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1.
Quant Imaging Med Surg ; 14(6): 3837-3850, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38846308

ABSTRACT

Background: Coronary artery disease (CAD) is the leading cause of mortality worldwide. Recent advances in deep learning technology promise better diagnosis of CAD and improve assessment of CAD plaque buildup. The purpose of this study is to assess the performance of a deep learning algorithm in detecting and classifying coronary atherosclerotic plaques in coronary computed tomographic angiography (CCTA) images. Methods: Between January 2019 and September 2020, CCTA images of 669 consecutive patients with suspected CAD from Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine were included in this study. There were 106 patients included in the retrospective plaque detection analysis, which was evaluated by a deep learning algorithm and four independent physicians with varying clinical experience. Additionally, 563 patients were included in the analysis for plaque classification using the deep learning algorithm, and their results were compared with those of expert radiologists. Plaques were categorized as absent, calcified, non-calcified, or mixed. Results: The deep learning algorithm exhibited higher sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy {92% [95% confidence interval (CI): 89.5-94.1%], 87% (95% CI: 84.2-88.5%), 79% (95% CI: 76.1-82.4%), 95% (95% CI: 93.4-96.3%), and 89% (95% CI: 86.9-90.0%)} compared to physicians with ≤5 years of clinical experience in CAD diagnosis for the detection of coronary plaques. The algorithm's overall sensitivity, specificity, PPV, NPV, accuracy, and Cohen's kappa for plaque classification were 94% (95% CI: 92.3-94.7%), 90% (95% CI: 88.8-90.3%), 70% (95% CI: 68.3-72.1%), 98% (95% CI: 97.8-98.5%), 90% (95% CI: 89.8-91.1%) and 0.74 (95% CI: 0.70-0.78), indicating strong performance. Conclusions: The deep learning algorithm has demonstrated reliable and accurate detection and classification of coronary atherosclerotic plaques in CCTA images. It holds the potential to enhance the diagnostic capabilities of junior radiologists and junior intervention cardiologists in the CAD diagnosis, as well as to streamline the triage of patients with acute coronary symptoms.

2.
Indian J Thorac Cardiovasc Surg ; 40(Suppl 1): 83-92, 2024 May.
Article in English | MEDLINE | ID: mdl-38827543

ABSTRACT

Infective endocarditis involving the aortic root is associated with a high degree of morbidity and mortality. Native aortic root infections can develop from aggressive organisms or from delays in diagnosis or definitive care, whereas prosthetic valve infections commonly result in extensive destruction of the aortic root and neighboring structures. Early detection, tailored antibiotic therapy, thoughtful pre-operative planning, and multidisciplinary heart team management are the keys to optimizing patient outcomes. Aggressive and complete surgical debridement are mandatory prior to aortic root reconstruction. Surgical experience and patient-centered decision making are critical in selecting the optimal reconstructive strategy for the aortic root and adjacent structures. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01604-6.

4.
A A Pract ; 18(6): e01790, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38785382

ABSTRACT

This case report describes the rare occurrence of a ventricular septal defect (VSD) after transcatheter aortic valve implantation (TAVI) in an 88-year-old male patient with aortic stenosis and other comorbidities. Initially asymptomatic, the patient was discharged but readmitted 2 weeks later with decompensated heart failure. Transesophageal echocardiography (TEE) revealed an increase in the size of the VSD and right ventricular dilation. Surgical intervention was chosen over percutaneous closure due to the patient's condition. A bovine pericardial patch was successfully used for repair. This case highlights the importance of vigilant post-TAVI monitoring and individualized treatment for TAVI-related complications.


Subject(s)
Aortic Valve Stenosis , Heart Septal Defects, Ventricular , Transcatheter Aortic Valve Replacement , Humans , Male , Transcatheter Aortic Valve Replacement/adverse effects , Aged, 80 and over , Heart Septal Defects, Ventricular/surgery , Aortic Valve Stenosis/surgery , Echocardiography, Transesophageal , Cattle , Animals , Treatment Outcome
5.
Eur Heart J ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38820201

ABSTRACT

BACKGROUND AND AIMS: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE. METHODS: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD). RESULTS: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant due to IE and 188 (50.5%) patients due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older (74.3 ± 8.6 vs. 71 ± 10.6 years) and had a lower Society of Thoracic Surgeons risk score [2.6% (1.8-5.0) vs. 3.3% (2.1-5.6), P = .029] compared to patients with BVD. Compared to BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality was 12.1%, 16.1%, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years postsurgery (29.6% for BVD vs. 43.9% for IE), Kaplan-Meier analysis showed no significant differences between groups (P = .16). CONCLUSIONS: In the EXPLANT-TAVR registry, patients undergoing THV explant for IE had higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE had a higher 3-year mortality rate, which did not reach statistical significance given the relatively small sample size of this unique cohort and the reduced number of events.

6.
Article in English | MEDLINE | ID: mdl-38692478

ABSTRACT

OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.

7.
Ann Plast Surg ; 92(5S Suppl 3): S366-S370, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38689421

ABSTRACT

BACKGROUND: Awareness of Medicare reimbursement is important for gender-affirming surgeons who treat transgender patients with Medicare. In 2014, Medicare began to provide coverage for medically necessary transition-related surgery. The purpose of this study was to analyze trends in Medicare reimbursement rates for gender-affirming surgery procedures from 2014 to 2022. METHODS: The Medicare Physician Fee Schedule Look-Up Tool provided by the Centers for Medicare and Medicaid Services was used, and the Current Procedural Terminology codes for 43 gender-affirming surgery services were obtained. Monetary units, conversion factors, relative value units (RVUs) for work, facility, and malpractice costs for 30 transmasculine and 13 transfeminine procedures were analyzed. Descriptive statistics were performed to account for inflation and to determine the relative differences between 2014 and 2022. RESULTS: For all gender-affirming surgery procedures covered by Medicare, the average relative difference of monetary units decreased by 2.99% between 2014 and 2022. On average, there was a 3.97% decrease of work-based RVU charges for transmasculine procedures and a 1.73% decrease of work-based RVU charges for transfeminine procedures. After adjusting for inflation, the average relative difference of monetary units for all gender-affirming surgery procedures decreased by 23.42% between 2014 and 2022. CONCLUSIONS: Reimbursement rates for gender-affirming surgery procedures covered under Medicare have decreased over the observed period, and trends in reimbursement rates have not kept up with consumer price index inflation. Gender-affirming surgeons should be conscious of these changes in reimbursement rates and advocate for fairer compensation to promote medical care among an underserved population.


Subject(s)
Medicare , Sex Reassignment Surgery , Humans , United States , Medicare/economics , Female , Male , Sex Reassignment Surgery/economics , Insurance, Health, Reimbursement/economics , Insurance, Health, Reimbursement/trends
8.
J Plast Reconstr Aesthet Surg ; 93: 30-35, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38631083

ABSTRACT

BACKGROUND: To date, there are no studies investigating the safety and outcomes of facial feminization surgery (FFS) as an outpatient procedure. This is the first study of its kind analyzing the outcomes of ambulatory FFS based on a comparison of complications, post-operative emergency department or urgent care (ED/UC) visits, and readmissions between patients who underwent FFS with admission versus same-day surgery. METHODS: A retrospective analysis was conducted on all patients who underwent FFS in a single integrated healthcare system. Patient charts were reviewed for operative details, complications, post-operative ED/UC visits, readmission, and demographic factors. Major outcomes including complications, readmissions, and ED/UC visits were compared between groups with same-day discharge and post-operative hospital admission. RESULTS: Of 242 patients included in the study, ED/UC visits were comparable between patients discharged same-day (18.2%) and patients admitted post-operatively (21.6%, p = 0.52). Logistic regression showed no significant difference in the composite outcomes of minor complications, major complications, and readmissions (15.6% for ambulatory versus 19.3% for admission, p = 0.46). Temporary nerve palsy, infection, and hematoma were the most common post-operative complications. However, covariates of a lower face procedure and operative time were shown to have significant differences in the composite complication outcome (p = 0.04 and p = 0.045, respectively). CONCLUSION: Ambulatory FFS is a safe practice with no associated increase in adverse outcomes including complications, ED/UC visits, and readmission when compared to post-operative admission. Adoption of same-day FFS should be considered by high-volume gender health centers to potentially benefit from increased scheduling flexibility and efficiency, increased access to care, and lower healthcare costs.


Subject(s)
Ambulatory Surgical Procedures , Patient Readmission , Postoperative Complications , Humans , Female , Ambulatory Surgical Procedures/adverse effects , Retrospective Studies , Postoperative Complications/epidemiology , Adult , Patient Readmission/statistics & numerical data , Male , Middle Aged , Face/surgery , Treatment Outcome , Emergency Service, Hospital/statistics & numerical data , Feminization , Sex Reassignment Surgery/methods
10.
Radiat Oncol ; 19(1): 45, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589961

ABSTRACT

BACKGROUND: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. METHODS: The implemented 'Pareto Guided Automated Planning' (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a 'Protocol Based Automatic Iterative Optimisation' planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions' clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. RESULTS: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. CONCLUSIONS: PGAP enabled intuitive adaptation of automated protocols to an institution's planning aims and yielded plans more congruent with the institution's clinical preference than the locally produced manual clinical plans.


Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Male , Humans , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Urinary Bladder , Prostatic Neoplasms/radiotherapy , Organs at Risk
11.
Int J Surg Pathol ; : 10668969241234321, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627896

ABSTRACT

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

12.
JACC Cardiovasc Interv ; 17(8): 979-988, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38658126

ABSTRACT

BACKGROUND: Symptomatic patients with severe aortic stenosis (AS) at high risk for surgical aortic valve replacement (SAVR) sustain comparable improvements in health status over 5 years after transcatheter aortic valve replacement (TAVR) or SAVR. Whether a similar long-term benefit is observed among intermediate-risk AS patients is unknown. OBJECTIVES: The purpose of this study was to assess health status outcomes through 5 years in intermediate risk patients treated with a self-expanding TAVR prosthesis or SAVR using data from the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial. METHODS: Intermediate-risk patients randomized to transfemoral TAVR or SAVR in the SURTAVI trial had disease-specific health status assessed at baseline, 30 days, and annually to 5 years using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Health status was compared between groups using fixed effects repeated measures modelling. RESULTS: Of the 1,584 patients (TAVR, n = 805; SAVR, n = 779) included in the analysis, health status improved more rapidly after TAVR compared with SAVR. However, by 1 year, both groups experienced large health status benefits (mean change in KCCQ-Overall Summary Score (KCCQ-OS) from baseline: TAVR: 20.5 ± 22.4; SAVR: 20.5 ± 22.2). This benefit was sustained, albeit modestly attenuated, at 5 years (mean change in KCCQ-OS from baseline: TAVR: 15.4 ± 25.1; SAVR: 14.3 ± 24.2). There were no significant differences in health status between the cohorts at 1 year or beyond. Similar findings were observed in the KCCQ subscales, although a substantial attenuation of benefit was noted in the physical limitation subscale over time in both groups. CONCLUSIONS: In intermediate-risk AS patients, both transfemoral TAVR and SAVR resulted in comparable and durable health status benefits to 5 years. Further research is necessary to elucidate the mechanisms for the small decline in health status noted at 5 years compared with 1 year in both groups. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement [SURTAVI]; NCT01586910).


Subject(s)
Aortic Valve Stenosis , Aortic Valve , Femoral Artery , Health Status , Heart Valve Prosthesis , Quality of Life , Recovery of Function , Severity of Illness Index , Transcatheter Aortic Valve Replacement , Humans , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Female , Male , Time Factors , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Treatment Outcome , Aged , Aged, 80 and over , Risk Factors , Aortic Valve/surgery , Aortic Valve/physiopathology , Aortic Valve/diagnostic imaging , Risk Assessment , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Catheterization, Peripheral/adverse effects , Punctures , Prosthesis Design
13.
J Am Coll Cardiol ; 83(17): 1656-1668, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38658105

ABSTRACT

BACKGROUND: Tricuspid valve annuloplasty (TA) during mitral valve repair (MVr) is associated with increased risk of permanent pacemaker (PPM) implantation, but the magnitude of risk and long-term clinical consequences have not been firmly established. OBJECTIVES: This study assesses the incidence rates of PPM implantation after isolated MVr and following MVr with TA as well as the associated long-term clinical consequences of PPM implantation. METHODS: State-mandated hospital discharge databases of New York and California were queried for patients undergoing MVr (isolated or with concomitant TA) between 2004 and 2019. Patients were stratified by whether or not they received a PPM within 90 days of index surgery. After weighting by propensity score, survival, heart failure hospitalizations (HFHs), endocarditis, stroke, and reoperation were compared between patients with or without PPM. RESULTS: A total of 32,736 patients underwent isolated MVr (n = 28,003) or MVr + TA (n = 4,733). Annual MVr + TA volumes increased throughout the study period (P < 0.001, trend), and PPM rates decreased (P < 0.001, trend). The incidence of PPM implantation <90 days after surgery was 7.7% for MVr and 14.0% for MVr + TA. In 90-day conditional landmark-weighted analyses, PPMs were associated with reduced long-term survival among MVr (HR: 1.96; 95% CI: 1.75-2.19; P < 0.001) and MVr + TA recipients (HR: 1.65; 95% CI: 1.28-2.14; P < 0.001). In both surgical groups, PPMs were also associated with an increased risk of HFH (HR: 1.56; 95% CI: 1.27-1.90; P < 0.001) and endocarditis (HR: 1.95; 95% CI: 1.52-2.51; P < 0.001), but not with stroke or reoperation. CONCLUSIONS: Compared to isolated MVr, adding TA to MVr was associated with a higher risk of 90-day PPM implantation. In both surgical groups, PPM implantation was associated with an increase in mortality, HFH, and endocarditis.


Subject(s)
Pacemaker, Artificial , Tricuspid Valve , Humans , Female , Male , Aged , Pacemaker, Artificial/adverse effects , Tricuspid Valve/surgery , Middle Aged , Mitral Valve/surgery , Retrospective Studies , Cardiac Valve Annuloplasty/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome
14.
Urology ; 186: 63-68, 2024 04.
Article in English | MEDLINE | ID: mdl-38350549

ABSTRACT

OBJECTIVE: To describe phalloplasty subunits and determine the preferred crowdsourced esthetics. Esthetic ideals are often used to guide reconstruction, and there has been an increase in the number of gender-affirming surgeries and reconstructive phalloplasties performed. However, there is a paucity of literature describing ideal phalloplasty esthetics. METHODS: Phallus esthetic subunits were defined, and a split testing-based survey was used. Subjects were solicited via Craigslist, Amazon Mechanical Turk, and Reddit and distributed among health care co-workers. Computer-generated images with variable ratios of glans, corona, and shaft were provided and respondents were asked to select the most esthetically pleasing photo. Demographic information was gathered. Univariate and multivariate regression were performed. RESULTS: A total of 1029 people responded to the survey request and 909 people (88.3%) completed the entire survey. There were 440 respondents who self-identified as male, 334 female, 92 transgender male, and 25 transgender female. The health care field was the profession for 55.4%. Health care providers had 65.3% higher odds of preferring the longer shaft length-to-width ratio, 30.3% less odds of preferring a bilateral taper of the glans, and 48.4% less odds of preferring an angulated shaft compared to non-health care providers (P = .006, P = .021, P <.001, respectively). When compared to males, transgender females were more than 13 times likely to prefer an angulated glans corona junction (P = .008). CONCLUSION: The ideal phallic esthetic varies by individual, and there were statistically significant preferences across age, education, health care status, gender, and sexual orientation. This study can serve as a guide on phalloplasties for patients and gender-affirming surgeons.


Subject(s)
Crowdsourcing , Transsexualism , Humans , Male , Female , Genitalia, Male , Transsexualism/surgery , Esthetics , Surveys and Questionnaires
16.
Nat Med ; 30(2): 543-551, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38177852

ABSTRACT

Due to evolving treatment standards for newly diagnosed multiple myeloma, many patients will be triple-class exposed after initial relapses and have poor survival. Novel therapies and combinations are therefore required to improve outcomes. B cell maturation antigen (BCMA)-targeted biologics have emerged as an important new area of therapeutics for relapsed multiple myeloma. The two-part ALGONQUIN trial evaluated various doses and schedules of the anti-BCMA antibody-drug conjugate belantamab mafodotin plus pomalidomide and dexamethasone for patients who are lenalidomide refractory and proteosome inhibitor exposed. The primary endpoints, including evaluating dose-limiting toxicities, establishing the recommended Part 2 dose (RP2D) and overall response rate for patients treated at the RP2D, were met. Secondary efficacy endpoints included progression-free survival and overall survival. Patients treated on study (N = 87) had a median of three previous regimens and 55.2% were triple-class refractory. At the RP2D the most common adverse events were decrease in best-corrected visual acuity (71.1%), keratopathy (65.8%), fatigue (57.9%), infection (47.4%; 7.9% grade ≥3), neutropenia (39.5%) and thrombocytopenia (39.5%). For RP2D patients (n = 38), the overall response rate was 85.3%, ≥very good partial response 75.7% and estimated two-year progression-free survival 52.8% (95% confidence interval, 33.9% to 82.4%), at a median follow-up of 13.9 months. The RP2D schedule was associated with manageable antibody-drug conjugate-associated corneal adverse events and improved tolerability without compromising efficacy. Belantamab mafodotin plus pomalidomide and dexamethasone induced durable responses with promising overall survival in relapsed multiple myeloma, the results of which are yet to be confirmed in the phase 3 DREAMM-8 study. ClinicalTrials.gov Identifier: NCT03715478 .


Subject(s)
Antibodies, Monoclonal, Humanized , Immunoconjugates , Multiple Myeloma , Thalidomide/analogs & derivatives , Humans , Multiple Myeloma/drug therapy , Treatment Outcome , Dexamethasone/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects
17.
Int J Mol Sci ; 25(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38203816

ABSTRACT

We recently demonstrated that a small subset of cells in FLT3-mutated acute myeloid leukemia (AML) cell lines exhibit SORE6 reporter activity and cancer stem-like features including chemoresistance. To study why SORE6+ cells are more chemoresistant than SORE6- cells, we hypothesized that these cells carry higher autophagy, a mechanism linked to chemoresistance. We found that cytarabine (Ara-C) induced a substantially higher protein level of LC3B-II in SORE6+ compared to SORE6- cells. Similar observations were made using a fluorescence signal-based autophagy assay. Furthermore, chloroquine (an autophagy inhibitor) sensitized SORE6+ but not SORE6- cells to Ara-C. To decipher the molecular mechanisms underlying the high autophagic flux in SORE6+ cells, we employed an autophagy oligonucleotide array comparing gene expression between SORE6+ and SORE6- cells before and after Ara-C treatment. ULK2 was the most differentially expressed gene between the two cell subsets. To demonstrate the role of ULK2 in conferring higher chemoresistance in SORE6+ cells, we treated the two cell subsets with a ULK1/2 inhibitor, MRT68921. MRT68921 significantly sensitized SORE6+ but not SORE6- cells to Ara-C. Using our in vitro model for AML relapse, we found that regenerated AML cells contained higher ULK2 expression compared to pretreated cells. Importantly, inhibition of ULK2 using MRT68921 prevented in vitro AML relapse. Lastly, using pretreatment and relapsed AML patient bone marrow samples, we found that ULK2 expression was higher in relapsed AML. To conclude, our results supported the importance of autophagy in the relapse of FLT3-mutated AML and highlighted ULK2 in this context.


Subject(s)
Drug Resistance, Neoplasm , Leukemia, Myeloid, Acute , Protein Serine-Threonine Kinases , Humans , Autophagy/genetics , Biological Assay , Chronic Disease , Cytarabine/pharmacology , Drug Resistance, Neoplasm/genetics , fms-Like Tyrosine Kinase 3/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Protein Serine-Threonine Kinases/genetics
18.
Can J Cardiol ; 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38218222

ABSTRACT

BACKGROUND: Accurate benchmarking of outcomes after elective open total arch replacement is important for surgical decision making and for comparisons with emerging endovascular technologies. METHODS: A multicentre registry of consecutive aortic arch procedures in 9 centres across Canada contained 250 elective total arch replacements from 2010 to 2021. A total of 728 patients undergoing elective hemiarch replacement over the same time period was used as a comparator group. Propensity score matching was used to construct 202 well matched pairs. RESULTS: Patients undergoing total arch replacement were 63.2 ± 13.6 years old, and 34% were female. These patients were more likely to have connective tissue disorders compared with patients undergoing hemiarch replacement. When under hypothermic circulatory arrest, the total arch group uniformly used antegrade cerebral perfusion with median nadir temperature of 24°C (interquartile range [IQR] 21-25°C), and median duration 33 minutes (IQR 23-51 minutes). Before matching, in-hospital mortality and stroke rates were 5.2% and 10%, respectively, for the total arch group. After matching, the total arch group had in-hospital mortality similar to the hemiarch group (P = 0.58). Rates of stroke were also not statistically different (P = 0.11). The total arch group was more likely to experience delirium, prolonged intubation, increased intensive care unit length of stay, and transfusions. CONCLUSIONS: Elective total arch replacement is performed with good in-hospital mortality rates that are similar to rates after elective hemiarch repairs. However, total arch replacement was associated with significantly higher rates of other morbidities, including delirium and prolonged intubation.

19.
Eur Heart J Open ; 4(1): oead128, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38162403

ABSTRACT

Aims: Thoracic aortic aneurysms (TAAs) carry a risk of catastrophic dissection. Current strategies to evaluate this risk entail measuring aortic diameter but do not image medial degeneration, the cause of TAAs. We sought to determine if the advanced magnetic resonance imaging (MRI) acquisition strategy, diffusion tensor imaging (DTI), could delineate medial degeneration in the ascending thoracic aorta. Methods and results: Porcine ascending aortas were subjected to enzyme microinjection, which yielded local aortic medial degeneration. These lesions were detected by DTI, using a 9.4 T MRI scanner, based on tensor disorientation, disrupted diffusion tracts, and altered DTI metrics. High-resolution spatial analysis revealed that fractional anisotropy positively correlated, and mean and radial diffusivity inversely correlated, with smooth muscle cell (SMC) and elastin content (P < 0.001 for all). Ten operatively harvested human ascending aorta samples (mean subject age 61.6 ± 13.3 years, diameter range 29-64 mm) showed medial pathology that was more diffuse and more complex. Nonetheless, DTI metrics within an aorta spatially correlated with SMC, elastin, and, especially, glycosaminoglycan (GAG) content. Moreover, there were inter-individual differences in slice-averaged DTI metrics. Glycosaminoglycan accumulation and elastin degradation were captured by reduced fractional anisotropy (R2 = 0.47, P = 0.043; R2 = 0.76, P = 0.002), with GAG accumulation also captured by increased mean diffusivity (R2 = 0.46, P = 0.045) and increased radial diffusivity (R2 = 0.60, P = 0.015). Conclusion: Ex vivo high-field DTI can detect ascending aorta medial degeneration and can differentiate TAAs in accordance with their histopathology, especially elastin and GAG changes. This non-destructive window into aortic medial microstructure raises prospects for probing the risks of TAAs beyond lumen dimensions.

20.
J Thorac Cardiovasc Surg ; 167(3): 935-943.e5, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37084820

ABSTRACT

OBJECTIVE: We compared perioperative outcomes of patients with acute type A aortic dissection undergoing hemiarch (HA) versus extended arch (EA) repair with or without descending aortic intervention. METHODS: Nine hundred twenty-nine patients underwent acute type A aortic dissection repair (2002-2021, 9 centers) including open distal repair (HA) with or without additional EA repair. EA with intervention on the descending aorta (EAD) included elephant trunk, antegrade thoracic endovascular aortic replacement, or uncovered dissection stent. EA with no descending intervention (EAND), included unstented suture-only methods. Primary outcomes were in-hospital mortality, permanent neurologic deficit, computed tomography malperfusion resolution, and a composite. Multivariable logistic regression was also performed. RESULTS: Mean age was 66 ± 18 years, 30% (278 out of 929) were women, and HA was performed more frequently (75% [n = 695]) than EA (25% [n = 234]). EAD techniques included: dissection stent (39 out of 234 [17%]), thoracic endovascular aortic replacement (18 out of 234 [7.7%]), and elephant trunk (87 out of 234 [37%]). In-hospital mortality (EA: n = 49 [21%] and HA: n = 129 [19%]; P = .42), and neurological deficit (EA: n = 43 [18%] and HA: n = 121 [17%]; P = .74) were similar. EA was not independently associated with death (EA vs HA odds ratio, 1.09; 95% CI, 0.77-1.54; P = .63) or neurologic deficit (EA vs HA odds ratio, 0.85; 95% CI, 0.47-1.55; P = .59). Composite adverse events differed significantly (EA vs HA odds ratio, 1.47; 95% CI, 1.16-1.87; P = .001). Malperfusion resolved more frequently after EAD (EAD: n = 32 [80%], EAND: n = 18 [56%], HA: n = 71 [50%]; P = .004), although multivariable analysis was not significant (EAD vs HA odds ratio, 2.17; 95% CI, 0.83-5.66; P = .10). CONCLUSIONS: Extended arch interventions pose similar perioperative mortality and neurologic risks as Hemiarch. Descending aortic reinforcement may promote malperfusion restoration. Extended techniques should be approached with caution in acute dissection due to increased risk of adverse events.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , Acute Disease , Treatment Outcome , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Aorta/surgery , Stents , Retrospective Studies , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/etiology
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