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1.
Surgeon ; 20(3): e36-e42, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33840595

RESUMO

INTRODUCTION: Wire guided localization has been widely utilized as the standard method of pre-operative localization of breast lesions. Magnetic seeds were developed to counter some of the disadvantages associated with wires. This aim of this study was to assess outcomes following the introduction of magnetic seeds at a tertiary specialist breast centre. METHODS: A retrospective review of a prospective database of the first 100 patients who underwent magnetic seed (Magseed) guided breast surgery between November 2018 and November 2019. Data was collected from 17 wire guided cases completed during the trial phase for comparison. The primary outcome measures were successful excision of index lesion and retrieval of the magnetic seed. Secondary outcomes analyzed included time ready for theatre, post-operative complications and breast margin re-excision rate. RESULTS: Of these 100 cases, 85 patients underwent Magseed guided wide local excision for invasive or in-situ carcinoma and 15 underwent Magseed guided diagnostic excision. The primary lesion was excised, and Magseed was retrieved in all 100 cases. 54% of patients were ready to proceed as the first scheduled theatre case of the day, compared to 0% of wire-guided cases. Amongst therapeutic Magseed guided cases, the re-excision rate for margin clearance was 9.4%. CONCLUSION: Magseed guided breast excision is a new technology that has been implemented with relative ease in our unit. We have shown that magnetic seed guided surgery reliably localizes lesions, is associated with low re-excision rates without an increase in patient morbidity or mortality and results in improvements in theatre planning and efficiency.


Assuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/cirurgia , Feminino , Humanos , Fenômenos Magnéticos , Margens de Excisão , Mastectomia , Mastectomia Segmentar/métodos , Centros de Atenção Terciária
2.
Breast Dis ; 40(3): 155-160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33749633

RESUMO

INTRODUCTION: Atypical intraductal epithelial proliferation (AIDEP) is a breast lesion categorised as "indeterminate" if identified on core needle biopsy (CNB). The rate at which these lesions are upgraded following diagnostic excision varies in the literature. Women diagnosed with AIDEP are thought to be at increased risk of breast cancer. Our aim was to identify the rate of upgrade to invasive or in situ carcinoma in a group of patients diagnosed with AIDEP on screening mammography and to quantify their risk of subsequent breast cancer. METHODS: We conducted a retrospective review of a prospectively maintained database containing all patients diagnosed with AIDEP on CNB between 2005 and 2012 in an Irish breast screening centre. Basic demographic data was collected along with details of the original CNB result, rate of upgrade to carcinoma and details of any subsequent cancer diagnoses. RESULTS: In total 113 patients were diagnosed with AIDEP on CNB during the study period. The upgrade rate on diagnostic excision was 28.3% (n = 32). 6.2% (n = 7) were upgraded to invasive cancer and 22.1% (n = 25) to DCIS. 81 patients were not upgraded on diagnostic excision and were offered 5 years of annual mammographic surveillance. 9.88% (8/81) of these patients went on to receive a subsequent diagnosis of malignancy. The mean time to diagnosis of these subsequent cancers was 65.41 months (range 20.18-145.21). CONCLUSION: Our data showing an upgrade rate of 28% to carcinoma reflects recently published data and we believe it supports the continued practice of excising AIDEP to exclude co-existing carcinoma.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Proliferação de Células , Detecção Precoce de Câncer/estatística & dados numéricos , Células Epiteliais/patologia , Mamografia/estatística & dados numéricos , Biópsia com Agulha de Grande Calibre/métodos , Mama/patologia , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Carcinoma Intraductal não Infiltrante/prevenção & controle , Bases de Dados Factuais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Biópsia Guiada por Imagem , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
3.
J Plast Reconstr Aesthet Surg ; 74(9): 2184-2193, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33531208

RESUMO

Local perforator flaps may be utilised to correct volume defects after breast-conserving surgery (BCS), improving the cosmetic outcome and avoiding the need for contralateral symmetrising surgery. The aims of this study were to assess longer term oncological outcomes following local perforator flap reconstruction, and to demonstrate the learning curve associated with incorporating such techniques within routine clinical practice. We report a consecutive case series of 116 local perforator flaps performed between January 2014 and May 2020. Data collected included patient demographics, tumour characteristics, surgical procedure data, complications and follow-up outcomes. All breast cancer patients are followed with annual mammographic surveillance for a minimum of five years. Of 116 procedures, 101 were performed as immediate partial breast reconstruction and 15 as delayed reconstructive procedures for patients who had prior breast surgery. The overall complication rate was 15%; the majority were minor surgical site infections, 1.7% required haematoma evacuation. At a median follow-up of 37 months, there were no local cancer recurrences. Three patients who underwent delayed reconstruction required revision procedures, and one required a contralateral symmetrisation procedure. One patient in the immediate reconstruction group required additional lipofilling. Over time, the mean lesion size selected for immediate local flap reconstruction increased, operative times decreased and the proportion of day case procedures increased. Our data confirm that local perforator flaps are associated with low morbidity, excellent oncological outcomes and long-term durability. The use of local flaps can increase the range of indications for BCS, reducing mastectomy rates and the associated revision and symmetrising procedures associated with them.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Retalho Perfurante , Adulto , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Estética , Feminino , Humanos , Curva de Aprendizado , Pessoa de Meia-Idade
4.
Breast J ; 26(11): 2151-2156, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176396

RESUMO

Management of the axilla in the era of neoadjuvant chemotherapy for breast cancer is evolving. The aim of this study is to determine if conventional gadolinium-enhanced breast MRI can aid in evaluation of the response to neoadjuvant chemotherapy in the axilla. A retrospective review of a prospectively maintained database of patients undergoing neoadjuvant chemotherapy for breast cancer was performed. Pre and post-neoadjuvant chemotherapy MRI reports for node-positive patients were examined in conjunction with demographic data, treatment type, and final histopathology reports. One-hundred and fourteen patients with breast cancer undergoing neoadjuvant chemotherapy were included in the study. The sensitivity of magnetic resonance imaging in detecting nodal response post-neoadjuvant chemotherapy was 33.93% and the specificity was 82.76%. Magnetic resonance imaging had a positive predictive value of 65.52% and a negative predictive value of 56.47%. MRI was found to be most specific in the detection of triple-negative cancer response. Specificity was 100% in this group and sensitivity was 75%. Magnetic resonance imaging has a relatively high specificity in detecting nodal response post-neoadjuvant chemotherapy but has a low sensitivity. Alone it cannot be relied upon to identify active axillary malignancy post-neoadjuvant chemotherapy. However, given its increased specificity among certain subgroups, it may have a role in super-selecting patients suitable for sentinel lymph node biopsy post-neoadjuvant chemotherapy.


Assuntos
Neoplasias da Mama , Gadolínio , Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Gadolínio/uso terapêutico , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela
5.
Plast Reconstr Surg Glob Open ; 8(12): e3263, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33425582

RESUMO

Local perforator flaps are used as immediate volume replacement techniques in breast conserving surgery. Here, we describe a case series of local perforator flaps used in the delayed setting to correct defects following previous breast surgery, including previous breast conservation surgery or mastectomy with reconstruction. All cases were performed in a tertiary referral breast unit between 2014 and 2020. Cases were identified using a prospectively maintained database. Indications, type of perforator flap used, immediate post-operative complications, and longer term outcomes were recorded. Fifteen cases were identified: 8 following previous breast conserving surgery and radiotherapy, 6 following mastectomy and reconstruction, and 1 for developmental breast asymmetry following childhood radiotherapy. Indications included volume deficit, contour defect, asymmetry, and capsular contracture. One patient a major complication requiring return to theater due to implant-related infection. There were no flap losses. Longer term, 2 patients underwent lipomodeling to further augment breast volume as part of a planned, staged revision. One patient subsequently elected to have bilateral breast implant exchange to increase volume. Our series shows the versatility of local perforator flaps in the correction of complex breast defects that can occur following previous breast surgery. Delayed local perforator flaps are associated with low morbidity, and further revision surgery is not commonly required.

6.
Breast J ; 26(4): 705-710, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31612568

RESUMO

In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6 months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.


Assuntos
Neoplasias da Mama , Papiloma Intraductal , Papiloma , Biópsia com Agulha de Grande Calibre , Mama , Neoplasias da Mama/cirurgia , Feminino , Humanos , Papiloma/cirurgia , Papiloma Intraductal/cirurgia , Estudos Retrospectivos
9.
Clin Breast Cancer ; 18(6): e1269-e1275, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30153977

RESUMO

INTRODUCTION: The information needs of breast cancer patients at diagnosis have been studied extensively. However, with cancer survival improving, the era of cancer care has entered a more chronic phase with an associated paucity of data related to longer term information requirements. The aim of the present study was to assess and compare the information needs of breast cancer patients during the first 5 years after the diagnosis. PATIENTS AND METHODS: A total of 105 follow-up consecutive patients presenting to a tertiary referral breast cancer center from August to October 2017 were recruited. The patients were divided into groups by the years after the diagnosis (1, 3, and 5 years). Each patient completed the Toronto Information Needs Questionnaire for Breast Cancer. RESULTS: The number of patients in each group was as follows: 23 at 1 year, 38 at 3 years, and 44 at 5 years after the initial diagnosis. The median Toronto Information Needs Questionnaire for Breast Cancer score was 4.15 on a 5-point Likert scale of breast cancer information needs (1, not important to 5, extremely important). No difference was found in the median scores at 1, 3, and 5 years. Information pertaining to the disease process was rated as most important (median, 4.50), and information regarding the psychosocial aspect of disease was ranked lowest (median, 3.75). CONCLUSION: The information needs of patients with breast cancer remain high throughout the follow-up period after the diagnosis. In an era of prolonged survival, attention to the information needs of patients at follow-up examinations is as important as at the time of diagnosis and treatment.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Informática Médica/normas , Avaliação das Necessidades , Educação de Pacientes como Assunto , Adulto , Idoso , Neoplasias da Mama/psicologia , Carcinoma Ductal de Mama/psicologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Fatores de Tempo
10.
Int J Surg ; 38: 1-8, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28011177

RESUMO

BACKGROUND: Preoperative anaemia is a risk factor for poorer postoperative outcomes and many colorectal cancer patients have iron-deficiency anaemia. The aim of this study was to assess if a preoperative iron-deficiency anaemia management protocol for elective colorectal surgery patients helps improve detection and treatment of iron-deficiency, and improve patient outcomes. MATERIALS AND METHODS: Retrospective data was collected from 95 consecutive patients undergoing colorectal cancer surgery to establish baseline anaemia correction rates and perioperative transfusion rates. A new pathway for early detection of iron-deficiency anaemia, and treatment with intravenous iron replacement, for colorectal cancer patients was then developed and implemented. Data from 81 patients was collected prospectively post-implementation to assess the impact of the pathway. RESULTS: Pre-intervention data showed anaemic patients were seventeen times more likely to require perioperative transfusion than non-anaemic patients (95% CI 1.9-151.0, p = 0.011). Post-intervention, fifteen patients with iron-deficiency were treated with either intravenous (n = 8) or oral iron (n = 7). Mean Day 3 postoperative haemoglobin levels were significantly lower in patients with uncorrected anaemia (9.5 g/dL, p = 0.004); those patients whose anaemia was corrected by iron replacement therapy preoperatively had similar postoperative results to non-anaemic patients (10.93 g/dL vs 11.4 g/dL, p = 0.781). Postoperative transfusion rates remained high at 38% in patients with uncorrected anaemia, compared to 0% in corrected anaemia and 3.5% in non-anaemic patients. CONCLUSIONS: Introduction of an iron-deficiency anaemia management pathway has resulted in improved perioperative haemoglobin levels, with a reduction in perioperative transfusion, in elective colorectal patients. Implementation of this pathway could result in similar outcomes across other categories of surgical patients.


Assuntos
Anemia Ferropriva/terapia , Transfusão de Sangue/estatística & dados numéricos , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos Eletivos , Ferro/administração & dosagem , Oligoelementos/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/complicações , Protocolos Clínicos , Neoplasias Colorretais/complicações , Estudos Controlados Antes e Depois , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
11.
Breast ; 24(1): 32-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25466502

RESUMO

Current guidelines do not recommend locoregional surgery for Stage IV breast cancer at presentation despite some studies suggesting a survival benefit. We aimed to assess outcomes in patients with Stage IV breast cancer who underwent surgery. In a cohort study of all Stage IV breast cancers diagnosed at our tertiary-referral specialist centre between 2006 and 2012, we assessed patient survival in the context of demographics, histopathology, metastatic burden, and type of surgery performed. One hundred and nine patients were included; 52 underwent surgery. Patients in the surgery group had longer 5-year-survival (p = 0.003). Survival was also significantly longer in those with just one site of metastatic disease (p < 0.001). Patients with axillary cytology positive for regional metastases were less likely to proceed to surgery. Locoregional surgery does confer a survival advantage in Stage IV breast cancer. Assessment of preoperative axillary cytology may preclude some patients from proceeding to potentially beneficial locoregional surgery.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Idoso , Axila , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Análise de Sobrevida
12.
J Surg Educ ; 71(4): 606-12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24776876

RESUMO

BACKGROUND: Journal club has become a signature pedagogy in postgraduate medical education. In this article, social learning theory, through the lens of "communities of practice" (CoP), is applied to elucidate the process of learning in journal club. MATERIALS AND METHODS: The study is a case study of a surgical journal club. Video recordings of 2 journal club sessions were followed by semistructured audio-recorded interviews with a sample of journal club participants. Thematic content analysis was performed, mapping data to themes arising based on the key tenets of CoP. RESULTS: Features of the 4 tenets of CoP learning (community, meaning, identity, and practice) were identified in both the video recordings of journal club and the participant interviews. A shared enterprise and common sense of purpose (community) was seen throughout the video recordings, but feelings of belonging to the community were much stronger for senior members (consultants/attending staff and senior trainees) compared with junior members (junior trainees and students). Experiences and perspectives were more commonly exchanged between senior trainees and consultants, with junior trainees not partaking in discussions, an example of newcomers beginning at the periphery. The main impediment to learning was found with low senior member attendance at journal club, thus limiting access to narratives of senior experience of practice and feedback. CONCLUSIONS: In attempting to improve journal club design for learning, ensuring the participation of senior community members and thus access to narratives of experience along with active engagement of junior members to allow them develop their own meaning should be incorporated into the journal club design.


Assuntos
Educação Médica Continuada/organização & administração , Cirurgia Geral/educação , Publicações Periódicas como Assunto , Ensino/métodos , Educação Médica Continuada/métodos , Humanos , Aprendizagem
13.
PLoS One ; 8(11): e78786, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24265716

RESUMO

BACKGROUND: Chronic ulcers affect roughly 60,000 Irish people, at a total cost of €600,000,000, or €10,000 per patient annually. By virtue of their chronicity, these ulcers also contribute a significant burden to tertiary outpatient vascular clinics. OBJECTIVE: We propose utilizing mobile phone technology to decentralise care from tertiary centres to the community, improving efficiency and patient satisfaction, while maintaining patient safety. METHODS: Bespoke mobile software was developed for Apples iPhone 4 platform. This allowed for the remote collection of patient images prospectively and their transmission with clinical queries, from the primary healthcare team to the tertiary centre. Training and iPhones were provided to five public health nurses in geographically remote areas of the region. Data were uploaded securely and user end software was developed allowing the review and manipulation of images, along with two way communication between the teams. Establishing reliability, patients were reviewed clinically as well as remotely, and concordance analysed. Qualitative data were collected through focus group discussion. RESULTS: From October to December 2011 eight patients (61-83 yrs, mean 75.3 yrs) with chronic venous ulceration and their five public health nurses were recruited. Data were transmitted using 3 G, Edge, GPRS and WiFi, at a mean speed of 69.03 kps. Concordance was 100% for wound bed assessment, 80% for skin integrity/colour and 60% for exudate assessment. Focus group analysis explored the concept, practicalities and future applications of the system. CONCLUSIONS: With an evolving national data network, the secure transmission of clinical images is a safe alternative to regular clinic appointments for patients with chronic venous ulceration. With further development, and packaged as a freely downloadable application, this has the potential to support the community care of chronic wounds.


Assuntos
Instituições de Assistência Ambulatorial , Telefone Celular , Características de Residência , Centros de Atenção Terciária , Atenção Terciária à Saúde/métodos , Úlcera Varicosa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Satisfação do Paciente
14.
PLoS One ; 8(4): e62232, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23638011

RESUMO

TLR signaling is a crucial component of the innate immune response to infection. MicroRNAs (miRNAs) have been shown to be upregulated during TLR signaling. Specifically, microRNA-146a (miR-146a) plays a key role in endotoxin tolerance by downregulating interleukin-1 receptor-associated kinase 1 (IRAK-1). The aim of this study was to assess the role of miR-146a in the TLR2 signaling and development of bacterial lipoprotein (BLP) self-tolerance and cross-tolerance to bacteria. Expression of miR-146a increased in a dose- and time-dependent manner in BLP-stimulated human THP-1 promonocytic cells. In BLP-tolerised cells miR-146a was even further upregulated in response to BLP re-stimulation (p<0.001). Re-stimulation of BLP-tolerised cells with heat-killed gram-negative Salmonella typhimurium (S. typhimurium), but not gram-positive Staphylococcus aureus (S. aureus), led to significant overexpression of miR-146a (p<0.05). Transfection of naive cells with a miR-146a mimic substantially suppressed TNF-α production (p<0.05). Furthermore, overexpression of miR-146a resulted in strong reduction in IRAK-1 and phosphorylated IκBα expression in naive and S. typhimurium-stimulated THP-1 cells. Collectively, miR-146a is upregulated in response to BLP and bacterial stimulation in both naive and BLP-tolerised cells. Overexpression of miR-146a induces a state analogous to tolerance in BLP-stimulated cells and therefore may represent a future target for exogenous modulation of tolerance during microbial infection and sepsis.


Assuntos
MicroRNAs/genética , Transdução de Sinais/genética , Receptor 2 Toll-Like/metabolismo , Regulação para Cima , Proteínas de Bactérias/farmacologia , Linhagem Celular , Humanos , Quinase I-kappa B/metabolismo , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Lipoproteínas/farmacologia , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/microbiologia , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Transdução de Sinais/efeitos dos fármacos , Transfecção , Regulação para Cima/efeitos dos fármacos
15.
Breast ; 22(1): 24-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22683246

RESUMO

OBJECTIVE: Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. METHODS: We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. RESULTS: Breast related topics had significantly more posts per day compared to others (mean 66.7, p < 0.01). Most posts were on media sites (65.8%). Accuracy levels were high (87.5%) but significantly lower where posted on blogs and discussion forums (p < 0.001). Anonymous posts were common (55%) and less likely to be accurate (p < 0.001). Use of discussion forums has exponentially increased over the last five years (p < 0.001). CONCLUSIONS: The internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves.


Assuntos
Neoplasias da Mama , Informação de Saúde ao Consumidor/estatística & dados numéricos , Disseminação de Informação/métodos , Internet/estatística & dados numéricos , Apoio Social , Blogging/normas , Blogging/estatística & dados numéricos , Neoplasias do Colo , Informação de Saúde ao Consumidor/métodos , Informação de Saúde ao Consumidor/normas , Feminino , Humanos , Internet/normas , Neoplasias Pulmonares , Masculino , Neoplasias da Próstata , Neoplasias Retais , Mídias Sociais/normas , Mídias Sociais/estatística & dados numéricos
16.
J Immunol ; 189(1): 347-55, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22661093

RESUMO

In addition to a well-documented role in regulating T cell-mediated immune responses, B7-H3, a newly discovered member of the B7 superfamily, has been recently identified as a costimulator in the innate immunity-mediated inflammatory response. In this study, we further report that B7-H3 participates in the development of pneumococcal meningitis in a murine model. Exogenous administration of B7-H3 strongly amplified the inflammatory response, exacerbated blood-brain barrier disruption, and aggravated the clinical disease status in Streptococcus pneumoniae-infected C3H/HeN wild-type mice. Consistent with the in vivo findings, B7-H3 substantially augmented proinflammatory cytokine and chemokine production, upregulated NF-κB p65 and MAPK p38 phosphorylation, and enhanced the nuclear transactivation of NF-κB p65 at both TNF-α and IL-6 promoters in S. pneumoniae-stimulated primary murine microglia cells. These B7-H3-associated in vitro and in vivo effects appeared to be dependent on TLR2 signaling, as B7-H3 almost completely lost its amplifying actions in both TLR2-deficient microglial cells and TLR2-deficient mice. Furthermore, administration of the anti-B7-H3 mAb (MIH35) attenuated the inflammatory response and ameliorated blood-brain barrier disruption in S. pneumoniae-infected wild-type mice. Collectively, our results indicate that B7-H3 plays a contributory role in the development of S. pneumoniae infection-induced bacterial meningitis.


Assuntos
Antígenos B7/fisiologia , Mediadores da Inflamação/fisiologia , Meningite Pneumocócica/imunologia , Meningite Pneumocócica/patologia , Receptor 2 Toll-Like/fisiologia , Animais , Antígenos B7/administração & dosagem , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/microbiologia , Barreira Hematoencefálica/patologia , Células Cultivadas , Mediadores da Inflamação/administração & dosagem , Meningite Pneumocócica/microbiologia , Camundongos , Camundongos Endogâmicos C3H , Microglia/metabolismo , Microglia/microbiologia , Microglia/patologia , Distribuição Aleatória , Transdução de Sinais/imunologia , Streptococcus pneumoniae/imunologia , Receptor 2 Toll-Like/deficiência
17.
World J Surg Oncol ; 10: 72, 2012 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-22540955

RESUMO

BACKGROUND: Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. METHODS: We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. RESULTS: There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. CONCLUSIONS: Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the nonemergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. TRIAL REGISTRATION: ISRCTN94715414.


Assuntos
Drenagem , Complicações Pós-Operatórias , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adolescente , Adulto , Feminino , Seguimentos , Doença de Graves/etiologia , Doença de Hashimoto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Ultrassom , Adulto Jovem
18.
Ann Surg Oncol ; 19(9): 3035-41, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22476755

RESUMO

BACKGROUND: Diagnosis of breast cancer recurrence can be difficult as a result of the presence of scar tissue in the breast. Magnetic resonance imaging (MRI) may be superior to traditional imaging in diagnosis of recurrence because of its ability to differentiate malignancy from scarring. Current guidelines on investigation of suspected breast cancer recurrence recommend MRI when other investigations have equivocal findings. We performed the first systematic review on this topic. METHODS: Literature search revealed 35 potentially relevant studies; 10 were included in final analysis. Included were clinical studies comparing MRI with another diagnostic modality for diagnosis of breast cancer recurrence, with at least 10 patients, in the English language. Data extraction focused on sensitivity and specificity of standard diagnostic modalities and MRI for diagnosis of local disease recurrence. RESULTS: In total 494 patients were assessed across 10 studies; all were case series. Sensitivity of MRI for detection of recurrence ranged 75-100 %, while specificity ranged 66.6-100 %. Both sensitivity and specificity increased when MRI was performed after a longer time interval from the original surgery, although the longest follow-up reported was only 36 months. A negative MRI can avoid the need for further biopsy. CONCLUSIONS: Available data are based on clinically heterogeneous case series and superiority over standard triple assessment for breast cancer recurrence has not been proven. At present, MRI cannot be recommended in the routine diagnostic assessment for breast cancer recurrence but has a potentially useful role as a second-line investigation. A negative MRI is more useful than a positive MRI as positive MRIs require further investigation.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Feminino , Humanos , Sensibilidade e Especificidade
19.
J Leukoc Biol ; 91(5): 721-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22389313

RESUMO

Endotoxin tolerance is a phenomenon where cells show reduced responsiveness toward repeated endotoxin stimulation. Regulation of tolerance occurs at multiple levels of the cell signaling cascade, and many of these levels are potentially regulated by miRNA, which are a class of small RNA that bind to mRNA to down-regulate gene expression at the post-transcriptional level. Roles have been identified for miR-146a, miR-221, miR-579, miR-125b, miR-155, let-7e, and miR-98 in regulating the TLR4 signaling pathway during the development of endotoxin tolerance at receptor, signaling pathway, and gene transcription and translational levels. miRNA represent exciting, new potential targets in attempts to exogenously modulate development of endotoxin tolerance.


Assuntos
Tolerância a Medicamentos/genética , Endotoxinas/farmacologia , MicroRNAs/efeitos dos fármacos , MicroRNAs/genética , Transcrição Gênica/efeitos dos fármacos , Animais , Humanos , Transdução de Sinais
20.
Ann Vasc Surg ; 26(5): 649-54, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22285348

RESUMO

BACKGROUND: Temporal artery biopsy (TAB) is performed during the diagnostic workup for giant cell arteritis (GCA), a vasculitis with the potential to cause irreversible blindness or stroke. However, treatment is often started on clinical grounds, and TAB result frequently does not influence patient management. The aim of this study was to assess the need for TAB in cases of suspected GCA. METHODS: We performed a retrospective review of 185 TABs performed in our institution from 1990 to 2010. Patients were identified through the Hospital In-Patient Enquiry database and theater records. Clinical findings, erythrocyte sedimentation rate, steroid treatment preoperatively, American College of Rheumatology (ACR) criteria for GCA score, biopsy result, and follow-up were recorded. RESULTS: Fifty-eight (31.4%) biopsies were positive for GCA. Presence of jaw claudication (P = 0.001), abnormal fundoscopy (P = 0.001), and raised erythrocyte sedimentation rate (P = 0.001) were significantly associated with GCA. The strongest association with positive biopsy was seen with the prebiopsy ACR score (P < 0.001). Twenty-four (13.7%) patients had undergone biopsy, despite no potential for meeting ACR criteria preoperatively. None of these were positive. Overall, 29 (16.4%) patients had management altered by TAB result. CONCLUSIONS: Our results confirm that TAB does not affect management in the majority of patients with suspected GCA. We conclude that TAB has benefit only for patients who score 2 or 3 on the ACR criteria for GCA without biopsy.


Assuntos
Arterite de Células Gigantes/diagnóstico , Artérias Temporais/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Sedimentação Sanguínea , Distribuição de Qui-Quadrado , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Glucocorticoides/uso terapêutico , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oftalmoscópios , Oftalmoscopia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
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