OBJECTIVE: To summarize the clinical and genetic characteristics of children with Silver-Russell syndrome (SRS) and improve the recognition of this disease. METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of 29 children with SRS diagnosed at the Children's Hospital Affiliated to Zhengzhou University between March 2016 and June 2025. RESULTS: The 29 children had included 18 boys and 11 girls, with the age ranging from 2 months to 16 years. Their primary clinical manifestations included postnatal growth retardation (100%), small for gestational age (SGA) (100%), characteristic facial features (90%), limb asymmetry (83%), feeding difficulties (76%), ulnar deviation of the fifth finger (69%), body mass index (BMI) of < -2 SD (62%), and abnormal bone age (55%), including 15 cases with delayed bone age for an average of 1.5 years and 1 case with advanced bone age for 2.5 years. Additional manifestations included abnormal sexual development in 11 cases (38%), dental malocclusion in 11 cases (38%), allergic diseases in 10 cases (34%), cardiac diseases in 9 cases (31%), skeletal abnormalities in 7 cases (24%), renal hypoplasia in 5 cases (17%), and abnormal cranial MRI findings in 5 cases (17%). Twenty children were treated with recombinant human growth hormone (rhGH) at a dose of 0.1 ~ 0.15 U/(kg.d). Among them, 7 cases achieved annual height increase of ≥ 10 cm, 11 cases achieved annual height increase of ≥ 5 ~ 9 cm, and 2 cases achieved annual height increase < 5 cm. Twenty three children exhibited hypomethylation of imprinted genes in the chromosome region of 11p15, 4 presented maternal uniparental disomy of chromosome 7 [UPD(7)mat], and 2 had harbored nonsense variants of the HMGA2 gene. CONCLUSION SRS patients may present with diverse clinical manifestations including postnatal growth retardation, SGA, characteristic facial features, limb asymmetry, feeding difficulties, and ulnar deviation of the fifth finger. Most patients may exhibit abnormal methylation in the 11p15 region. rhGH therapy can improve the height of these patients.
Humans ; Silver-Russell Syndrome/diagnosis* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Retrospective Studies

Bullous hemorrhagic dermatosis (BHD) is a rare cutaneous manifestation characterized by tense hemorrhagic bullae that appear at sites distant from low molecular weight heparin (LMWH) injections, typically within seven days of exposure. As of March 2022, only 94 cases have been reported. It most commonly affects elderly males with predisposing factors for thromboembolism, such as carcinoma, and usually involves the extremities.

This case highlights the importance of maintaining a high index of suspicion for bullous hemorrhagic dermatosis (BHD) in patients receiving low molecular weight heparin, even beyond the typical 7-day window and in demographics not commonly affected. Early recognition and prompt discontinuation of the offending agent, as demonstrated in this atypical presentation involving a Filipino elderly woman with multiple comorbidities and no malignancy, can lead to favorable outcomes. Clinicians should be aware of this rare but reversible complication to avoid misdiagnosis and ensure appropriate management.

Human ; Female ; Aged: 65-79 Yrs Old ; Affect ; Aged ; Blister ; Carcinoma ; Causality ; Demography ; Diagnostic Errors ; Enoxaparin ; Extremities ; Heparin ; Heparin, Low-molecular-weight ; Index ; Injections ; Lead ; Male ; Molecular Weight ; Neoplasms ; Patients ; Research Report ; Skin Diseases ; Thromboembolism ; Women

OBJECTIVES

Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.

METHODS

This was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.

RESULTS

Two hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.

CONCLUSION

Overall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.

Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce

Human ; Metals, Heavy ; Tobacco ; Tobacco Products

BACKGROUND: As research progresses, there is a growing body of evidence indicating that urinary metallothionein (MT) levels may be elevated in individuals exposed to cadmium (Cd). This study aimed to investigate the potential association between urinary MT levels and causes of mortality among residents of the Kakehashi River Basin who have been exposed to Cd. METHOD: The study involved a total of 1,398 men and 1,731 women were conducted between 1981 and 1982, with follow-up until November 2016. The study employed the Cox proportional-hazards model to examine the association between higher urinary MT concentrations and the risk of all-cause or cause-specific mortality within the population. Furthermore, the Fine and Gray competing risks regression model was used to evaluate the links between specific causes of death. RESULTS: The findings revealed that elevated urinary MT concentrations were linked to increased all-cause mortality and higher mortality rates from renal and urinary tract diseases across all participants. Specifically, in men, higher urinary MT levels were associated with elevated all-cause mortality, while in women, increased concentrations were linked to higher mortality from endocrine, nutritional, and metabolic diseases, as well as cardiovascular diseases. Even after adjusting for competing risks, higher urinary MT concentrations were associated with tumor-related mortality in men and continued to be associated with cardiovascular disease mortality in women. CONCLUSIONS In conclusion, the results suggest that women may face a greater risk of adverse health effects due to prolonged exposure to Cd. Urinary MT levels could potentially serve as a biomarker for mortality from these diseases in populations chronically exposed to Cd.
Humans ; Male ; Female ; Cadmium/urine* ; Japan/epidemiology* ; Metallothionein/metabolism* ; Middle Aged ; Cause of Death ; Adult ; Follow-Up Studies ; Aged ; Environmental Exposure/analysis* ; Proportional Hazards Models

BACKGROUND: Lead is a persistent inorganic environmental pollutant with global implication for human health. Among the diseases associated with lead exposure, the damage to the central nervous system has received considerable attention. It has been reported that long-term lead exposure increases the risk of meningioma; however, the underlying mechanism remains poorly understood. Clinical studies have indicated that loss-of-function and mutations in the neurofibromin-2 (NF2) gene play a crucial role in promoting meningioma formation. METHODS: The effect of Pb on meningioma were tested in-vitro and in-vivo. Two human meningioma cell lines were used in this study, including NF2-wildtype IOMM-Lee cell and NF2-null CH157-MN cell. Cell viability, cell cycle and cell size were examined after Pb exposure. The expression of Merlin, mammalian sterile 20-like kinases 1 and 2 (MST1/2) and Yes-associated protein (YAP) from these two meningioma cells were analyzed by Western blot. A xenograft mouse model was constructed by subcutaneous injection of IOMM-Lee meningioma cells. RESULTS: This study demonstrated that treatment with lead induce dose-dependent proliferation in IOMM-Lee cell (with an EC₅₀ value of 19.6 µM). Moreover, IOMM-Lee cell exhibited augmented cell size in conjunction with elevated levels of phosphorylated histone H3, indicative of altered cell cycle progression resulting from lead exposure. However, no significant change was observed in the CH157-MN cell. Additionally, the Merlin-Hippo signaling pathway was inactivated with decreased Merlin and phosphorylation levels of MST1/2 and YAP, leading to increased YAP nuclear translocation in IOMM-Lee cells. However, there was no change in the Merlin-Hippo signaling pathway in CH157-MN cells after lead treatment. The administration of Pb resulted in an acceleration of the subcutaneous IOMM-Lee meningioma xenograft growth in mice. CONCLUSIONS Overall, the current study elucidates the potential mechanism by which lead exposure promotes the proliferation of meningioma with NF2 expression for the first time.
Meningioma/genetics* ; Neurofibromin 2/genetics* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Signal Transduction/drug effects* ; Mice ; Hippo Signaling Pathway ; Lead/adverse effects* ; Cell Line, Tumor ; Protein Serine-Threonine Kinases/genetics* ; Meningeal Neoplasms ; Environmental Pollutants/adverse effects* ; Female

BACKGROUND: Heavy metals are significant risk factors for kidney function. Numerous studies have shown that exposure to heavy metals negatively correlates with kidney function through oxidative stress pathways, and serum α-klotho is linked to oxidative stress. However, the role of α-klotho in the relationship between blood lead, mercury, and kidney function remains unclear. METHOD: This study evaluated the mediating role of alpha-klotho in the relationship between lead, mercury and renal function, using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) in U.S. adults aged 40-79. The sample included 11,032 participants, with blood lead, mercury, α-klotho, and other relevant covariates measured. Inductively coupled plasma mass spectrometry was used to assess blood lead and mercury levels, and enzyme-linked immunosorbent assay (ELISA) was employed to measure serum α-klotho. Kidney function was evaluated using estimated glomerular filtration rate (eGFR) based on creatinine levels. Multivariable linear regression was conducted to analyze the relationships between blood lead, mercury, α-klotho, and eGFR. A mediation analysis model was used to assess whether α-klotho influenced these associations. RESULTS: We observed a significant association between blood lead and eGFR. Mediation analysis revealed that α-klotho accounted for 12.76% of the relationship between serum lead and eGFR in the NHANES population. Subgroup analysis showed that α-klotho mediated 12.43%, 6.87%, 21.50% and 5.44% of the relationship between blood lead and eGFR in women, middle-aged adults (40-59 years old), without cardiovascular disease and hypertension, respectively. However, α-klotho did not mediate the relationship between blood mercury and eGFR in terms of gender or age. This newly identified pathway may provide valuable insights for the prevention and treatment mechanisms related to kidney function impairment. CONCLUSION We found that blood lead was associated with renal function. According to the results of subgroup analysis, for blood lead, serum α-klotho mediated the association in females, middle aged 60-79 years. The relationship between blood mercury and renal function was not clinically significant, and serum α-Klotho mediated the relationship between blood mercury and renal function without significant clinical significance.
Humans ; Middle Aged ; Lead/blood* ; Female ; Klotho Proteins ; Male ; Aged ; Adult ; Mercury/blood* ; Glomerular Filtration Rate ; Nutrition Surveys ; United States ; Kidney/physiology* ; Glucuronidase/blood* ; Environmental Pollutants/blood*

BACKGROUND: Research has demonstrated that heavy metals and cholesterol are associated with stress urinary incontinence (SUI) in women and that heavy metal exposure can cause dyslipidemia in humans. However, the potential mediating role of cholesterol in the relationship between heavy metals and female SUI remains unexplored. METHODS: The study utilized data from the National Health and Nutrition Examination Survey database from 2013-2018. Blood lead (Pb), cadmium (Cd), total mercury (Hg), manganese (Mn), selenium (Se), and methyl mercury (MeHg) were included in the study. The single and combined effects of the six metals exposure on SUI were examined using logistic analysis, restricted cubic spline (RCS) curves, weighted quantile sum (WQS) regression, and bayesian kernel machine regression (BKMR). The mediating effects of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were investigated through mediation analysis. RESULTS: The study included 2241 females, with 42.66% experiencing SUI. Initial analysis of six heavy metals revealed the associations between MeHg, Pb, Cd, total Hg, and SUI (all P < 0.05). WQS regression identified that Cd, Se, and Pb were major contributors to the mixed effect causing SUI. BKMR results indicated a positive mixed effect between six heavy metals and SUI. TC partially mediated the relationship of Pb, MeHg, and total Hg with SUI, and LDL-C partially mediated the association of Pb with SUI (all P for mediation < 0.05). CONCLUSIONS Blood heavy metal concentrations influence the development of female SUI, with blood cholesterol mediating the association between different heavy metals and SUI.
Humans ; Female ; Metals, Heavy/blood* ; Nutrition Surveys ; Middle Aged ; Adult ; United States/epidemiology* ; Urinary Incontinence, Stress/chemically induced* ; Environmental Pollutants/blood* ; Aged ; Cholesterol/blood* ; Environmental Exposure

BACKGROUND: Since the accident at Fukushima Daiichi Nuclear Power Plant (FDNPP), concerns have arisen in Japan regarding the presence of radionuclides in food. Moreover, exposure levels to ⁹⁰Sr and Pu isotopes in adults and those to ¹³⁴Cs+¹³⁷Cs, ⁹⁰Sr, and Pu (where Cs, Sr, and Pu are cesium, strontium, and plutonium, respectively) in children have not been examined. Therefore, this study employed a duplicate portion approach to examine dietary exposure levels of radionuclides in adults and children following the FDNPP accident. METHODS: The study spanned fiscal years 2012-2014 and was conducted in 10 prefectures: Hokkaido, Iwate, Miyagi, Fukushima, Ibaraki, Saitama, Tokyo, Kanagawa, Osaka, and Kochi. The participants provided portions of their meals for two non-consecutive days and completed questionnaires on the meal items. The activity concentrations of ¹³⁴Cs, ¹³⁷Cs, ⁹⁰Sr, and ^239+240Pu, which are targets of standard limits for radionuclides in foods in Japan, were determined according to the Radioactivity Measurement Series. The daily intake was calculated based on the radionuclide activity concentrations in the duplicate portion samples, and the committed effective doses were estimated using dose coefficients for the ingestion of each radionuclide provided by the International Commission on Radiological Protection. RESULTS: Approximately 80 duplicate samples were obtained in each fiscal year, and 242 samples were collected. The highest summed activity concentration of ¹³⁴Cs and ¹³⁷Cs was 11 Bq/kg, which was recorded in Date City (child) in 2013; this level was approximately one-ninth of the standard limit for general foods (100 Bq/kg). The committed effective dose from annual ingestion of the sample described above was 74 µSv, approximately 14 times lower than the maximum permissible level of 1 mSv/y. Pu was not detected and the ⁹⁰Sr activity concentrations were similar to those before the FDNPP accident. CONCLUSIONS For the samples examined in the present study, the ¹³⁴Cs, ¹³⁷Cs, ⁹⁰Sr, and ^239+240Pu dietary exposure levels were considerably lower than the regulatory levels and may not pose a health risk.
Fukushima Nuclear Accident ; Cesium Radioisotopes/analysis* ; Humans ; Japan ; Dietary Exposure/statistics & numerical data* ; Adult ; Plutonium/analysis* ; Child ; Food Contamination, Radioactive/analysis* ; Strontium Radioisotopes/analysis* ; Male ; Female ; Middle Aged ; Child, Preschool ; Radiation Monitoring ; Young Adult ; Adolescent ; Aged ; Radiation Exposure/analysis*

BACKGROUND: Dental caries is a chronic childhood disease and one of the most prevalent public health problems worldwide. Lead is a heavy metal that is taken up by the teeth and bones. However, the association between lead exposure during pregnancy, when the tooth germs are formed, and the prevalence of dental caries in the primary dentition remains unclear. This study aimed to examine the association between maternal blood lead levels and the prevalence of dental caries in the primary dentition of children. METHODS: This cross-sectional study was conducted as an Adjunct Study to the Japan Environment and Children's Study (JECS), which is an ongoing nationwide birth-cohort study. Among children participating in the JECS at the University of Occupational and Environmental Health Sub-Regional Center, those aged 7-8 years underwent oral examination and questionnaire administration. The dft (i.e., sum of the number of decayed and filled primary teeth) was then determined. The dft numerically expresses the dental caries prevalence in the primary dentition (larger value indicates more prevalent dental caries). Poisson regression analyses with robust standard errors were performed to evaluate the association between maternal blood lead levels during pregnancy, measured using frozen samples, and the dft. RESULTS: The study included 139 children, of whom 54.7% were girls, and 89.2% were 7 years old. The median maternal blood lead level was 6.1 ng/g (25-75 percentile, 5.0-7.3). The median dft was 0 (25-75 percentile, 0-4). After adjusting for covariates including age, sex, and oral health status and behavior, maternal blood lead levels were significantly associated with increased dft (prevalence ratio, 1.6; 95% confidence interval, 1.3-1.8; per one standard deviation increase in natural log-transformed maternal blood lead levels). CONCLUSIONS This study found an association between maternal blood lead levels and the prevalence of dental caries in the primary dentition of children aged 7-8 years. Maternal exposure to lead during mid- to late-term pregnancy may affect the caries susceptibility of children after birth.
Humans ; Lead/blood* ; Female ; Dental Caries/epidemiology* ; Prevalence ; Tooth, Deciduous ; Male ; Japan/epidemiology* ; Child ; Cross-Sectional Studies ; Pregnancy ; Adult ; Maternal Exposure/adverse effects* ; Environmental Pollutants/blood* ; Prenatal Exposure Delayed Effects/epidemiology*