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Analysis of MTHFR gene variants in fifteen children with hyperhomocysteinemia

Zhonghua Yi Xue Za Zhi. 2024 Jun 25;104(24):2256-2259. doi: 10.3760/cma.j.cn112137-20240125-00192.

ABSTRACT

The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children’s Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) μmol/L and (69.96±32.88) μmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (P<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) μmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.

PMID:38901983 | DOI:10.3760/cma.j.cn112137-20240125-00192

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The value of midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test in the diagnosis of primary aldosteronism subtypes

Zhonghua Yi Xue Za Zhi. 2024 Jun 25;104(24):2242-2248. doi: 10.3760/cma.j.cn112137-20231115-01104.

ABSTRACT

Objective: To explore the value of the midnight 1 mg dexamethasone suppression test combined with adrenocorticotropic hormone (ACTH) stimulation test in the diagnosis of primary aldosteronism (PA) subtypes. Methods: A cross-sectional study. Clinical data of patients diagnosed with PA at the First Medical Center of Chinese PLA General Hospital from January 2020 to September 2022, who completed the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test, were analysed retrospectively. The clinical characteristics and trial results of patients with aldosterone-producing adenoma (APA) and idiopathic hyper aldosteronism (IHA)were compared. The efficacy of the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test in distinguishing APA and IHA was evaluated by drawing receiver operating characteristic (ROC) curves, and the cut-off value of the diagnostic indicator was determined with the maximum Youden index. Results: A total of 82 patients with PA were included, including 43 males and 39 females, aged (50.8±11.4) years old. They were divided into APA group (n=49) and IHA group (n=33) based on PA subtype. There was no statistically significant difference in body mass index, systolic and diastolic blood pressure between the two groups (all P>0.05). The blood potassium and orthostatic renin levels in the APA group were lower than those in the IHA group, and the differences were statistically significant (all P<0.001). The orthostatic plasma aldosterone concentration (PAC), orthostatic aldosterone to renin ratio (ARR), PAC before and after captopril challenge test(CCT), ARR after CCT, PAC before and after saline infusion test (SIT), and the proportion of unilateral lesions in the APA group were all higher than those in the IHA group, and the differences were statistically significant (all P<0.001). After the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test (30, 60, 90, 120 min), the PAC and PAC/cortisol levels in the APA group were significantly higher than those in the IHA group (all P<0.05). The PAC at 90 min showed the highest diagnostic capability according to the area under the ROC(AUC) (0.930,95%CI:0.874-0.986), and the Youden index was the highest at a PAC cut-off value of 39.05 ng/dl(0.766). The sensitivity and specificity for distinguishing APA from IHA were 91.8% and 84.8%, respectively. Conclusions: The midnight 1 mg dexamethasone suppression test with ACTH stimulation test could be useful for differentiating the subtypes of PA. Among them, the PAC and PAC/cortisol at 90 min showed best diagnostic efficacy.

PMID:38901981 | DOI:10.3760/cma.j.cn112137-20231115-01104

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Relationship between bioelectrical impedance analysis-derived fluid status and nutritional indicators and the prognosis in patients undergoing maintenance hemodialysis

Zhonghua Yi Xue Za Zhi. 2024 Jun 25;104(24):2234-2241. doi: 10.3760/cma.j.cn112137-20240113-00100.

ABSTRACT

Objective: To explore the relationship between bioelectrical impedance analysis (BIA)-derived fluid status and nutritional indicators and the prognosis in patients undergoing maintenance hemodialysis (MHD). Methods: A retrospective cohort study was conducted. The clinical data of MHD patients in Jiangsu Province Hospital between January 2014 and December 2016 were analyzed. BIA data of healthy volunteers in Gulou District, Nanjing City, collected between April and October 2022, were used to determine the cut-off value of body cell mass index (BCMI). Referring to previous research, using 0.15 as the cut-off value for the ratio of overhydration and extracellular water (OH/ECW). The data were transformed into binary variables based on these cut-off values to categorize patients into different groups. Kaplan-Meier analysis was used to plot survival curves, and the Cox proportional hazards model was performed to analyze risk factors for all-cause mortality. Results: A total of 706 MHD patients (407 males and 299 females) were included, aged (54±15) years. MHD patients were classified into four groups based on whether BCMI was<5.4 kg/m2 and OH/ECW was≥0.15, which included non-overhydration and non-malnutrition group, overhydration group, malnutrition group, and overhydration and malnutrition group, with 269, 186, 151, and 100 patients, respectively. During a median follow-up of [M(Q1, Q3)] 33 (26, 37) months, 162 patients died. Kaplan-Meier analysis showed that the median survival periods of the four groups were 52 months (95%CI: 41-54 months), 46 months (95%CI: 44-49 months), 37 months (95%CI: 34-40 months), and 34 months (95%CI: 30-38 months), respectively, with a statistically significant difference (P<0.001). The 1-year survival rates were 95.5%, 93.5%, 92.1%, and 88.0% (P<0.001), respectively, and the 2-year mortality rates were 92.6%, 87.1%, 83.4%, and 77.0% (P<0.001), respectively. Multivariate Cox regression analysis showed that compared with non-overhydration and non-malnutrition group, the risk of all-cause mortality increased by 1.18 times in the malnutrition group (HR=2.18, 95%CI: 1.29-3.71, P=0.004), and by 1.59 times in the overhydration and malnutrition group (HR=2.59, 95%CI: 1.48-4.54, P=0.001). Conclusions: BIA-derived fluid status and nutritional indicators are associated with the prognosis of MHD patients. Compared with patients without fluid overload and malnutrition, patients with malnutrition and fluid overload have an increased risk of all-cause mortality.

PMID:38901980 | DOI:10.3760/cma.j.cn112137-20240113-00100

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Efficacy and safety of flexible ureteral lithotripsy for upper urinary tract calculi in patients aged 80 years and older

Zhonghua Yi Xue Za Zhi. 2024 Jun 25;104(24):2229-2233. doi: 10.3760/cma.j.cn112137-20231205-01294.

ABSTRACT

Objective: To assess the efficacy and safety of flexible ureteral lithotripsy (FURL) for treating upper urinary tract calculi in patients ≥80 years. Methods: This study retrospectively analyzed the clinical data of 297 elderly patients who underwent FURL for unilateral upper urinary tract calculi at Beijing Hospital from January 2019 to September 2023. Patients were divided into elderly group (≥80 years) and low-middle aged group (≥60-<80 years). Propensity score matching (PSM) was used to match preoperative clinical data of patients. After PSM, the basic, perioperative and postoperative data of the two groups were compared. Results: After PSM, 116 patients were enrolled, including 58 patients in each group. The age [M (Q1, Q3)] of elderly group was 83.0 (81.0, 86.0) years, which included 29 males. The age of low-middle aged group was 69.5 (64.8, 74.0) years, which included 33 males. The duration of postoperative hospitalization [M (Q1, Q3)] in elderly group was longer than that in low-middle aged group [2 (1, 3) d vs 1 (1, 2) d, P=0.002]. Serious postoperative complications occurred in 3 cases in the elderly group and 1 case in the low-middle aged group, respectively, without surgical intervention. There was no significant statistical difference in stone-free rate (SFR) [79.3% (46/58) vs 84.5% (49/58)], operation time [M (Q1, Q3), 70.0 (48.3, 100.0) vs 65.0 (46.5, 101.2) min] and postoperative complication rate [25.9% (15/58) vs 22.4% (13/58)] between two groups (all P>0.05). Conclusions: In the treatment of upper urinary tract calculi in patients ≥80 years, the SFR, operation time and postoperative complication rate of FURL are comparable to those in low-middle aged elderly patients. FURL has good safety and effectiveness in the treatment of upper urinary tract calculi in patients ≥80 years.

PMID:38901979 | DOI:10.3760/cma.j.cn112137-20231205-01294

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Risk factors for progression to chronic kidney disease in patients with cardiac valve replacement surgery-associated acute kidney injury

Zhonghua Yi Xue Za Zhi. 2024 Jun 25;104(24):2222-2228. doi: 10.3760/cma.j.cn112137-20231219-01422.

ABSTRACT

Objective: To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). Methods: A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min-1·(1.73 m2)-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as M (Q1,Q3). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. Results: A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min-1·(1.73 m2)-1], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) μmol/L], and the differences were statistically significant (all P<0.05). The multivariate logistic regression analysis results revealed that older age (OR=1.063, 95%CI: 1.001-1.129, P=0.047), preoperative hypertension (OR=3.070, 95%CI: 1.105-8.532, P=0.031) and higher serum creatinine at discharge (OR=1.026, 95%CI:1.013-1.038, P<0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95%CI: 0.790-0.940, P<0.001]. Conclusion: Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.

PMID:38901978 | DOI:10.3760/cma.j.cn112137-20231219-01422

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Diagnostic Reference Levels in PET Imaging at Chulabhorn Hospital, Thailand

J Nucl Med Technol. 2024 Jun 20:jnmt.124.267576. doi: 10.2967/jnmt.124.267576. Online ahead of print.

ABSTRACT

Diagnostic reference levels (DRLs) are an important tool for controlling radiation exposure and ensuring safety in medical applications. In Thailand, DRL data have been gathered and established for nuclear medicine diagnostics since 2021. However, there is a lack of information on PET imaging examinations. At the National Cyclotron and PET Scan Centre, Chulabhorn Hospital, radiopharmaceuticals are produced for medical imaging and research, and a wide range of PET/CT and PET/MRI examinations are performed. Our objective was to investigate the administered activity of radiopharmaceuticals in patients undergoing PET imaging, especially the existing data on DRLs in medical diagnostic imaging. Methods: This was a retrospective study on nuclear medicine patients at the National Cyclotron and PET Scan Centre in 2023. Statistical analysis, including the mean and the 75th percentile values, was conducted to determine DRLs according to the International Commission on Radiological Protection guidelines. Results: The center performed 8,711 PET/CT and PET/MRI studies with 13 protocols in 2023. The most commonly administered activity was 18F-FDG in oncology and neurology examinations, with DRLs of 186.11 and 136.16 MBq, respectively. These values were notably almost twice lower than several reports in other countries. Conclusion: There is a lack of comprehensive data on most DRLs for PET imaging at this center because of the nonwidespread use of several radiopharmaceuticals. However, the lower DRLs for 18F-FDG can highlight the need for ongoing investigation toward the establishment of local DRLs, as well as assurance on the safety and efficiency of radiation used in nuclear medicine.

PMID:38901963 | DOI:10.2967/jnmt.124.267576

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Temporal patterns of food consumption and their association with cardiovascular risk in rotating shift workers

Clin Nutr ESPEN. 2024 Aug;62:95-101. doi: 10.1016/j.clnesp.2024.04.023. Epub 2024 May 18.

ABSTRACT

OBJECTIVE: We aimed to evaluate the association of temporal patterns of food consumption with cardiovascular disease (CVD) risk.

METHODS: This cross-sectional study included male rotating shift workers in an iron ore extraction company. Data on food consumption was collected using a 24 h recall, applied by trained interviewers. The variables for temporal patterns of food consumption were: eating window, eating at night, number of meals and omission of breakfast. CVD-risk was measured by calculating the Framingham coronary heart disease risk score (FCRS), and classified as low risk or intermediate to high risk. Descriptive, univariate and multivariate logistic regression analyses examined the association between variables related to temporal patterns of food consumption and CVD-risk.

RESULTS: The study assessed 208 workers, the majority with 20-34 years (45.1%), non-white (77.2%), and 5 years or more in shift work (76.0%). Most participants had a feeding window exceeding 12 h (63.9%), consumed meals until 10 p.m. (68.1%), had five or more meals per day (54.8%), and did not skip breakfast (86.5%). Regarding CVD-risk, 43.8% of the participants were classified with intermediate to high risk for CVD. In the multivariate model, a feeding window (OR: 2.32; 95%CI: 1.01-5.35), eating after 10 p.m. (OR: 3.31; 95%CI: 1.01-11.0), and skipping breakfast (OR: 2.58; 95%CI: 1.07-6.19) increased the likelihood of intermediate to high CVD-risk. Conversely, having five or more meals per day decreased the odds (OR: 0.27; 95%CI: 0.08-0.92).

CONCLUSION: Eating window longer than 12 h, eating after 10 p.m., less than four meals a day and omission of breakfast, are associated with cardiovascular risk in shift workers.

PMID:38901954 | DOI:10.1016/j.clnesp.2024.04.023

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Causal relationships between gut microbiota, gut metabolites, and diabetic neuropathy: A mendelian randomization study

Clin Nutr ESPEN. 2024 Aug;62:128-136. doi: 10.1016/j.clnesp.2024.04.019. Epub 2024 May 23.

ABSTRACT

BACKGROUND: Previous studies have shown a strong correlation between gut microbiota and diabetes and its associated complications. We aimed to evaluate the causal relationships between the gut microbiota, gut metabolites, and diabetic neuropathy.

METHODS: Summary statistics of 211 gut microbiota and 12 gut-related metabolites (β-hydroxybutyric acid, betaine, trimethylamine-N-oxide, carnitine, choline, glutamate, kynurenine, phenylalanine, propionic acid, serotonin, tryptophan, and tyrosine) were obtained from previous genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) design was used to estimate the effects of gut microbiota and gut metabolites on the risk of diabetic neuropathy based on FinnGen GWAS.

RESULTS: Higher levels of Acidaminococcaceae (OR = 0.62; 95%CI = 0.46 to 0.84; P = 0.002), Peptococcaceae (OR = 0.70; 95%CI = 0.54 to 0.90; P = 0.006), and Eubacterium coprostanoligenes group (OR = 0.68; 95%CI = 0.50 to 0.93; P = 0.016) are genetically determined to provide protection against diabetic neuropathy. Conversely, the presence of Alistipes (OR = 1.65; 95%CI = 1.18 to 2.31; P = 0.003), ChristensenellaceaeR7 group (OR = 1.52; 95%CI = 1.03 to 2.23; P = 0.033), Eggerthella (OR = 1.28; 95%CI = 1.05 to 1.55; P = 0.014), RuminococcaceaeUCG013 (OR = 1.35; 95%CI = 1.01 to 1.82; P = 0.046), and Firmicutes (OR = 1.42; 95%CI = 1.05 to 1.93; P = 0.023) increases the risk of diabetic neuropathy. Moreover, a correlation has been identified between diabetic neuropathy and two gut metabolites: betaine (OR = 0.95; 95%CI = 0.90 to 1.00; P = 0.033) and tyrosine (OR = 1.03; 95%CI = 1.01 to 1.06; P = 0.019). Sensitivity analysis indicated robust results with no sign of heterogeneity or pleiotropy.

CONCLUSION: The present study elucidated the impact of specific gut microbiota and gut metabolites on the susceptibility to diabetic neuropathy. Interventions targeting the improvement of the gut microbiota diversity and composition hold considerable promise as a potential strategy.

PMID:38901934 | DOI:10.1016/j.clnesp.2024.04.019

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Standardising and simplifying the Global Leadership Initiative on Malnutrition (GLIM) for its more general application

Clin Nutr ESPEN. 2024 Aug;62:120-127. doi: 10.1016/j.clnesp.2024.05.010. Epub 2024 May 18.

ABSTRACT

BACKGROUND: Malnutrition is present in 20-50% of hospital patients but its recognition is often neither timely nor complete. The Global Leadership Initiative on Malnutrition (GLIM) aims to improve this, but its successful implementation may be compromised by its dependence on (a choice of) prior screening tools and difficulties in consistent assessment of muscle mass.

AIMS: To explore different approaches to screening and muscle assessment in GLIM and to offer simpler choices for its more widespread application.

METHODS: (1) Data from 300 consenting in-patients provided Nutritional Risk Screening (NRS-2002), Malnutrition Universal Screening Tool (MUST), and Subjective Global Assessment (SGA) scores. GLIM scoring was preceded by NRS-2002 or MUST (using threshold scores of 1 or 2 for MUST), or no prior screening. The results of GLIM scoring preceded by different screening approaches were compared with those of SGA. (2) The literature on mid-upper arm circumference (MUAC) and calf circumference (CC) as simple, non-invasive, objective methods of muscle assessment methods was reviewed (3) The cumulative times taken to obtain GLIM scores were measured and corrected for the different screening strategies.

RESULTS: (1) Participants’ mean age was 60 years, 157 (52%) were female and mean BMI was 27.8 kg/m2. In comparison with SGA, GLIM with no prior screening had the highest sensitivity (65%) and negative predictive value (NPV) (76%), but the lowest specificity (90%) and positive predictive value (PPV) (84%). The equivalent figures for GLIM with prior MUST “1” were 62%, 75%, 93% and 88%; with prior NRS-2002, 55%∗, 73%, 98%∗ and 95%∗; and with prior MUST “2”, 44%∗, 69%∗, 98%∗, 95%∗. The area under an ROC curve was the highest (0.78) when GLIM was performed without screening or with prior MUST “1”. (2) Being less affected by oedema and gender differences than calf circumference, MUAC could serve as a standard globally accessible muscle mass assessment method which can be supplemented by technical approaches if available and deemed necessary. (3) The overall per-capita time requirement of GLIM was 240-245 s without prior screening, and was increased by 2-3% with prior MUST “1”, by 27-29% with prior NRS-2002 and decreased by 8-9% with prior MUST “2”.

CONCLUSIONS: Preceding GLIM by screening can decrease its sensitivity and increase overall time utilisation; “gold standard” muscle assessment is not globally accessible. Our results therefore support considering using GLIM as a combined screening and assessment tool, with MUAC as the method of muscle assessment which can be supplemented by technical approaches if available and deemed necessary. This could potentially both simplify the use of GLIM and improve the early detection of malnutrition. ∗Indicates statistically significant difference from use of GLIM without prior screening.

PMID:38901933 | DOI:10.1016/j.clnesp.2024.05.010

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A systematic review and meta-analysis of Dietary Inflammatory Index and the likelihood of multiple sclerosis/ demyelinating autoimmune disease

Clin Nutr ESPEN. 2024 Aug;62:108-114. doi: 10.1016/j.clnesp.2024.04.022. Epub 2024 May 22.

ABSTRACT

Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association between proinflammatory diet, as estimated by the Dietary Inflammatory Index (DII®), and the likelihood of developing MS or other demyelinating autoimmune diseases. A systematic search was performed of search engines and databases (PubMed, ISI Web of Sciences, Scopus, and Embase) to identify relevant studies before 10th June 2023. The search identified 182 potential studies, from which 39 full-text articles were screened for relevance. Five articles with case-control design (n = 4,322, intervention group: 1714; control group: 2608) met the study inclusion criteria. The exposure variable was DII, with studies using two distinct models: quartile-based comparisons of DII and assessment of continuous DII. The meta-analysis of high versus low quartiles of DII with four effect sizes showed a significant association with MS/demyelinating autoimmune disease likelihood, with an odds ratio (OR) of 3.26 (95% confidence interval (CI) 1.16, 9.10). The meta-analysis of four studies with DII fit as a continuous variable showed a 31% increased likelihood of MS per unit increment; which was not statistically significant at the nominal alpha equals 0.05 (OR 1.31; 95% CI 0.95, 1.81). In conclusion, this systematic review and meta-analysis provides evidence of a positive association between higher DII scores with the likelihood of developing MS, highlighting that diet-induced inflammation could play a role in MS or other demyelinating autoimmune diseases risk.

PMID:38901931 | DOI:10.1016/j.clnesp.2024.04.022