Clinical Test Results Research Articles

The value of nomogram for predicting microvascular invasion based on clinical and Gd-EOB-DTPA-enhanced magnetic resonance imaging features

Objective: To investigate the risk factors of microvascular invasion (MVI) in China liver cancer staging system stage Ⅰa (CNLC Ⅰa) hepatocellular carcinoma (HCC), and develop a nomogram for predicting MVI based on clinical and radiographic data. Methods: This retrospective study focused on CNLC Ⅰa HCC patients who underwent radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2020. Patients' clinical characteristics and laboratory test results and pre-surgery gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging results were collected. The clinical and radiographic risk factors for MVI were identified by univariate and multivariate logistic regression analyses and used for the construction of the predictive nomogram. The nomogram model was then internally validated, and its performance was assessed. Results: A total of 104 patients were divided into the MVI-positive group (n=28) and the MVI-negative group (n=76). Multivariate logistic regression analysis at the P<0.1 level identified serum alpha-ferroprotein >7 ng/ml, total bilirubin >21 μmol/L, prothrombin time >12.5 s, non-smooth margin, and incomplete or absent capsule as risk factors of MVI, based on which a nomogram model was built. The model achieved an area under the curve (AUC) value of 0.867 (95% confidence interval, 0.791-0.944) in the internal validation. The sensitivity and specificity of the nomogram model were 0.786 and 0.829, respectively, with the prediction curve nearly overlapping the ideal curve. Based on the Hosmer-Lemeshow test, the predicted and real results were not significantly different (P=0.956). Conclusions: The probability of MVI of CNLC Ⅰa HCC can be objectively predicted by the monogram model that quantifies the clinical and radiographic risk factors. The model can also help clinicians select individualized surgical plans to improve the long-term prognosis of patients.

Development of a droplet digital PCR method for detection of porcine circovirus 4

BackgroundPorcine circovirus 4 (PCV4), a newly emerging virus that was first discovered in 2019, may pose a potential threat to the pig industry. Droplet digital PCR (ddPCR) is an absolute quantitative method that has high sensitivity and accuracy. In this study, we developed a novel ddPCR assay to detect PCV4. Furthermore, we evaluated the detection limit, sensitivity, specificity and reproducibility of the ddPCR and TaqMan real-time quantitative PCR (qPCR) and tested 160 clinical samples to compare the detection rate of the two methods.ResultsThe detection limit for ddPCR was 0.54 copies/µL, 10.6 times greater sensitivity than qPCR. Both ddPCR and qPCR assays exhibited good linearity and repeatability, and the established ddPCR method was highly specific for PCV4. The results of clinical sample testing showed that the positivity rate of ddPCR (5.6%) was higher than that of qPCR (4.4%).ConclusionsThis study successfully developed a sensitive, specific and repeatable ddPCR assay for PCV4 detection, which can be widely used in clinical diagnosis of PCV4 infections.

Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations

To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children. A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed. Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered. Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.

Utilization of hydralazine as a reactive matrix for enhanced detection and on-MALDI-target derivatization of saccharides

Saccharides are a sort of ubiquitous and vital molecules within the whole life. However, the application of saccharides analysis with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is restricted by their low ionization efficiency and the instability of the sialic acid fraction. Derivatization strategy based on nonreductive amination provides a good solution, however, this is often time consuming and may result in sample loss due to removal of excessive derivatization reagents. Herein, hydralazine (HZN) was utilized as a reactive matrix for labeling reducing saccharides directly on MALDI target which eliminated tedious sample preparation and avoided sample loss. After optimization, effective and reproducible on-MALDI-target derivatization of neutral and acidic saccharides was achieved in both positive and negative modes. Compared with 2,5-dihydroxybenzoic acid (DHB) and 9-aminoacridine (9-AA), HZN improved the detection sensitivity of reducing saccharides and provided more abundant fragment ions in MS/MS analysis. Moreover, 26 kinds of neutral glycans and 5 kinds of sialic glycans were identified from ovalbumin (OVA) and bovine fetuin, respectively. Combined with the statistical models, this strategy could be used to distinguish and predict samples of 6 brands of beer, and discriminate 2 kinds of beer fermentation modes. In addition, HZN was applied for quantitative analysis of glucose in urine samples, and the obtained urine glucose concentrations of diabetic patients were consistent with the clinical test results, showing the potential of qualitative and quantitative analysis of reducing saccharides in complex samples.

A case report of unexplained persistent conjugated hyperbilirubinemia with normal liver transaminases over 23 years: remember Dubin-Johnson syndrome!

ObjectivesIn clinical practice, clinicians usually ignore the possibility of a rare genetic disease, i.e., Dubin-Johnson Syndrome (DJS), for conjugated hyperbilirubinemia caused by a mutation in the ABCC2 gene or in the MRP2 protein. Therefore, the objective is to alert the readers about our third reported case of DJS in Pakistan. Moreover, we also want to draw the attention of health professionals to potential pharmacotherapeutic management of DJS, and the management of the potential increased susceptibility to drug toxicity.Case reportWe present a case of 23 years old Asian man, with unexplained persistent conjugated hyperbilirubinemia and normal liver transaminases. In 1999, the patient was admitted to a tertiary care hospital for raised conjugated bilirubin (CB), i.e., 67% of total bilirubin (CB; 11 mg/dl, total bilirubin; 16.4 mg/dl). After 19 years, in 2018, during regular checkup by a family physician, the CB was 73% of total bilirubin (CB; 3 mg/dl, total bilirubin; 4.1 mg/dl), while the results of other clinical tests were unremarkable. Soon after 3 years, in 2021, the patient visited a gastroenterologist for jaundiced eyes. Comprehensive clinical tests (CB was 53% of total bilirubin) were accomplished to exclude the other causes of conjugated hyperbilirubinemia, and DJS was diagnosed.ConclusionsIn summary, it is strongly recommended that the cases of unexplained persistent conjugated hyperbilirubinemia should be evaluated for the presence of DJS. Similarly, the drugs that increase the clearance of CB could prove to be a potential management strategy for cases that negatively affect patient’s quality of life.

Predictive Value of COPD History on In-Stent Restenosis in Coronary Arteries Following Percutaneous Coronary Intervention.

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic respiratory disease that poses a significant health risk to individuals. Patients with COPD are predisposed to a higher incidence of coronary artery disease (CAD) than the general population. This study aims to investigate the correlation between COPD and the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). This study retrospectively analyzed the clinical data and laboratory test results of patients who underwent PCI at our hospital between January 2018 and December 2021 to investigate the relationship between COPD and drug-Eluting Stents (DES) postoperative ISR. We employed the best subset method to select the most suitable combination of predictive factors, utilizing the data, and verified the precision of the model by means of internal validation. We ultimately assessed the performance of the prediction model using an ROC curve. The research indicates that COPD is an independent risk factor for ISR after PCI (OR=2.437, 95% CI [1.336, 4.495], P=0.004). The analysis revealed an area under the receiver operating characteristic (ROC) curve of 0.783 for the training group and 0.705 for the testing group, indicating a model fitting for both groups (both > 0.5). COPD history is a dependable predictor of stent restenosis post percutaneous coronary intervention.

FIB‑4 index and serum α‑fetoprotein are useful predictors of hepatocellular carcinoma occurrence in hepatitis B patients with nucleos(t)ide analogs therapy.

Current antiviral therapies cannot achieve eradication of hepatitis B virus (HBV) and can reduce but not eliminate the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. The present study aimed to identify the risk factors for HCC development by analyzing nucleoside analogue (NA)-treated patients as a retrospective cohort using fibrosis-4 index (FIB-4 index) as a non-invasive fibrosis marker. A total of 260 patients with HBV receiving NAs without a history of HCC between January 2001 and January 2021 were included in the present study. The incidence of HCC in patients with HBV during NA therapy and the factors contributing to HCC occurrence were identified using clinical characteristics and blood test results. Among the 260 patients, 40 patients (15.4%) developed HCC. Univariate and multivariate analysis showed that age [hazard ratio (HR), 1.03; P=0.045], male sex (HR, 3.14; P<0.01) and FIB-4 index at 6 months after NA treatment <1.95 (HR, 4.35; P<0.01) correlated with the incidence of HCC. The cumulative incidence of HCC in patients with FIB-4 index at 6 months after NA treatment >1.95 was significantly higher compared with that in patients with FIB-4 index ≤1.95 (P<0.01). Multivariate analysis in patients in which serum α-fetoprotein (AFP) level at 6 months after NA treatment was measured showed that FIB-4 index >1.95 (HR, 8.27; P=0.014) and serum AFP level >4 ng/ml (HR, 4.26; P=0.033) contributed to HCC occurrence. FIB-4 index at 6 months after NA treatment and serum AFP levels at 6 months after NA treatment were predictors for the development of HCC in patients with HBV during NA treatment. Further study of hepatocarcinogenesis during NA with a longer follow-up period and larger numbers of participants is required.

Detailed clinical characteristics and its correlation with the diagnostic test results in patients with defined Mnire&apos;s disease.

Mnire&apos;s disease is characterized by vertigo episodes with nausea and vomiting accompanied by aural symptoms. Diagnosis is based on clinical manifestation and sensorineural hearing loss confirmed in pure tone audiometry. The purpose was to evaluate clinical features and audiological and vestibular tests in patients with definite Mnire&apos;s disease. Seventy patients were enrolled in this study. The severity of the main clinical symptoms and audiological and vestibular tests were evaluated. The correlation between the clinical features and test results was evaluated. 14.29% of patients presented complete clinical characteristics as the first manifestation of Mnire&apos;s disease. 50% of patients suffered from isolated aural symptoms during the early stage of the disease. The subpopulation reporting hearing improvement after vertigo attack (28.57%) was characterized by shorter disease duration than the rest of the group. A statistically significant correlation between disease duration and pure tone average was found. 17.14% of patients reported Tumarkin drop attacks in their past medical history. Neither disease duration nor functional level scale was different in these patients compared to other patients. Mnire&apos;s disease is often characterized by isolated aural symptoms or incomplete clinical manifestation during the early stage of the disease. The correlation between disease duration and pure tone average confirms that endolymphatic hydrops evolution causes hearing loss. A patient&apos;s quality of life is a fundamental aspect of clinical assessment. No significant correlation between disease duration and functional level scale was found. Thus Mnire&apos;s disease should be considered an individually variable and dynamic phenomenon.

Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children

To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Value of metagenomic next-generation sequencing in children with hematological malignancies complicated with infections

To explore the value of metagenomic next-generation sequencing (mNGS) in the pathogen identification in children with hematological malignancies complicated with infections. A retrospective analysis was conducted on clinical data and pathogenic test results of 43 children with hematological malignancies who underwent microbial culture and mNGS due to infections in the Third Xiangya Hospital of Central South University between June 2020 and July 2022. Differences in detection rates and characteristics of pathogenic microorganisms detected by mNGS and microbial culture were compared. A total of 54 specimens were examined, and the overall detection rate of pathogen by mNGS (80%, 43/54) was significantly higher than that by microbial culture (30%, 16/54) (P<0.001). The most commonly detected infection type by mNGS was viral infection, followed by fungal infection combined viral infection, while that by microbial culture was bacterial infection, followed by fungal infection. The detection rate of fungi by mNGS (33%, 18/54) was higher than that by microbial culture (6%, 3/54) (P<0.001). The detection rate of two or more pathogenic microorganisms by mNGS was higher at 48% compared to microbial culture at 9% (P<0.05). The detection rate of two or more types of pathogenic microorganisms by mNGS was also significantly higher at 33% compared to microbial culture at 2% (P<0.05). The most commonly detected bacteria and fungi by mNGS were Pseudomonas aeruginosa and Candida tropicalis, respectively, in peripheral blood, while Streptococcus pneumoniae and Pneumocystis jirovecii were most commonly detected in bronchoalveolar lavage fluid. Treatment adjustments based on mNGS results were beneficial for 35% (15/43) of the cases. mNGS has a higher detection rate than microbial culture and has obvious advantages in diagnosing mixed and fungal infections, making it a useful supplementary diagnostic method to microbial culture.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter > 4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules > 4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Healthcare providers consistently overestimate the diagnostic probability of ventilator-associated pneumonia.

To assess the accuracy of provider estimates of ventilator-associated pneumonia (VAP) diagnostic probability in various clinical scenarios. We conducted a clinical vignette-based survey of intensive care unit (ICU) physicians to evaluate provider estimates of VAP diagnostic probability before and after isolated cardinal VAP clinical changes and VAP diagnostic test results. Responses were used to calculate imputed diagnostic likelihood ratios (LRs), which were compared to evidence-based LRs. Michigan Medicine University Hospital, a tertiary-care center. This study included 133 ICU clinical faculty and house staff. Provider estimates of VAP diagnostic probability were consistently higher than evidence-based diagnostic probabilities. Similarly, imputed LRs from provider-estimated diagnostic probabilities were consistently higher than evidence-based LRs. These differences were most notable for positive bronchoalveolar lavage culture (provider-estimated LR 5.7 vs evidence-based LR 1.4; P < .01), chest radiograph with air bronchogram (provider-estimated LR 6.0 vs evidence-based LR 3.6; P < .01), and isolated purulent endotracheal secretions (provider-estimated LR 1.6 vs evidence-based LR 0.8; P < .01). Attending physicians and infectious disease physicians were more accurate in their LR estimates than trainees (P = .04) and non-ID physicians (P = .03). Physicians routinely overestimated the diagnostic probability of VAP as well as the positive LRs of isolated cardinal VAP clinical changes and VAP diagnostic test results. Diagnostic stewardship initiatives, including educational outreach and clinical decision support systems, may be useful adjuncts in minimizing VAP overdiagnosis and ICU antibiotic overuse.

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.

1336-P: Predicting the Progression of Stages of Neuropathy Using Routine Eye and Kidney Tests—An Application of Novel Statistical Methods in the Diabetes Control and Complications Trial (DCCT)

Despite recent advances, neuropathy screening is not consistently performed in clinical practice. We aimed to determine if neuropathy risk could be predicted using the trajectories of routinely-performed eye and kidney screening tests in T1D. We used 28-year data from the DCCT/EDIC study, available via the NIH public repository. We used the Early Treatment Diabetic Retinopathy Study Research (ETDRS) Group 23-point scale, albumin excretion rate (AER), and eGFR treated as longitudinal outcomes. Simultaneously, we represented neuropathy as a 3-state progressive multistate outcome using nerve conduction studies and the Michigan Neuropathy Screening Instrument (MNSI) for early-stage neuropathy and the occurrence of serious foot ulcer or amputation for late-stage neuropathy. To model these interrelated disease processes, we used and developed joint models with multistate submodels. Our “joint multistate model” accounted for interval censoring: due to the visit schedule, the exact time of transition to early-stage neuropathy was known only to occur in between consecutive visits. A Bayesian estimation procedure was used. We found that the risk of transition from no to early-stage neuropathy was affected by the current value of ETDRS, the current slope of ETDRS, and the current value of AER. For example, controlling for all covariates including eGFR, the there was a 23% higher rate of occurrence of this early-stage for a 3-step higher ETDRS scale. In the same model controlling for all covariates, progression from early-stage to late-stage neuropathy was affected mainly by AER (11% higher rate for a doubling of AER). Routinely-performed clinical eye and kidney test results can be leveraged to help identify the risk of neuropathy. Future work will develop dynamic predictions integrated into an electronic medical record. Disclosure L.Lovblom: None. L.Briollais: None. G.Tomlinson: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO).

High AST/ALT Ratio Is Associated with Cardiac Involvement in Acute COVID-19 Patients.

Background and Objectives: We aimed to assess the effect of AST/ALT ratio on echocardiographic and cardiac magnetic resonance imaging (CMRI) parameters after COVID-19 patients recover. Materials and Methods: 87 patients with COVID-19 were included in the study. The patients were hospitalized with COVID-19 pneumonia, but the patients did not need intensive care unit follow-up or non-invasive mechanical ventilation support. After a discharge and two weeks following the positive swab test result, patients were considered eligible if they had any symptoms. Transthoracic echocardiography (TTE) was performed within 24 h prior to CMRI. The median value of AST/ALT ratio was found, and the study population was divided into two subgroups based on the median AST/ALT ratio value. The clinical features, blood test, TTE and CMRI results were compared between subgroups. Results: C-reactive protein, D-dimer and fibrinogen were found to be significantly higher in patients with high AST/ALT ratio. LVEF, TAPSE, S', and FAC were significantly lower in patients with high AST/ALT ratio. LV-GLS were significantly lower in patients with high AST/ALT ratio. In CMRI, native T1 mapping signal, native T2 mapping signal and extracellular volume raised significantly in patients with high AST/ALT ratio. Right ventricle stroke volume and right ventricle ejection fraction were significantly lower in patients with high AST/ALT ratio, but right ventricle end systolic volume was significantly higher in patients with high AST/ALT ratio. Conclusion: High AST/ALT ratio is related to impaired right ventricular function parameters with CMRI and echocardiography after recovery from acute COVID-19. Assessment of AST/ALT ratio at hospital admission may be used to assess the risk of cardiac involvement in COVID-19 disease, and these patients may require closer follow-up during and after the course of COVID-19.

A report on SARS-CoV-2 first wave in Ecuador: drug consumption dynamics.

Introduction: The first COVID-19 wave in Ecuador started in March 2020 and extended until November. Several types of drugs have been proposed as a potential treatment during this period, and some affected people have self-medicated. Method: A retrospective study was conducted with 10,175 individuals who underwent RT-PCR tests for SARS-CoV-2 from July to November 2020. We compared the number of positive and negative cases in Ecuador with symptoms and drug consumption. The Chi-square test of independence compared clinical and demographic data and PCR test results. Odds ratios analyzed drug consumption dynamics. Results: Of 10,175 cases, 570 were positive for COVID-19, while 9,605 were negative. In positive cases, there was no association between the RT-PCR result and sex, age, or comorbidities. When considering demographic data, Cotopaxi and Napo had the highest rates of positive cases (25.7% and 18.8%, respectively). Manabí, Santa Elena, and Guayas regions had fewer than 10% positive cases. The Drug consumption dynamic analysis showed that negative COVID-19 cases presented higher drug consumption than positive cases. In both groups, the most consumed medication was acetaminophen. Acetaminophen and Antihistamines had higher odds of consumption in positive PCR cases than in negative. Symptoms like fever and cough were more related to positive RT-PCR results. Conclusion: The first COVID-19 wave in Ecuador has affected the provinces differently. At a national level, the consumption of drugs has been highly associated with self-medication.

Machine learning integrated patient flow simulation: why and how?

ABSTRACT Stochastic distribution methods were used to construct patient flow simulation sub-models such as patient inflow, length of stay (LoS), cost of treatment (CoT) and clinical pathways (CPs). However, the patient inflow rate demonstrates seasonality, trend, and variation due to natural and human-made factors. LoS, CoT and CPs are determined by social-demographics factors, clinical and laboratory test results, resource availability and healthcare structure. For this reason, patient flow simulation models developed using stochastic methods have limitations including uncertainty, not recognising patient heterogeneity, and not representing personalised and value-based healthcare. This, in turn, results in a low acceptance level and implementation of solutions suggested by patient flow simulation models. On the other hand, machine learning becomes effective in predicting patient inflow, LoS, CoT, and CPs. This paper, therefore, describes why coupling machine learning with patient flow simulation is important, proposes a conceptual architecture for machine learning integrated patient flow simulation and demonstrates its implementation with examples.

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

This single-center, retrospective study aimed to investigate the course and prognostic factors of patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD). We included 120 pSS patients who underwent at least two high-resolution computed tomography (HRCT) scans between 2013 and 2021. Clinical symptoms, laboratory data, HRCT findings, and pulmonary function test results were collected. Two thoracic radiologists reviewed the HRCT findings. In patients with pSS without ILD at baseline (n = 81), no development of ILD was found on follow-up (median, 2.8 years). In patients with pSS-ILD (n = 39), total disease extent, extent of coarse reticulation, and traction bronchiectasis increased on HRCT, whereas the extent of ground glass opacity (GGO) decreased at follow-up (median, 3.2 years) (each p < 0.001). In progressive group of pSS-ILD (48.7%), the extent of coarse reticulation and coarseness score of fibrosis were increased at follow-up (p < 0.05). Usual interstitial pneumonia pattern on CT (OR, 15.237) and follow-up duration (OR, 1.403) were independent risk factors for disease progression in patients with pSS-ILD. In both progressive and non-progressive pSS-ILD, GGO decreased, whereas the extent of fibrosis increased even after treatment with glucocorticoid and/or immunosuppressants. In conclusion, progression occurred in approximately half of the pSS-ILD patients with slow gradual deterioration. Our study identified a definite group of progressive pSS-ILD who did not respond to current anti-inflammatory treatment.

Intramolecular fluorescence resonance energy transfer strategy for accurate detection of AFP-L3% and improved diagnosis of hepatocellular carcinoma

Early and accurate diagnosis of hepatocellular carcinoma (HCC) is of significant importance for improving the survival rate and quality of life for HCC patients. The combined detection of alpha-fetoprotein (AFP) and alpha-fetoprotein-L3 (AFP-L3), namely AFP-L3%, can greatly improve the accuracy of HCC diagnosis compared with AFP detection. Herein, we developed a novel intramolecular fluorescence resonance energy transfer (FRET) strategy for sequential detection of AFP and AFP-specific core fucose to improve the diagnosis accuracy of HCC. Firstly, fluorescence-labeled AFP aptamer (AFP Apt-FAM) was used to specifically recognize all AFP isoforms, and total AFP was quantitatively determined using fluorescence intensity of FAM. Then, 4-((4-(dimethylamino)phenyl)azo)benzoic acid (Dabcyl) labeled lectins (PhoSL-Dabcyl) were used to specifically recognize the core fucose expressed on AFP-L3 that does not bind to other AFP isoforms. The combination of FAM and Dabcyl on the same AFP molecule could generate FRET effect, thereby quenching the fluorescence signal of FAM and quantitatively determining AFP-L3. After that, AFP-L3% was calculated according to the ratio of AFP-L3 to AFP. With this strategy, the concentration of total AFP, AFP-L3 isoform as well as the AFP-L3% were sensitively detected. Detection limits of 0.66 and 0.186 ng/mL were obtained for AFP and AFP-L3 in human serum, respectively. Clinical human serum test results showed that AFP- L3 % test was more accurate than AFP assay to distinguish healthy people, HCC patients and benign liver disease patients. Therefore, the proposed strategy is simple, sensitive and selective, which can improve the accuracy of early diagnosis of HCC, and has good clinical application potential.

Long-term outcomes in a population-based cohort of 2,967 uveal melanoma patients clinically tested with the 15-gene expression profile: A collaborative study with the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program Registries.

e21574 Background: Metastatic risk prediction in uveal melanoma is commonly performed using a commercially available 15-gene expression profile (15-GEP) test. A recent collaborative effort with the NCI’s SEER program registries allowed for serial linkage of UM patients captured by SEER registries with clinical 15-GEP test results. The objective of this study was to confirm the 15-GEP test’s performance in clinically tested uveal melanoma patients with long-term outcomes at the population level. Methods: Following established operating procedures, SEER registries linked UM cases diagnosed from 2010–2019 to 15-GEP test results provided by Castle Biosciences using a trusted third-party (honest broker). The patients were clinically tested as recommended by guidelines (testing was performed either on fine needle aspiration biopsy tissue or formalin-fixed, paraffin-embedded tissue from enucleations). De-identified data were provided to NCI and Castle Biosciences scientists for this study. Kaplan-Meier analysis with log-rank test was used to evaluate the available endpoints of melanoma-specific survival (MSS) and overall survival (OS). Multivariable analysis was performed with Cox proportional hazards modeling. Results: A total of 2,967 UM patients ≥ 18 years of age with localized disease (excluding Stage IV) and 15-GEP test result were included in this study (Class 1, 1904; Class 2, 1063). The cohort was 51.7% male, with a median age of 63 years. Median follow-up time was 2.2 years. Patients with a low-risk (Class 1) vs. high-risk (Class 2) result had significantly higher 7-year survival outcomes (OS, 78.9 vs. 31.8%, p &lt; 0.001; MSS, 90.4 vs. 41.6%, p &lt; 0.001, respectively). Patients with a Class 2 result were over six times more likely to experience a UM-related death than those with a Class 1 result (31.8 [338/1063] vs. 5.0% [96/1904]; p &lt; 0.001). Multivariable analysis showed that the 15-GEP was the strongest independent predictor of MSS when compared with clinicopathologic features (tumor diameter or thickness) and age, with a Class 2 hazard ratio of 6.2 (95% CI, 3.9–9.7; p &lt; 0.001). Notably, there was no association between GEP class call distribution and socioeconomic status as measured by the Yost index (p = 0.79). Conclusions: In this analysis, the 15-GEP accurately stratified risk of death from UM in a clinically tested, population-based cohort of patients, confirming previous studies. Socioeconomic status did not impact the likelihood of getting a high-risk result, suggesting equitable access to care for patients who receive 15-GEP testing. Ongoing analyses of SEER-linked UM data will include patients who received a PRAME test result, allowing for assessment of this adjunctive biomarker in combination with the 15-GEP result.