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PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .
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Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadjuvante , Ftalazinas , Piperazinas , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas/uso terapêutico , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Genes BRCA1 , Genes BRCA2 , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Resposta Patológica Completa , Ftalazinas/administração & dosagem , Ftalazinas/uso terapêutico , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Estudos Prospectivos , Análise de Sobrevida , Fatores de Tempo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/cirurgia , Adolescente , Adulto JovemRESUMO
SUMMARYStreptococcus dysgalactiae subsp. equisimilis (SDSE) is an increasingly recognized cause of disease in humans. Disease manifestations range from non-invasive superficial skin and soft tissue infections to life-threatening streptococcal toxic shock syndrome and necrotizing fasciitis. Invasive disease is usually associated with co-morbidities, immunosuppression, and advancing age. The crude incidence of invasive disease approaches that of the closely related pathogen, Streptococcus pyogenes. Genomic epidemiology using whole-genome sequencing has revealed important insights into global SDSE population dynamics including emerging lineages and spread of anti-microbial resistance. It has also complemented observations of overlapping pathobiology between SDSE and S. pyogenes, including shared virulence factors and mobile gene content, potentially underlying shared pathogen phenotypes. This review provides an overview of the clinical and genomic epidemiology, disease manifestations, treatment, and virulence determinants of human infections with SDSE with a particular focus on its overlap with S. pyogenes. In doing so, we highlight the importance of understanding the overlap of SDSE and S. pyogenes to inform surveillance and disease control strategies.
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Group A Streptococcal M-related proteins (Mrps) are dimeric α-helical-coiled-coil cell membrane-bound surface proteins. During infection, Mrp recruit the fragment crystallizable region of human immunoglobulin G via their A-repeat regions to the bacterial surface, conferring upon the bacteria enhanced phagocytosis resistance and augmented growth in human blood. However, Mrps show a high degree of sequence diversity, and it is currently not known whether this diversity affects the Mrp-IgG interaction. Herein, we report that diverse Mrps all bind human IgG subclasses with nanomolar affinity, with differences in affinity which ranged from 3.7 to 11.1 nM for mixed IgG. Using surface plasmon resonance, we confirmed Mrps display preferential IgG-subclass binding. All Mrps were found to have a significantly weaker affinity for IgG3 (p < 0.05) compared to all other IgG subclasses. Furthermore, plasma pulldown assays analyzed via Western blotting revealed that all Mrp were able to bind IgG in the presence of other serum proteins at both 25 °C and 37 °C. Finally, we report that dimeric Mrps bind to IgG with a 1:1 stoichiometry, enhancing our understanding of this important host-pathogen interaction.
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Proteínas de Bactérias , Streptococcus pyogenes , Humanos , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Imunoglobulina G/metabolismo , Streptococcus pyogenes/metabolismoRESUMO
Protein glycosylation is a ubiquitous process observed across all domains of life. Within the human pathogen Acinetobacter baumannii, O-linked glycosylation is required for virulence; however, the targets and conservation of glycosylation events remain poorly defined. In this work, we expand our understanding of the breadth and site specificity of glycosylation within A. baumannii by demonstrating the value of strain specific glycan electron-transfer/higher-energy collision dissociation (EThcD) triggering for bacterial glycoproteomics. By coupling tailored EThcD-triggering regimes to complementary glycopeptide enrichment approaches, we assessed the observable glycoproteome of three A. baumannii strains (ATCC19606, BAL062, and D1279779). Combining glycopeptide enrichment techniques including ion mobility (FAIMS), metal oxide affinity chromatography (titanium dioxide), and hydrophilic interaction liquid chromatography (ZIC-HILIC), as well as the use of multiple proteases (trypsin, GluC, pepsin, and thermolysis), we expand the known A. baumannii glycoproteome to 33 unique glycoproteins containing 42 glycosylation sites. We demonstrate that serine is the sole residue subjected to glycosylation with the substitution of serine for threonine abolishing glycosylation in model glycoproteins. An A. baumannii pan-genome built from 576 reference genomes identified that serine glycosylation sites are highly conserved. Combined this work expands our knowledge of the conservation and site specificity of A. baumannii O-linked glycosylation.
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Acinetobacter baumannii , Glicoproteínas , Polissacarídeos , Proteômica , Serina , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Acinetobacter baumannii/química , Glicosilação , Serina/metabolismo , Serina/química , Proteômica/métodos , Glicoproteínas/metabolismo , Glicoproteínas/química , Glicoproteínas/genética , Polissacarídeos/metabolismo , Polissacarídeos/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Glicopeptídeos/análise , Glicopeptídeos/química , Glicopeptídeos/metabolismo , Cromatografia LíquidaRESUMO
OBJECTIVE: Inframalleolar disease is present in most diabetic patients presenting with tissue loss. Inframalleolar (pedal) artery disease and pedal medial arterial calcification (pMAC) are associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). This study aimed to examine the impact of pMAC on the outcomes after isolated inframalleolar (pedal artery) interventions. METHODS: A database of lower extremity endovascular intervention for patients with tissue loss between 2007 and 2022 was retrospectively queried. Patients with CLTI were selected, and those undergoing isolated inframalleolar intervention on the dorsalis pedis and medial and lateral tarsal arteries and who had foot x-rays were identified. X-rays were assessed blindly for pMAC and scored on a scale of 0 to 5. Patients with concomitant superficial femoral artery and tibial interventions were excluded. Intention to treat analysis by the patient was performed. Amputation-free survival (survival without major amputation) was evaluated. RESULTS: A total of 223 patients (51% female; 87% Hispanic; average age, 66 years; 323 vessels) underwent isolated infra-malleolar intervention for tissue loss. All patients had diabetes, 96% had hypertension, 79% had hyperlipidemia, and 63% had chronic renal insufficiency (55% of these were on hemodialysis). Most of the patients had Wound, Ischemia, and foot Infection (WIfI) stage 3 disease and had various stages of pMAC: severe (score = 5) in 48%, moderate (score = 2-4) in 31%, and mild (score = 0-1) in 21% of the patients. Technical success was 94%, with a median of one vessel treated per patient. All failures were in severe pMAC. Overall, major adverse cardiovascular events was 0.9% at 90 days after the procedure. Following the intervention, most patients underwent a planned forefoot amputation (single digit, multiple digits, ray amputation, or trans-metatarsal amputation). WIfI ischemic grade was improved by 51%. Wound healing at 3 months was 69%. Those not healing underwent below-knee amputations. The overall 5-year amputation-free survival rate was 35% ± 9%. The severity of pMAC was associated with decreased AFS. CONCLUSIONS: Increasing severity of pMAC influences the technical and long-term outcomes of infra-malleolar intervention in diabetes. Severe pMAC is associated with amputation and should be considered as a variable in the shared decision-making of diabetic patients with CLTI.
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Amputação Cirúrgica , Isquemia Crônica Crítica de Membro , Procedimentos Endovasculares , Salvamento de Membro , Doença Arterial Periférica , Calcificação Vascular , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/mortalidade , Calcificação Vascular/complicações , Calcificação Vascular/terapia , Calcificação Vascular/cirurgia , Pessoa de Meia-Idade , Fatores de Risco , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Isquemia Crônica Crítica de Membro/cirurgia , Isquemia Crônica Crítica de Membro/complicações , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/terapia , Bases de Dados Factuais , Fatores de Tempo , Resultado do Tratamento , Medição de Risco , Intervalo Livre de Progressão , Isquemia/cirurgia , Isquemia/mortalidade , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Failure to achieve timely arteriovenous fistulae (AVFs) utilization due to excessive depth (>6 mm) remains an ongoing concern for dialysis access. This study evaluates the outcomes of radiocephalic (RCF) and brachiocephalic (BCF) fistula elevation required for access utilization. METHODS: A retrospective review of all patients undergoing first-time autologous access over 10 years was undertaken. RCF and BCF were analyzed, and cases of initial access failure due to depth alone were selected for study. Primary and staged brachio-basilic AVF were excluded. Outcomes of early thrombosis, line placement, maturation (successful progression to hemodialysis [HD), reintervention, and functional dialysis (continuous HD for 3 consecutive months) were examined. RESULTS: From January 2012 to December 2022, 1733 patients (67% female; mean age, 61 ± 14 years) underwent autologous AVF placement. Of these, 298 patients (17%) had depth-related AVF access issues (BCF, 71% and RCF, 29%). Nineteen percent of these AVFs underwent a primary balloon-assisted maturation (BAM), and 2% had side branch coil embolization before consideration for elevation. The average time to intervention for depth was 11 ± 4 weeks after primary creation. During elevation, side branch ligation occurred in 38% of cases, and 15% underwent intraoperative BAM, The pre-elevation depth was 8.2 ± 3.1 mm, and the mean post-elevation depth was 4.7 ± 2.9 mm (P = .002). Early thrombosis (<18 days) occurred in 4% of cases. There was no mortality, and the 30-day major adverse cardiac event rate was 2%, with a 30-day morbidity of 5%, which was driven by wound issues. Six percent of the AVFs underwent follow-up BAM within 3 months. Mean maturation of the AVFs was 74% ± 3% vs 72% ± 3% (P = .58) for the elevation vs no-elevation groups at 24 weeks, respectively. However, there was an increase in tunneled central line placement in pre-emptive fistula patients due to the delay in maturation (elevation, 17% vs no-elevation, 8%; P = .008). There was a mean successful access time of 6 ± 3 weeks after elevation (16 ± 4 weeks after access creation). There was a median of 2.4 secondary interventions per year after elevation compared with a median of 2.7 secondary interventions per year without elevation. Mean access functionality was 68% ± 8% vs 75% ± 8% at 3 years for the elevation vs no-elevation groups, respectively (P = .25). CONCLUSIONS: Elevation of deep BCF and RCF occurs late after placement but can be successfully achieved with low morbidity and satisfactory long-term functionality. It results in an increase in tunneled central line placement in pre-emptive fistula patients. Elevation is a valuable adjunct to AVF maturation and enhances an autologous access policy.
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Derivação Arteriovenosa Cirúrgica , Diálise Renal , Humanos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Idoso , Resultado do Tratamento , Artéria Radial/cirurgia , Fatores de Risco , Grau de Desobstrução Vascular , Embolização Terapêutica/efeitos adversos , Artéria Braquial/cirurgia , Veias Braquiocefálicas/cirurgia , Veias Braquiocefálicas/diagnóstico por imagem , Extremidade Superior/irrigação sanguínea , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/terapia , Oclusão de Enxerto Vascular/fisiopatologiaRESUMO
AIM: Obesity has a significant impact on all-cause mortality rate and overall health care resource use (HCRU). These outcomes are also strongly linked to age, sex and local deprivation of the population. We aimed to establish the lifetime costs of obesity by demographic group/geographic area using published mortality rates and HCRU use for integrated care boards (ICB) in England in the context of costs of therapeutic intervention. METHODS: Population and expected mortality rates by age, sex and deprivation were obtained from national data. Obesity class prevalence was taken from the health of the nation study. The published impact of obesity by age, group, sex and deprivation on mortality and HCRU were applied to estimate life years lost and lifetime HCRU [by sex, age band and body mass index (BMI) class for each ICB]. The year 2019 was chosen as the study basis data to avoid influences of COVID-19 pandemic on obesity rates with application of 2022/23 HCRU values. Outcomes including prevalence, deaths, life years lost, HCRU and lifetime HCRU were compared by age and sex groups across four BMI classes normal/underweight (BMI <25 kg/m2 ), overweight (25-29.9 kg/m2 ), obese class I and II (30-39.9 kg/m2 ), and obese class III (≥40), with benchmarking being set against all population being BMI <25 kg/m2 overall and by each of the 42 ICBs. We also associated future life with deaths to provide an estimate of 'future life years lost' occurring each year. RESULTS: Total population aged >16 years was 45.4 million (51% female). PREVALENCE: 13.7 million (28% of the total adult population) had a BMI ≥30 mg/m2 and BMI ≥40 kg/m2 were 1.50 million (12%) of these 1.0 million (68%) were female and of these 0.6 million 40% were women aged 16-49 years. In addition, 35% of those with a BMI ≥40 kg/m2 were in the top deprivation quintile (i.e. overall 20%). Mortality was based on expected deaths of 518K/year, and modelling suggested that if a BMI <25 kg/m2 was achieved in all individuals, the death rate would fall by 63K to 455K/year for the English population (12% reduction). For those with a BMI ≥40 kg/m2 the predicted reduction was 12K deaths (54% lower); while in those aged 16-49 years with a BMI ≥40 kg/m2 72% of deaths were linked to obesity. For future life years lost, we estimated 2.5 years were lost in people with BMI 30-39.9 kg/m2 6.7 years when BMI ≥40 kg/m2 . However, for those aged 16-49 years with a BMI ≥40 kg/m2 , 8.3 years were lost. HCRU, for weight reduction, the annual HCRU decrease from BMI ≥40 kg/m2 to BMI 30-39.9 kg/m2 was £342 per person and from BMI 30-39.9 to 25-29.9 kg/m2 the reduction was £316/person. However, lifetime costs were similar because of reduced life expectancy for obese individuals. In quality adjusted life years (QALY), overall, 791 689 future life years were lost (13.1% of all) in people with BMI ≥25 kg/m2 and were related to excess weight. When the NICE £30 000 per QALY value was applied to the estimated total 791 689 future life years lost then the potential QALY value reduction lost was equivalent to £24 billion/year or £522/person in the obese population. For morbidly obese men and women the potential QALY value lost was £2864/person/year. Regarding geography, across the 42 ICBs, we observed significant variation in the prevalence of BMI ≥40 (1.8%-4.3%), excess mortality (11.6%-15.4%) and HCRU linked to higher BMI (7.2%-8.8%). The areas with the greatest impact on HCRU were in the north-west, north-east and Midlands of England, while the south shows less impact. CONCLUSION: The expected increases in annual HCRU because of obesity, when considered over a lifetime, are being mitigated by the increased mortality of obese individuals. Our data suggest that simple short-term HCRU reduction brought about through BMI reduction will be insufficient to fund additional specialist weight reduction interventions. The HRCUs associated with BMI are not in most cases related to short-term health conditions. They are a cumulative result over a number of years, so for age 16-49 years reducing BMI from ≥40 to 30-39.9 kg/m2 might show an annual decrease in HCRU/person by £325/year for women and £80/year for men but this might not have immediately occurred within that year. For those aged >70 years reducing BMI from ≥40 to 30-39.9 kg/m2 might show an annual decrease in HCRU/person by £777/year for women and £796/year for men but also may not be manifest within that year. However, for the morbidly obese men and women, the potential QALY value lost was £2864 per person per year with the potential for these funds to be applied to intensive weight management programmes, including pharmacotherapy.
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Obesidade Mórbida , Adulto , Masculino , Humanos , Feminino , Obesidade Mórbida/complicações , Pandemias , Anos de Vida Ajustados por Qualidade de Vida , Inglaterra/epidemiologia , Redução de PesoRESUMO
OBJECTIVES: The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. RESULTS: The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. CONCLUSION: Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. CLINICAL RELEVANCE STATEMENT: These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. KEY POINTS: An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.
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PURPOSE: Percutaneous renal artery revascularization for hypertension and renal dysfunction remains common. The frequency, cause, and outcomes of anatomic injury associated with renal intervention are poorly delineated. This study aims to determine the frequency of acute anatomic renal injury after renal artery interventions, identify factors associated with anatomic renal injury, and determine whether anatomic renal injury related to renal intervention is associated with late adverse clinical events. METHODS: A retrospective analysis of patients undergoing renal artery interventions for atherosclerotic renal artery disease between 2002 and 2022 was performed. Acute anatomic renal injury encompassed renal artery dissection, renal artery perforation, acute occlusion, renal parenchymal infarction, and renal parenchymal perforation. Freedom from renal-related morbidity (increase in persistent creatinine >20% of baseline, progression to hemodialysis, death from renal-related causes) and patient survival were measured. RESULTS: A total of 968 patients underwent 1309 renal artery interventions: 47% for hypertension, 25% for hypertension associated with chronic renal dysfunction, and 28% for chronic renal dysfunction. An acute anatomic renal injury occurred in 5.9% of the patients. The occurrence of an anatomic injury was associated with a significant decrement in freedom from renal-related morbidity (79±2% vs 55±8%, no-injury vs injury group, mean±standard error of the mean; p=0.003) and markedly decreased survival at 5 year follow-up (78±3% vs 48±8%; p=0.002). No factor was identified that predicted anatomic injury. In those patients with anatomic injury, perforation was associated with decreased survival, while estimated glomerular filtration rate <60, resistive index >0.8, and dissection were associated with a lack of retained renal benefit. CONCLUSION: Acute anatomic renal injury occurs in approximately 6% of patients undergoing percutaneous renal artery intervention and is a negative predictor of survival and is associated with subsequent renal failure, need for dialysis, and death from renal-related causes. CLINICAL IMPACT: Acute anatomic renal injury occurs in approximately 5% of patients undergoing percutaneous renal artery intervention. Modern endovascular interventions allow for the control and remediation of injuries in the majority of cases with an overall low mortality and morbidity. There is a significant early occlusion of renal arteries following the injury within 1 month. In the long term, the occurrence of injury is a negative predictor of survival and is associated with subsequent renal failure, the need for dialysis, and death from renal-related causes.
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OBJECTIVE: This study aimed to measure the value of increasing lung cancer screening rates for high-risk individuals and its impact on health disparities. METHODS: The model estimated changes in health economic outcomes if low-dose computed tomography screening increased from current to 100% compliance, following clinical guidelines. Current low-dose computed tomography screening rates were estimated by income, education, and race, using 2017-2019 Behavioral Risk Factor Surveillance System data. The model contained a decision tree module to segment the population by screening outcomes and a Markov chain module to estimate cancer progression over time. Model parameters included information on survival, quality of life, and costs related to cancer diagnosis, treatment, and adverse events. Distributional cost-effectiveness analysis estimated the net monetary value from reduced health disparities-measured using quality-adjusted life expectancy-across income, education, and race groups. Outcomes were assessed over 30 years. RESULTS: Lung cancer screening eligibility using US Preventive Services Task Force guidelines was higher for individuals with income <$15 000 (47.2%) and without a high-school education (46.1%) than individuals with income >$50 000 (16.6%) and with a college degree (13.5%), respectively. Increasing lung cancer screening to 100% compliance was cost-effective ($64 654 per quality-adjusted life-year) and produced economic value by up to $560 per person ($182.1 billion for United States overall). Up to 32.2% of the value was due to reductions in health disparities. CONCLUSIONS: Significant value in increasing lung cancer screening rates derived from reducing health disparities. Policy makers and clinicians may not be appropriately prioritizing cancer screening if value from reducing health disparities is unconsidered.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Estados Unidos , Qualidade de Vida , Programas de Rastreamento , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Análise Custo-Benefício , Tomografia Computadorizada por Raios X/métodos , Desigualdades de SaúdeRESUMO
BACKGROUND: Massive pulmonary embolism (MPE) carries significant 30-day mortality risk, and a change in societal guidelines has promoted the increasing use of extracorporeal membrane oxygenation (ECMO) in the immediate management of MPE-associated cardiovascular shock. This narrative review examines the current status of ECMO in MPE. METHODS: A literature review was performed from 1982 to 2022 searching for the terms "Pulmonary embolism" and "ECMO," and the search was refined by examining those publications that covered MPE. RESULTS: In the patient with MPE, veno-arterial ECMO is now recommended as a bridge to interventional therapy. It can reliably decrease right ventricular overload, improve RV function, and allow hemodynamic stability and restoration of tissue oxygenation. The use of ECMO in MPE has been associated with lower mortality in registry reviews, but there has been no significant difference in outcomes between patients treated with and without ECMO in meta-analyses. Applying ECMO is also associated with substantial multisystem morbidity due to systemic inflammatory response, bleeding with coagulopathy, hemorrhagic stroke, renal dysfunction, and acute limb ischemia, which must be factored into the outcomes. CONCLUSIONS: The application of ECMO in MPE should be combined with an aggressive interventional pulmonary interventional program and should strictly adhere to the current selection criteria.
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Oxigenação por Membrana Extracorpórea , Embolia Pulmonar , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Embolia Pulmonar/terapia , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/mortalidade , Embolia Pulmonar/diagnóstico por imagem , Resultado do Tratamento , Fatores de Risco , Hemodinâmica , Recuperação de Função Fisiológica , Tomada de Decisão Clínica , Medição de RiscoRESUMO
BACKGROUND: Arteriovenous accesses develop aneurysms (FA) during their active use, resulting in pain, erosion, bleeding, and difficulty in cannulation. This study aims to evaluate the outcomes of open and endovascular management of single FA in arteriovenous fistulas (AVF). METHODS: A retrospective review of all upper extremity primary AVFs over 12 years was undertaken at a single center. Patients undergoing elective open and endovascular repair of a single FA were identified. Thirty-day outcomes, cannulation failure, line placement, re-intervention, and functional dialysis (continuous hemodialysis) for 3 consecutive months were examined. RESULTS: Three hundred and seventy nine patients presented with a single FA that met the requirements for intervention: 126 (33%) underwent endovascular repair, and the remainder 253 (67%) underwent open repair. Preoperative fistulogram identified anatomically significant issues in 91% of the cases, and these were treated by balloon angioplasty: 10% within the fistula tract, 44% within the outflow tract, and 47% in the central veins. In open repair, 57% underwent plication, 35% underwent resection and re-anastomosis, and the remainder (8%) underwent interposition grafting. In endovascular repair, successful placement of a stent was achieved in all cases with 1 ± 2 (mean ± standard deviation [SD]) covered stents (diameter: 6 -8 mm) placed, achieving successful exclusion of the FA. The combination of early thrombosis and cannulation failures led to the greater need for a tunneled central line in endovascular repair (6.5% vs. 2.4%; endovascular versus open repair; P = 0.04). As a result, the mean time for establishing renewed access in the index AVF was significantly higher in endovascular repair (2 ± 3 vs. 2 ± 2 weeks, mean ± SD; endovascular open repair versus open repair; P = 0.001). In follow-up, there were more secondary interventions per year in the endovascular compared to open repair groups (3.1 vs. 1.4 secondary interventions per year; endovascular versus open repair; P = 0.04). Median functional dialysis durations were superior in the open repair (48 ± 6%, mean + standard error) compared to the endovascular repair at 5 years. (26 ± 7%; P = 0.03). CONCLUSIONS: Open repair results in a more rapid return to access use, lower need for a tunneled central line, lower secondary re-intervention rates, and superior functional dialysis durations compared to endovascular repair. Open FA repair should be considered for symptomatic single FA repairs before endovascular FA repair.
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Angioplastia com Balão , Aneurisma da Aorta Abdominal , Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Correção Endovascular de Aneurisma , Oclusão de Enxerto Vascular , Grau de Desobstrução Vascular , Aneurisma da Aorta Abdominal/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Fístula Arteriovenosa/cirurgia , Diálise Renal , Estudos RetrospectivosRESUMO
BACKGROUND: Infra-popliteal interventions for chronic limb-threatening ischemia (CLTI) can be impacted by the morphology of the tibial vessels. The aim of this study was to examine the impact of a novel morphology-driven classification on the outcomes of isolated tibial intervention for CLTI. METHODS: A database of patients undergoing isolated tibial interventions for CLTI at a single center between 2010 and 2020 was retrospectively queried. Patients with isolated infra-popliteal disease were identified, and their anatomy was scored as present or absent for lesion calcification (1 point), target vessel diameter<3.0 mm (1 point), lesion length>300 mm (1 point), and poor pedal runoff score (1 point). Patients were then divided into 3 groups: low risk (0 or 1 points), moderate risk (2 points), and high risk (3 or 4 points). Intention to treat analysis by the patient was performed. Limb-based patency (the absence of reintervention, occlusion, critical stenosis [>70%], or hemodynamic compromise with ongoing symptoms of CLTI as it related to the patency of the preoperatively determined target artery pathway) was assessed. Patient-oriented outcomes of amputation-free survival (AFS; survival without major amputation) and freedom from major adverse limb events (MALE; above ankle amputation of the index limb or major reintervention: new bypass graft, jump/interposition graft revision) were evaluated. RESULTS: 1,607 patients (55% male, average age 60 years, 3,846 vessels) underwent tibial intervention for CLTI. The majority of the patients were diabetic and of Hispanic origin. Morphologically, 27%, 31%, and 42% of the vessels were categorized as low risk, moderate risk, and high risk, respectively. There was a significant worsening of the infra-popliteal Global Limb Anatomic Staging System (GLASS) grading as the morphological risk increased. The 30-day major adverse cardiac events (MACE) were equivalent across the groups and were under the stated objective performance goal (OPG) of ≤10%. In contrast, both the 30-day MALE and the 30-day major amputations were significantly different across the groups, with the low-risk group remaining under the OPG of ≤9% and ≤4%, respectively, while the moderate risk and high risk exceeded the goal threshold. For the OPG, freedom from MALE was 60 ± 5%, 46 ± 5%, and 22 ± 9% at 5 years for low-, moderate-, and high-risk groups, respectively (mean ± standard error of the mean; P = 0.008). Overall AFS was 55 ± 5%, 37 ± 6%, and 18 ± 7% at 5 years for low-, moderate-, and high-risk groups, respectively (mean ± standard error of the mean; P = 0.003). CONCLUSIONS: Tibial anatomic morphology impacts isolated tibial endovascular intervention with adverse morphology associated with poorer short- and long-term outcomes. Risk stratification based on anatomic predictors should be an additional consideration as one intervenes on infra-popliteal vessels for CLTI.
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Amputação Cirúrgica , Isquemia Crônica Crítica de Membro , Bases de Dados Factuais , Salvamento de Membro , Doença Arterial Periférica , Artérias da Tíbia , Grau de Desobstrução Vascular , Humanos , Masculino , Estudos Retrospectivos , Feminino , Idoso , Fatores de Risco , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/cirurgia , Artérias da Tíbia/fisiopatologia , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/cirurgia , Fatores de Tempo , Pessoa de Meia-Idade , Medição de Risco , Isquemia Crônica Crítica de Membro/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Intervalo Livre de Progressão , Idoso de 80 Anos ou mais , Resultado do Tratamento , Isquemia/fisiopatologia , Isquemia/cirurgia , Isquemia/diagnóstico por imagem , Isquemia/terapiaRESUMO
Approximately 3% of all patients presenting with Thoracic Outlet Syndrome have a venous etiology (vTOS), which is considered "effort thrombosis". These patients will present with symptomatic deep venous thrombosis or focal subclavian vein (SCV) stenosis. Endovascular management of vTOS occurs in several phases: diagnostic, preoperative therapeutic intervention before decompression, postoperative interventions after decompression, and delayed interventions in the follow-up after decompression. In the diagnostic phase, dynamic SCV venography can establish functional vTOS. Approximately 4,000 patients have been treated for vTOS and reported in the literature since 1970. Declotting of the SCV was followed by surgical decompression in 53% of patients, while in the remainder, surgical decompression alone (18%), endovascular intervention alone (15%), or conservative therapy with anticoagulation (15%) was performed. The initial intervention was predominantly catheter-directed thrombolysis, with <10% of cases undergoing concomitant balloon angioplasty. 93% of cases were successful. In the postoperative phase, balloon angioplasty was performed to correct residual intrinsic SCV disease after vTOS decompression in under 15% of cases. Stents were rarely deployed. Symptom relief was reported as 94 ± 12% (mean ± SD) and 90 ± 23%, respectively for declotting with decompression and declotting alone. In the delayed phase, balloon angioplasty was performed in under 15% of cases to re-establish patency.
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BACKGROUND: Hip transposition surgery after surgical resection of large pelvic tumours is a well-established alternate to endoprosthetic reconstruction. The major goals of surgery are to ensure adequate resection margins with limb salvation, albeit with acceptable levels of morbidity. While surveillance is aimed at diagnosing local recurrence or distant metastasis primarily, other complications may occasionally be seen.The aim of this study was to assess incidence of avascular necrosis (AVN) in the preserved native femoral heads after hip transposition surgery for periacetabular malignancies, also known as hanging hip surgery. PATIENTS AND METHODS: Patient records and follow-up imaging of 22 patients who had undergone hanging hip surgery from 1999 to 2020 were retrospectively analysed to assess for any probable causes of AVN. RESULTS: Of the 22 patients, 5 (22.7%) had developed AVN on follow-up with a mean time of onset of about 10.5 months from surgery (5 months-2 years). A review of the patient demographics, surgical notes, preoperative management did not offer any clues as to the cause of AVN in these patients. Osteopenia was the most common radiological finding (59%) in most patients, but this also did not herald AVN onset. CONCLUSIONS: The theory that loss of major vascular supply to the femoral head from capsular disruption during hip transposition surgery would lead to AVN in most patients did not hold true as AVN occurred in a small number of patients.
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Introduction: Titanium-based implants can be used to fill voids in bone reconstruction surgery. Through additive manufacturing (AM), it is possible to produce titanium implants with osteoconductive properties such as high porosity and low stiffness. AM facilitates a level of design flexibility and personalization that is not feasible with traditional techniques. Methods: In this study, osseointegration into titanium alloy (Ti-6Al-4V) lattices was investigated for 12 weeks post-implantation using a novel bicortical load-bearing ovine model. The objective was to assess the safety and efficacy of AM-fabricated implants using two lattice structures of contrasting stiffness spanning the full width of the femoral condyle. Results: This was achieved by evaluating implant osseointegration and bone-implant contact properties by histomorphometry, scoring local implant tissue responses via histopathology, and micro-computed tomography reconstruction. Discussion: We found that Ti-6Al-4V implants facilitated widespread and extensive osseointegration, with bone maturation ongoing at the conclusion of the trial period. Following the implantation period, no adverse clinical indications that could be directly ascribed to the presence of the implanted device were identified, as determined by macroscopic and microscopic observation.
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Bacterial species often consist of strains with variable gene content, collectively referred to as the pangenome. Variations in the genetic makeup of strains can alter bacterial physiology and fitness. To define biologically relevant genes of a genome, genome-wide transposon mutant libraries have been used to identify genes essential for survival or virulence in a given strain. Such phenotypic studies have been conducted in four different genotypes of the human pathogen Streptococcus pyogenes, yet challenges exist in comparing results across studies conducted in different genetic backgrounds and conditions. To advance genotype to phenotype inferences across different S. pyogenes strains, we built a pangenome database of 249 S. pyogenes reference genomes. We systematically re-analyzed publicly available transposon sequencing datasets from S. pyogenes using a transposon sequencing-specific analysis pipeline, Transit. Across four genetic backgrounds and nine phenotypic conditions, 355 genes were essential for survival, corresponding to ~24% of the core genome. Clusters of Orthologous Genes (COG) categories related to coenzyme and lipid transport and growth functions were overrepresented as essential. Finally, essential operons across S. pyogenes genotypes were defined, with an increased number of essential operons detected under in vivo conditions. This study provides an extendible database to which new studies can be added, and a searchable html-based resource to direct future investigations into S. pyogenes biology.IMPORTANCEStreptococcus pyogenes is a human-adapted pathogen occupying restricted ecological niches. Understanding the essentiality of genes across different strains and experimental conditions is important to direct research questions and efforts to prevent the large burden of disease caused by S. pyogenes. To this end we systematically reanalyzed transposon sequencing studies in S. pyogenes using transposon sequencing-specific methods, integrating them into an extendible meta-analysis framework. This provides a repository of gene essentiality in S. pyogenes which was used to highlight specific genes of interest and for the community to guide future phenotypic studies.
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Elementos de DNA Transponíveis , Genes Essenciais , Genoma Bacteriano , Streptococcus pyogenes , Streptococcus pyogenes/genética , Genes Essenciais/genética , Genoma Bacteriano/genética , Elementos de DNA Transponíveis/genética , Humanos , Genótipo , Virulência/genética , Infecções Estreptocócicas/microbiologia , Fenótipo , Óperon/genéticaRESUMO
Background A widely accepted set of imaging criteria or classification has not yet been adopted to evaluate response to treatment by percutaneous sclerotherapy for aneurysmal bone cyst (ABC). In this article, we described and illustrated the Royal Orthopaedic Hospital (ROH) scoring system which is a new, reproducible, and objective tool to evaluate the radiological response. We also reported our institutional experience in the efficacy of computed tomography (CT)-guided sclerotherapy for treating such lesions. Patients and Methods A retrospective analysis was conducted for 19 patients who underwent CT-guided sclerotherapy with doxycycline and albumin to treat ABC. Follow-up magnetic resonance imaging, at a minimum of 12 months, was assessed according to the four ROH scoring system parameters: cystic component, fluid-fluid level, presence of consolidation, and cortical integrity. The cumulative score was used to grade response as either: excellent, good, equivocal, or poor. Results Out of 19 patients with a mean age of 17.8 years, 11 cases occurred in the long bones, 5 cases in the pelvis, and 1 in each of the C3 vertebral body, scapula, and talus. The mean parameter of response score for cystic component was 2, fluid-fluid level was 1.3, consolidation was 2, and cortical integrity was 2.1. Four cases showed excellent response, 12 cases showed good response, 2 cases showed equivocal response, and 1 case showed poor response. Interrater reliability was excellent (κ = 0.9). Conclusion The ROH scoring system provides the radiologist and surgeon with an objective method to score imaging parameters of response independently and achieve a grade based on the cumulative score.
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PURPOSE: Increased intramedullary signal intensity (IISI) on T2 weighted MRI scan (T2WI) can be a radiological feature of spinal cord degeneration. However, the association of IISI to degeneration of the spinal column that protects the spinal cord remains unclear. The purpose of this study was to determine the prevalence of IISI and analyze the independent relationship between IISI and cervical degenerative parameters on X-ray and magnetic resonance imaging (MRI). METHODS: A retrospective review of MRI, X-ray, and radiology data (n = 144) adult patients with both cervical MRI and X-ray scans was conducted. A total of 39 (27 %) patients with IISI was identified. The remaining 105 patients without IISI made up the control group. RESULTS: IISI was most frequent in C6-C7 cervical levels. The likelihood of having IISI was 1.947 (Exp(B) 1.947, 95 %CI [1.004-3.776]) times higher in segmental levels with facet joint degeneration. There was an increased likelihood of IISI within the spinal cord with increasing age (Exp(B) 1.034, 95 %CI [1.008-1.060]), maximum spinal cord compression (MSCC) (Exp(B) 1.038, 95 %CI [1.003-1.075]), rotational angle (Exp(B) 1.082, 95 %CI [1.020-1.148]) and posterior disc herniation width (Exp(B) 1.333, 95 %CI [1.017-1.747]) and decreasing Torg-Pavlov ratio (Exp(B) 0.010, 95 %CI [0.001-0.068]). CONCLUSION: IISI was independently associated with increased age, facet joint degeneration, MSCC, rotational angle, posterior herniation width and decreasing Torg-Pavlov angle. Radiologicaldegenerative changesassociated with IISI indicates a potential for identifying predictors of age related spinal cord morphological changes in DCM, which may allow for early intervention strategies in the future.
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Degeneração do Disco Intervertebral , Imageamento por Ressonância Magnética , Medula Espinal , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/epidemiologia , Idoso , Adulto , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Envelhecimento/patologia , Vértebras Cervicais/diagnóstico por imagem , Idoso de 80 Anos ou maisRESUMO
Introduction: The efficacy of de novo cardiac resynchronisation therapy (CRT) in patients with heart failure (HF), left ventricular systolic dysfunction (LVSD), and a broad QRS morphology is well established. However, the optimal stage for upgrading patients with existing pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) and HF with high-burden right ventricular (RV) pacing remains uncertain. Thus, this multicentre retrospective analysis compared patients with pre-existing PPMs or ICDs who underwent CRT upgrades to investigate the appropriate stage for CRT implantation in these patients and to assess the validity of treating both PPM and ICD recipients under the same recommendation level in the current guidelines. Materials and Methods: A total of 151 participants underwent analysis in this study, comprising 93 upgrades to cardiac resynchronisation therapy with pacemaker (CRT-P) and 58 upgrades to cardiac resynchronisation therapy with defibrillator (CRT-D) across three centres in the UK. The aim of the study was to investigate the safety and efficacy of upgrading to CRT from an existing conventional pacemaker or an ICD in the context of high-burden RV pacing. The analysis was conducted separately for each group, assessing changes in echocardiographic parameters, functional New York Heart Association (NYHA) class, and procedure-related complications. Results: The PPM group had a higher percentage RVP burden compared to the ICD group. Post-upgrade, NYHA functional class and EF and LV volumes improved in both groups; however, the response to an upgrade from a pacemaker was greater compared to an upgrade from an ICD. Post-procedural complication risks were similar across the two subgroups but significantly higher compared to de novo implantation. Conclusions: Within the CRT-P subgroup, participants exhibited better responses than their CRT-D counterparts, evident both in echocardiographic improvements and clinical outcomes. Furthermore, patients with non-ischemic cardiomyopathy (NICM) were better responders than those with ischaemic cardiomyopathy. These findings suggest that international guidelines should consider approaching each subgroup separately in the future.