Development and external validation of machine learning-based models to predict patients with cellulitis developing sepsis during hospitalisation.

OBJECTIVE: Cellulitis is the most common cause of skin-related hospitalisations, and the mortality of patients with sepsis remains high. Some stratification models have been developed, but their performance in external validation has been unsatisfactory. This study was designed to develop and compare different models for predicting patients with cellulitis developing sepsis during hospitalisation. DESIGN: This is a retrospective cohort study. SETTING: This study included both the development and the external-validation phases from two independent large cohorts internationally. PARTICIPANTS AND METHODS: A total of 6695 patients with cellulitis in the Medical Information Mart for Intensive care (MIMIC)-IV database were used to develop models with different machine-learning algorithms. The best models were selected and then externally validated in 2506 patients with cellulitis from the YiduCloud database of our university. The performances and robustness of selected models were further compared in the external-validation group by area under the curve (AUC), diagnostic accuracy, sensitivity, specificity and diagnostic OR. PRIMARY OUTCOME MEASURES: The primary outcome of interest in this study was the development based on the Sepsis-3.0 criteria during hospitalisation. RESULTS: Patient characteristics were significantly different between the two groups. In internal validation, XGBoost was the best model, with an AUC of 0.780, and AdaBoost was the worst model, with an AUC of 0.585. In external validation, the AUC of the artificial neural network (ANN) model was the highest, 0.830, while the AUC of the logistic regression (LR) model was the lowest, 0.792. The AUC values changed less in the boosting and ANN models than in the LR model when variables were deleted. CONCLUSIONS: Boosting and neural network models performed slightly better than the LR model and were more robust in complex clinical situations. The results could provide a tool for clinicians to detect hospitalised patients with cellulitis developing sepsis early.

Brachial-ankle pulse wave velocity as a risk factor for high body fat mediated by blood pressure.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) is an important clinical indicator of aortic stiffness and a risk predictor of cardiovascular disease and associated with obesity. However, whether body mass index (BMI) is associated with baPWV remains controversial. In our study, body fat-related indicators, including BMI, body fat rate (BFR), body fat volume (BFV), waist circumference (WC) were examined from healthy volunteers. We investigated the correlation of baPWV with these indicators and also assessed whether baPWV has the potential to predict these indicators. METHODS: A total of 429 healthy participants were enrolled in this study. Body fat indices, blood pressures, baPWV and blood metabolic indices were measured and recorded. The association of baPWV and indices reflecting body fat and blood pressure, as well as mediation effect were analyzed. RESULTS: Three different types of baPWV values were significantly correlated. Mean level of baPWV was an independent risk factor for WC, BMI, BFR, and BFV (exp(ß) = 1.011, 1.004, 1.010 and 1.009, respectively, P < .001 for all) but not BMR. As for mediation effects, baPWV positively influenced WC (Total effect = 0.011, P < .001), BMI (Total effect = 0.004, P < .001) and BFV (Total effect = 0.009, P < .001) in indirect way mediated by SBP and DBP, while baPWV influenced BFR in both direct (Effect = 0.004, P = .018) and indirect way. CONCLUSIONS: Levels of baPWV correlated with obesity and is an independent risk factor for WC, BMI, BFR and BFV. Besides, baPWV positively associated with WC, BMI and BFV mainly in indirect way mediated by SBP and DBP, and baPWV associated with BFR in both direct and indirect way.

Platelet-to-lymphocyte ratio predicts the duration of glucocorticoid therapy in the treatment of cutaneous adverse drug reactions.

BACKGROUND: Glucocorticoid (GC) remains the mainstay of treatment for cutaneous adverse drug reactions (cADRs) but has been associated with side effects, emphasizing the importance of precisely managing the duration of high-dose GC treatment. Although the platelet-to-lymphocyte ratio (PLR) has been proven to be closely related to inflammatory disorders, its ability to predict the timing of GC dose reduction (Tr) during cADRs treatment remains obscure. METHODS: Hospitalized patients diagnosed with cADRs treated with glucocorticoids were analyzed in the present study to evaluate the association between PLR values and Tr values using linear, locally weighted scatter plot smoothing (LOWESS) and Poisson regression. Subgroup and ROC curve analyses were conducted to identify confounding variables and assess the predictive performance, respectively. RESULTS: A total of 308 patients were included in the study, with a median age of 47.0 (31.0-62.0) years old and a median incubation period of 4 days. Antibiotics (n = 113, 36.7%) were the most common cause of cADRs, followed by Chinese herbs (n = 76, 24.7%). PLR values were positively correlated with Tr values during linear regression (P < 0.001, r = 0.414) and LOWESS regression analyses. Poisson regression showed PLR was an independent risk factor for higher Tr values (the incidence rate ratio ranged from 1.016 to 1.070 and P < 0.05 for all). The area under the curve of PLR for predicting Tr < 7 days was 0.917. CONCLUSIONS: PLR is a simple and convenient parameter with huge prospects for application as a biomarker to assist clinicians in optimally managing patients treated with glucocorticoid therapy for cADRs.

Analysis of the Efficacy and Recurrence of Omalizumab Use in the Treatment of Chronic Spontaneous Urticaria and Chronic Inducible Urticaria.

INTRODUCTION: Chronic urticaria (CU) is a common skin condition that can be divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is one treatment option for CU, but currently there are limited clinical studies of omalizumab's efficacy for treating CU in Chinese patients. This study sought to investigate the efficacy and safety of omalizumab treatment for CU patients in a Chinese patient population. Specifically, we aimed to compare the differential efficacy of omalizumab for CSU and CIndU patients and predict risk factors for recurrence. METHODS: We completed a retrospective clinical data review of 130 CU patients who received omalizumab treatment from August 2020 to May 2022, with a maximum follow-up period of 18 months. RESULTS: A total of 108 CSU patients and 22 CIndU patients were included in the study. After treatment with omalizumab, the response rate in the CSU group was higher than that in the CIndU group (93.5% vs. 68.2%), and CSU patients accounted for a higher proportion of responders and early responders (responders: 87.1% vs. 12.9%, p < 0.001; early responders: 95.7% vs. 4.3%, p = 0.001). Nonresponders had lower total immunoglobulin E (IgE) levels (75.0 vs. 167.5 IU/mL, p = 0.046) and a relatively shorter duration of treatment (1.0 vs. 3.0 months, p = 0.009) compared to responders. Early responders had shorter disease duration (1.0 vs. 3.0 years, p = 0.028), higher baseline UCT (4.0 vs. 2.0, p = 0.034), lower baseline DLQI (18.0 vs. 18.5, p = 0.026), and shorter total treatment time (2.0 vs. 4.0 months, p < 0.001) compared to late responders. All adverse events reported during treatment were mild. Seventy-four patients with CU discontinued the drug after achieving complete disease control, of which 26 (35.1%) relapsed for 2.0 months (interquartile range: 1.0-3.0 months). Compared with nonrelapsed patients, relapsed patients often had other allergic diseases (42.3% vs. 18.8%, p = 0.029), higher basal levels of total IgE (263.0 vs. 140.0 IU/mL, p = 0.033), and longer disease duration (4.2 vs. 1.0 years, p = 0.002). Relapsed patients could still achieve good disease control after restarting omalizumab therapy. CONCLUSION: Omalizumab was effective and safe for CSU and CIndU patients. Patients with CSU responded more quickly to omalizumab and showed a relatively better treatment effect. However, there was a possibility of relapse after discontinuation of omalizumab after complete control of CU, and in these cases, restarting omalizumab treatment after relapse was effective.

Predicting the Risk of Nail Involvement in Psoriasis Patients: Development and Assessment of a Predictive Nomogram.

BACKGROUND: Nail involvement has a tremendous impact on psoriasis patients. Early detection and prompt intervention of psoriatic nail damage are necessary. METHODS: A total of 4290 patients confirmed to have psoriasis between June 2020 and September 2021 were recruited from the Follow-up Study of Psoriasis database. Among them, 3920 patients were selected and divided into the nail involvement group (n = 929) and the non-nail involvement group (n = 2991) by inclusion and exclusion criteria. Univariate and multivariable logistic regression analyses were performed to identify the predictors of nail involvement for the nomogram. Calibration plots, the receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the discriminative and calibrating ability and clinical utility of the nomogram. RESULTS: Sex, age at onset, duration, smoking, drug allergy history, comorbidity, sub-type of psoriasis, scalp involvement, palmoplantar involvement, genital involvement, and PASI score were selected to establish the nomogram for nail involvement. AUROC (0.745; 95% CI: 0.725-0.765) indicated the satisfactory discriminative ability of the nomogram. The calibration curve showed favorable consistency, and the DCA showed the good clinical utility of the nomogram. CONCLUSION: A predictive nomogram with good clinical utility was developed to assist clinicians in evaluating the risk of nail involvement in psoriasis patients.

Herpes Zoster Ophthalmicus Clinical Presentation and Risk Factors for Lesion Recovery.

Purpose: Herpes zoster ophthalmicus (HZO) causes trouble in patients' daily life and work. In severe cases, it may even lead to a decrease or loss of vision. To understand the demographic information and ocular symptoms of hospitalized patients with HZO, and to find potential factors related to improvement time of skin rash and duration of ocular symptoms at discharge, we design this study. Patients and Methods: This is a retrospective study. All patients diagnosed with HZO who were hospitalized in the Department of Dermatology of a hospital in Chongqing, China from January 1, 2015 to December 30, 2021 were included in this study. A total of 189 patients were included in this study. Clinical manifestations of the disease during hospitalization, improvement time of ocular skin lesions, and whether ocular skin lesions disappeared completely at discharge were recorded. Results: The most common ocular symptom was eyelid swelling (92.6%), followed by eye pain (48.7%). The most common ocular sign was conjunctivitis (78.3%), followed by keratitis (15.9%). There were 149 cases without residual ocular symptoms and 40 cases with residual ocular symptoms. There was no statistically significant difference in demographic characteristics between the two groups (P>0.05). Age ≥70 years (B=0.381, -0.061~0.022, P=0.005), use of glucocorticoids (B=0.260, 0.024~0.496, P=0.031), and use of topical antiviral drugs (B=0.380, 0.054~0.705, P=0.023) were factors affecting the time interval from admission to improvement of skin rash. Tearing (HR, OR=4.827, 1.956~11.909, P<0.001) and blood urea nitrogen (OR=0.787, 0.620-1.000, P=0.050) were factors influencing residual ocular symptoms. Conclusion: This study could help clinicians gain a deeper understanding of the clinical manifestations and partial influencing factors of HZO patients, which may contribute to future clinical work.

Nomogram model predicts the risk of visual impairment in diabetic retinopathy: a retrospective study.

BACKGROUND: To develop a model for predicting the risk of visual impairment in diabetic retinopathy (DR) by a nomogram. METHODS: Patients with DR who underwent both optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA) were retrospectively enrolled. FFA was conducted for DR staging, swept-source optical coherence tomography (SS-OCT) of the macula and 3*3-mm blood flow imaging by OCTA to observe retinal structure and blood flow parameters. We defined a logarithm of the minimum angle of resolution visual acuity (LogMAR VA) ≥0.5 as visual impairment, and the characteristics correlated with VA were screened using binary logistic regression. The selected factors were then entered into a multivariate binary stepwise regression, and a nomogram was developed to predict visual impairment risk. Finally, the model was validated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration plots, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 parameters were included in the analysis, and 13 characteristics were used to develop a nomogram model. Finally, diabetic macular ischaemia (DMI) grading, disorganization of the retinal inner layers (DRIL), outer layer disruption, and the vessel density of choriocapillaris layer inferior (SubVD) were found to be statistically significant (P < 0.05). The model was found to have good accuracy based on the ROC (AUC = 0.931) and calibration curves (C-index = 0.930). The DCA showed that risk threshold probabilities in the (3-91%) interval models can be used to guide clinical practice, and the proportion of people at risk at each threshold probability is illustrated by the CIC. CONCLUSION: The nomogram model for predicting visual impairment in DR patients demonstrated good accuracy and utility, and it can be used to guide clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200059835. Registered 12 May 2022, https://www.chictr.org.cn/edit.aspx?pid=169290&htm=4.

Predictive value of tumor-infiltrating lymphocytes detected by flow cytometry in colorectal cancer.

The high heterogeneity of tumor cells and the surrounding immune microenvironment affects the response to treatment in colorectal cancer (CRC) patients. Therefore, there is a need to identify new immune biomarkers to predict the treatment efficacy of CRC. This study aimed to explore the predictive value of tumor-infiltrating lymphocytes (TIL) for survival in CRC patients. Flow cytometry and gated analysis were performed to measure the TILs in tissue samples obtained from 536 CRC patients. The COX regression analysis showed that the CD8 + CD279+ cells had the highest impact of all evaluated TILs on postoperative disease-free survival (DFS) (P < 0.05). The optimal CD8 + CD279+ cutoff point for the prediction of survival was 12.2%. The Kaplan-Meier analysis showed significantly higher DFS in the high CD8 + CD279+ group compared with the low CD8 + CD279+ group (P < 0.05). CD8 + CD279+ cells were associated with DFS in CRC patients with the KARS mutation, MSI/MMR, perineural invasion, and those treated with neoadjuvant chemotherapy and other chemotherapeutic treatments (P < 0.05). After the multivariate adjustment, the expression of CD8 + CD279+ remained an independent risk factor for DFS. Overall, the CD8 + CD279+ cells were identified as an independent prognostic factor in CRC patients and could be used as a potential marker for postoperative DFS.

Hepatitis B Virus Reactivation Increased the Risk of Developing Hepatic Failure and Mortality in Cirrhosis With Acute Exacerbation.

Background and Aims: Hepatitis B virus (HBV) reactivation is a serious condition and has been extensively described in chemotherapeutic immunosuppressive population. However, little is known about HBV reactivation in immunocompetent patients with chronic hepatitis B (CHB). In this study, we evaluated the prevalence and the clinical significance of HBV reactivation in CHB patients with acute exacerbations. Method: Patients were screened from two prospective multicenter observational cohorts (CATCH-LIFE cohort). A total of 1,020 CHB patients with previous antiviral treatment history were included to assess the prevalence, risk factors, clinical characteristics of HBV reactivation, and its influence on the progression of chronic liver disease. Results: The prevalence of HBV reactivation was 51.9% in CHB patients with acute exacerbations who had antiviral treatment history in our study. Among the 529 patients with HBV reactivation, 70.9% of them were triggered by discontinued antiviral treatment and 5.9% by nucleos(t)ide analogs (NUCs) resistance. The prevalence of antiviral treatment disruption and NUCs resistance in patients with HBV reactivation is much higher than that in the patients without (70.9% vs. 0.2%, and 5.9% vs. 0, respectively, both p < 0.001). Stratified and interaction analysis showed that HBV reactivation was correlated with high short-term mortality in cirrhosis subgroup (HR = 2.1, p < 0.001). Cirrhotic patients with HBV reactivation had a significantly higher proportion of developing hepatic failure (45.0% vs. 20.3%, p < 0.001), acute-on-chronic liver failure (ACLF; 31.4% vs. 21.8%, p = 0.005), and short-term death (14.0% vs. 5.9% for 28-day, and 23.3% vs. 12.4% for 90-day, both p < 0.001) than those without. HBV reactivation is an independent risk factor of 90-day mortality for cirrhosis patients (OR = 1.70, p = 0.005), as well as hepatic encephalopathy, ascites, and bacterial infection. Conclusion: This study clearly demonstrated that there was a high prevalence of HBV reactivation in CHB patients, which was mainly triggered by discontinued antiviral treatment. The HBV reactivation strongly increased the risk of developing hepatic failure, ACLF and short-term death in HBV-related cirrhotic patients, which may suggest that HBV reactivation would be a new challenge in achieving the WHO target of 65% reduction in mortality from hepatitis B by 2030.

Clinical diagnostic algorithm in defining tuberculous unilateral pleural effusion in high tuberculosis burden areas short of diagnostic tools.

Background: Empirical treatment was introduced when pathological or microbiological results of tuberculosis (TB) were not available. This report was designed to evaluate an algorithm based on empirical treatment in defining tuberculous pleural effusion (TPE) in high burden areas but short of diagnostic tools. Methods: In this retrospective study, a total of 924 eligible patients were enrolled and 203 (22.0%) were primarily diagnosed as TPE by our diagnostic algorithm based on effusion characteristics [adenosine deaminase (ADA) and exudate] and immunoassays [purified protein derivative (PPD), M. tuberculosis antibody (TB-Ab) and interferon-gamma release assay (IGRA)]. All diagnosed cases received World Health Organization (WHO) standard anti-TB treatment and 187 of them had at least one year of follow-up. The final diagnosis and prognosis of these patients were traced and recorded. Results: A total of 177 (94.65%) cases benefited from standard treatment, 5 (2.67%) failed due to early termination or drug resistance, and 5 (2.67%) were finally confirmed as misdiagnosis. Regarding diagnostic efficacy, 72 (30.13%) patients received four TB tests, and the combination of the four tests could increase the diagnosis of TPE. Besides, receiving operating characteristics curve (ROC) analysis revealed that our algorithm was the best method to differentiate TPE from malignant pleural effusion (MPE) with higher sensitivity and specificity than other serum markers. Conclusions: This clinical diagnostic algorithm was an efficient and available method for the diagnosis of TPE. This diagnostic algorithm should be implemented in regions with high TB prevalence but short of diagnostic tools.

Combined use of cyclosporine in the treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis.

The exact efficacy of cyclosporine in the treatment of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) still needs evidence from more clinical data. This study was designed to compare the effectiveness and side-effects of combined use of cyclosporine in the treatment TEN with glucocorticoids (GC)/i.v. immunoglobulin G (IVIG). A total of 46 patients with SJS/TEN were enrolled and classified into two groups based on the therapeutic drugs used. Clinical characteristics, interventions, outcomes, and disease progressions were collected and compared between the two groups. In our cohort, seven patients eventually died and the overall fatality rate was 15.2%, but there was no difference between the two groups (p = 0.557). On discharge, the median SCORe of Toxic Epidermal Necrosis (SCORTEN) fell from 2.0 at admission to 1.0 and the median body surface area detached fell from 32.0% at admission to 9.5%. Patients in the cyclosporine group had a higher rate of re-epithelialized area than patients in the non-cyclosporine group (p < 0.05). Cyclosporine significantly reduced the length of stay (19.0 vs. 13.0 days, p = 0.019) and the rate of systemic infection (71.4% vs. 36.0%, p = 0.017) compared with the non-cyclosporine group. SCORTEN was the only significant risk factor for death and the risk ratio was 1.96 (1.17-3.31, p = 0.011). Conclusively, the combined use of cyclosporine could reduce the occurrence of systemic infection and accelerate the re-epithelialization.

Differential Mutation Detection Capability Through Capture-Based Targeted Sequencing in Plasma Samples in Hepatocellular Carcinoma.

Circulating tumor DNA (ctDNA) is a promising biomarker for accurate monitoring and less invasive assessment of tumor burden and treatment response. Here, targeted next-generation sequencing (NGS) with a designed gene panel of 176 cancer-relevant genes was used to assess mutations in 90 ctDNA samples from 90 patients with multiple types of liver disease and 10 healthy donor samples for control. Using our ctDNA detection panel, we identified mutations in 98.89% (89/90) of patient plasma biopsy samples, and 19 coding variants located in 10 cancer-related genes [ACVR2A, PCLO, TBCK, adhesion G protein-coupled receptor (ADGRV1), COL1A1, GABBR1, MUC16, MAGEC1, FASLG, and JAK1] were identified in 96.7% of patients (87/90). The 10 top mutated genes were tumor protein p53 (TP53), ACVR2A, ADGRV1, MUC16, TBCK, PCLO, COL11A1, titin (TTN), DNAH9, and GABBR1. TTN and TP53 and TTN and DNAH9 mutations tended to occur together in hepatocellular carcinoma samples. Most importantly, we found that most of those variants were insertions (frameshift insertions) and deletions (frameshift deletions and in-frame deletions), such as insertion variants in ACVR2A, PCLO, and TBCK; such mutations were detected in almost 95% of patients. Our study demonstrated that the targeted NGS-based ctDNA mutation profiling was a useful tool for hepatocellular carcinoma (HCC) monitoring and could potentially be used to guide treatment decisions in HCC.

Effect of SARS-CoV-2 coinfection was not apparent on the dynamics of chronic hepatitis B infection.

In patients coinfected with SARS-CoV-2 and HBV, liver injury was common. However, the interactions between SARS-CoV-2 and HBV coinfection remained unknown. Sixty-seven COVID-19 patients from the previous cohort were enrolled and classified into 2 groups (7 with HBsAg+ and 60 with HBsAg-). The association of HBV- and SARS-CoV-2-related markers were analyzed. During the acute course of SARS-CoV-2 infection, markers of HBV replication did not extensively fluctuate during SARS-CoV-2 infection. Coinfection with HBV did not extend the viral shedding cycle or incubation periods of SARS-CoV-2. Effects of SARS-CoV-2 on the dynamics of chronic HBV infection seemed not apparent. SARS-CoV-2 infection would not be the source of HBV reactivation in these individuals.

Shorter incubation period is associated with severe disease progression in patients with COVID-19.

The diagnosed COVID-19 cases revealed that the incubation periods (IP) varied a lot among patients. However, few studies had emphasized on the different clinical features and prognosis of patients with different IP. A total of 330 patients with laboratory-confirmed COVID-19 were enrolled and classified into immediate onset group(IP<3 days, I group, 57 cases) and late onset group(IP>10 days, L group, 75 cases) based on IP. The difference of clinical characteristics and prognosis of the two groups were compared. There were more patients with fever in I group than in L group(P = 0.003), and counts of all the total lymphocytes, total T lymphocytes, CD4 + and CD8 + T lymphocytes were significantly different between the two groups(all P < 0.01). Besides, patients in L group had more GGOs in CT scan than I group and there were more patients in I group receiving antibiotic treatment than in L group(P < 0.001). For disease aggravation, the median CT scores were comparable between the two groups, but individually, there were more patients with increased CT score during hospitalization in I group than in L group. The aggravation incidence of CT presentation was 21.1% in I group, significantly higher than L group(8.0%, P = 0.042). Multivariable COX models suggested that IP was the only independent factors for CT aggravation. Conclusively, patients with different IP were different in clinical symptoms, laboratory tests, and CT presentations. Shorter IP was associated with the aggravation of lung involvement in CT scan.

A patient with glycogen storage disease type Ia combined with chronic hepatitis B infection: a case report.

BACKGROUND: Glycogen storage disease type I (GSD I), also known as von Gierk disease, is a metabolic disorder leading to the excessive accumulation of glycogen and fat in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay and growth retardation, which can be indicated by height, weight, blood glucose and blood lipids. CASE PRESENTATION: Here we present a 16-year-old male patient with GSD Ia complicated with hepatic adenoma and combined with hepatitis B. As a chronic hepatitis B patient, the patient was admitted to hospital in order to further clarify the nature of hepatic space occupancy because of suspicion of hepatocellular carcinoma. However, the imaging studies did not support hepatocellular carcinoma certainly. And by tracing his clinical history, we suggested that he might suffer from GSD I. Finally the diagnosis was confirmed by MRI (Gd-EOB-DTPA), liver biopsy and whole exome sequencing (WES). The WES discovered a homozygous point mutation at the exon 5 of G6PC gene at 17th chromosome, c.G648 T (p.L216 L, NM_000151, rs80356484). This pathogenic mutation causes CTG changing to CTT at protein 216. Though both codons encode leucine, this silent mutation creates a new splicing site 91 bp downstream of the authentic splice site. According to previous research, this mutation is a disease causal variant for GSD Ia, and has a high frequency among GSD patients in China and Japan. This patient was finally diagnosed as GSD Ia complicated with hepatic adenoma and combined with chronic hepatitis B, and received corn starch therapy immediately after GSD was suspected. After receiving corn starch therapy, the height and weight of the patient were increased, and the secondary sexual characteristics were developed, including beard, pubic hair and seminal emission. Unexpectedly, the liver adenomas were still increasing, and we did not find any cause to explain this phenomenon. CONCLUSION: This patient was diagnosed as GSD Ia combined with chronic hepatitis B, who responded to corn starch intervention. For childhood patients with hypoglycaemia, hyperlipidemia, puberty delay and growth retardation, GSD should be considered. Gene sequencing is valuable for the quick identification of GSD subtypes.

A novel mutation in the BCHE gene and phenotype identified in a child with low butyrylcholinesterase activity: a case report.

BACKGROUND: Butyrylcholinesterase (BChE), an ester hydrolase produced mainly by the liver, hydrolyzes certain short-acting neuromuscular blocking agents, like succinylcholine and mivacurium that are widely used during anesthesia. Patients with BChE deficiency are possibly in danger of postanesthetic apnea. Hereditary BChE deficiency results from the mutations of BCHE gene located on chromosome 3, 3q26.1-q26.2, between nucleotides 165,490,692-165,555,260. CASE PRESENTATION: This study describes a novel mutation in a child with BChE deficiency. In general, this child appeared healthy and well-developed with a normal appearance. However, the results of Wechsler Intelligence Scale showed that the full-scale intelligence quotient (FIQ) was 53, classified into the group with the minor defect. The BChE activity was 32.0 U/L, considerably lower than the normal lower limit (reference range: 5000-12,000 U/L). Sanger sequencing showed that there were 2 mutations in the exon 2 of BCHE gene of this child. One is a heterozygous mutation rs764588882 (NM_000055.3: c.401_402insA, p.Asn134Lysfs*23). The other one is a heterozygous mutation (NM_000055.3: c.73A > T, p.Lys25Ter) that has never been reported before. The two mutations lead to a premature stop of transcription. CONCLUSIONS: Double heterozygous recessive mutations are the cause of BChE deficiency of this boy in this study, including a novel mutation c.73A > T. Intellectual disability is a new phenotype that is probably associated with this mutation.

Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data.

BACKGROUND: Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied. METHODS: A total of 14,861 samples were tested in Southwest Hospital in over 2 years' time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively. RESULTS: A total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0-33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0-348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time. CONCLUSIONS: Our data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.