimentos , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Taxa de Sobrevida
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