Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Clinical value of patient-specific three-dimensional printing of congenital heart disease: Quantitative and qualitative assessments

Objective: Current diagnostic assessment tools remain suboptimal in demonstrating complex morphology of congenital heart disease (CHD). This limitation has posed several challenges in preoperative planning, communication in medical practice, and medical education. This study aims to investigate the dimensional accuracy and the clinical value of 3D printed model of CHD in the above three areas. Methods: Using cardiac computed tomography angiography (CCTA) data, a patient-specific 3D model of a 20-month-old boy with double outlet right ventricle was printed in Tango Plus material. Pearson correlation coefficient was used to evaluate correlation of the quantitative measurements taken at analogous anatomical locations between the CCTA images pre- and post-3D printing. Qualitative analysis was conducted by distributing surveys to six health professionals (two radiologists, two cardiologists and two cardiac surgeons) and three medical academics to assess the clinical value of the 3D printed model in these three areas. Results: Excellent correlation (r = 0.99) was noted in the measurements between CCTA and 3D printed model, with a mean difference of 0.23 mm. Four out of six health professionals found the model to be useful in facilitating preoperative planning, while all of them thought that the model would be invaluable in enhancing patient-doctor communication. All three medical academics found the model to be helpful in teaching, and thought that the students will be able to learn the pathology quicker with better understanding. Conclusion: The complex cardiac anatomy can be accurately replicated in flexible material using 3D printing technology. 3D printed heart models could serve as an excellent tool in facilitating preoperative planning, communication in medical practice, and medical education, although further studies with inclusion of more clinical cases are needed

Analysing functional implications of differences in left ventricular morphology using statistical shape modelling

Functional implications of left ventricular (LV) morphological characterization in congenital heart disease are not widely explored. This study qualitatively and quantitatively assessed LV shape associations with a) LV function and b) thoracic aortic morphology in patients with aortic coarctation (CoA) with/without bicuspid aortic valve (BAV), and healthy controls. A statistical shape modelling framework was employed to analyse three-dimensional (3D) LV shapes from cardiac magnetic resonance (CMR) data in isolated CoA (n = 25), CoA + BAV (n = 30), isolated BAV (n = 30), and healthy controls (n = 25). Average 3D templates and deformations were computed. Correlations between shape data and CMR-derived morphometric parameters (i.e., sphericity, conicity) or global and apical strain values were assessed to elucidate possible functional implications. The relationship between LV shape features and arch architecture was also explored. The LV template was shorter and more spherical in CoA patients. Sphericity was overall associated with global and apical radial (p = 0.001, R(2) = 0.09; p < 0.0001, R(2) = 0.17) and circumferential strain (p = 0.001, R(2) = 0.10; p = 0.04, R(2) = 0.04), irrespective of the presence of aortic stenosis and/or regurgitation and controlling for age and hypertension status. LV strain was not associated with arch architecture. Differences in LV morphology were observed between CoA and BAV patients. Increasing LV sphericity was associated with reduced strain, independent of aortic arch architecture and functional aortic valve disease

MicroRNAs as potential biomarkers in congenital heart surgery

Objective: Pediatric congenital heart surgery (CHS)involves intracardiac, valvular, and vascular repairs. Accurate tools to aid short-term outcome prediction in pediatric CHS are lacking. Clinical scores, such as the vasoactive-inotrope score and ventilation index, are used to define outcome in clinical studies. MicroRNA-1-3p (miR-1)is expressed by both cardiomyocytes and vascular cells and is regulated by hypoxia. In adult patients, miR-1 increases in the circulation after open-heart cardiac surgery, suggesting its potential as a clinical biomarker. Thus, we investigated whether perioperative circulating miR-1 measurements can help predict post-CHS short-term outcomes in pediatric patients. Methods: Plasma miR-1 was retrospectively measured in a cohort of 199 consecutive pediatric CHS patients (median age 1.2 years). Samples were taken before surgery and at the end of the operation. Plasma miR-1 concentration was measured by reverse transcription-quantitative polymerase chain reaction and expressed as miR-1 copies/μL and as relative expression to spiked-in exogenous cel-miR-39. Results: Baseline plasma miR-1 did not vary across different diagnoses, increased during surgery (204-fold median relative increase, P &lt;.001), and was associated with aortic crossclamp duration postoperatively (P &lt;.001). Importantly, miR-1 levels at the end of the operation positively correlated with intensive care stay (P &lt;.001), early severe cardiovascular events (P =.01), and with high vasoactive-inotrope score (P =.001)and ventilation index (P &lt;.001), suggesting that miR-1 could accelerate the identification of patients with cardiopulmonary bypass−related ischemic complications, requiring more intensive support.Conclusions: Our study suggests miR-1 as a novel potential circulating biomarker to predict early postoperative outcome and inform clinical management in pediatric heart surgery.</p

Prognostic Role of CMR and Conventional Risk Factors in Myocardial Infarction With Nonobstructed Coronary Arteries

Objectives: This study sought to assess the prognostic impact of cardiac magnetic resonance (CMR) and conventional risk factors in patients with myocardial infarction with nonobstructed coronaries (MINOCA). Background: Myocardial infarction with nonobstructed coronary arteries (MINOCA) represents a diagnostic dilemma, and the prognostic markers have not been clarified. Methods: A total of 388 consecutive patients with MINOCA undergoing CMR assessment were identified retrospectively from a registry database and prospectively followed for a primary clinical endpoint of all-cause mortality. A 1.5-T CMR was performed using a comprehensive protocol (cines, T2-weighted, and late gadolinium enhancement sequences). Patients were grouped into 4 categories based on their CMR findings: myocardial infarction (MI) (embolic/spontaneous recanalization), myocarditis, cardiomyopathy, and normal CMR. Results: CMR (performed at a median of 37 days from presentation) was able to identify the cause for the troponin rise in 74% of the patients (25% myocarditis, 25% MI, and 25% cardiomyopathy), whereas a normal CMR was identified in 26%. Over a median follow-up of 1,262 days (3.5 years), 5.7% patients died. The cardiomyopathy group had the worst prognosis (mortality 15%; log-rank test: 19.9; p &lt; 0.001), MI had 4% mortality, and 2% in both myocarditis and normal CMR. In a multivariable Cox regression model (including clinical and CMR parameters), CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation electrocardiogram (ECG) remained the only 2 significant predictors of mortality. Using presentation with ECG ST-segment elevation and CMR diagnosis of cardiomyopathy as risk markers, the mortality risk rates were 2%, 11%, and 21% for presence of 0, 1, and 2 factors, respectively (p &lt; 0.0001). Conclusions: In a large cohort of patients with MINOCA, CMR (median 37 days from presentation) identified a final diagnosis in 74% of patients. Cardiomyopathy had the highest mortality, followed by MI. The strongest predictors of mortality were a CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation ECG.</p

Pediatric Visceral Leishmaniasis in Albania: A Retrospective Analysis of 1,210 Consecutive Hospitalized Patients (1995–2009)

Albania is a developing country that is rapidly improving in social, economic and sanitary conditions. The health care system in still in progress and the impact of some infectious diseases remains poorly understood. In particular, little information is available on incidence, clinical features and response to treatment of visceral leishmaniasis (VL) in childhood. We performed a retrospective analysis of data recorded from 1995 to 2009 at the national pediatric reference hospital of Tirana where any child suspected for VL is referred for specific diagnosis and treatment. Epidemiology, clinical features and management of the disease were considered. The main findings can be summarized as follows: i) The incidence of the disease in Albanian children (25/100,000 in the age group 0–6 years) is much higher than in developed Mediterranean countries endemic for VL; ii) The disease is associated with poor sanitary conditions as suggested by the high rate of severe clinical features and frequency of co-morbidities; iii) The cheapest drug available for Mediterranean VL treatment (meglumine antimoniate) is highly effective (99% full cure rate) and well tolerated. Limitations were identified in the low standard laboratory diagnostic capability and unsatisfactory medical surveillance in less urbanized areas. An improvement is warranted of a disease-specific surveillance system in Albania

Assessment of post-infarct ventricular septal defects through 3D printing and statistical shape analysis: Supplementary table

Table 1: Examples of feedback from clinicians in relation to dominant themes from analysis of model evaluation.Background: Post-infarct ventricular septal defect (PIVSD) is a serious complication of myocardial infarction. We evaluated 3D-printing models in PIVSD clinical assessment and the feasibility of statistical shape modeling for morphological analysis of the defects. Methods: Models (n = 15) reconstructed from computed tomography data were evaluated by clinicians (n = 8). Statistical shape modeling was performed on 3D meshes to calculate the mean morphological configuration of the defects. Results: Clinicians’ evaluation highlighted the models’ utility in displaying defects for interventional/surgical planning, education/training and device development. However, models lack dynamic representation. Morphological analysis was feasible and revealed oval-shaped (n = 12) and complex channel-like (n = 3) defects. Conclusion: 3D-PIVSD models can complement imaging data for teaching and procedural planning. Statistical shape modeling is feasible in this scenario.The authors gratefully acknowledge the support of the British Heart Foundation (CH/17/1/32804), the Bristol BHF Accelerator Award (AA/18/1/34219), The Grand Appeal (Bristol Children’s Hospital Charity), and the Bristol National Institute for Health Research (NIHR) Biomedical Research Centre (BRC). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Peer reviewe

Assessment of post-infarct ventricular septal defects through 3D printing and statistical shape analysis

© 2023 Giovanni Biglino. This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Background: Post-infarct ventricular septal defect (PIVSD) is a serious complication of myocardial infarction. We evaluated 3D-printing models in PIVSD clinical assessment and the feasibility of statistical shape modeling for morphological analysis of the defects. Methods: Models (n = 15) reconstructed from computed tomography data were evaluated by clinicians (n = 8). Statistical shape modeling was performed on 3D meshes to calculate the mean morphological configuration of the defects. Results: Clinicians’ evaluation highlighted the models’ utility in displaying defects for interventional/surgical planning, education/training and device development. However, models lack dynamic representation. Morphological analysis was feasible and revealed oval-shaped (n = 12) and complex channel-like (n = 3) defects. Conclusion: 3D-PIVSD models can complement imaging data for teaching and procedural planning. Statistical shape modeling is feasible in this scenario.The authors gratefully acknowledge the support of the British Heart Foundation (CH/17/1/32804), the Bristol BHF Accelerator Award (AA/18/1/34219), The Grand Appeal (Bristol Children’s Hospital Charity), and the Bristol National Institute for Health Research (NIHR) Biomedical Research Centre (BRC).Peer reviewe