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1.
Article in English | MEDLINE | ID: mdl-37839658

ABSTRACT

OBJECTIVE: Transatrial transcatheter mitral valve replacement reduces complexity during mitral valve replacements involving high-risk patients with mitral annular calcification. This study examines trends in transatrial transcatheter mitral valve replacement use and outcomes. METHODS: Patients in the Society of Thoracic Surgeons database from 2014 to 2021 with mitral annular calcification undergoing transatrial transcatheter mitral valve replacement were included. Exclusion criteria were hypertrophic cardiomyopathy, congenital mitral valve disease, ventricular assist device placement, or prior mitral valve surgery. Primary outcomes were operative mortality and major adverse cardiac events compared between the Early (2014-2017, N = 71) and Recent (2018-2021, N = 151) eras. Parsimonious multivariable regression assessed select possible confounders for trends in major adverse cardiac events. RESULTS: Overall, 222 transatrial transcatheter mitral valve replacements at 104 hospitals were identified. Annual volume increased from 6 in 2014 to 43 in 2021. Median hospital volume was 1, maximum hospital volume was 17, and 10 or more replacements were performed at 4 hospitals. Mortality and major adverse cardiac events occurred in 10.4% and 22.5% of patients, respectively. Compared with the Early era patients, Recent era patients were more often elective (79.5% vs 64.8%) and were approached via sternotomy (90.1% vs 80.3%, all P < .05). Despite similar predicted risk of mortality (9.6% ± 11.1% vs 11.0% ± 6.0%; P = .61), Recent patients had reduced mortality (3.3% vs 25.4%, P < .001) and major adverse cardiac events (18.5% vs 31.0%; P = .057). On univariate and multivariable analyses, the Recent surgical era was significantly associated with lower mortality (0.10 [0.04-0.29]; P < .001) and lower major adverse cardiac events (0.48 [0.25-0.94]; P = .032), respectively. There were no preoperative characteristics that were significant confounders for the difference in major adverse cardiac events. CONCLUSIONS: Mortality and major adverse cardiac events after transatrial transcatheter mitral valve replacement have decreased significantly in the contemporary era independent of changes in major patient and operative characteristics. Transatrial transcatheter mitral valve replacement will have a future role in patients with mitral annular calcification.

2.
Emerg Med J ; 40(2): 101-107, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35473753

ABSTRACT

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.


Subject(s)
Acute Coronary Syndrome , Emergency Medical Services , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Acute Coronary Syndrome/therapy , Retrospective Studies , Analgesics, Opioid/therapeutic use , Treatment Outcome
3.
JTCVS Open ; 16: 93-102, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38204628

ABSTRACT

Objectives: The use of bioprosthetic aortic valve replacement (AVR) is inherently associated with a risk of structural valve degeneration (SVD) and the need for aortic valve (AV) reintervention. We sought to evaluate whether AV reintervention, in the form of repeat surgical AVR (SAVR) or valve-in-valve transcatheter aortic valve replacement (ViV-TAVR), negatively affects patients' subsequent long-term survival after index SAVR. Methods: We identified patients who had undergone bioprosthetic SAVR from 2002 to 2017 at our institution. Median longitudinal follow-up after index SAVR was 7.3 years (10.9 years for those with and 7.2 years for those without AV reintervention), and median follow-up after AV reintervention was 1.9 years. Cox regression analyses using AV reintervention (re-SAVR and ViV-TAVR) as a time-varying covariate were used to determine the impact of reintervention on subsequent survival. Results: Of 4167 patients who underwent index SAVR, 139 (3.3%) required AV reintervention for SVD, with re-SAVR being performed in 65 and ViV-TAVR in 74. Median age at the index SAVR was 73 years (interquartile range, 64-79 years), and 2541 (61%) were male. Overall, there were total of 1171 mortalities observed, of which 13 occurred after re-SAVR and 9 after ViV-TAVR. AV reintervention was associated with a greater risk of subsequent mortality compared with those patients who did not require AV reintervention (hazard ratio, 2.53; 95% confidence interval, 1.64-3.88, P < .001). This increased risk of subsequent mortality was more pronounced for those who received their index AVR when <65 years of age (hazard ratio, 5.60; 95% confidence interval, 2.57-12.22, P < .001) versus those ≥65 years (2.06, 1.21-3.52, P = .008). Direct comparison of survival between those who underwent re-SAVR versus ViV-TAVR showed 5-year survival to be comparable (re-SAVR: 74% vs ViV-TAVR: 80%, P = .67). Conclusions: Among patients receiving bioprosthetic AVR, an AV reintervention for SVD is associated with an increased risk of subsequent mortality, regardless of re-SAVR or ViV-TAVR, and this risk is greater among younger patients. These findings should be balanced with individual preferences at index AVR in the context of patients' lifetime management of aortic stenosis.

4.
Am J Cardiol ; 177: 14-21, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35773044

ABSTRACT

Cardiogenic shock is associated with a high risk for morbidity and mortality. The impact of gender on treatment and outcomes is poorly defined. This study aimed to evaluate whether gender influences the clinical management and outcomes of patients with prehospital cardiogenic shock. Consecutive adult patients with cardiogenic shock who were transferred to hospital by emergency medical services (EMS) between January 1, 2015 and June 30, 2019 in Victoria, Australia were included. Data were obtained from individually linked ambulance, hospital, and state death index datasets. The primary outcome assessed was 30-day mortality, stratified by patient gender. Propensity score matching was performed for risk adjustment. Over the study period a total of 3,465 patients were identified and 1,389 patients (40.1%) were women. Propensity score matching yielded 1,330 matched pairs with no differences observed in baseline characteristics, including age, initial vital signs, pre-existing co-morbidities, etiology of shock, and prehospital interventions. In the matched cohort, women had higher rates of 30-day mortality (44.7% vs 39.2%, p = 0.009), underwent less coronary angiography (18.3% vs 27.2%, p <0.001), and revascularization with percutaneous coronary intervention (8.9% vs 14.2%, p <0.001), compared with men. In conclusion, in this large population-based study, women with cardiogenic shock who were transferred by EMS to hospital had significantly worse survival outcomes and reduced rates of invasive cardiac interventions compared to men. These data underscore the urgent need for targeted public health measures to redress gender differences in outcomes and variation with clinical care for patients with cardiogenic shock.


Subject(s)
Percutaneous Coronary Intervention , Shock, Cardiogenic , Female , Hospital Mortality , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Treatment Outcome , Victoria/epidemiology
6.
Heart Lung Circ ; 31(5): 711-715, 2022 May.
Article in English | MEDLINE | ID: mdl-34838453

ABSTRACT

BACKGROUND: Problematic mitral regurgitation (MR) may develop following lung transplantation (LTx). There is limited information on the management of MR in LTx patients, as such we sought to evaluate our centre's experience. METHODS: From 2000 to 2019, 1,054 patients underwent LTx at our centre (896 bilateral, 158 single). We identified patients in whom significant MR developed at any point post-LTx. The aetiology of MR, management and outcome were retrospectively analysed. RESULTS: Eight (8) patients developed severe MR post-LTx, six following bilateral LTx and two following single LTx. Lung transplantation indications included interstitial lung disease (n=5), chronic obstructive pulmonary disease (n=2) and pulmonary arterial hypertension (n=1). Severe MR occurred intraoperatively (n=1), postoperative day 1 (n=1) with the remaining six cases between 80 and 263 days post-LTx. The aetiology was noted to be due to severe left ventricular dysfunction following unmasking of a chronically pulmonary hypertension-related under-preloaded left ventricle in one case, and in the remaining seven patients causes included myxomatous degeneration, ischaemic MR, and functional MR due to annular dilatation. In the patient with intraoperative severe MR, the MR became mild with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in the remaining seven patients a variety of procedures were used, including mitral valve repair, valve replacement and transcatheter edge-to-edge mitral valve repair. All patients survived the mitral procedure. Two (2) deaths occurred at 12.9 years (stroke) and 5 years (cancer) from mitral valve surgery. CONCLUSIONS: Development of significant mitral valve regurgitation is a rare but morbid complication after lung transplantation. This may represent the progressive natural history of pre-existing degenerative mitral valve disease and rarely, early after transplantation may be related to changes in ventricular geometry. Management of severe MR can follow the same management approach as in the non-transplant community, with the expectation of similarly good results.


Subject(s)
Lung Transplantation , Mitral Valve Insufficiency , Humans , Lung Transplantation/adverse effects , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/surgery , Retrospective Studies , Treatment Outcome
7.
Ann Cardiothorac Surg ; 10(6): 801-803, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34926185
8.
Eur Heart J Acute Cardiovasc Care ; 10(10): 1140-1147, 2021 Dec 18.
Article in English | MEDLINE | ID: mdl-34189566

ABSTRACT

AIMS: This study aims to evaluate if pre-hospital heparin administration by paramedics is safe and improves clinical outcomes. METHODS AND RESULTS: Using the multicentre Victorian Cardiac Outcomes Registry, linked with state-wide ambulance records, we identified consecutive patients undergoing primary percutaneous coronary intervention for STEMI between January 2014 and December 2018. Information on thrombolysis in myocardial infarction (TIMI) flow at angiography was available in a subset of cases. Patients receiving pre-hospital heparin were compared to those who did not receive heparin. Findings at coronary angiography and 30-day clinical outcomes were compared between groups. Propensity-score matching was performed for risk adjustment. We identified a total of 4720 patients. Of these, 1967 patients had TIMI flow data available. Propensity-score matching in the entire cohort yielded 1373 matched pairs. In the matched cohort, there was no observed difference in 30-day mortality (no-heparin 3.5% vs. heparin 3.0%, P = 0.25), MACCE (no-heparin 7% vs. heparin 6.2%, P = 0.44), and major bleeding (no-heparin 1.9% vs. heparin 1.4%, P = 0.64) between groups. Propensity-score analysis amongst those with TIMI data produced 552 matched pairs. The proportion of cases with TIMI 0 or 1 flow in the infarct-related artery (IRA) was lower among those receiving pre-hospital heparin (66% vs. 76%, P < 0.001) compared to those who did not. CONCLUSION: In this multicentre, propensity-score matched study, the use of pre-hospital heparin by paramedics was safe and is associated with fewer occluded IRAs in patients presenting with STEMI.


Subject(s)
ST Elevation Myocardial Infarction , Angiography , Heparin , Hospitals , Humans , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/surgery
9.
J Ultrasound Med ; 40(2): 369-376, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32770569

ABSTRACT

OBJECTIVES: We are studying a new method for estimating blood volume flow that uses 3-dimensional ultrasound to measure the total integrated flux through an ultrasound-generated Gaussian surface that intersects the umbilical cord. This method makes none of the assumptions typically required with standard 1-dimensional spectral Doppler volume flow estimates. We compared the variations in volume flow estimates between techniques in the umbilical vein. METHODS: The study was Institutional Review Board approved, and all 12 patients gave informed consent. Because we had no reference standard for the true umbilical vein volume flow, we compared the variations of the measurements for the flow measurement techniques. At least 3 separate spectral Doppler and 3 separate Gaussian surface measurements were made along the umbilical vein. Means, standard deviations, and coefficients of variation (standard deviation/mean) for the flow estimation techniques were calculated for each patient. P < .05 was considered significant. RESULTS: The ranges of the mean volume flow estimates were 174 to 577 mL/min for the spectral Doppler method and 100 to 341 mL/min for the Gaussian surface integration (GSI) method. The mean standard deviations (mean ± SD) were 161 ± 95 and 45 ± 48 mL/min for the spectral Doppler and GSI methods, respectively (P < .003). The mean coefficients of variation were 0.46 ± 0.17 and 0.18 ± 0.14 for the spectral Doppler and GSI methods respectively (P < 0.002). CONCLUSIONS: The new volume flow estimation method using 3-dimensional ultrasound appears to have significantly less variation in estimates than the standard 1-dimensional spectral Doppler method.


Subject(s)
Ultrasonography, Doppler , Ultrasonography, Prenatal , Blood Flow Velocity , Blood Volume , Female , Humans , Pregnancy , Umbilical Veins/diagnostic imaging
11.
JAMA Oncol ; 6(5): 650-659, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32215577

ABSTRACT

Importance: Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT). Objective: To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer. Design, Setting, and Participants: The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized. Interventions: Patients were randomized in a 2:1 ratio to receive SABR or observation. Main Outcomes and Measures: The primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease. Results: In the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03). Conclusions and Relevance: Treatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates. Trial Registration: ClinicalTrials.gov Identifier: NCT02680587.


Subject(s)
Prostatic Neoplasms/radiotherapy , Radiosurgery/methods , Aged , Humans , Male , Middle Aged , Treatment Outcome
13.
Ann Thorac Surg ; 109(4): 1127-1131, 2020 04.
Article in English | MEDLINE | ID: mdl-31518586

ABSTRACT

BACKGROUND: Limited data exist on long-term pulmonary valve function after the Ross procedure. This study sought to determine the long-term function of the pulmonary valve in 443 consecutive adult patients who underwent a Ross procedure. METHODS: All 443 patients who underwent a Ross procedure between November 1992 and March 2018 were reviewed retrospectively. All underwent pulmonary valve replacement using a cryopreserved pulmonary allograft. Freedom from the study's outcomes were calculated using Kaplan Meier survival. Risk factors for valve failure were analyzed using Cox regression. RESULTS: Mean age at time of operation was 39 years (range: 15-66 years). There was 1 (0.2%, 1 of 443) operative mortality. Nine patients required reintervention on the pulmonary allograft at a mean 6.1 years (range: 1-12 years) after Ross procedure. Patients required pulmonary allograft reintervention for infective endocarditis (n = 4), severe pulmonary stenosis (n = 4), or severe pulmonary regurgitation (n = 1). Freedom from pulmonary allograft reintervention was 98.9% (95% confidence interval [CI] 97.1%-99.6%), 97.7% (95% CI 95.1%-98.9%), 96.6% (95% CI 93.3%-98.3%), and 96.6% (95% CI 93.3%-98.3%) at 5, 10, 15, and 20 years, respectively. Freedom from pulmonary allograft dysfunction (at least moderate pulmonary regurgitation and/or mean systolic gradient ≥ 25 mm Hg and/or reintervention) was 94.5% (95% CI 91.6%-96.4%), 88.1% (95% CI 83.6%-91.4%), 84.9% (95% CI 79.6%-88.9%), and 78.3% (95% CI 69.5%-84.9%) at 5, 10, 15, and 20 years, respectively. No risk factors were identified to influence pulmonary valve durability. CONCLUSIONS: The pulmonary valve allograft gives excellent long-term function when used in adults undergoing the Ross procedure. Reintervention on the pulmonary valve is rare and significant pulmonary allograft dysfunction is uncommon.


Subject(s)
Heart Valve Prosthesis Implantation/methods , Heart Ventricles/physiopathology , Pulmonary Valve Insufficiency/surgery , Pulmonary Valve Stenosis/surgery , Pulmonary Valve/physiopathology , Ventricular Function, Right/physiology , Adolescent , Adult , Aged , Echocardiography, Stress/methods , Female , Follow-Up Studies , Heart Ventricles/diagnostic imaging , Humans , Magnetic Resonance Imaging, Cine/methods , Male , Middle Aged , Postoperative Period , Prosthesis Design , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Pulmonary Valve Insufficiency/diagnosis , Pulmonary Valve Insufficiency/physiopathology , Pulmonary Valve Stenosis/diagnosis , Pulmonary Valve Stenosis/physiopathology , Reoperation , Retrospective Studies , Transplantation, Autologous , Young Adult
15.
Ann Thorac Surg ; 107(3): 852-859, 2019 03.
Article in English | MEDLINE | ID: mdl-30300642

ABSTRACT

BACKGROUND: A subset of patients who underwent Fontan operations has two adequate-sized ventricles, but an anatomic biventricular circulation cannot be achieved because of complex morphology or for technical reasons. This study sought to determine whether these patients with two-ventricle Fontan circulation had superior outcomes compared with those with a single ventricle. METHODS: A binational Fontan Registry of patients (n = 1,377) was analyzed to identify those patients with two adequate ventricles. This cohort was compared with patients with single-ventricle Fontan circulation. The primary end point was a composite end point called "Fontan failure" encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV. RESULTS: A total of 79 Fontan patients with two adequate ventricles (2V) were compared with 1,291 single ventricle (1V) Fontan patients. Median follow-up for the entire cohort was 11.5 years (interquartile range, 5.1 to 18.8 years). There was no difference in unadjusted 15-year freedom from Fontan failure (2V: 81% [95% confidence interval (CI), 69% to 94%] vs 1V: 86% [95% CI, 83% to 88%], p = 0.4). Propensity-score matching for potential confounding factors yielded 75 two-ventricle Fontan patients matched with 604 single-ventricle Fontan patients, in which 15-year freedom from Fontan failure was also not different (2V: 79% [95% CI, 67% to 94%] vs 1V: 87% [95% CI, 84% to 91%], p = 0.3). CONCLUSIONS: The two-ventricle Fontan circulation does not have better outcomes compared with the single-ventricle Fontan circulation. Late outcomes may depend more on other characteristics of the Fontan circulation. This finding is relevant when the Fontan procedure is being considered as an alternative to anatomic repair in patients with complex two-ventricle morphologies.


Subject(s)
Fontan Procedure/methods , Heart Defects, Congenital/surgery , Heart Ventricles/surgery , Registries , Australia/epidemiology , Child , Child, Preschool , Female , Humans , Incidence , Male , Postoperative Complications/epidemiology , Propensity Score , Risk Factors , Survival Rate/trends , Treatment Outcome
16.
Intern Med J ; 49(3): 364-372, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30151969

ABSTRACT

BACKGROUND: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. AIM: To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. METHODS: Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). RESULTS: Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. CONCLUSIONS: Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.


Subject(s)
Antitubercular Agents/adverse effects , Hypothyroidism/chemically induced , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Victoria , Young Adult
17.
Cancer Discov ; 9(4): 500-509, 2019 04.
Article in English | MEDLINE | ID: mdl-30578357

ABSTRACT

Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation-informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specificity. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, P = 0.02) and cytology and cystoscopy combined (P ≤ 0.006), detecting 100% of bladder cancer cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of bladder cancer. SIGNIFICANCE: This study shows that utDNA can be detected using HTS with high sensitivity and specificity in patients with early-stage bladder cancer and during post-treatment surveillance, significantly outperforming standard diagnostic modalities and facilitating noninvasive detection, genotyping, and monitoring.This article is highlighted in the In This Issue feature, p. 453.


Subject(s)
Biomarkers, Tumor/metabolism , DNA, Neoplasm/urine , Urinary Bladder Neoplasms/diagnosis , Female , Humans , Male , Urinary Bladder Neoplasms/urine
19.
Circulation ; 138(4): 367-376, 2018 07 24.
Article in English | MEDLINE | ID: mdl-29514799

ABSTRACT

BACKGROUND: Long-term outcomes for childhood left ventricular noncompaction (LVNC) are uncertain. We examined late outcomes for children with LVNC enrolled in a national population-based study. METHODS: The National Australian Childhood Cardiomyopathy Study includes all children in Australia with primary cardiomyopathy diagnosed before 10 years of age between 1987 and 1996. Outcomes for subjects with LVNC with a dilated phenotype (LVNC-D) were compared with outcomes for those with dilated cardiomyopathy. Propensity-score analysis was used for risk factor adjustment. RESULTS: There were 29 subjects with LVNC (9.2% of all cardiomyopathy subjects), with a mean annual incidence of newly diagnosed cases of 0.11 per 100 000 at-risk individuals. Congestive heart failure was the initial symptom in 24 of 29 subjects (83%), and 27 (93%) had LVNC-D. The median age at diagnosis was 0.3 (interquartile interval, 0.08-1.3) years. The median duration of follow-up was 6.8 (interquartile interval, 0.7-24.0) years for all subjects and 24.7 (interquartile interval, 23.3 - 27.7) years for surviving subjects. Freedom from death or transplantation was 48% (95% confidence interval [CI], 30-65) at 10 years after diagnosis and 45% (95% CI, 27-63) at 15 years. In competing-risk analysis, 21% of subjects with LVNC were alive with normal left ventricular systolic function, and 31% were alive with abnormal function at 15 years. Propensity-score matching between subjects with LVNC-D and those with dilated cardiomyopathy suggested a lower freedom from death/transplantation at 15 years after diagnosis in the subjects with LVNC-D (LVNC-D, 46% [95% CI, 26-66] versus dilated cardiomyopathy, 70% [95% CI, 42-97]; P=0.08). Using propensity-score inverse probability of treatment-weighted Cox regression, we found evidence that LVNC-D was associated with a greater risk of death or transplantation (hazard ratio, 2.3; 95% CI, 1.4-3.8; P=0.0012). CONCLUSIONS: Symptomatic children with LVNC usually present in early infancy with a predominant dilated phenotype. Long-term outcomes are worse than for matched children with dilated cardiomyopathy.


Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Isolated Noncompaction of the Ventricular Myocardium , Australia/epidemiology , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/therapy , Child , Child, Preschool , Disease Progression , Female , Heart Failure/diagnostic imaging , Heart Failure/mortality , Heart Failure/physiopathology , Heart Failure/therapy , Heart Transplantation , Humans , Incidence , Infant , Isolated Noncompaction of the Ventricular Myocardium/diagnostic imaging , Isolated Noncompaction of the Ventricular Myocardium/mortality , Isolated Noncompaction of the Ventricular Myocardium/physiopathology , Isolated Noncompaction of the Ventricular Myocardium/therapy , Longitudinal Studies , Male , Phenotype , Prognosis , Risk Assessment , Risk Factors , Time Factors , Ventricular Function, Left
20.
Heart Lung Circ ; 27(8): e93-e95, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29503243

ABSTRACT

Ascertaining the correct length of neochords during mitral valve repair is challenging. We describe a modified technique of chordal replacement where a GoreTex (W.L. Gore and Assoc, Inc, Flagstaff, AZ, USA) sutures are repeatedly tied so as to braid the suture to the optimal length before sutures are passed through the mitral leaflet. The length of the braided chord remains fixed when tying on the atrial side. For bileaflet repairs, a second suture is incorporated into the initial chord to create a "Y" braided neo-chord configuration. This technique facilitates precision in mitral repair.


Subject(s)
Cardiac Surgical Procedures/methods , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Polytetrafluoroethylene , Suture Techniques/instrumentation , Sutures , Adult , Echocardiography, Transesophageal , Equipment Design , Humans , Male , Mitral Valve/diagnostic imaging , Mitral Valve Insufficiency/diagnosis
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