The prognostic significance of HIST1H3B/C and H3F3A K27M mutations in diffuse midline gliomas is influenced by patient age.

INTRODUCTION: Diffuse midline gliomas (DMGs) are infiltrative midline gliomas harboring H3K27M mutations and are generally associated with poor outcomes. H3K27M mutations include mutations in HIST1H3B/C (H3.1), HIST2H3B/D (H3.2), or H3F3A (H3.3) genes. It is still unclear whether these mutations each portend a universally poor prognosis, or if there are any factors which modulate outcome. The main objective of this study was to study overall survival (OS) of H3.1 versus H3.3 K27M-mutant DMGs in pediatric and adult patients. METHODS: PubMed and Web of Science were searched, and we included studies if they have individual patient data of DMGs with available H3K27M genotype. Kaplan-Meier analysis and Cox regression models were used to analyze the survival of H3.1 and H3.3 mutations in each subgroup. RESULTS: We included 26 studies with 102 and 529 H3.1 and H3.3-mutant DMGs, respectively. The H3.1 mutation was more commonly seen in younger age. In pediatric population, H3.3 mutation conferred a shorter survival (median OS of 10.1 vs 14.2 months; p < 0.001) in comparison to H3.1-positive patients, which was further confirmed in the multivariate Cox analysis. Conversely, H3.3 was associated with a prolonged survival in adult patients as compared with H3.1 mutation (median OS of 14.4 vs 1.7 months; p = 0.019). CONCLUSION: We demonstrated that the prognosis of H3.1 and H3.3 K27M mutation in DMG patients is modulated by patient age. Routine H3K27M mutation genotyping in newly diagnosed DMGs may further stratify patients with these difficult tumors.

Consolidating the Hyams grading system in esthesioneuroblastoma - an individual participant data meta-analysis.

INTRODUCTION: Esthesioneuroblastoma (ENB) is an uncommon primary sinonasal tumor which can extend intracranially. Exactly how to classify them pathologically still remains discrepant; the Hyams grading system, for example, has not been universally adopted. This individual patient data (IPD) meta-analysis aimed to investigate the prognostic implication of each Hyams grade on patient outcomes. METHODS: We accessed two electronic databases including PubMed and Web of Science. Raw patient data from potential articles were extracted. To examine the associations of various clinicopathological factors with the Hyams grades, we utilized Chi-square, t-test, and Mann-Whitney, as appropriate. Log-rank test and Cox regression analysis were used to elucidate the impact of the Hyams grades on recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS) of ENB patients. RESULTS: We included 33 studies with 492 ENB patients. We found significant associations of Kadish stages, Dulguerov stages, rates of recurrence, metastasis, and patient mortality with Hyams grade. Log-rank tests and Cox regression models demonstrated significant differences in RFS and OS of Hyams grade I - II, grade III, and grade IV patients. There was no statistical difference in RFS and OS of Hyams grade I and II. Radiotherapy was only effective in grade III - IV ENBs and chemotherapy showed no benefits to patients. CONCLUSION: We verify that the Hyams grading system appears to be a reliable prognostic indicator to assess ENB patient outcomes. Consolidating the Hyams grading system into a three-tier system based on similar clinical outcomes of grades I and II may simplify this classification schema.

H3K27M-mutant diffuse midline gliomas should be further molecularly stratified: an integrated analysis of 669 patients.

INTRODUCTION: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients. METHODS: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS). RESULT: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR 1.446; 95% CI 1.143-1.829) whereas ACVR1 (HR 0.712; 95% CI 0.518-0.976) and FGFR1 mutations (HR 0.408; 95% CI 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR 0.620; 95% CI 0.386-0.996). Adjusted for age, gender, and tumor location, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors. CONCLUSIONS: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. This may aid neuro-oncologists in appropriate risk stratification.

Machine learning method for predicting pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: An accurate assessment of permanent pacemaker implantation (PPI) risk following transcatheter aortic valve replacement (TAVR) is important for clinical decision making. The aims of this study were to investigate the significance and utility of pre- and post-TAVR ECG data and compare machine learning approaches with traditional logistic regression in predicting pacemaker risk following TAVR. METHODS: Five hundred fifity seven patients in sinus rhythm undergoing TAVR for severe aortic stenosis (AS) were included in the analysis. Baseline demographics, clinical, pre-TAVR ECG, post-TAVR data, post-TAVR ECGs (24 h following TAVR and before PPI), and echocardiographic data were recorded. A Random Forest (RF) algorithm and logistic regression were used to train models for assessing the likelihood of PPI following TAVR. RESULTS: Average age was 80 ± 9 years, with 52% male. PPI after TAVR occurred in 95 patients (17.1%). The optimal cutoff of delta PR (difference between post and pre TAVR PR intervals) to predict PPI was 20 ms with a sensitivity of 0.82, a specificity of 0.66. With regard to delta QRS, the optimal cutoff was 13 ms with a sensitivity of 0.68 and a specificity of 0.59. The RF model that incorporated post-TAVR ECG data (AUC 0.81) more accurately predicted PPI risk compared to the RF model without post-TAVR ECG data (AUC 0.72). Moreover, the RF model performed better than logistic regression model in predicting PPI risk (AUC: 0.81 vs. 0.69). CONCLUSIONS: Machine learning using RF methodology is significantly more powerful than traditional logistic regression in predicting PPI risk following TAVR.

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis.

BACKGROUND: There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients. METHODS: Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies. RESULTS: A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55-0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54-2.26; p-value < 0.001). TERT-mutated glioblastoma (GBM) patients with MGMT methylation benefited from temozolomide (TMZ) treatment (HR = 0.33; 95% CI = 0.23-0.47; p-value < 0.001). MGMT methylation was not related with any improvement in OS in TERT-wild type GBMs (HR = 0.80; 95% CI = 0.56-1.15; p-value = 0.23). CONCLUSIONS: The prognostic value of TERT promoter mutation may be modulated by MGMT methylation status. Not all MGMT-methylated GBM patients may benefit from TMZ; it is possible that only TERT-mutated GBM with MGMT methylation, in particular, may respond.

Left and right atrial speckle tracking: Comparison of three methods of time reference gating.

BACKGROUND: Atrial function has a close interdependence with ventricular function and plays a central role in maintaining optimal cardiac function. There are two well-defined timing methods used to determine the start point. The aim of this prospective study was to objectively assess the influence of gating method selection on reported left and right strain values within the same group of healthy subjects. METHODS: 101 volunteers (44 male, 57 female) had adequate tracking for analysis on TomTec Imaging Systems (Unterschleissheim, Germany). The median age was 41 years (range 19-79 years, interquartile range 30-52 years). Atrial strain by 2D-speckle tracking echocardiography was evaluated using two commonly applied zero baseline time reference methods: R-R gating and P-P gating, in addition to volume gating (defining end-systole at the atrial maximum and end-diastole at the atrial minimum). RESULTS: True atrial minimum occurred prior to the onset of the QRS in most healthy volunteers. There was a significant difference for LA and RA reservoir strain between volume gating and R-R gating (mean difference, 4.63%; P < .001 for LA; mean difference, 4.23%; P < .001 for RA), as well as volume gating and P-P gating (mean difference, 5.26%; P < .001 for LA; mean difference, 6.24%; P < .001 for RA). Noticeably, reservoir strain was comparable between R-R gating and P-P gating (mean difference, 0.58%, P = .06) in LA, but not on RA (mean difference, 2.02%, P < .001). CONCLUSIONS: There was variability in atrial strain values depending on the zero baseline time reference method used.

Effect of transcatheter aortic valve replacement on left atrial function.

OBJECTIVES: To investigate the effect of transcatheter aortic valve replacement on left atrial volumetric function and left atrial volume for the prediction of adverse outcomes. METHODS: This is a retrospective analysis of 121 patients in sinus rhythm who underwent TAVR for severe AS. Maximum LA volume index (LAVI max), minimum LA volume index (LAVI min), and "pre-A" volume index (LAVIpre-A, the volume before atrial contraction) were measured by biplane Simpson's method at baseline, 1 month, and 1 year. The reservoir function, conduit function, booster pump function were calculated. All patients were followed for new-onset of atrial fibrillation, hospitalization and all-cause mortality. RESULTS: The reservoir function, conduit function and booster function before TAVR were 46%, 21%, 32%, respectively. LA volumetric function assessment demonstrated that reservoir function, conduit function increased over the time (all P < 0.01). There was no difference in booster function after TAVR (P = 0.18). Baseline markedly enlarged LA was significantly increased for AF (HR: 4.72; 95% CI, 1.11-20.13, P = 0.04). In addition, There was a progressive decrease in LAVI max (P = 0.02) and RVSP (P = 0.03) over the time in non-AF group but not in AF group (P = 0.62 and P = 0.65, respectively). Although, the proportion of high left ventricular filling pressure decreased in both groups but a marked decrease was noted in non AF group in compared with AF group. CONCLUSION: Reservoir function, conduit function increased over time. Lack of negative LA remodeling post TAVR was associated with higher incidence of AF.

Absence of Survival Improvement for Patients with Esthesioneuroblastoma Over the Past 2 Decades: A Population-Based Study.

OBJECTIVE: Esthesioneuroblastoma (ENB) is a rare malignancy of the sinonasal tract and its infrequency has confounded efforts at clearly describing the survival trends associated with this neoplasm over the years. In this study, we reviewed survival trends in ENB and investigated the impact of treatment extent and modality on patient outcomes. METHODS: We accessed the Surveillance, Epidemiology, and End Result (SEER) program to identify ENB cases from 1998 to 2016. A χ2 test was used to compare the categorical covariates and a t test or Mann-Whitney U test was utilized for continuous variables. The impact of prognostic factors on survival was computed using a Kaplan-Meier analysis and multivariate Cox proportional hazards model. We divided ENB patients into 4 periods including 1998-2002, 2003-2007, 2008-2012, and 2013-2016, and investigated survival trends using the Kaplan-Meier curve and log-rank test. RESULTS: ENB patients who underwent biopsy alone were associated with older age, larger tumor diameter, increased rates of tumor extension, nodal/distant metastases, and advanced stages as compared with patients undergoing tumor resection. Our results also demonstrated that surgical resection and adjuvant radiotherapy could confer survival advantages, whereas chemotherapy was associated with reduced survival in patients with ENB. Over the past 2 decades, surprisingly, there has been no change in survival rates for patient with ENB (P = 0.793). CONCLUSIONS: Despite advanced diagnostic studies and modernized treatment approaches, ENB survival has remained unchanged over the years, calling for improved efforts to develop appropriate individualized interventions for this rare tumor entity. Our results also confirmed that surgery and adjuvant radiotherapy is associated with improved patient survival whereas the use of chemotherapy should be considered carefully.

Prognostic Implication of Patient Age in H3K27M-Mutant Midline Gliomas.

Introduction: Pediatric and adult H3K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups. Methods: PubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of H3K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS). Results: We included 43 studies comprising 272 adults and 657 pediatric midline gliomas with H3K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of H3.1 K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric H3K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, ACVR1 mutations were more common whereas MGMT methylation, FGFR1, and NF1 mutations were less prevalent in the pediatric cohort. Conclusion: Pediatric H3K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.

Ventriculo-arterial coupling in patients with stable ischemic heart disease undergoing percutaneous coronary intervention.

To investigate ventriculo-arterial coupling (VAC) and its components (Ea, Ees) in patients with stable ischemic heart disease and changes following percutaneous coronary intervention (PCI). 129 patients with stable ischemic heart disease (SIHD) undergoing PCI (study group) and 40 individuals without IHD (control group) were enrolled. VAC was calculated using echocardiography method at baseline and 1, 3, and 6 months after PCI. A linear mixed-effects models with restricted maximum likelihood were used to assess the impact of PCI on Ea, Ees, VAC over 6-month follow-up. Mean age of the SIHD group was 67.8 ± 8.1 (years), and predominantly men (73.6%). In the SIHD group, baseline median Ea, Ees and VAC were 2.52 (IQR 1.89-3.28) (mmHg/ml), 3.87 (IQR 2.90-4.95) (mmHg/ml), and 0.64 (IQR 0.54-0.79), respectively. Patients with SIHD had significantly lower Ees and higher VAC when compared to the control group (p < 0.05). Ees (p = 0.01) and VAC (p < 0.001) were significantly improved over 6 month follow-up after PCI. Notably, the degree of VAC improvement appears to be related to stented artery (Table 3). VAC obtained from echocardiographic methodology demonstrated a significant increase in patients with SIHD at baseline. This observation may represent a plausible mechanism for the benefit of PCI in SIHD. Hence, VAC may be a feasible parameter in the assessment of patients with SIHD.

Normal Ranges of Global Left Ventricular Myocardial Work Indices in Adults: A Meta-Analysis.

BACKGROUND: Recent studies have demonstrated that left ventricular myocardial work (MW) is incremental in diagnosis and prognostication compared with left ventricular ejection fraction and myocardial strain. The authors performed a meta-analysis of normal ranges of noninvasive MW indices including global work index, global constructive work, global wasted work, and global work efficiency and determined confounders that may contribute to variance in reported values. METHODS: Four databases (PubMed, Scopus, Embase, and the Cochrane Library) were searched through January 2021 using the key terms "myocardial work," "global constructive work," "global wasted work," "global work index," and "global work efficiency." Studies were included if the articles reported LV MW using two-dimensional transthoracic echocardiography in healthy normal subjects, either in a control group or comprising the entire study cohort. The weighted mean was estimated by using the random-effect model with a 95% CI. Heterogeneity across included studies was assessed using the I2 test. Funnel plots and the Egger regression test were used to assess potential publication bias. RESULTS: The search yielded 476 articles. After abstract and full-text screening, we included 13 data sets with 1,665 patients for the meta-analysis. The reported normal mean values of global work index and global constructive work among the studies were 2,010 mm Hg% (95% CI, 1,907-2,113 mm Hg%) and 2,278 mm Hg% (95% CI, 2,186-2,369 mm Hg%), respectively. Mean global wasted work was 80 mm Hg% (95% CI, 73-87 mm Hg%), and mean global work efficiency was 96.0% (95% CI, 96%-96%). Furthermore, gender significantly contributed to variations in normal values of global work index, global wasted work, and global work efficiency. No evidence of significant publication bias was observed. CONCLUSIONS: In this meta-analysis, the authors provide echocardiographic reference ranges for noninvasive indices of MW. These normal values could serve as a reference for clinical and research use.

Incidence, Prognostic Factors, and Survival Trend in Pineal Gland Tumors: A Population-Based Analysis.

INTRODUCTION: Pineal gland tumors are exceedingly rare and account for 0.4-1.0% of brain neoplasms. Their rarity has confounded a clear understanding of the prognostic factors and standards of care for these neoplasms. In this study, we aimed to investigate the incidence, prognostic indicators, and survival trend of tumors emanating from the pineal gland. METHODS: We accessed the Surveillance, Epidemiology, End Results (SEER) Program for pineal gland tumors from 1975-2016. A multivariate Cox regression model was used to investigate the impact of clinicopathological parameters on all-cause mortality. For survival trend analysis, we employed the Kaplan Meier curve and pairwise comparisons to examine the trend. RESULTS: We found 1,792 and 310,003 pineal gland and brain neoplasms during 1975-2016 resulting in an incidence of 0.6%. In the multivariate Cox proportional hazards model, older age, male gender, non-germ cell tumor, and receipt of chemotherapy were significantly associated with poor survival (p < 0.001). The extent of resection and radiotherapy administration did not produce survival advantages. Our result also highlighted an increased survival of pineal gland tumors over the years. CONCLUSION: Our study investigated the prognostic factors that influenced survival in patients with pineal gland tumors. Chemotherapy use adversely affected patient outcomes and should be considered carefully in specific circumstances to avoid its harmful effects. These findings provide important evidence to improve current standards of care for this rare group of tumors. The survival of pineal tumors has improved over time reflecting improvements in current practice.

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta-analysis.

INTRODUCTION: IDH1/2 mutations are prevalent in cartilaginous tumors including chondrosarcoma. This meta-analysis using individual patient data (IPD) aimed to investigate the clinical and prognostic association of these mutations in chondrosarcoma patients. METHODS: Two electronic databases including PubMed and Web of Science were searched for relevant data. We included studies providing IPD of chondrosarcoma with available IDH1/2 mutational status for meta-analysis. Chi-square and t-test were performed to compare the groups with and without IDH1/2 mutations. For survival analysis, log-rank test, and Cox proportional hazards model were used to investigate the association of IDH mutations with patient outcomes. RESULTS: Fourteen studies with 488 patients were analyzed. IDH1 and IDH2 mutations were detected in 38.7% and 12.1% of cases, respectively. IDH1/2 mutations were significantly associated with an older age (p = 0.003), tumor origins (p < 0.001), tumor grades (p < 0.001), larger diameter (p = 0.003), relapse (p = 0.014), and patient mortality (p = 0.04). Multivariate Cox regression analysis adjusted for age, gender, tumor grade, and tumor sites confirmed the negative impact of IDH1/2 mutations on patient overall survival (HR = 1.90; 95% CI = 1.06-3.42; p = 0.03). CONCLUSION: Our meta-analysis demonstrated the distinct characteristics of IDH1/2-mutated chondrosarcomas in comparison to those without mutations. These mutations could serve as an independent prognostic biomarker to better prognosticate patient outcomes and design appropriate treatment plans.

Incidence, risk factors, and prognosis of meningiomas with distant metastases at presentation.

BACKGROUND: Distant metastases (DM) at presentation in meningiomas is a very rare event, and the incidence and factors predicting this are uncertain. This population-based study also aimed to investigate the prognostic implication of DM at presentation and clinical parameters to prognosticate the overall survival (OS) of meningiomas presenting with DM (M1). METHODS: We accessed the Surveillance, Epidemiology, and End Results program to search for patients who were diagnosed with meningioma between 2004 and 2016. The log-rank test was used to compare Kaplan-Meier survival curves and multivariate Cox regression model was utilized to evaluate the prognostic parameters of meningiomas with DM at presentation. RESULTS: The incidence of DM at presentation among all meningiomas was 0.18%. Clinical variables associated with this event were male gender, large tumor size, and WHO grade III. The presence of DM at diagnosis conferred a shorter survival in comparison to those without DM (HR = 2.015; 95% CI = 1.600-2.536). Older patient age, male gender, malignant histology, and the lesser extent of resection were independent prognostic factors that could negatively impact OS of M1 meningiomas. Radiotherapy and chemotherapy were not associated with an improved outcome for these patients. CONCLUSION: Our study highlighted the clinical and prognostic factors of M1 meningiomas. These data suggest that a greater extent of resection is associated with increased OS across a nationwide analysis and emphasize the need to establish the standards of care in these patients.

Long-term outcomes of primary cardiac malignant tumors: Difference between African American and Caucasian population.

BACKGROUND: The survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long-term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations. METHODS: The 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety-four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log-rank test was used to compare the difference in mortality between two populations and presented by the Kaplan-Meier curves. A multivariate Cox proportional hazards regression was used to determine the independent predictors of all-cause mortality. RESULTS: The overall 30-day, 1-year, and 5-year survival rates were 74%, 44.3%, and 16.6%, respectively, with a median survival of 10 months. There was no significant difference in survival rate between the two races (p-value = 0.55). The 1-year survival rate improved significantly during the study timeline in the AA population (13.3% during 1975-1998, 40.9% during 1999-2004, 50% during 2005-2010, and 59.7% during 2011-2016, p-value = 0.0064). Age of diagnosis, type of tumor, disease stage, and chemotherapy administration are the main factors that predict survival outcomes of PMCT patients. Interactive nomogram was developed based on significant predictors. CONCLUSIONS: PMCTs have remained one of the most lethal diseases with poor survival outcome. Survival rate improved during the timeline in AA patients, but in general, racial differences in survival outcome were not observed.

Clinicopathological Implications of RHOA Mutations in Angioimmunoblastic T-Cell Lymphoma: A Meta-analysis: RHOA mutations in AITL.

BACKGROUND: Studies have recently shown that RHOA mutations play a crucial role in angioimmunoblastic T-cell lymphoma (AITL) pathogenesis. We aimed to pool data from these studies to provide a comparison of clinicopathological features between the RHOA mutant and RHOA wild-type groups in the AITL population. METHODS: We searched PubMed and Web of Science for the keywords "RHOA AND lymphoma" and selected only studies reporting the clinical significance of RHOA mutations in AITL. We calculated the odds ratios (OR) or the mean difference with 95% CI using a random effect model. RESULTS: Our pooled results showed a significant association between RHOA mutations and a T-follicular helper cell (TFH) phenotype, especially CD10 (OR, 5.16; 95% CI, 2.32-11.46), IDH2 mutations (OR, 10.70; 95% CI, 4.22-27.15), and TET2 mutations (OR, 7.03; 95% CI, 2.14-23.12). Although DNMT3A together with TET2 and IDH2 mutations are epigenetic gene alterations, we found an insignificant association between RHOA and DNMT3A mutations (OR, 1.72; 95% CI, 0.73-4.05). No significant associations of RHOA mutations with other clinicopathological features and overall survival were found. CONCLUSIONS: RHOA mutations are strongly correlated with a T-follicular helper cell phenotype and epigenetic mutations such as TET2 and IDH2. Further studies with large AITL samples should be conducted to validate the relationship of TET2, DNMT3A, and RHOA co-mutations.

Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data.

Primary (or de novo) anaplastic thyroid carcinoma (ATC) is ATC without pre-existing history of differentiated thyroid carcinoma (DTC) and no co-existing DTC foci at the time of diagnosis. Secondary ATC is diagnosed if the patient had a history of DTC or co-existing DTC components at time of diagnosis. This study aimed to investigate the incidence, clinical presentations, outcomes, and genetic backgrounds of primary versus secondary ATCs. We searched for ATCs in our institutional databases and the Surveillance, Epidemiology, and End Result (SEER) database. We also performed a systematic review and meta-analysis to analyze the genetic alterations of primary and secondary ATCs. From our multi-institutional database, 22 primary and 23 secondary ATCs were retrieved. We also identified 620 and 24 primary and secondary ATCs in the SEER database, respectively. Compared to primary ATCs, secondary ATCs were not statistically different in terms of demographic, clinical manifestations, and patient survival. The only clinical discrepancy between the two groups was a significantly larger tumor diameter of the primary ATCs. The prevalence of TERT promoter, PIK3CA, and TP53 mutations was comparable between the two subtypes. In comparison to primary ATCs, however, BRAF mutations were more prevalent (OR = 4.70; 95% CI = 2.84-7.78) whereas RAS mutations were less frequent (OR = 0.43; 95% CI = 0.21-0.85) in secondary tumors. In summary, our results indicated that de novo and secondary ATCs might share many potential developmental steps, but there are other factors that suggest distinct developmental pathways.

Right ventricular dysfunction and tricuspid regurgitation in functional mitral regurgitation.

AIM: The objective of this study was to investigate the prognostic importance of right ventricular dysfunction (RVD) and tricuspid regurgitation (TR) in patients with moderate-severe functional mitral regurgitation (FMR) receiving MitraClip procedure. RVD and TR grade are associated with cardiovascular mortality in the general population and other cardiovascular diseases. However, there are limited data from observational studies on the prognostic significance of RVD and TR in FMR receiving MitraClip procedure. METHODS AND RESULTS: A systemic review and meta-analysis were performed using MEDLINE, Scopus, and Embase to assess the prognostic value of RVD and TR grade for mortality in patients with functional mitral regurgitation (FMR) receiving MitraClip procedure. Hazard ratios were extracted from multivariate models reporting on the association of RVD and TR with mortality and described as pooled estimates with 95% confidence intervals. A total of eight non-randomized studies met the inclusion criteria with seven studies having at least 12 months follow-up with a mean follow-up of 20.9 months. Among the aforementioned studies, a total of 1112 patients (71.5% being male) were eligible for being included in our meta-analysis with an overall mortality rate of 28.4% (n = 316). Of the enrolled patients, RVD was present in 46.1% and moderate-severe TR in 29.2%. RVD was significantly associated with mortality compared to normal RV function (HR, 1.79, 95% CI, 1.39-2.31, P < 0.001, I2  = 0). Patients with moderate-severe TR showed increased risk of mortality compared with those in the none-mild TR group (HR, 1.61. 95% CI, 1.11-2.33, P = 0.01, I2  = 14). CONCLUSIONS: This meta-analysis demonstrates the prognostic importance of RVD and TR grade in predicting all-cause mortality in patients with significant FMR. RV function and TR parameters may therefore be useful in the risk stratification of patients with significant FMR undergoing MitraClip procedure.

Right Atrial Deformation Using Cardiovascular Magnetic Resonance Myocardial Feature Tracking Compared with Two-Dimensional Speckle Tracking Echocardiography in Healthy Volunteers.

Speckle tracking echocardiography (STE), and more recently, cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) provides insight into all phases of atrial function. The aim of our study was to compare all phases of RA strain using CMR-FT and STE and also assess the relationship between RA and LA strain. A total of 61 healthy volunteers with mean age of 45 ± 13 years had adequate tracking for analysis on CMR-FT and 2D-STE. Females had larger RA reservoir strain (39 ± 15% vs. 32 ± 13%, p = 0.046) and conduit strain (26 ± 12% vs. 20 ± 9%, p = 0.03) when compared to males, but was not the case with booster strain (14 ± 7% vs. 12 ± 6%, p = 0.45). In comparison with STE derived strain, the RA reservoir and conduit strain were not significantly different between CMR-FT and the three echocardiography gating methods (p > 0.05 for all). Noticeably, there were no significant differences in strain and strain rate between RA and LA function using CMR-FT (p > 0.05 for all). RA strain and strain rate using CMR-FT had fair and good intra- and inter-observer reproducibility and had superior reproducibility compared to STE derived strain.