Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
1.
Nature ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837071

RESUMO

Confocal microscopy1 remains a major workhorse in biomedical optical microscopy owing to its reliability and flexibility in imaging various samples, but suffers from substantial point spread function anisotropy, diffraction-limited resolution, depth-dependent degradation in scattering samples and volumetric bleaching2. Here we address these problems, enhancing confocal microscopy performance from the sub-micrometre to millimetre spatial scale and the millisecond to hour temporal scale, improving both lateral and axial resolution more than twofold while simultaneously reducing phototoxicity. We achieve these gains using an integrated, four-pronged approach: (1) developing compact line scanners that enable sensitive, rapid, diffraction-limited imaging over large areas; (2) combining line-scanning with multiview imaging, developing reconstruction algorithms that improve resolution isotropy and recover signal otherwise lost to scattering; (3) adapting techniques from structured illumination microscopy, achieving super-resolution imaging in densely labelled, thick samples; (4) synergizing deep learning with these advances, further improving imaging speed, resolution and duration. We demonstrate these capabilities on more than 20 distinct fixed and live samples, including protein distributions in single cells; nuclei and developing neurons in Caenorhabditis elegans embryos, larvae and adults; myoblasts in imaginal disks of Drosophila wings; and mouse renal, oesophageal, cardiac and brain tissues.

2.
Br J Cancer ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728792

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Surgical resection remains the definitive curative treatment for early-stage disease offering an overall 5-year survival rate of 62%. Despite careful case selection, a significant proportion of early-stage cancers relapse aggressively within the first year post-operatively. Identification of these patients is key to accurate prognostication and understanding the biology that drives early relapse might open up potential novel adjuvant therapies. METHODS: We performed an unsupervised interrogation of >1600 serum-based autoantibody biomarkers using an iterative machine-learning algorithm. RESULTS: We identified a 13 biomarker signature that was highly predictive for survivorship in post-operative early-stage lung cancer; this outperforms currently used autoantibody biomarkers in solid cancers. Our results demonstrate significantly poor survivorship in high expressers of this biomarker signature with an overall 5-year survival rate of 7.6%. CONCLUSIONS: We anticipate that the data will lead to the development of an off-the-shelf prognostic panel and further that the oncogenic relevance of the proteins recognised in the panel may be a starting point for a new adjuvant therapy.

3.
J Drugs Dermatol ; 20(8): 901-904, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397194

RESUMO

Anti-epidermal growth factor receptor (EGFR) antibodies and anti-programmed cell death 1 protein (PD-1) antibodies have been used separately to treat metastatic cutaneous squamous cell carcinoma (cSCC). While two anti-EGFR antibodies have similar clinical activity, cetuximab is administered weekly, whereas panitumumab is administered every two weeks. This report details findings using panitumumab in combination with anti-PD-1 antibody in patients with relapsed refractory cSCC. Three consecutive patients with poor performance status and rapidly progressive recurrent cutaneous squamous cell carcinoma (cSCC) of the face or scalp signed informed consent to receive an anti-PD-1 antibody with the option to add panitumumab were there inadequate response. After 2, 5, and 7 cycles of anti-PD-1 antibody treatment, respectively, panitumumab was added and the combination was continued for 27, 7, and 5 cycles, respectively. Fatigue, rash, and hypomagnesemia were reported, consistent with expectations for either agent alone. All three patients achieved durable complete response. The favorable clinical outcomes support further evaluation of the combination of anti-PD1 and anti-EGFR antibodies to control refractory cSCC of the face or scalp. J Drugs Dermatol. 2021;20(8):901-904. doi:10.36849/JDD.6175.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Panitumumabe/uso terapêutico , Neoplasias Cutâneas , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
4.
Artigo em Inglês | MEDLINE | ID: mdl-34036799

RESUMO

Significance: Systemic autoimmunity affects 3%-5% of the population worldwide. Systemic lupus erythematosus (SLE) is a prototypical form of such condition, which affects 20-150 of 100,000 people globally. Liver dysfunction, defined by increased immune cell infiltration into the hepatic parenchyma, is an understudied manifestation that affects up to 20% of SLE patients. Autoimmunity in SLE involves proinflammatory lineage specification in the immune system that occurs with oxidative stress and profound changes in cellular metabolism. As the primary metabolic organ of the body, the liver is uniquely capable to encounter oxidative stress through first-pass derivatization and filtering of waste products. Recent Advances: The traffic of immune cells from their development through recirculation in the liver is guided by cell adhesion molecules (CAMs) and integrins, cell surface proteins that tightly anchor cells together. The surface expression of CAMs and integrins is regulated via endocytic traffic that is sensitive to oxidative stress. Reactive oxygen species (ROS) that elicit oxidative stress in the liver may originate from the mitochondria, the cytosol, or the cell membrane. Critical Issues: While hepatic ROS production is a source of vulnerability, it also modulates the development and function of the immune system. In turn, the liver employs antioxidant defense mechanisms to protect itself from damage that can be harnessed to serve as therapeutic mechanisms against autoimmunity, inflammation, and development of hepatocellular carcinoma. Future Directions: This review is aimed at delineating redox control of integrin signaling in the liver and checkpoints of regulatory impact that can be targeted for treatment of inflammation in systemic autoimmunity.

5.
J Surg Case Rep ; 2021(4): rjab112, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33854762

RESUMO

Our case report illustrates effective implementation of conservative measures without the need for more invasive procedures, which can be required in refractory cases. Our patient was a 42-year-old female who fell from a horse and presented with a 1-week history of dyspnoea. Investigations revealed her to have a large right chylothorax, which was treated conservatively with chest drainage and octreotide. The patient remained in hospital for a total of 3 days prior to being discharged home without further complications. Blunt traumatic chylothorax should be considered as part of the differential diagnosis in patients who present with ongoing dyspnoea or chest discomfort within a 2-week preceding history of blunt trauma. Radiological imaging should be mandatory and the absence of posterior thoracic fractures does not exclude the diagnosis. Conservative management with pleural drainage, medium-chain triglyceride diet and octreotide yielded excellent results in our case.

6.
J Surg Case Rep ; 2021(3): rjab106, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33815759

RESUMO

We present the case of a 28 year-old lady with a history of intravenous drug use who presented to our institution with symptomatic right heart failure secondary to tricuspid valve regurgitation. She presented with infective endocarditis leading to dyspnoea and peripheral oedema secondary to torrential tricuspid regurgitation. Transthoracic echocardiography confirmed right ventricular dysfunction and congestive hepatomegaly. Intra-operatively findings an infected and destroyed anterior leaflet of the tricuspid valve with posterior leaflet prolapse was found to cause severe tricuspid regurgitation. She had complex tricuspid valve reconstruction using anterior leaflet reconstruction using Admedus Cardiocel™ patch, posterior leaflet prolapse correction and commissural reduction with a McGoon imbrication and annuloplasty ring to stabilize the repair. This case demonstrates the importance of reconstructive tricuspid valve surgery in the setting of infective endocarditis. Furthermore, this case demonstrates the possibility of anterior leaflet excision and reconstruction with an excellent durable functional result.

7.
Ann Thorac Surg ; 112(5): e387-e390, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33744219

RESUMO

Pectus excavatum affects about 1 in 500 people. Several surgical procedures have been proposed, including correction of the chest wall through a Nuss or modified Ravitch procedure. Further corrective revision operations remain challenging, and certainly potential life-threatening complications are described with less predictable outcomes. Secondary surgical procedures with a deep customized 3-dimensional elastomer implant are an elegant, effective, and safe solution compared with further corrective revision surgery.


Assuntos
Desenho Assistido por Computador , Tórax em Funil/cirurgia , Equipamentos Ortopédicos , Próteses e Implantes , Implantação de Prótese/métodos , Humanos , Desenho de Prótese , Reoperação
8.
Ann Thorac Surg ; 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33757740

RESUMO

Emergency medical assistance is rare when concerning air travel. Pulmonary barotrauma during air travel can occur in asymptomatic patients who have underlying intra-parenchymal pulmonary pathology such as bullae or bronchogenic cysts. During aircraft travel, the resultant decrease in pressure during the ascent can lead to expansion of the cyst volume culminating in tears and leakage of air into the surrounding vasculature and thus potential for air embolism. We describe a case of massive cerebral air embolism secondary to pulmonary barotrauma in a previously asymptomatic patient.

9.
J Surg Case Rep ; 2020(11): rjaa486, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33294167

RESUMO

Pulmonary lymphangioleiomyomatosis (LAM) is a rare, well-described pathology and usually is exclusive to females of a reproductive age. We present a 45 year-old lady who presented to the surgeons 1 year after an admission with acute dyspnoea following influenza infection. Initial computed tomography imaging findings demonstrated severe, heterogenous right-sided bullous emphysematous changes, but histopathological analysis of the post-operative specimen favoured a diagnosis of LAM. This case demonstrates the importance of considering LAM as a differential diagnosis for findings of unilateral emphysema or lobar emphysema, in which alpha 1-antitrypsin deficiency has been excluded and in those without a significant smoking history.

10.
Indian J Thorac Cardiovasc Surg ; : 1-5, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33223630

RESUMO

The demands of curtailing the impact of the coronavirus disease 2019 (COVID-19) global pandemic have disrupted the world's ability to care for patients with thoracic pathologies. Those who undergo thoracic surgical therapeutic procedures are a high-risk category, likely to have impaired lung function but also high risk for exposing clinical teams to aerosolised viral loads. In light of this global pandemic, thorough pre-procedural planning, adequate personal protective equipment (PPE), experienced personnel and judicious anaesthetic and intra-operative measures will serve to be instrumental in ensuring positive patient outcomes whilst still protecting the safety of healthcare workers.

11.
J Surg Case Rep ; 2020(10): rjaa356, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33072255

RESUMO

Ischaemic heart disease and aortic stenosis are potentially life-threatening conditions. A post-infarct left ventricular aneurysm, when combined with the above, is particularly hazardous. We present a case where all three conditions occurred simultaneously and describe the surgical approach undertaken to attempt correction. The patient underwent aneurysmectomy together with aortic valve replacement and two-vessel coronary artery bypass grafting. The aneurysm was excised with direct linear closure of the walls using a Teflon-buttressed interrupted mattress suture technique. Post-operatively, ventricular systolic function was good (LVEF 40%) together with a well-seated aortic valve showing no paravalvular leaks. This case highlights the importance of meticulous removal of thrombus from the aneurysm and everting the edges thereby eliminating a thrombogenic surface and the risk of embolic stroke. The restorative procedure itself serves to underline the importance of ventricular shape in the effective functioning of the myocardium for sustaining an adequate stroke volume with normalized physiology.

12.
Interact Cardiovasc Thorac Surg ; 31(4): 536-539, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964931

RESUMO

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'What is the role of non-radiation-based imaging modalities in the management of pectus deformities?'. Altogether 29 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that non-radiation-based imaging modalities provide a safe and easily implemented alternative to traditional computed tomography scan assessment for pectus deformities. This is particularly true for deformities on the more severe end of the spectrum and as an aid in providing an on-going assessment tool particularly in treatment modalities requiring a high degree of compliance (external bracing or vacuum bell therapy).


Assuntos
Diagnóstico por Imagem/métodos , Tórax em Funil/diagnóstico , Monitorização Fisiológica/métodos , Cooperação do Paciente , Humanos
13.
J Surg Case Rep ; 2020(8): rjaa272, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32904681

RESUMO

Metastatic breast carcinoma is a relatively common clinical entity. However, the prognosis of oligometastatic and polygometastatic disease differs considerably pertaining to five-year survival. Metastatic breast carcinoma to the sternum has been described as early as 1988. We describe two cases in our institution who presented with solitary sternal metastases with a previous history of treated breast cancer. In both cases, there had been a history of previous left breast cancer treated aggressively with surgical resection and adjuvant oncological therapy and maintenance hormonal therapy. Partial sternectomy or total sternectomy for solitary metastatic sternal deposits is well established with relatively low morbidity and mortality and improvement in quality of life and possible improvement in long-term survival. Furthermore, reconstructive options are inherently dependent on extent of resection performed. These techniques can incorporate the use of sternal plates in order to approximate defects and reinforce the sternum in the setting of partial sternectomy.

14.
J Intensive Care Soc ; 21(3): 230-231, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32782462

RESUMO

The 65 trial is a pragmatic, multicentre, parallel-group, open-label, randomised clinical trial of permissive hypotension (targeting a mean arterial pressure target of 60-65 mmHg during vasopressor therapy) versus usual care in critically ill patients aged 65 years or over with vasodilatory hypotension. The trial will recruit 2600 patients from 65 United Kingdom adult general critical care units. The primary outcome is all-cause mortality at 90 days. An economic evaluation is embedded. This paper describes the proposed statistical and health economic analysis for the 65 trial.

15.
J Thorac Cardiovasc Surg ; 160(4): 980-987, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32605730

RESUMO

OBJECTIVES: The coronavirus 2019 (COVID-19) pandemic has overwhelmed health care systems and disrupted routine care internationally. Health care workers face disruption to their work routines and professional development, as well as an elevated risk of infection and morbidity. We sought to establish the impact of the COVID-19 pandemic on the well-being, practice, and progression of all trainees in cardiothoracic surgery in the United Kingdom. METHODS: A 31-item questionnaire was designed, validated, and disseminated via e-mail and an instant-messaging platform. RESULTS: In total, 76 (of 118, 64%) cardiothoracic surgical trainees responded, representing all training grades and programs nationally; 48 (63%) and 24 (32%) were concerned about their physical and mental health, respectively, 25 (33%) had taken time off work due to COVID-19, 65 (86%) had treated patients with COVID-19, 36 of whom (55%) were wearing satisfactory personal protective equipment at the time, 41 (54%) remain concerned about personal protective equipment provision at their institution, 42 (55%) had been redeployed to cover other specialties, and 23 (30%) had encountered ethical dilemmas related to care of patients. There was a significant impact on time spent in outpatient clinics (44% reduction), multidisciplinary team meetings (79% reduction), and operating theaters (78% reduction). In total, 67 (88%) of respondents were concerned about the impact on their training, and 54 (71%) felt that the deviation may require an extension in their planned training time. CONCLUSIONS: The duration and impact of the current pandemic is, as yet, uncertain. Timely sharing of experiences, concerns, and expectations will inform health care and education policy and influence practice in the pandemic era and beyond.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Educação de Pós-Graduação em Medicina , Estresse Ocupacional/etiologia , Pandemias , Pneumonia Viral , Estudantes de Medicina/psicologia , Cirurgiões/psicologia , Cirurgia Torácica/educação , Adulto , Atitude do Pessoal de Saúde , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Saúde do Trabalhador , Estresse Ocupacional/diagnóstico , Estresse Ocupacional/psicologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , SARS-CoV-2 , Inquéritos e Questionários , Reino Unido
16.
J Surg Case Rep ; 2020(7): rjaa135, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32699591

RESUMO

Aorto-oesophageal fistula is a rarely described but life-threatening complication presenting with upper gastrointestinal haemorrhage. We present a case of a 58-year-old gentleman who presented to a peripheral hospital with a short duration of haematemesis and melaena and recent onset symptoms of dysphagia. This gentleman had a past medical history of alcohol excess and a history of trauma following a road traffic accident 38 years ago. Initial computer tomography scan demonstrated a large saccular aneurysm arising from the descending thoracic aorta adjacent to the oesophagus. The patient underwent radiological stenting of the large aneurysm with thoracic endovascular aortic replacement procedure. Follow-up computerized tomography (CT) angiography demonstrated satisfactory appearances of the thoracic aortic stent graft with no evidence of endo-leak. The triad of dysphagia, occult gastrointestinal blood loss and CT findings of a large aneurysm should prompt diagnosis or aorto-oesophageal fistula until proven otherwise.

17.
J Surg Case Rep ; 2020(7): rjaa169, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32699603

RESUMO

Aspergillus is a common environmental pathogen. However, clinically significant disease only occurs in a small proportion of patients. Although rare in its occurrence, it remains a considerable cause of morbidity and mortality in certain cohorts of patients. We describe a rare case of Aspergillus disease masquerading as a primary lung malignancy. Computer tomography pulmonary angiogram scan demonstrated a right upper lobe 8 x 6.5 cm soft-tissue lesion. Positron emission tomography CT demonstrated this lesion to be intensely fluorodeoxyglucose avid. Initial bronchoscopy demonstrated occluded subsegmental right upper lobe bronchus with white friable material. Follow-up bronchoscopy demonstrated evidence of a previous inflammatory process with cavitation and destruction of sub-lobar bronchial tree. Serial chest radiographs demonstrated almost complete resolution of the right upper lobe mass. Thus, this presentation of an Aspergillus-related lung mass masquerading as a primary lung malignancy provided several important learning points pertaining to diagnosis and ensuing management.

18.
J Thorac Dis ; 12(5): 2236-2246, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32642129

RESUMO

Background: Infections remain a part of the natural course of cancer, and lung cancer patients often present with some form of respiratory infection that can lead to their ultimate demise. Methods: Data was gathered concerning all unplanned hospital admissions (UHAs) to our centre from three separate patient cohorts; non-small cell lung cancer (NSCLC) patients (cohort 1), "other cancer" patients (breast, prostate, colon) (cohort 2) and all non-cancer patients (cohort 3). Results: Across the three cohorts, there were 455, 1,190 and 54,158 individual patient UHAs to our centre respectively. Within the NSCLC cohort, 164 UHAs were as a direct result of pneumonia (36.0%), compared to 1.3% and 2.2% in the other two cohorts (P<0.0001). In-hospital mortality and length of hospital stay were significantly higher in the pneumonia sub-group of NSCLC patients only compared with the other two patient cohorts (P<0.0001 and P=0.011 respectively). Within the NSCLC cohort, Patient age, pneumococcal vaccination status, pneumonia admission, smoking status and specific tumour stages were identified as significant independent risk factors for in-hospital mortality. Odds ratios of 0.160 for positive vaccination status and 9.522 for pneumonia admission indicate that for NSCLC patients admitted to hospital with a pneumonia without previous pneumococcal vaccination in the last 5 years, the odds of death were almost 60-fold higher. Conclusions: Vigilance for infection, early diagnosis with adequate assessment and efforts to identify a culprit organism should be a priority when faced with these patients. Infection prevention strategies should be further explored to address this high mortality risk in NSCLC.

20.
J Surg Case Rep ; 2020(6): rjaa193, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32665833

RESUMO

The following report describes a case in which air in the aorta led to stroke from cerebral emboli in a patient with distal oesophageal cancer. The patient presented with clinical features of a right-sided stroke. Computed tomography scans revealed air in the ascending aorta and brachiocephalic artery as a result of an oesophago-atrial fistula. The patient deteriorated and died soon after hospital admission despite conservative measures successfully dissipating the air. When encountered, emergent treatment of the underlying cause should be addressed but the outcome remains poor.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...