Pathological findings in congenital diaphragmatic hernia on necropsy studies: A single-center case series.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidities. The objective of this study was to delineate the histopathological features observed in necropsies of CDH patients and correlate these with their clinical manifestations. METHODS: We retrospectively reviewed the postmortem findings and corresponding clinical characteristics in eight CDH cases from 2017 to July 2022. RESULTS: The median survival time was 46 (8-624) hours. Autopsy reports showed that diffuse alveolar damage (congestion and hemorrhage) and hyaline membrane formation were the primary pathological lung changes observed. Notably, despite significant reduction in lung volume, the lung development appeared normal in 50% of the cases, while lobulated deformities were present in three (37.5%) cases. All patients displayed a large patent ductus arteriosus (PDA) and a patent foramen ovale, resulting in increased right ventricle (RV) volume, and myocardial fibers appeared slightly congested and swollen. The pulmonary vessels indicated thickening of the arterial media and adventitia. Lung hypoplasia and diffuse lung damage resulted in impaired gas exchange, while PDA and pulmonary hypertension led to RV failure, subsequent organ dysfunction and ultimately death. CONCLUSIONS: Patients with CDH typically succumb to cardiopulmonary failure, a condition driven by a complex interplay of pathophysiological factors. This complexity accounts for the unpredictable response to currently available vasodilators and ventilation therapies.

Thin-section computed tomography-histopathologic comparisons of pulmonary focal interstitial fibrosis, atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma with pure ground-glass opacity.

OBJECTIVE: To retrospectively compare focal interstitial fibrosis (FIF), atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) with pure ground-glass opacity (GGO) using thin-section computed tomography (CT). MATERIALS AND METHODS: Sixty pathologically confirmed cases were reviewed including 7 cases of FIF, 17 of AAH, 23of AIS, and 13 of MIA. All nodules kept pure ground glass appearances before surgical resection and their last time of thin-section CT imaging data before operation were collected. Differences of patient demographics and CT features were compared among these four types of lesions. RESULTS: FIF occurred more frequently in males and smokers while the others occurred more frequently in female nonsmokers. Nodule size was significant larger in MIA (P<0.001, cut-off value=7.5mm). Nodule shape (P=0.045), margin characteristics (P<0.001), the presence of pleural indentation (P=0.032), and vascular ingress (P<0.001) were significant factors that differentiated the 4 groups. A concave margin was only demonstrated in a high proportion of FIF at 85.7% (P=0.002). There were no significant differences (all P>0.05) in age, malignant history, attenuation value, location, and presence of bubble-like lucency. CONCLUSION: A nodule size >7.5mm increases the possibility of MIA. A concave margin could be useful for differentiation of FIF from the other malignant or pre-malignant GGO nodules. The presence of spiculation or pleural indentation may preclude the diagnosis of AAH.

[Effects of huannao yicong recipe extract on the learning and memory and related factors of Abeta generation in the brain of APP transgenic mice].

OBJECTIVE: To study the effects of Huannao Yicong Recipe (HNYCR)extract on the learning and memory ability, and the expressions of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), presenilin-1 (PS-1), and beta amyloid protein (Abeta)in hippocampus CA1 area of APP transgenic mice, and to explore its mechanisms for treating Alzheimer's disease (AD). METHODS: Totally 3-month-old APP695V7171 transgenic mice were used to establish the AD model in this research. They were randomly divided into the model group, the Donepezil group, the large dose HNYCR extract group, the small dose HNYCR extract group, and the normal control group (C57BL/6J mice), 15 in each group. These animals were gavaged for 4 continuous months. Relevant indicators were detected: Morris water maze test was used to measure the spatial learning and memory ability. The immunohistochemical assay was used to detect the expressions of APP, BACE1, PS-1, and Abeta. RESULTS: The times of crossing the original platform and the swimming time and distance in the fourth quadrant of the 7-month-old APP transgenic mice were significantly reduced in Morris water maze test, when compared with the normal control group (P < 0.01). The times of crossing original platform and the swimming time and distance in the fourth quadrant of all treatment groups significantly increased in Morris water maze test, when compared with the model group (P < 0.05). The expressions of APP, BACE1, PS-1, and Abeta in hippocampus CA1 area of 7-month-old model mice increased significantly (P < 0.01), when compared with the normal control group. The expressions of APP, BACE1, PS-1, and Abeta in each 7-month-old intervention groups were significantly reduced, when compared with the model group (P < 0.01). CONCLUSION: Early application of HNYCR extract can obviously improve the learning and memory ability of APP transgenic mice that has declined, reduce the expressions of APP, BACE1, PS-1, and Abeta in the hippocampal CA1 area, reduce the production of Abeta, and slow down the pathological process of brains in APP transgenic mice.

Association of early versus late initiation of dialysis with mortality: systematic review and meta-analysis.

BACKGROUND/AIMS: The association of the timing of dialysis initiation with mortality is controversial. We conducted a meta-analysis to determine the relationship between the risk of death and early initiation of dialysis, when the patient has a greater estimated glomerular filtration rate (eGFR). METHODS: Prospective and retrospective cohort studies that independently measured the effect of early vs. late initiation of dialysis on risk of death were identified by review of several databases. Odds ratios (ORs) were estimated by comparison of the highest and lowest quartiles and combined by a random-effects model. RESULTS: 15 studies (1,285,747 patients) met the inclusion criteria. Summary estimates indicated that early start of dialysis was associated with increased risk of mortality (OR = 1.33, 95% confidence interval (CI): 1.18-1.49, p < 0.00001). Subgroup analysis indicated that early starters were 6.61 years older (p < 0.00001) and more likely to have diabetes (OR = 2.23, 95% CI: 1.83-2.71, p < 0.00001) than late starters. Analysis of pooled results of early and late starters indicated that older age (OR = 1.18, 95% CI: 1.05-1.33, p = 0.006), diabetes (OR = 1.61, 95% CI: 1.38-1.87, p < 0.00001), and high comorbidity index score (OR = 2.38, 95% CI: 1.75-3.25, p < 0.00001) were strongly associated with increased risk of death. CONCLUSION: Our meta-analysis indicates that early initiation of dialysis (at higher eGFR) was associated with an increased risk of death. Older age, greater likelihood of diabetes, and the presence of severe comorbid disease(s) partly explain this effect.

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials.

The efficacy of homocysteine (Hcy)-lowering therapy in reducing the risk of CVD among patients with chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to determine whether pooling the data from the few small randomised, controlled trials that address this topic would improve the statistical power of the analysis and resolve some of the inconsistencies in the results. Randomised, controlled clinical trials (RCT) were identified from MEDLINE, EMBASE, www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database and Nephrology Filters. Independent extraction of articles was performed using predefined data fields. The primary outcome was relative risk (RR) of CVD, CHD, stroke and all-cause mortality for the pooled trials. A stratified analysis was planned, assessing the RR for cardiovascular events between the patients on and not on dialysis. Overall, ten studies met the inclusion criteria. The estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P = 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P = 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P = 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P = 0·98). In the stratified analysis, the estimated RR were not significantly different for cardiovascular events regardless of dialysis or in combination with vitamin B therapy or the degree of reduction in Hcy levels. Our meta-analysis of RCT supports the conclusion that Hcy-lowering therapy was not associated with a significant decrease in the risk for CVD events, stroke and all-cause mortality among patients with CKD.

[A novel KCNQ1 mutation in Chinese with congenital long QT syndrome].

OBJECTIVE: Congenital long QT syndrome (LQTS) is an inherited disorder of cardiac repolarization characterized by prolongation of QT interval and polymorphic ventricular tachycardia torsade de pointes (TdP) in the electrocardiogram (ECG). Clinical symptoms include recurrent syncope, seizure or even sudden death. It is caused by mutations of at least seven genes, six of them encoding ion channels that determine the duration of ventricular action potentials. One of these genes, KCNQ1, encodes an alpha-subunit of cardiac slowly activated delayed rectifier potassium channel. Patients carrying mutations of KCNQ1 are named as LQT1, which accounts for 42% of patients with LQTS. This study sought to analyze the clinical data of Chinese with LQTS and to screen for the mutations of KCNQ1. METHODS: The universally accepted phenotypic criteria of LQTS was used for identification of probands. There were six families with LQTS. They were enrolled in this study. Clinical and ECG data of each family member were recorded. Genomic DNA was prepared from peripheral blood lymphocytes. Polymerase chain reaction-single strand conformation polymorphism analysis was used to screen for mutations throughout the whole coding region of KCNQ1 and DNA sequencing was performed to determine the exact mutation site. RESULTS: There were totally 13 patients in the six LQTS families. Five were male and eight female. One suffered from sudden death, 10 had syncope and 2 were asymptomatic. Eleven of the 13 patients had ECG data. Their QT and QTc (mean +/- SD) were (0.460 +/- 0.058) s and (0.516 +/- 0.058) s, respectively. TdP was observed in 3 patients (27%) during the syncope attack. By PCR-SSCP analysis, two novel KCNQ1 deletion mutations 356-357 Delta QQ and 626-631 Delta GSGGPP were identified in 7 patients of 2 families. None of 50 normal individuals carried these mutations, indicating these two mutations were likely to cause the disease. In addition, P448R was found in one affected and some unaffected members in other two families and in 7 of 50 (14%) normal individuals, indicating that this might be a polymorphism. All the three mutations located in C-terminal domain of KCNQ1 protein. CONCLUSIONS: Two novel deletion mutations and one novel polymorphism of KCNQ1 gene were identified among 6 Chinese families with LQTS.