Nanomedicine as a putative approach for active targeting of hepatocellular carcinoma.

The effectiveness of chemotherapy in hepatocellular carcinoma (HCC) is restricted by chemo-resistance and systemic side effects. To improve the efficacy and safety of chemotherapeutics in HCC management, scientists have attempted to deliver these drugs to malignant tissues using targeted carriers as nanoparticles (NPs). Among the three types of NPs targeting (active, passive, and stimuli-responsive), active targeting is the most commonly investigated in HCC treatment. Despite the observed promising results so far, clinical research on nanomedicine targeting for HCC treatment still faces many challenges.These include batch-to-batch physicochemical properties' variations, limiting large scale production and insufficient data on human and environmental toxicities. This review summarized the characteristics of different nanocarriers, ligands, targeted receptors on HCC cells and provided recommendations to overcome the challenges, facing this novel line of treatment for HCC.

Two-year outcomes after transcatheter aortic valve-in-valve implantation in degenerated surgical valves.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.

Radiation reduction in a modern catheterization laboratory: A single-center experience.

BACKGROUND: Measures were undertaken at the Cleveland Clinic to reduce radiation exposure to patients and personnel working in the catheterization laboratories. We report our experience with these improved systems over a 7-year period in patients undergoing diagnostic catheterization (DC) and percutaneous coronary interventions (PCIs). METHODS: Patients were categorized into preinitiative (2009-2012) and postinitiative (2013-2019) groups in the DC and PCI cohorts. Propensity score matching was done between the pre- and postinitiative groups for both cohorts based on age, sex, body surface area, total fluoroscopy time, and total acquisition time. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (Ka,r ), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups. RESULTS: In the DC cohort, there was a significant reduction in Ka,r in the postinitiative group in comparison to the preinitiative group (median, 396 vs. 857 mGy; p < 0.001). In the PCI cohort, Ka,r in the postinitiative group was 1265 mGy, which was significantly lower than the corresponding values in the preinitiative group (1994 mGy; p < 0.001). We also observed a significant reduction in fluoroscopy- and acquisition-based air kerma rates, and air kerma area product in the postinitiative group in comparison to the preinitiative group in both matched and unmatched DC and PCI cohorts after the institution of radiation reduction measures. CONCLUSION: There was a significant and sustained reduction in radiation exposure to patients in the catheterization laboratory with the implementation of advanced protocols. Similar algorithms can be applied in other laboratories to achieve a similar reduction in radiation exposure.

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies.

BACKGROUND: Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. METHODS: PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. RESULTS: Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as "very low." CONCLUSIONS: Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017.

BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Three-Year Outcomes of Balloon-Expandable Transcatheter Aortic Valve Implantation According to Annular Size.

Data on the association between annular size and transcatheter aortic valve implantation (TAVI) outcomes beyond 1 year are limited. The present study assessed the association between the aortic annulus size and TAVI clinical and hemodynamic outcomes at 3 years of follow-up. Patients were classified according to the aortic annulus size as having small, intermediate, and large annuli (size <400, 400 to 574, and ≥575 mm2, respectively). The co-primary endpoints were all-cause mortality and heart failure hospitalization. Further, the changes in hemodynamic outcomes over the follow-up period (median 37, interquartile range: 26 to 45 months) were assessed. The present analysis included 850 patients, with 182 patients (21.4%), 538 patients (63.3%), and 130 patients (15.3%) in the small, intermediate, and large-sized aortic annulus groups, respectively. The groups had comparable age and pre-TAVI pressure gradients; however, patients with small annuli had higher Society of Thoracic Surgeons risk scores. Adjusted Cox regression analysis showed that compared to patients with intermediate-sized annuli, patients with small and large annuli had similar all-cause mortality (hazard ratio [HR] = 1.11, 95% confidence interval [CI] 0.72 to 1.69 and HR = 0.74, 95% CI 0.48 to 1.16, respectively) and heart failure hospitalization rates (HR = 0.96, 95% CI 0.55 to 1.69 and HR = 1.26, 95% CI 0.73 to 2.17, respectively). However, patients with small annuli had consistently higher mean and peak pressure gradients and a higher risk of patient-prosthesis mismatch. The risks of moderate-to-severe regurgitation and structural valve deterioration were similar between the three groups. In conclusion, although patients with small annuli had higher transvalvular gradients, there was no significant association between the aortic annulus size and TAVI clinical outcomes at 3 years of follow-up. Future studies should compare the performance of transcatheter valve types in patients with different aortic annulus sizes.

The underutilization of preventive cardiovascular measures in patients with cancer: an analysis of the Behavioural Risk Factor Surveillance System, 2011-22.

AIMS: This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD). METHODS AND RESULTS: Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011-22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported a history of CVD (coronary disease or stroke), and 842 221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with vs. without CVD (P-value for interaction: <0.001). Among patients with CVD, a cancer diagnosis was associated with a lower use of blood pressure-lowering medications {AME: -1.46% [95% confidence interval (CI): -2.19% to -0.73%]}, lipid-lowering medications [AME: -2.34% (95% CI: -4.03% to -0.66%)], and aspirin [AME: -6.05% (95% CI: -8.88% to -3.23%)]. Among patients without CVD, there were no statistically significant differences between patients with and without cancer regarding pharmacological therapies. Additionally, cancer was associated with a significantly lower likelihood of engaging in physical activity in the overall cohort and in using post-CVD rehabilitation regimens, particularly post-stroke rehabilitation. CONCLUSION: Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD. LAY SUMMARY: •This paper compared the use of preventive cardiovascular measures, both pharmaceutical and non-pharmaceutical, in patients with and without cancer.•In patients with cardiovascular disease and cancer, there is a lower use of preventive cardiovascular medications compared with those with cardiovascular disease but without cancer. This includes a lower utilization of blood pressure-lowering medications, cholesterol-lowering medications, and aspirin.•Patients with cancer reported lower levels of exercise but higher levels of smoking cessation compared with those without cancer.

Short-Term Outcomes Following Left Atrial Appendage Closure in the Very Elderly: A Population-Based Analysis.

Background Data on percutaneous left atrial appendage closure (LAAC) outcomes in the very elderly with atrial fibrillation are limited. We aimed to investigate the clinical characteristics and short-term outcomes of patients 80 years or older following percutaneous LAAC in a large nationwide database. Methods and Results Using the Nationwide Readmissions Database, we identified patients who underwent percutaneous LAAC between January 2016 and December 2018. Patients were categorized based on age (≥80 and <80 years old). The primary outcome was in-hospital mortality. Secondary outcomes were in-hospital end points including periprocedural complications, 30-day outcomes, and all-cause 30-day readmissions. A propensity score-matched model (1:1) was used to adjust for baseline characteristics among the study groups. A total of 13 208 patients were included in this study (43% women, median age in years [interquartile range] 79.5 [73-84]) and matched one-to-one (6604 and 6604 patients were ≥80 and <80 years old, respectively). In-hospital mortality was not statistically different between the study groups and occurred in 21 patients ≥80 years old (0.32%) and in 14 patients <80 years old (0.21%); P=0.236. Rates of in-hospital stroke/transient ischemic attack were higher in patients ≥80 years old compared with those <80 years old (1.22% versus 0.77%; P=0.009). In-hospital bleeding requiring transfusion, vascular complications, systemic embolization, and pericardial effusion/tamponade requiring pericardiocentesis or surgical intervention occurred more frequently in patients ≥80 years old. Furthermore, the elderly group was more likely to be readmitted within 30 days compared with those <80 years old (9.91% versus 8.4%; P=0.004); however, rates of 30-day complications were not statistically different between the study groups. Conclusions In a large nationwide database, patients ≥80 years old undergoing percutaneous LAAC were found to have similar in-hospital mortality but an increased risk of periprocedural complications and 30-day readmission compared with younger patients. Our data suggest that LAAC should be considered on a case-by-case basis in the very elderly, taking into consideration the risks and benefits of this intervention. Further studies are needed to assess long-term LAAC outcomes in this high-risk population.

Expression of oncolong noncoding RNA taurine-upregulated gene-1 in colon cancer: A clinical study supported by in silico analysis.

Context: Recent studies confirmed that dysregulation of long noncoding RNAs (lncRNAs) is a potential contributor to the development and progression of colon cancer. However, the prognostic value of these RNA molecules remains controversial. Aims: This study aimed to investigate the expression of taurine-upregulated gene-1 (TUG1) lncRNA in colon cancer and its clinical implications. Subjects and Methods: A retrospective study on 47 formalin-fixed, paraffin-embedded samples of surgically resected primary colon cancer specimens was done. Total RNA purified from the colon cancer samples and noncancer adjacent tissue sections was quantified by real-time reverse transcription-polymerase chain reaction (qRT-PCR) to assess TUG1 relative expression levels normalized to GAPDH endogenous control. Also, in silico data analysis was applied. Statistical Analysis Used: The relative expression levels were calculated using the LIVAK method. The survival rates were assessed using the Kaplan-Meier curves and the Cox proportional model. P < 0.05 was considered statistically significant. Results: TUG1expression in the colon cancer specimens was significantly overexpressed (median = 21.50, interquartile range [IQR]: 7.0-209.2; P = 0.001) relative to the noncancerous tissues. In silico analysis confirmed TUG1 upregulation in colon carcinoma (median = 13.92, IQR: 13.5-1432). There were no significant associations between TUG1 expression and clinicopathological characteristics, such as the site, grade, stage, histopathological type, or the rates of lymphovascular invasion and relapse. Similarly, Kaplan-Meir and Cox multivariate regression analyses showed that TUG1 expression could not predict the overall survival and progression-free survival in colon cancer patients of our population. Conclusions: This study confirms the overexpression of TUG1 lncRNA in colon cancer tissues. Larger sample size is warranted to further elucidate the specific role of TUG1 in colon cancer.

Fixed-Dose Combination (Polypill) for Cardiovascular Disease Prevention: A Meta-Analysis.

INTRODUCTION: This meta-analysis was performed to assess the efficacy of fixed-dose combination (polypill) in reducing the risk of mortality and cardiovascular events. METHODS: Medline, Scopus, Web of Science, and Cochrane Central were searched during May 2021. All randomized trials investigating the efficacy of antihypertensive and lipid-lowering ± antiplatelet drug combinations in patients at cardiovascular risk were included. Outcomes were presented as risk ratios or standardized mean differences with 95% CIs. RESULTS: A total of 16 trials (N = 26,567 participants) were included. The risk reduction for all-cause mortality (risk ratio = 0.90; 95% CI = 0.79, 1.01; I2 = 0%; moderate certainty) and major adverse cardiac events (risk ratio=0.84; 95% CI=0.68, 1.04; I2=51%; very low certainty) did not reach statistical significance in comparison with those of the control group. Subgroup analysis of studies that used an active control yielded similar results. However, significant reductions in major adverse cardiac event risk were observed in studies that exclusively targeted primary prevention, followed patients for ≥4 years, and had a low risk of bias. The polypill group had significantly higher adherence (risk ratio=1.18; 95% CI=1.06, 1.32; I2=96%; very low certainty) and comprable rates of adverse side effects (risk ratio=1.10; 95% CI=0.98, 1.23; I2=58%; moderate certainty) with those of the control group. Patients randomized to the polypill had significant reductions in systolic and diastolic blood pressure as well as in total and low-density lipoprotein cholesterol. DISCUSSION: Despite reductions in cardiovascular risk factors, the observed mortality benefit for the polypill did not reach statistical significance. Further studies are needed to validate its clinical benefits and determine the patient populations likely to achieve such benefits.

Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

BACKGROUND: Since the initial clinical description of hypertrophic cardiomyopathy (HCM) over 60 years ago, sudden cardiac death (SCD) has been the most visible and feared complication of HCM. OBJECTIVES: This study sought to characterize the temporal, geographic, and age-related trends of reported SCD rates in adult HCM patients. METHODS: Electronic databases were systematically searched up to November 2021 for studies reporting on SCD event rates in HCM patients. Patients with SCD equivalents (appropriate implantable cardioverter-defibrillator [ICD] shocks and nonfatal cardiac arrests) were not included. A random-effects model was used to pool study estimates calculating the overall incidence rates (IR) for each time-era, geographic region, and age group. We analyzed 2 periods (before vs after 2000, following clinical implementation of ICD in HCM). Following 2000, 5-year intervals were used to demonstrate the temporal change in SCD rates. RESULTS: A total of 98 studies (N = 70,510 patients and 431,407 patient-years) met our inclusion criteria. The overall rate of HCM SCD was 0.43%/y (95% CI: 0.37-0.50%/y; I2 = 75%; SCD events: 1,938; person-years of follow-up: 408,715), with young patients (<18 years of age) demonstrating a >2-fold-risk for sudden death vs adult patients 18-60 years of age (IR: 1.09%; 95% CI: 0.69%-1.73% vs IR: 0.43%; 95% CI: 0.37%-0.50%) (P value for subgroup differences <0.01). Contemporary SCD rates from 2015 to present were 0.32%/y and significantly lower compared with 2000 or earlier (IR: 0.32%; 95% CI: 0.20%-0.52% vs IR: 0.73%; 95% CI: 0.53%-1.02%, respectively). Reported SCD rates for HCM were lowest in North America (IR: 0.28%; 95% CI: 0.18%-0.43%,) and highest in Asia (IR: 0.67%; 95% CI: 0.54%-0.84%). CONCLUSIONS: Contemporary HCM-related SCD rates are low (0.32%/y) representing a 2-fold decrease compared with prior treatment eras. Young HCM patients are at the highest risk. The maturation of SCD risk stratification strategies and the application of primary prevention ICD to HCM are likely responsible for the notable decline over time in SCD events. In addition, worldwide geographic disparities in SCD rates were evident, underscoring the need to increase access to SCD prevention treatment for all HCM patients.

Impact of post-procedural length of stay on short-term outcomes and readmissions after TAVR and MitraClip.

Background: Post-procedural hospital length of stay (P-LOS) is an important determinant of cost-related outcomes. In the present study, we aimed to assess the impact of P-LOS on short-term outcomes after transcatheter aortic valve replacement (TAVR) and MitraClip. Methods: We performed a retrospective cohort study, retrieving data from the National Readmissions Database (NRD) for patients who underwent transfemoral TAVR and MitraClip between January 2014 and December 2017. We employed multivariable logistic regression to evaluate the association between P-LOS and 30-day all-cause mortality and readmissions. Results: A total of 65,726 and 7347 patients underwent TAVR and MitraClip, respectively within the study period. After 30 days of discharge, 13.7% and 15.1% of TAVR and MitraClip patients were readmitted for any reason, while 0.5% and 0.9% died within the readmission hospitalization. A longer P-LOS was associated with an increased risk of 30-day all-cause readmission in both TAVR (OR = 1.027, 95% CI [1.023-1.032]) and MitraClip (OR = 1.025, 95%CI [1.012-1.038]) patients. This finding remained true for patients who developed or did not develop complications after both procedures. In terms of 30-day inhospital mortality, a longer P-LOS was associated with a higher risk in TAVR patients (OR = 1.039, 95%CI [1.028-1.049]), but no increased risk in MitraClip patients (OR = 1.014, 95%CI [0.985-1.044]). Other predictors of 30-day readmission after both procedures included heart failure, post-procedural acute kidney injury, and discharge with disability. Conclusion: The current study shows that shorter P-LOS was associated with reduced risk of short-term readmission after both TAVR and MitraClip and reduced short-term mortality after TAVR (mainly in patients who developed post-procedural complications). Shorter P-LOS is a predictor of readmission and sicker patient group. Patients requiring longer LOS should be followed closely to prevent readmission and enhance better outcomes. Future studies evaluating P-LOS impact on long-term and patient-oriented outcomes are needed.

Quality Assessment of Published Systematic Reviews in High Impact Cardiology Journals: Revisiting the Evidence Pyramid.

Objective: Systematic reviews are increasingly used as sources of evidence in clinical cardiology guidelines. In the present study, we aimed to assess the quality of published systematic reviews in high impact cardiology journals. Methods: We searched PubMed for systematic reviews published between 2010 and 2019 in five general cardiology journals with the highest impact factor (according to Clarivate Analytics 2019). We extracted data on eligibility criteria, methodological characteristics, bias assessments, and sources of funding. Further, we assessed the quality of retrieved reviews using the AMSTAR tool. Results: A total of 352 systematic reviews were assessed. The AMSTAR quality score was low or critically low in 71% (95% CI: 65.7-75.4) of the assessed reviews. Sixty-four reviews (18.2%, 95% CI: 14.5-22.6) registered/published their protocol. Only 221 reviews (62.8%, 95% CI: 57.6-67.7) reported adherence to the EQUATOR checklists, 208 reviews (58.4%, 95% CI: 53.9-64.1) assessed the risk of bias in the included studies, and 177 reviews (52.3%, 95% CI: 45.1-55.5) assessed the risk of publication bias in their primary outcome analysis. The primary outcome was statistically significant in 274 (79.6%, 95% CI: 75.1-83.6) and had statistical heterogeneity in 167 (48.5%, 95% CI: 43.3-53.8) reviews. The use and sources of external funding was not disclosed in 87 reviews (24.7%, 95% CI: 20.5-29.5). Data analysis showed that the existence of publication bias was significantly associated with statistical heterogeneity of the primary outcome and that complex design, larger sample size, and higher AMSTAR quality score were associated with higher citation metrics. Conclusion: Our analysis uncovered widespread gaps in conducting and reporting systematic reviews in cardiology. These findings highlight the importance of rigorous editorial and peer review policies in systematic review publishing, as well as education of the investigators and clinicians on the synthesis and interpretation of evidence.

Predictors of Procedural Success in Patients With Degenerated Surgical Valves Undergoing Transcatheter Aortic Valve-in-Valve Implantation.

Background: Valve-in-Valve transcatheter aortic valve implantation (ViV-TAVI) is a growing alternative for redo-surgery in patients with degenerated surgical valves. To our knowledge, data are lacking on the determinants on ViV-TAVI procedural success in patients with degenerated surgical valves. Methods: All consecutive patients undergoing ViV-TAVI for degenerated surgical valves at the Cleveland Clinic were analyzed. Data were extracted from our patient registry on baseline patient characteristics, echocardiographic parameters, and procedural details. To identify possible predictors of ViV-TAVI procedural success, we employed a multivariate logistic regression model. Results: A total of 186 patients who underwent ViV-TAVI were analyzed, with procedural success (VARC-2 device success and absence of periprocedural MACCE) reported in 165 (88.7%) patients. Patients with successful ViV-TAVI were significantly younger and had more frequent utilization of the transfemoral access than those with failed procedure. Other baseline and procedural characteristics were comparable between both groups. In terms of echocardiographic parameters, the procedural success group had a significantly lower AV peak pressure gradient (62.1 ± 24.7 vs. 74.1 ± 34.6 mmHg; p = 0.04) and lower incidence of moderate-to-severe aortic regurgitation [AR] (30.4 vs. 55%; p = 0.04). However, no significant differences between both groups were noted in terms of AV mean pressure gradient and left ventricular measurements. In multivariate analysis, lower AV peak pressure gradient (OR = 0.97, 95% CI: 0.95-0.99) and absence of moderate-to-severe AR (OR = 0.65, 95% CI: 0.44-0.95) at baseline emerged as independent predictors of ViV-TAVI procedural success. Conclusion: Valve-in-Valve TAVI for degenerated surgical valves is a feasible approach with high success rates, especially in those with lower AV peak pressure gradient and absence of moderate-to-severe AR. Studies with larger sample size and longer follow-up are required to further characterize the predictors of ViV-TAVI success and other clinical outcomes.

Awareness of Rheumatic Heart Disease in Egypt: A National Multicenter Study.

BACKGROUND: While the prevalence of rheumatic heart disease (RHD) in Egypt is relatively high, data on the awareness of Egyptians about the cause of RHD are lacking. METHODS: Using a pre-tested questionnaire, we performed a multicenter survey of outpatients attending 15 university hospitals across Egypt. RESULTS: A total of 6958 participants were interviewed. Most subjects (81.7%) reported a previous experience of sore throat. Seeking treatment, most patients (69.3%) consulted a medical professional, while the others relied on self/peer medication. Individuals consulting a physician received antibiotics more frequently than those who did not (89.1 vs. 38.7%; OR: 12.4, 95% CI 10.8-14.1). The median RHD knowledge score in our sample was 4 (IQR = 6). While most subjects (56.3%) claimed knowledge of the complications of an untreated sore throat, only a third (34%) were aware of the association between sore throat and RHD. In a multivariate analysis, older age (Mean Difference [MD]: 1.58, 95% CI 1.37-1.79), female gender (MD: 0.89, 95% CI 0.75-1.04), higher education (MD: 1.10, 95% CI 0.90-1.30), and being interviewed outside Cairo (MD: 0.67, 95% CI 0.51-0.82) were significant predictors of knowledge about RHD. CONCLUSION: The current study showed low levels of awareness on the cause of RHD among Egyptians and highlights a pressing need for interventions to address this public knowledge gap.

KAP-COVIDGLOBAL: a multinational survey of the levels and determinants of public knowledge, attitudes and practices towards COVID-19.

OBJECTIVE: The adherence to public health recommendations to control COVID-19 spread is influenced by public knowledge, attitudes and practices (KAP). We performed this cross-sectional study to assess the levels and determinants of public KAP towards COVID-19 in a large, multinational sample. DESIGN: Cross-sectional study (survey). SETTING: The questionnaire was distributed to potential respondents via online platforms. PARTICIPANTS: 71 890 individuals from 22 countries. METHODS: We formulated a four-section questionnaire in English, followed by validation and translation into seven languages. The questionnaire was distributed (May to June 2020) and each participant received a score for each KAP section. RESULTS: Overall, the participants had fair knowledge (mean score: 19.24±3.59) and attitudes (3.72±2.31) and good practices (12.12±1.83) regarding COVID-19. About 92% reported moderate to high compliance with national lockdown. However, significant gaps were observed: only 68.2% knew that infected individuals may be asymptomatic; 45.4% believed that antibiotics are an effective treatment; and 55.4% stated that a vaccine has been developed (at the time of data collection). 71.9% believed or were uncertain that COVID-19 is a global conspiracy; 36.8% and 51% were afraid of contacting doctors and Chinese people, respectively. Further, 66.4% reported the pandemic had moderate to high negative effects on their mental health. Female gender, higher education and urban residents had significantly (p≤0.001) higher knowledge and practice scores. Further, we observed significant correlations between all KAP scores. CONCLUSIONS: Although the public have fair/good knowledge and practices regarding COVID-19, significant gaps should be addressed. Future awareness efforts should target less advantaged groups and future studies should develop new strategies to tackle COVID-19 negative mental health effects.

Protective Effects of Evening Primrose Oil against Cyclophosphamide-Induced Biochemical, Histopathological, and Genotoxic Alterations in Mice.

Cyclophosphamide (CP) is a well-known antineoplastic agent; however, its clinical use can be associated with various organ toxicities. Evening primrose oil (EPO) contains several phytoconstituents with potent anti-oxidant and anti-inflammatory activities. This experimental study was performed to investigate the chemoprotective effects of EPO in the liver and pancreas of CP-intoxicated mice. Thirty-two albino mice were randomly divided into 4 equal groups: group I received saline (control mice), group II were treated with CP at 100 mg/kg/day for two subsequent days, and groups III and VI were treated with 5 and 10 mg/kg/day bw EPO, respectively for 14 days, followed by two doses of CP at the 15th and 16th days of the experiment. Then, mice were sacrificed and histopathological examinations, biochemical studies, and DNA laddering tests were conducted for hepatic and pancreatic tissues. Cyclophosphamide-intoxicated mice showed significant increases (p < 0.05) in the serum levels of liver enzymes, pancreatic amylase and tissue levels of malondialdehyde, and TNF-α, as well as a significant decrease (p < 0.05) in the serum insulin level. In addition, both hepatic and pancreatic tissues showed disturbed tissue architecture, hydropic degeneration, congested vessels, and inflammatory infiltrates, as well as increased DNA fragmentation. In a dose-dependent manner, pretreatment with EPO was associated with significant improvements (p < 0.05) in all biochemical parameters and significant amelioration of histopathological alterations and DNA fragmentation in CP-intoxicated mice. Pretreatment with EPO showed significant antioxidant, anti-inflammatory, and genoprotective effects against the toxic effects of CP in mice hepatic and pancreatic tissues.

Diagnosis and Management of Hematological Adverse Events Induced by Immune Checkpoint Inhibitors: A Systematic Review.

There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.