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Article: Long-Term Non-Congenital Cardiac and Renal Complications in Down Syndrome: A Study of 32,936 Patients.

Huang, Yu-Nan / Huang, Jing-Yang / Wang, Chung-Hsing / Su, Pen-Hua

2023 Volume 10, Issue 8

Abstract: Background: Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10- ...

Abstract	Background: Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10-year incidence of cardiac, renal, and urinary tract complications in Down syndrome versus matched controls. Methods: This retrospective cohort study utilized a large collaborative database. We identified 32,444 patients with Down syndrome and matched controls, excluding those with pre-follow-up target events. Covariates included demographics, lifestyle factors, and comorbidities. Outcomes were ischemic heart disease, hypertension, hypothyroidism, epilepsy, urinary tract infections and chronic kidney disease. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression and plotted Kaplan-Meier survival curves. Findings: Over 10 years, Down syndrome patients showed a 3.7-fold higher ischemic heart disease risk (95% CI: 3.0-4.6) and a 1.6-fold higher hypertension risk (95% CI: 1.4-1.8) versus controls. Hypothyroidism (HR = 2.0; 95% CI: 1.7-2.4), epilepsy (HR = 4.5; 95% CI: 3.5-5.8), and urinary tract infection (HR = 3.9; 95% CI: 3.4-4.6) risks were also higher. Chronic kidney disease risk was 2.7-fold greater (95% CI: 2.1-3.5). Survival analysis confirmed a significantly higher incidence of all outcomes in Down syndrome ( Interpretation: This large study found major health challenges in Down syndrome, with risks 3- to 5-fold higher for chronic conditions versus matched controls over 10 years. Though survival remains high with proper care, focusing resources on the prevention and management of complications in this high-risk group can optimize well-being across the lifespan. Future research accounting for limitations here would provide definitive estimates of disease risk in Down syndrome to guide targeted health strategies.
Language	English
Publishing date	2023-08-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children10081351
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Article ; Online: The efficacy and limitation of lumboperitoneal shunt in normal pressure hydrocephalus.

Liu, Jung-Tung / Su, Pen-Hua

Clinical neurology and neurosurgery

2020 Volume 193, Page(s) 105748

Abstract: Objective: To investigate whether the efficacy of the lumbar-peritoneal (LP) shunt is sustainable, we measured the outcomes of patients with idiopathic NPH (iNPH) preoperatively and postoperatively.: Patients and methods: We retrospective reviewed ... ...

Abstract	Objective: To investigate whether the efficacy of the lumbar-peritoneal (LP) shunt is sustainable, we measured the outcomes of patients with idiopathic NPH (iNPH) preoperatively and postoperatively. Patients and methods: We retrospective reviewed records of 58 patients with iNPH from 2013 to 2015. Exclusion of 7 patients expired, 1 patient shunt infection, and 8 patients was loss of follow-up. In the remaining 42 patients, the mood, talking response, movement, attention, recalling memory, and mini-mental state examination (MMSE), representing patient outcomes, were measured. All of whom were follow-up for 3 years. Results: Mood (1.91 ± 0.30), talking response (1.98 ± 0.15), movement (1.71 ± 0.51), attention (1.95 ± 0.22), and recalling memory (1.86 ± 0.35) were significantly improved after surgery (1 week;p <  0.0001). However, the indicators significantly declined after 3 years (mood: 0.31 ± 0.52, talking response: 0.50 ± 0.59, movement: 0.17 ± 0.38, attention: 0.40 ± 0.59, recalling memory: 0.21 ± 0.42). The MMSE was also significantly improved after 3 months of surgery (17.9 5 ± 2.80 vs. 25.02 ± 3.36; p <  0.0001). However, it declined after 3 years (17.83 ± 3.66; p = 0.83). Conclusion: The iNPH is considered potentially reversible. Our data supported that the LP shunt was efficient in the short term. However, the neurological degeneration was still progressive.
MeSH term(s)	Aged ; Aged, 80 and over ; Cerebrospinal Fluid Shunts ; Female ; Follow-Up Studies ; Humans ; Hydrocephalus, Normal Pressure/psychology ; Hydrocephalus, Normal Pressure/therapy ; Infections/etiology ; Lumbosacral Region/surgery ; Male ; Mental Status and Dementia Tests ; Neuropsychological Tests ; Peritoneovenous Shunt/adverse effects ; Psychomotor Performance ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2020-02-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	193107-6
ISSN	1872-6968 ; 0303-8467
ISSN (online)	1872-6968
ISSN	0303-8467
DOI	10.1016/j.clineuro.2020.105748
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Article: Phthalates exposure and pubertal development in a 15-year follow-up birth cohort study in Taiwan.

Su, Pen-Hua / Huang, Jing-Yang / Wang, Shu-Li Julie / Chang, Hua-Pin

Frontiers in endocrinology

2023 Volume 14, Page(s) 1065918

Abstract: Purpose: Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored.: Methods: We conduct a population-based ... ...

Abstract	Purpose: Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored. Methods: We conduct a population-based birth cohort study to investigate the association between prenatal and childhood exposure to phthalates and pubertal development. Initially, a total of 445 children were recruited from 2000 to 2001, of which 90 children were followed for 15 years which measurements of urine and development assessed at 2, 5, 8, 11, and 14 years. We defined higher Tanner stage as the 14-year-old Tanner stage ≥ 4 and 5 for boys and girls, respectively. A logistic regression analysis was conducted to estimate the crude and adjusted odds ratio of a higher Tanner stage at 14 years old. The Pearson correlation coefficient and multiple linear regression were used to estimate the association of testicular volume, uterine volume, ovarian volume, and blood hormones at 14 years of age with the log-transformed concentration of phthalates at 2, 5, 8, 11, and 14 years. Results: In boys, a significantly different geometric mean of mono-benzyl phthalate (MBzP) was observed in 11-year-olds; 6.82 and 2.96 in the lower Tanner stage group and higher Tanner stage group. In girls, a significant difference in the geometric mean of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in 11-year-olds and mono-ethyl phthalate (MEP) in 2-year-olds was observed; MEHHP was 32.97 and 18.13 in the lower Tanner stage group and higher Tanner stage group, and MEP was 26.54 and 65.74 in the lower Tanner stage group and higher Tanner stage group, respectively. Uterine volume at 14 years old was negatively associated with several phthalate metabolites (MEHP at 8 years old, MnBP at 8 years old, MBzP at 14 years old, MMP prenatally, MMP at 8 years old, and MEP at 8 years old) after adjusting for covariates. However, no significant correlations were found between phthalate metabolites and ovarian or testicular volume. Conclusion: Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be conducted to determine the causal nature of this association.
MeSH term(s)	Male ; Child ; Pregnancy ; Female ; Humans ; Child, Preschool ; Adolescent ; Cohort Studies ; Environmental Exposure/adverse effects ; Follow-Up Studies ; Taiwan/epidemiology ; Phthalic Acids/adverse effects
Chemical Substances	phthalic acid (6O7F7IX66E) ; Phthalic Acids ; mono-benzyl phthalate (27NM8BNV1K)
Language	English
Publishing date	2023-05-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1065918
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Article: Amelioration of cognitive impairment following growth hormone replacement therapy: A case report and review of literature.

Liu, Jung-Tung / Su, Pen-Hua

World journal of clinical cases

2018 Volume 8, Issue 22, Page(s) 5773–5780

Abstract: Background: Stroke is one of the leading causes of death and disability worldwide. In patients suffering from strokes and other acute brain injuries, the prevalence of pituitary dysfunction is high, and growth hormone deficiency is commonly found. ... ...

Abstract	Background: Stroke is one of the leading causes of death and disability worldwide. In patients suffering from strokes and other acute brain injuries, the prevalence of pituitary dysfunction is high, and growth hormone deficiency is commonly found. Previous studies have demonstrated that administration of recombinant human growth hormone provides adult growth hormone deficiency (AGHD) patients with beneficial effects such as improving body compositions and quality of life. Nevertheless, other physiological benefits of growth hormone substitution are still controversial and inconclusive. Case summary: A female with a history of hypertension suffered intracranial hemorrhage, intraventricular hemorrhage, and hydrocephalus at 56 years of age. Her mobility, fluency of speech, and mentality were impaired ever since the event occurred. After five years, the 61-year-old patient was further diagnosed with AGHD and received six-month growth hormone replacement therapy (GHRT). After six months of GHRT, the patient's body composition was improved. A substantial improvement in Mini-Mental State Examination score was also observed, accompanying with ameliorations in mobility, fluency of speech, and mentality. Conclusion: In addition to improvements in body composition, GHRT for AGHD may provide further beneficial effects in patients with cognitive or motor impairments due to intracerebral hemorrhage.
Language	English
Publishing date	2018-09-04
Publishing country	United States
Document type	Case Reports
ISSN	2307-8960
ISSN	2307-8960
DOI	10.12998/wjcc.v8.i22.5773
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Article ; Online: Monitoring Adherence Rate to Growth Hormone Therapy and Growth Outcomes in Taiwanese Children Using Easypod Connect: Observational Study.

Su, Pen-Hua / Yang, Chen / Chao, Mei-Chyn / Chiang, Chung-Lin

JMIR pediatrics and parenting

2021 Volume 4, Issue 1, Page(s) e14774

Abstract: Background: Adherence to growth hormone therapy is difficult to detect reliably. Devices such as easypod have been developed for electronic recording of injections. The easypod connect observational study (ECOS) was an open-label, observational, ... ...

Abstract	Background: Adherence to growth hormone therapy is difficult to detect reliably. Devices such as easypod have been developed for electronic recording of injections. The easypod connect observational study (ECOS) was an open-label, observational, multinational, phase IV study conducted in 24 countries around the world. The final results from ECOS in the Taiwanese cohort are reported in this paper. Objective: This study aimed to evaluate the adherence and long-term outcomes of growth hormone therapy in pediatric subjects using the easypod electromechanical device. Methods: Subjects (aged 2-18 years or >18 years without fusion of growth plates) who received Saizen (recombinant human growth hormone, somatropin) via the easypod device were enrolled in this study. The primary objective was to assess the level of adherence in subjects receiving Saizen via easypod. Results: In Taiwan, a total of 35 and 13 children fulfilled the criteria of full analysis set and complete analysis set, respectively. The mean (SD) age of the complete analysis set was 12.08 (2.72) years. All subjects were growth hormone-naïve, with 38% (5/13) females. The mean adherence rates of 13 subjects were 87.6% at 3 months and 84.3% at 6 months, that of 8 subjects was 81.0% at 9 months, and that of 4 subjects was 91.6% at 1 year. After 1 year of treatment, subjects had a median (Q1:Q3) change in height SD score of 0.30 (0.06:0.48), median height velocity of 6.50 (4.33:8.24) cm/year, and median change in height velocity SD score of 1.81 (-0.04:3.52). Conclusions: With the easypod device, patients with inadequate adherence and poor response to treatment can be identified. Adherence to growth hormone therapy administered via easypod was generally high in the first year of treatment but the adherence gradually decreased over time. Overall, growth outcomes after 1 year indicated a positive growth response to growth hormone treatment. Future efforts should be focused on personalized management of adherence by using the easypod system.
Language	English
Publishing date	2021-01-15
Publishing country	Canada
Document type	Journal Article
ISSN	2561-6722
ISSN (online)	2561-6722
DOI	10.2196/14774
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Article ; Online: Congenital anomalies: current knowledge and future prospects.

Su, Pen-Hua

Pediatrics and neonatology

2013 Volume 54, Issue 3, Page(s) 145–146

MeSH term(s)	Chromosome Aberrations ; Congenital Abnormalities/epidemiology ; Congenital Abnormalities/genetics ; Humans ; Incidence ; Taiwan/epidemiology
Language	English
Publishing date	2013-06
Publishing country	Singapore
Document type	Editorial
ZDB-ID	2441816-X
ISSN	2212-1692 ; 1875-9572
ISSN (online)	2212-1692
ISSN	1875-9572
DOI	10.1016/j.pedneo.2013.02.002
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Article ; Online: Incidence of Pulmonary and Respiratory Conditions in Gaucher Disease from 2000 to 2020: A Multi-institutional Cohort Study.

Huang, Yu-Nan / Huang, Jing-Yang / Liao, Wen-Ling / Chiang, Shang-Lun / Liu, Kai-Wen / Bau, DA-Tian / Wang, Chung-Hsing / Su, Pen-Hua

In vivo (Athens, Greece)

2023 Volume 37, Issue 5, Page(s) 2276–2283

Abstract: Background/aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. ... ...

Abstract	Background/aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. We analyzed electronic health records for 11,004 patients with GD over 10-20 years to determine the incidence of pulmonary hypertension (PH), lung disease, and other respiratory comorbidities and better understand disease course to guide management. Patients and methods: We conducted a retrospective cohort study using the TriNetX research database of 130 million international patients. The incidence of primary/secondary PH, pulmonary heart disease, interstitial/obstructive/restrictive lung disease, pulmonary hemorrhage, and pulmonary embolism was assessed in patients with GD from 2000-2020. Results: Incidence rates of all conditions assessed increased from 10 to 20 years of follow-up. Excess risk of PH, lung disease, and pulmonary hemorrhage was significantly higher in GD patients after 20 versus 10 years. Conclusion: Extended follow-up in GD is associated with substantially higher risks of PH, lung disease and other respiratory comorbidities, highlighting the need for close monitoring and early intervention to mitigate long-term pulmonary decline. Improved understanding of mechanisms driving respiratory deterioration can support the development of novel treatments to optimize outcomes in this population at high risk of pulmonary morbidity and mortality.
MeSH term(s)	Humans ; Gaucher Disease/complications ; Gaucher Disease/epidemiology ; Incidence ; Retrospective Studies ; Lung ; Lung Diseases/etiology ; Lung Diseases/complications ; Cohort Studies ; Hemorrhage/epidemiology ; Hemorrhage/etiology
Language	English
Publishing date	2023-08-29
Publishing country	Greece
Document type	Multicenter Study ; Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13330
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Article ; Online: The Long-term Lung and Respiratory Outcomes of Acid Sphingomyelinase Deficiency: A 10- and 20-year Follow-up Study.

Huang, Yu-Nan / Chiang, Shang-Lun / Huang, Jing-Yang / Lu, Wen-Li / Bau, DA-Tian / Su, Pen-Hua / Wang, Chung-Hsing

In vivo (Athens, Greece)

2023 Volume 38, Issue 1, Page(s) 437–444

Abstract: Background/aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death.: Patients and methods: This retrospective ... ...

Abstract	Background/aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death. Patients and methods: This retrospective observational study used the TriNetX database of electronic health records for 15,108 patients with ASMD from 2000-2020. After exclusions, 8,980 individuals were followed for 10 or 20 years. Outcomes included incidence and prevalence of respiratory disorders. Associations of age, sex and race were assessed. Results: Nearly all respiratory outcomes increased significantly over 20 versus 10 years. Other respiratory disorders, specified respiratory disorders and secondary pulmonary hypertension exhibited the greatest increases, reflecting progressive lung damage in ASMD. While outcomes were poor overall, older age, male sex, and racial minority status associated with greater risks, indicating differences in disease progression or care. Conclusion: This study confirms the progressive nature of ASMD and need for close monitoring and treatment of pulmonary complications to reduce long-term morbidity and mortality. Genetic testing enabling diagnosis even for milder, adult-onset forms is critical to optimize outcomes.
MeSH term(s)	Adult ; Humans ; Male ; Follow-Up Studies ; Sphingomyelin Phosphodiesterase/genetics ; Niemann-Pick Disease, Type A/diagnosis ; Niemann-Pick Disease, Type A/genetics ; Niemann-Pick Diseases ; Lung
Chemical Substances	Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
Language	English
Publishing date	2023-12-24
Publishing country	Greece
Document type	Observational Study ; Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13457
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Article ; Online: Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients.

Tsai, Tsung-Hsun / Wang, Chung-Hsing / Chiang, Shang-Lun / Huang, Jing-Yang / Bau, DA-Tian / Huang, Yu-Nan / Su, Pen-Hua

In vivo (Athens, Greece)

2023 Volume 37, Issue 6, Page(s) 2609–2617

Abstract: Background/aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and ... ...

Abstract	Background/aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes. Patients and methods: This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and end-stage renal disease (ESRD). Results: The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity. Conclusion: This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes.
MeSH term(s)	Female ; Humans ; Fabry Disease/complications ; Fabry Disease/epidemiology ; Cohort Studies ; Retrospective Studies ; Prevalence ; alpha-Galactosidase/adverse effects ; Kidney ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology ; Kidney Failure, Chronic/etiology ; Kidney Failure, Chronic/complications
Chemical Substances	alpha-Galactosidase (EC 3.2.1.22)
Language	English
Publishing date	2023-10-30
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13368
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Article ; Online: Elucidating the Cancer Phenotype in Turner Syndrome: A 20-Year Observational Cohort Study.

Huang, Yu-Nan / Chen, Shao-Chia / Chen, Jo-Ching / Liu, Kai-Wen / Chiang, Shang-Lun / Bau, DA-Tian / Su, Pen-Hua / Wang, Chung-Hsing

Anticancer research

2023 Volume 43, Issue 11, Page(s) 5073–5081

Abstract: Background/aim: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 ... ...

Abstract	Background/aim: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 years of age to inform screening strategies. Patients and methods: We performed a retrospective cohort analysis of 11,502 patients with Turner syndrome from 2000 to 2020 utilizing the TriNetX research network database. The outcomes encompassed the incidence and prevalence of 20 cancers. Stratified analyses were used to evaluate variations in age, sex, and race. Results: Key findings demonstrated markedly elevated risks of breast (1.7%), colon (1.0%), renal (0.4%), gonadoblastoma (0.4%), and other cancers. Significant demographic variations were observed in the incidence of cancers, such as gonadoblastoma, renal, and colon cancer. Conclusion: This large real-world study offers novel insights into the spectrum of cancer risk across adulthood in Turner syndrome. Our findings elucidate Turner syndrome's complex cancer phenotype to inform clinical decision-making, prognostication, and tailored screening strategies to ultimately advance patient care.
MeSH term(s)	Humans ; Female ; Adult ; Gonadoblastoma ; Turner Syndrome/complications ; Turner Syndrome/epidemiology ; Turner Syndrome/genetics ; Retrospective Studies ; Colonic Neoplasms ; Cohort Studies ; Phenotype ; Ovarian Neoplasms
Language	English
Publishing date	2023-11-01
Publishing country	Greece
Document type	Observational Study ; Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16707
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