Long-Term Outcomes and Prognosticators of Pediatric Primary Dilated Cardiomyopathy in an Asian Cohort

Background: Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy. The epidemiological profiles and prognosticators of clinical outcomes in Asian populations are not well elucidated.Methods: Data of 104 children aged <18 years with a diagnosis of primary DCM from January 1990 to December 2019 in our institutional database were retrospectively investigated. Relevant demographic, echocardiographic, and clinical variables were recorded for analysis. A P <0.05 was considered statistically significant.Results: The median age at diagnosis was 1.4 years (interquartile range = 0.3–9.1 years), and 52.9% were males. During a median follow-up duration of 4.8 years, 48 patients (46.2%) were placed on the transplantation waitlist, and 52.1% of them eventually received heart transplants. An exceptionally high overall waitlist mortality rate was noted (27.1%), which was even higher (43.5%) if the diagnostic age was <3 years. The 1-, 5-, and 10-year transplant-free were 61.1, 48.0, and 42.8%. Age at diagnosis >3 years and severe mitral regurgitation at initial diagnosis were independent risk factors for death or transplantation (hazard ratios = 2.93 and 3.31, respectively; for both, P <0.001). In total, 11 patients (10.6%) experienced ventricular function recovery after a median follow-up of 2.5 (interquartile range = 1.65–5) years. Younger age at diagnosis was associated a higher probability of ventricular function recovery.Conclusions: Despite donor shortage for heart transplantation and subsequently high waitlist mortality, our data from an Asian cohort indicated that transplant-free long-term survival was comparable with that noted in reports from Western populations. Although younger patients had exceptionally higher waitlist mortality, lower diagnostic age was associated with better long-term survival and higher likelihood of ventricular function recovery.

Survival and diagnostic age of 175 Taiwanese patients with mucopolysaccharidoses (1985–2019)

Background Mucopolysaccharidoses (MPSs) are a group of inherited metabolic diseases, which are characterized by the accumulation of glycosaminoglycans, and eventually lead to the progressive damage of various tissues and organs. Methods An epidemiological study of MPS in Taiwan was performed using multiple sources. The survival and diagnostic age for different types of MPS between 1985 and 2019 were evaluated. Results Between 1985 and 2019, there were 175 patients diagnosed with MPS disorders in the Taiwanese population, with a median diagnostic age of 3.9 years. There were 21 (12%), 78 (45%), 33 (19%), 32 (18%) and 11 (6%) patients diagnosed with MPS I, II, III, IV and VI, respectively, with median diagnostic ages of 1.5, 3.8, 4.7, 4.5 and 3.7 years, respectively. Diagnosis of MPS patients was significantly earlier in recent decades (p < 0.01). Pilot newborn screening programs for MPS I, II, VI, IVA, and IIIB were progressively introduced in Taiwan from 2016, and 48% (16/33) of MPS patients diagnosed between 2016 and 2019 were diagnosed by one of these screening programs, with a median diagnostic age at 0.2 years. For patients born between 2016 and 2019, up to 94% (16/17) were diagnosed with MPS via the newborn screening programs. At the time of this study, 81 patients had passed away with a median age at death of 15.6 years. Age at diagnosis was positively correlated with life expectancy (p < 0.01). Life expectancy also significantly increased between 1985 and 2019, however this increase was gradual (p < 0.01). Conclusions The life expectancy of Taiwanese patients with MPS has improved in recent decades and patients are being diagnosed earlier. Because of the progressive nature of the disease, early diagnosis by newborn screening programs and timely implementation of early therapeutic interventions may lead to better clinical outcomes.

Survival and diagnostic age of 175 Taiwanese patients with mucopolysaccharidoses (1985-2019)

Background Mucopolysaccharidoses (MPSs) are a group of inherited metabolic diseases, which are characterized by the accumulation of glycosaminoglycans, and eventually lead to the progressive damage of various tissues and organs.Methods An epidemiological study of MPS in Taiwan was performed using multiple sources. The survival and diagnostic age for different types of MPS between 1985 and 2019 were evaluated.Results Between 1985 and 2019, there were 175 patients diagnosed with MPS disorders in the Taiwanese population, with a median diagnostic age of 3.9 years. There were 21 (12%), 78 (45%), 33 (19%), 32 (18%) and 11 (6%) patients diagnosed with MPS I, II, III, IV and VI, respectively, with median diagnostic ages of 1.5, 3.8, 4.7, 4.5 and 3.7 years, respectively. Diagnosis of MPS patients was significantly earlier in recent decades (p<0.01). Pilot newborn screening programs for MPS I, II, VI, IVA, and IIIB were progressively introduced in Taiwan from 2016, and 48% (16/33) of MPS patients diagnosed between 2016 and 2019 were diagnosed by one of these screening programs, with a median diagnostic age at 0.2 years. For patients born between 2016 and 2019, up to 94% (16/17) were diagnosed with MPS via the newborn screening programs. At the time of this study, 81 patients had passed away with a median age at death of 15.6 years. Age at diagnosis was positively correlated with life expectancy (p<0.01). Life expectancy also significantly increased between 1985 and 2019, however this increase was gradual (p<0.01).Conclusions The life expectancy of Taiwanese patients with MPS has improved in recent decades and patients are being diagnosed earlier. Because of the progressive nature of the disease, early diagnosis by newborn screening programs and timely implementation of early therapeutic interventions may lead to better clinical outcomes.

Clinical Characteristics and prognostic implications of BRCA-Associated Tumors in Males: A Pan-tumor Survey

PurposeBRCA mutations (BRCAm) in males have been reported to confer a higher risk in the development of various tumors. However, little is known about the characteristics and prognosis of BRCA-associated tumors in males.DesignWe conducted a pan-tumor survey on BRCA-associated tumors in males (n=346). Comparative analyses with female BRCAm carriers (n=349) and male non-BRCAm carriers (n=4577) were proceed.ResultsSimilar BRCAm incidence and diagnostic age were observed in male and female patients. Carcinomas of lung (19.4%), bladder (15.6%), stomach (11.9%), and cutaneous melanoma (16.3%) were the frequent tumors demonstrating BRCAm in males. The majority were stage II/III diseases with a higher frequency of BRCA2 mutation (65.6%). A total of 127 BRCA1 and 311 BRCA2 mutations were identified in males, of which 21.8% and 28.6% were deleterious, respectively. Deleterious variants were commonly identified in cancer of breast, colorectum, prostate, and stomach. Recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected in males, while N1784K/Tfs*3 were frequently observed in both males and females. BRCAm in males was associated with a decrease OS and PFS than in females, as well as an increased OS than in non-BRCAm carriers. Subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancer, decreased PFS in cancer of prostate, esophagus, head and neck, and a decreased OS in glioma/glioblastoma in males.ConclusionOur findings provide an overview of the distinct characteristics and clinical outcomes in BRCA-associated tumors in males, suggesting the importance of further BRCA testing in males.

Survival and diagnostic age of 175 Taiwanese patients with mucopolysaccharidoses (1985-2019)

BackgroundMucopolysaccharidoses (MPSs) are a group of inherited metabolic diseases, which are characterized by the accumulation of glycosaminoglycans, and eventually lead to the progressive damage of various tissues and organs.MethodsAn epidemiological study of MPS in Taiwan was performed using multiple sources. The survival and diagnostic age for different types of MPS between 1985 and 2019 were evaluated.ResultsBetween 1985 and 2019, there were 175 patients diagnosed with MPS disorders in the Taiwanese population, with a median diagnostic age of 3.9 years. There were 21 (12%), 78 (45%), 33 (19%), 32 (18%) and 11 (6%) patients diagnosed with MPS I, II, III, IV and VI, respectively, with median diagnostic ages of 1.5, 3.8, 4.7, 4.5 and 3.7 years, respectively. Diagnosis of MPS patients was significantly earlier in recent decades (p<0.01). Pilot newborn screening programs for MPS I, II, VI, IVA, and IIIB were progressively introduced in Taiwan from 2016, and 48% (16/33) of MPS patients diagnosed between 2016 and 2019 were diagnosed by one of these screening programs, with a median diagnostic age at 0.2 years. For patients born between 2016 and 2019, up to 94% (16/17) were diagnosed with MPS via the newborn screening programs. At the time of this study, 81 patients had passed away with a median age at death of 15.6 years. Age at diagnosis was positively correlated with life expectancy (p<0.01). Life expectancy also significantly increased between 1985 and 2019, however this increase was gradual (p<0.01).ConclusionsThe life expectancy of Taiwanese patients with MPS has improved in recent decades and patients are being diagnosed earlier. Because of the progressive nature of the disease, early diagnosis by newborn screening programs and timely implementation of early therapeutic interventions may lead to better clinical outcomes.

P766 ABO blood groups and ulcerative colitis: A hospital-based study in central Taiwan

Background The variations in ABO blood groups are reported to be associated with multiple disorders. Ulcerative colitis (UC) is a chronic and relapsing disease of the gastrointestinal tract with unclear etiology. The incidence and prevalence of UC are low but increasing in Taiwan The aim of our current study was to investigate the distribution of ABO blood groups in patients with UC and to explore its impact on disease severity. Methods From January 2000 to November 2019, we retrospectively collected patients diagnosed as UC in our hospital, a tertiary referral center in central Taiwan. Clinical characteristics of patients with UC including gender, age at diagnosis, ABO blood groups, disease phenotype and behaviour, operation rate and baseline laboratory data were collected. Results A total of 129 patients with UC were enrolled into our current study (Table 1). We found out male predominance as 62.8% of all patients. The mean diagnostic age of all UC patients was 39.0 years. Of 129 UC patients, 43 (33.3%) were blood type O, 41 (31.8%) were blood type A, 38 (29.5%) were blood type B, and the remainders 7 (5.4%) were blood type AB. However, there was no significant association between the ABO blood groups and UC patients compared with the general population of Taiwanese1 (p = 0.1906) (Table 2). In the subgroup analysis of each blood type, there were no significant difference of disease location and operation rate between groups. Furthermore, blood type A UC patients had higher hemoglobin level compared with blood type O patients (13.31 g/dl vs. 12.30 g/dl, p = 0.0347). Blood type A UC patients had lower erythrocyte sedimentation rate (ESR) level compared with blood type O patients (12.46 mm/h vs. 21.5 mm/h, p = 0.0288). Blood type O UC patients had the highest ESR level compared with non-O groups (p = 0.0228) (Table 3). We analysed the characteristics of UC patients between the diagnostic age older or younger than 40 years. However, there were no significant difference between two age groups (Table 4). Conclusion ABO blood groups were not associated with the prevalence of UC, although UC patients with blood type A had the higher prevalence in our current study compared with the general populations with blood type A. UC patients with blood type O had higher baseline ESR level. UC patients with blood type A had higher baseline hemoglobin level.

Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

SUMMARYMammals progress through similar physiological stages during life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects conserved molecular events is unclear. Here, we map common epigenetic changes experienced by mammalian genomes as they age, focusing on evolutionary comparisons of humans to dogs, an emerging model of aging. Using targeted sequencing, we characterize the methylomes of 104 Labrador retrievers spanning a 16 year age range, achieving >150X coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship which translates dog to human years, aligns the timing of major physiological milestones between the two species, and extends to mice. Conserved changes center on specific developmental gene networks which are sufficient to capture the effects of anti-aging interventions in multiple mammals. These results establish methylation not only as a diagnostic age readout but as a cross-species translator of physiological aging milestones.

Comparison of Long-Term Outcome between Apical and Asymmetric Septal Hypertrophic Cardiomyopathy

Objectives: As reported, diagnostic age, gender and presence of outflow tract obstruction have an impact on prognosis in patients with hypertrophic cardiomyopathy. The aim of this study was to compare the long-term outcome between apical hypertrophic cardiomyopathy (ApHCM) and asymmetric septal hypertrophic cardiomyopathy (ASHCM) after the exclusion of these factors. Methods: A total of 540 patients (270 with ApHCM and 270 with ASHCM) identified in a consecutive single-center cohort were retrospectively studied. The two groups were matched by diagnostic age, gender and the presence of outflow tract obstruction. Clinical characteristics and long-term outcomes were compared. Results: The mean follow-up duration in ASHCM and ApHCM were 6.6 ± 5.5 and 7.6 ± 4.1 years, respectively. During follow-up, 16 patients experienced cardiovascular death in the ASHCM group, while 2 patients experienced cardiovascular death in the ApHCM group (6.3 vs. 0.7%, p < 0.01). Cardiovascular morbidity in the ASHCM and ApHCM groups were 39.9 and 18.5% (p < 0.01). In the multivariate Cox regression analysis late gadolinium enhancement (LGE; HR 4.81, 95% CI 1.28-78.0, p = 0.03) and unexplained syncope (HR 9.68, 95% CI 1.9-17.2, p < 0.01) were independent predictors for cardiovascular mortality. Unexplained syncope was independently associated with a higher risk for sudden cardiac death (HR 4.3, 95% CI 1.2-15.3, p = 0.02). Conclusions: After eliminating the interference of diagnostic age, gender and outflow tract obstruction, ASHCM represented a worse prognosis with a higher incidence of cardiovascular mortality and morbidity than ApHCM. LGE was a strong predictor for cardiovascular death.