Tissue mapping by cardiac magnetic resonance imaging for the prognostication of cardiac amyloidosis: A systematic review and meta-analysis.

BACKGROUND: Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV). METHODS: Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis. RESULTS: A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m2 vs 127 ± 37 g/m2, p = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all p > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; p = 0.003; I2 = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I2 = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I2 = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean). CONCLUSION: Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis.

Assessments of right ventricular strain using cardiac magnetic resonance imaging following kidney transplantation.

Although kidney transplantation (KT) has been shown to ameliorate adverse left ventricular (LV) remodelling associated with end stage kidney disease, its effects on the right ventricle have not been well studied. Recently, strain imaging has been shown to be a sensitive measure of early subclinical myocardial dysfunction. Using cardiac magnetic resonance imaging (MRI), we examined the effects of KT on right ventricular (RV) strain parameters. In a cohort of 81 patients (39 patients underwent KT and 42 patients remained on dialysis as control group), cardiac MRI studies were obtained at baseline and at 1 year follow-up. There were no significant differences in RV strain values between the groups at baseline. After 1 year, RV strain values did not significantly change in patients who received KT, and changes in RV strain over 1 year were not significantly different between the KT and the dialysis groups. Given the previously demonstrated improvement in LV strain post-KT, the current study suggests that RV and LV remodelling post-KT may have different mechanisms. Further studies elucidating the effects of KT on RV remodelling are needed.

Natural history of severe tricuspid regurgitation: Outcomes after transcatheter tricuspid valve intervention compared to medical therapy.

AIMS: We aimed to identify the clinical characteristics and examine outcomes in patients with significant tricuspid regurgitation (TR) who received transcatheter tricuspid valve intervention (TTVI) compared with guideline directed medical therapy (GDMT). METHODS AND RESULTS: Between 2015 and 2019, 124 patients with symptomatic severe TR were assessed at St. Michael's Hospital. Seventy-one patients were ineligible and received GDMT only while 53 patients received TTVI and GDMT. During follow-up, TTVI was associated with significant improvements in NYHA functional class and 6-min walk distance (p < .001). GDMT patients had lower survival (46.9% vs 75.1%, p = .047) and lower freedom from heart failure hospitalization (HHF) and mortality (33.2% vs 62.7%, p = .027), higher incidences per 100 person-year of gastrointestinal bleeding [15.58 (95% CI 8.90-25.31) vs 4.24 (95% CI 0.85-12.37), p = .04] and acute kidney injury [36.98 (95% CI 26.17-50.76) vs 14.12 (95% CI 6.76-25.96), p = .001] compared with TTVI patients. CONCLUSION: TTVI in addition to GDMT was effective at improving TR symptoms, functional status, and was associated with lower rates of all-cause mortality, the combined endpoint of HHF and mortality, AKI and GI bleeding. Future randomized controlled trials on TTVI are needed.

Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.

BACKGROUND: Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. METHODS: We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52 weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. RESULTS: Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index (60.6 ± 4.3 mL/m2 vs 64.2 ± 5.1 mL/m2, p = 0.99) or PAT index (60.0 ± 5.4 mL/m2 vs 53.2 ± 5.9 mL/m2, p = 0.42) between INHD and CHD groups. Over 52 weeks, EAT index and PAT index did not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EAT index and PAT index did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT index inversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PAT index inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT index or PAT index with changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52 weeks (all p > 0.30). CONCLUSIONS: INHD was not associated with any changes in EAT index and PAT index over 12 months. Changes in EAT index were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PAT index, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. GOV IDENTIFIER: NCT00718848.

Intravenous miR-144 reduces left ventricular remodeling after myocardial infarction.

MicroRNA-144 is a cytoprotective miRNA. Our previous study showed that miR-144 provides potent acute cardioprotection in an ischemia/reperfusion injury model. This study was performed to further assess whether miR-144 improves post-MI remodeling in a non-reperfused myocardial infarction (MI) model. C57BL/6 mice were subjected to MI by permanent left anterior descending artery (LAD) ligation. miR-144 was delivered by intravenous injections of 8 mg/kg, 16 mg/kg, or 32 mg/kg at day 0, day 1, day 3, and then a similar dose given once every 3 days, until day 28 after MI. Cardiac function was evaluated using echocardiography. At the end of the study, heart function was also evaluated using a pressure volume catheter. The percentage of the length of the infarct scar on the left ventricle (LV) circumferential length was calculated for heart each section. The miR-144 KO mice showed a worse heart failure phenotype with ventricular dilation and impaired contractility after LAD ligation. Ischemia decreased miR-144 levels, and the miR-144 level was restored to baseline by administration of intravenous miR-144. Cy3-labeled miR-144 was localized to the infarct and border zone, and was taken up by cardiomyocytes and macrophages. In miR-144-treated groups, at 28 days MI size was significantly reduced, and cardiac function was improved [LV fractional shortening, end-systolic volume (µL), end-diastolic volume (µL), ejection fraction (%), dP/dt max (mmHg/s), dP/dt min (mmHg/s), Tau (ms)], compared with controls (p < 0.01). This beneficial effect was associated with reduced border zone fibrosis, inflammation and apoptosis, these effects were associated with significant changes in autophagy signaling. Intravenous miR-144 has potent effects on post-MI remodeling. These findings suggest that miR-144 has potential as a therapeutic agent after MI.

Real-world treatment patterns and effectiveness among patients with metastatic colorectal cancer treated with ziv-aflibercept in community oncology practices in the USA.

Routine clinical practice data often differ from clinical trials. This study describes real-world treatment patterns and effectiveness among patients with metastatic colorectal cancer (mCRC) receiving ziv-aflibercept in non-academic, community oncology practices in the USA. De-identified electronic medical records from Vector Oncology and Altos Solutions databases were analysed. We identified 218 patients diagnosed with mCRC who had received prior oxaliplatin therapy and initiated ziv-aflibercept as part of second-line or later-line therapy. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier analysis. Mean age was 62.8 years at ziv-aflibercept initiation. Most patients (91.7%) received bevacizumab before ziv-aflibercept, 95.4% initiated ziv-aflibercept with FOLFIRI or another irinotecan-based regimen, and 59.6% had received prior irinotecan. Overall, 24.8% of patients initiated ziv-aflibercept in second line, 31.7% in third line, 21.6% in fourth line and 22.0% in later lines of therapy. Mean duration of ziv-aflibercept treatment was 5.3 months. For patients initiating ziv-aflibercept in second-, third- and fourth-line therapy, median OS was 11.9 (95% confidence interval 5.1-16.2), 11.1 (6.9-16.7) and 8.1 (5.2-11.4) months, respectively, and median PFS was 4.4 (2.8-6.5), 4.3 (2.9-6.3) and 3.4 (2.2-5.2) months, respectively. Common adverse events (AEs) (any grade) included gastrointestinal disorders (64.7%) and asthenia/fatigue (63.3%). In routine clinical practice, ziv-aflibercept was frequently initiated in third line or later lines of therapy. Although patients receiving ziv-aflibercept were more heavily pretreated and potentially less robust compared with the VELOUR trial, median OS for patients receiving second-line ziv-aflibercept was comparable. AE rates were similar to or lower than the VELOUR trial.

Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison.

This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression-Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was -14.98 (-17.14, -12.80) for lisdexamfetamine dimesylate (LDX), -9.33 (-11.63, -7.04) for methylphenidate (MPH) extended release, -8.68 (-10.63, -6.72) for guanfacine extended release (GXR), and -6.88 (-8.22, -5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.

Time Dependent Distribution of MicroRNA 144 after Intravenous Delivery.

BACKGROUND: miR-144 has potential benefits in protecting against myocardial ischemia and suppression of tumor growth. We have previously shown that a single intravenous injection of miR-144 provides potent cardioprotection, but its kinetics and distribution are not known. METHODS: Single stranded mature miR-144 or Cy3-labelled-miR-144 was delivered into C57/B6 mice by tail vein injection. RESULTS: After intravenous injection, the signal of Cy3-labelled-miR-144 in the kidney, brain, heart and liver peaks at 60 minutes, and is predominantly localised to the endothelium at that stage. In the kidney and heart, Cy3-labelled-miR-144 signal is detectable within the parenchymal tissues for at least 3 days, after which it starts to decrease, but brain Cy3-miR-144 signal rapidly decreases after 1 hour, and is lost at day 1, with no parenchymal uptake detected. Cy3-miR-144 signal can be detected until day 28 in the liver. Stem loop RTPCR confirmed the temporal pattern shown by miR-144 in kidney, brain and heart, but in liver there was a continuous rise following the initial injection until day 28 with no signs of decrease, suggesting de-novo synthesis. CONCLUSION: There is early endothelial uptake of injected miR-144 followed by organ-specific distribution and kinetics. In the liver, there appears to be a positive feedback process that leads to continued accumulation of miR-144 that persists for at least 28 days. These observations should be taken into account when designing experiments utilizing parenteral miR-144 and assessing the biology of its actions.

Brentuximab vedotin compared with other therapies in relapsed/refractory Hodgkin lymphoma post autologous stem cell transplant: median overall survival meta-analysis.

OBJECTIVE: This meta-analysis compared the median overall survival (mOS) of brentuximab vedotin reported in the pivotal phase 2 study with published results of other therapies for the treatment of relapsed/refractory (R/R) Hodgkin lymphoma (HL) post autologous stem cell transplant (ASCT). RESEARCH DESIGN AND METHODS: A systematic literature review identified studies that reported survival outcomes following conventional/experimental therapies in R/R HL patients, with ≥50% having failed ≥1 ASCT. Kaplan-Meier curves were used to reconstruct individual patient level survival data. Patients were grouped by treatment type and reconstructed data were used to estimate the mOS. Censored median regression modeling was used to compare mOS in each group with the mOS in the pivotal brentuximab vedotin trial. All patients in the pivotal trial had undergone ASCT, therefore a sensitivity analysis was conducted among studies with a 100% post-ASCT patient population. RESULTS: The mOS reported for brentuximab vedotin was 40.5 (95% CI 30.8-NA) compared with 26.4 months (95% CI 23.5-28.5) across all 40 studies identified (n = 2518 excluding the brentuximab vedotin trial) (p < 0.0001). The difference in mOS between brentuximab vedotin and chemotherapy, allogeneic stem cell transplant (allo-SCT), and other therapies, was 17.7 (95% CI 10.6-24.7; p < 0.0001), 12.5 (95% CI 8.2-16.9; p < 0.0001), and 15.2 months (95% CI 4.9-25.5; p = 0.0037), respectively. For the 11 studies reporting a 100% prior-ASCT rate (n = 662 excluding the brentuximab vedotin trial), the mOS was 28.1 months (95% CI 23.9-34.5), and the difference in mOS between brentuximab vedotin, chemotherapy, allo-SCT, and other therapies was 19.0 (95% CI 12.9-25.1; p < 0.0001), 9.4 (p > 0.05), and 6.8 months (95% CI 1.2-12.5; p = 0.0018), respectively. CONCLUSIONS: While some selection bias may occur when comparing trials with heterogeneous eligibility criteria, in the absence of randomized controlled trial data these results suggest brentuximab vedotin improves long-term survival and is associated with longer mOS in R/R HL post-ASCT compared with other therapies.

Effect of clinic experience on pre-service professionals perceptions of applied special needs services / Effect of clinic experience on pre-service professionals perceptions of applied special needs services

With the understanding that the attitudes and expectations a teacher carries into the classroom directly affect student achievement, this study was administered to evaluate the cognitive affect that clinical experience incorporating individuals with disabilities had on pre-service exercise science professionals. University Students with and withoutexperience in an adapted clinical environment were given surveys covering attitudes and perceptions towards classroom atmosphere, teachers? instructional techniques, inclusion, and self-efficacy. Data were analyzed and used to determine pedagogical implications. Findings suggest that pre-service educators tend to feel unprepared and ill-equipped to work in an inclusive educational environment. Therefore, pre-service teacher programs should ideally include coursework in adaptive education and experiential components such as practicum, experience, and clinical experience. In addition, a school-universitycollaborative relationship can facilitate beneficial outcomes to future educators as well as special needs populations.

Considerando que as atitudes e expectativas que o professor tem na sala de aula afetam diretamente o desempenho do aluno, este estudo teve como objetivo avaliar o efeito cognitivo da experiência clínica acumulada no atendimento com sujeitos portadores de necessidade especiais por profissionais de ciências do exercício. Estudantes universitários com e sem experiência em atividades laborais adaptadas participaram do estudo. Foram fornecidas informações que abrangiam as atitudes e percepções sobre o ambiente da sala de aula, orientações pedagógicas, inclusão e autoeficácia. Os resultados foram analisados e usados para implicações pedagógicas. Os resultados sugerem que os pré-educadores tendem a sentir-se despreparados e mal equipados para trabalhar em um ambiente educacional de inclusão. Portanto, os programas colaborativos de formação de pré-professores deveriam contemplar os cursos de formação educacional, com experiências práticas para o attendimento em ambientes de inclusão social, tais como estágio, experiência de campo e experiência clínica. Além disso, os cursos escola universidade podemoportunizar experiências que facilitem os resultados benéficos para futuros educadores, bem como a atuação junto a populações com necessidades especiais.