Cut-off Index Research Articles

Real-World Evaluation of Point-of-Care Testing for Hepatitis C Antibodies: Navigating Hepatitis C Elimination Effort.

An HCV elimination program aims to diagnose more than 90% of Chronic HCV cases. We critically evaluated the performance of a point-of-care test (POCT) using an HCV Rapid Antibody Test. PWID from 4 Halfway Houses (HWH) in Singapore were recruited from March 2022 to April 2023. Participants were concurrently screened for HCV via venous blood for anti-HCV serology and using fingerstick capillary whole blood (FSWB) and oral mucosal transudates (OMT) for POCT, which were interpreted by trained personnel. A blinded study team member independently assessed images of POCTs. Of 207 participants, 37.3% were anti-HCV positive. Compared to anti-HCV serology, POCT performance on FSWB and OMT were: Sensitivity 81.8 (73.2-90.4), 74.0 (64.2-83.8), p = 0.014; Specificity 100.0 (100.0-100.0), 98.5 (96.3-100), p = 0.157. Sub-group analysis of strict 30-min pre-test nil-by-mouth instruction in 103 subjects reported Sensitivity 77.5 (64.6-90.4), 77.5 (64.6-90.4) and Specificity 100.0 (100.0-100.0) and 98.4 (95.3-100.0). OMT positivity and false-negative outcomes did not correlate with the sample analytical cutoff index signal distribution of anti-HCV Serology. Inter-class correlation between real-time and imaging readings of POCT for FSWB and OMT at 20 and 40 min were Kappa 0.9666, 0.9674; 0.8803, 0.8940. Proper preparation and patient selection enhance test performance. Differences in oral fluid immunoglobulin secretion, oral pathology, age, and sample collection can affect POCT OMT readings. POCT OMT is promising in serial and self-testing, complementing its convenience in testing.

Glycomics as prognostic biomarkers of hepatocellular carcinoma: A systematic review.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, which is associated with a low 5-year survival rate. The importance of effective disease monitoring and prognostic evaluation is undeniable. For the present study, a systematic review was performed using extensive searches in Medline, Embase, Web of Science and Scopus up to December 29, 2023. The aim of the present study was to examine whether N-glycomics could predict the risk of developing HCC in adults with chronic liver disease and, if HCC was present, predict overall survival. As a secondary outcome, the prediction capability of HCC recurrence was assessed. After deduplication, 3,904 studies were identified, of which 30 were included. Overall, the median size of the study cohort was 144 patients, with a median follow-up time of 63.6 months. Three studies explored N-glycomics in whole serum, whereas the rest focused on individual glycoproteins, with Mac-2 binding protein glycosylation isomer (M2BPGi) being the most commonly studied. Most articles investigated baseline M2BPGi values as predictors for the development of HCC and demonstrated a median area under the curve of 0.83 with a cut-off index value of 1.8. In conclusion, it was revaled that N-glycan changes exhibit added value in determining patient prognosis in terms of survival, monitoring HCC development and recurrence.

Characteristics of diabetes mellitus patients with nonviral chronic liver disease who developed hepatocellular carcinoma.

Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease. Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. Theclinical and laboratory parameters of patients with and without HCC were compared. Age ≥65years, alcohol intake, lack of hepatic steatosis, triglyceride level <111mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5ng/mL, and des-γ-carboxy prothrombin concentration ≥26mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p<0.001) was associated with HCC development in patients aged <65years, and medication for diabetes mellitus (OR 5.72, p=0.001), lack of hepatic steatosis (OR 4.47, p=0.002), lactate dehydrogenase ≥198IU/L (OR 2.751, p=0.031), M2BPGi ≥1.18 COI (OR 9.05, p<0.001), and FIB-4 index ≥2.59 (OR 3.22, p=0.017) were associated with HCC development in patients aged ≥65years. In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging.

Pulse oximetry-based perfusion index as a non-invasive indicator of systemic hemodynamics during spinal anesthesia in cesarean delivery

Background &amp; Objectives: Placental perfusion is not autoregulated and is susceptible to effects of spinal anesthesia (SA) induced hypotension. The perfusion index (PI) is a non-invasive marker of peripheral vascular tone, and a higher PI indicates increased risk of hypotension following SA. This study aims to establish preoperative baseline PI in our local population and its correlation with incidence of intraoperative hypotension. Methods: This prospective observational study recruited 35 parturients who underwent elective lower segment cesarean section (LSCS). Preoperatively, baseline heart rate (HR), systolic blood pressure (SBP), mean arterial pressure (MAP) and PI were documented. SA was performed with 8 to 10 mg of injection bupivacaine 0.5% (hyperbaric) at L3–L4 interspace followed by co-loading with 1 L Hartmann solution. Hypotension was defined as SBP less than 80% of baseline or less than 90 mmHg. A bolus of phenylephrine 50 µg was given as rescue medication to treat the hypotension. Intraoperatively, degree of decrease in SBP, MAP and HR, as well as the amount of phenylephrine required was recorded every minute until delivery of the baby and 3 min thereafter. Results: The correlations between parturients’ baseline PI with the degree of decreases in systolic and mean arterial pressure (r = 0.81, P &lt; 0.001 and r = 0.76, P &lt; 0.001, respectively) and phenylephrine requirement (r = 0.761, p &lt; 0.005) were recorded. This study identified that the patients with cut-off PI value of 3.2 were at higher risk for SA induced hypotension with a sensitivity of 85.9% and a specificity of 87.5% (P = 0.001). Conclusion: The patients with baseline cut-off perfusion index value of more than 3.2 were at higher risk for spinal anesthesia induced hypotension in elective cesarean section. Abbreviations: CO - cardiac output; LSCS - lower segment cesarean section MAP - mean arterial pressure; PI - perfusion index; SA - spinal anesthesia Keywords: Hypotension; Pulse Oximeter; Perfusion Index; Spinal Anesthesia; Cesarean section; Citation: Manap NSA, Zaini RHM, Shukeri WFWM, Omar SC, Abu Bakar MZ, Seevaunnamtum P. Pulse oximetry-based perfusion index as a non-invasive indicator of systemic hemodynamics during spinal anesthesia in cesarean delivery. Anaesth. pain intensive care 2024;28(5):927−932; DOI: 10.35975/apic.v28i5.2570 Received: July 23, 2024; Reviewed: September 02, 2024; Accepted: September 10, 2024

Impact of the fibrosis-4 index in patients with ST-elevated myocardial infarction.

The fibrosis-4 (FIB4) index, a simple, noninvasive marker used for hepatic diseases, represents adverse outcomes. The aim of the present study was to evaluate whether the FIB4 index can predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI). We investigated patients with STEMI who underwent primary percutaneous coronary intervention (PCI) and were alive at discharge. The cut-off FIB4 index at discharge was investigated using the survival classification and regression tree (CART) model to predict adverse outcomes. The primary outcome was all-cause mortality. Between January 2006 and December 2018, 1354 patients with STEMI (median age, 68 years; men, 76.1%) were investigated. The median value of the FIB4 index was 1.21 (0.84-1.78). The CART model divided the study population into low (FIB4 index <0.945; n = 435), intermediate (0.945 ≤ FIB4 index < 2.185; n = 692), and high (FIB4 index ≥2.185; n = 227) groups based on the significant predictive values for all-cause death. During a median follow-up period of 4.3 years, all-cause death occurred in 208 patients (15.4%). The Kaplan-Meier analysis showed a significant increase in mortality with higher FIB4 index values (log-rank, P < 0.001). The multivariate Cox regression model revealed that the FIB4 index was an independent risk predictor for all-cause death in patients with STEMI [low group as reference vs. intermediate group, hazard ratio: 1.975; 95% confidence interval (CI): 1.166-3.346; P = 0.011 and vs. high group, hazard ratio: 4.633; 95% CI: 2.549-8.418; P < 0.001]. The FIB4 index was associated with the risk of all-cause mortality in patients with STEMI who underwent primary PCI.

B-080 Development and Validation of a GQ1b IgG ELISA as a Diagnostic Aid for Subacute Demyelinating Polyneuropathies

Abstract Background Autoimmunity targeting GQ1b is associated with group of disorders that includes Miller-Fisher Syndrome (MFS), Bickerstaff Brainstem Encephalitis (BBE) and classic Guillain Barre Syndrome (GBS) with ophthalmoplegia. Collectively these are referred to as GQ1B-IgG related syndromes. The prevalence of GQ1b-IgG in this population of patients is high and has been reported to be &amp;gt;80% in well-defined clinical cohorts. Clinical phenotypic presentation is diverse and requires highly accurate antibody testing. The objective of this study was to evaluate a newly developed custom GQ1b-IgG assay, using a semi-quantitative ELISA-based method. Methods A GQ1b-IgG ELISA was developed and validated. Patient sera along with assay controls and a single-point calibrator are diluted and incubated in duplicate wells in a 96-well plate coated with GQ1b antigen. The plate is washed and incubated with anti-human-IgG secondary antibody conjugated with HRP. After a colorimetric reaction, optical densities (OD) are read. The OD of patient samples are compared against the calibrator, generating a cut-off index (COI). Samples ≥1.0 COI are considered positive. During the validation phase, analytical and clinical performance characteristics were evaluated. Studies included assessment of imprecision at multiple concentrations of GQ1b-IgG, accuracy using method comparison, analytical sensitivity and specificity, reference range, common interferences, plate drift, and clinical performance in relevant disease and control cohorts. Results Intra-assay imprecision (coefficient of variation; %CV) ranged from 1.0 - 16% across all concentrations of GQ1b-IgG. Inter-assay imprecision (%CV) ranged from 12.4 - 44.5% but was &amp;lt;20% at or above the assay cut-off. We found perfect qualitative agreement with an independent ELISA reference method (20 positive and 20 negative samples selected based on reference method results [reference interval &amp;lt;1:100]). Limit of detection (LOD) was calculated at a COI of 0.22. To assess analytical specificity, 40 samples with high concentrations of immunoglobulins (hypergammaglobulinemia [N=15], IgG M-protein [N=15] and systemic lupus erythematosus [N=10] were tested and all were negative. A reference interval study was performed on 140 healthy donor serums, all were negative. Interference studies were conducted on 2 positive and 2 negative serum samples, spiked for highly hemolytic (1000 mg/dL), lipemic (2000 mg/dL) and icteric (60 mg/dL) conditions. There was no impact on the assay even with high levels of a given interferent. Plate drift on 2 distinct patient pools tested across the plate (COI range 0.7 - 1.3) had overall plate CV’s ≤10%. ROC analysis was performed on a cohort of 278 patient samples (15 MFS cases and 263 controls [suspected demyelinating neuropathy or disease mimics]). A cut-off value of 1.0 (COI) was selected based on the Youden index. At this cut-off, clinical sensitivity for MFS was 87% while clinical specificity was 99.2%. Conclusions The observed performance of the GQ1b-IgG ELISA was acceptable for clinical laboratory implementation. A COI of ≥ 1.0 was selected for clinical use.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis in Chronic Hepatitis B Patients: A Stepwise Diagnostic Analysis.

The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

ObjectivesTo evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible...

MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.

Impact of Hepatitis B Surface and Core Antibody Levels on Hepatitis B Virus Reactivation.

Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.

Determination of initial hepatitis B surface antigen (HBsAg) cutoff index (COI) threshold for reporting HBsAg reactivity

Determination of initial hepatitis B surface antigen (HBsAg) cutoff index (COI) threshold for reporting HBsAg reactivity

Utility of the LACE index to assess risk of mortality and readmission in patients with spinal infections

Retrospective cohort study. To assess the utility of the LACE index for predicting death and readmission in patients with spinal infections (SI). SIs are severe conditions, and their incidence has increased in recent years. The LACE (Length of stay, Acuity of admission, Comorbidities, Emergency department visits) index quantifies the risk of mortality or unplanned readmission. It has not yet been validated for SIs. LACE indices were calculated for all adult patients who underwent surgery for spinal infection between 2012 and 2021. Data were collected from a single academic teaching hospital. Outcome measures included the LACE index, mortality, and readmission rate within 30 and 90 days. In total, 164 patients were analyzed. Mean age was 64.6 (± 15.1) years, 73 (45%) were female. Ten (6.1%) patients died within 30 days and 16 (9.8%) died within 90 days after discharge. Mean LACE indices were 13.4 (± 3.6) and 13.8 (± 3.0) for the deceased patients, compared to 11.0 (± 2.8) and 10.8 (± 2.8) for surviving patients (p = 0.01, p < 0.001), respectively. Thirty-seven (22.6%) patients were readmitted ≤ 30 days and 48 (29.3%) were readmitted ≤ 90 days. Readmitted patients had a significantly higher mean LACE index compared to non-readmitted patients (12.9 ± 2.1 vs. 10.6 ± 2.9, < 0.001 and 12.8 ± 2.3 vs. 10.4 ± 2.8, p < 0.001, respectively). ROC analysis for either death or readmission within 30 days estimated a cut-off LACE index of 12.0 points (area under the curve [AUC] 95% CI, 0.757 [0.681–0.833]) with a sensitivity of 70% and specificity of 69%. Patients with SI had high LACE indices that were associated with high mortality and readmission rates. The LACE index can be applied to this patient population to predict the risk of early death or unplanned readmission.

Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis: A Stepwise Diagnostic Analysis

Abstract* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

A comparative analysis of screening technologies for transfusion-transmitted infectious diseases

Abstract: BACKGROUND AND OBJECTIVES: Ensuring the safety of blood supply relies on robust screening and donor selection processes. This study assessed the technical performance of automated enzyme-linked immunosorbent assay (ELISA) (EVOLIS, Bio-Rad, France) and electrochemiluminescence immunoassay (ECLIA) (COBAS 6000 e601 and COBAS e411, Roche Diagnostics, Germany) in detecting hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections. MATERIALS AND METHODS Retrospective data of transfusion transmissible infections (TTI) screening test results were collected from blood center records, encompassing two phases: January 2020 to May 2020 (phase 1) and March 2021 to April 2021 (phase 2). The sensitivity, specificity, positive predictive value, and negative predictive value of ELISA and ECLIA were calculated. Performance evaluation was conducted using the Youden’s index and the kappa coefficient. RESULTS: The study included a total of 824, 755, and 830 donor samples in phase 1 and 1237, 1238, and 1236 donor samples in phase 2 for HIV, HBV, and HCV testing, respectively. High agreement (kappa 0.88, 0.95) existed between ELISA and COBAS e601 for HIV and HBV, with substantial agreement (kappa 0.66) for HCV. Likewise, substantial agreement (kappa 0.66, 0.79, 0.79) was found between ELISA and COBAS e411 for all three parameters HIV, HBV and HCV, respectively. Notably, nearly all false-positive samples detected by ECLIA had low cutoff index values ranging from 1 to 6.5. CONCLUSION: The differences in sensitivity and specificity contribute to the discrepancy observed between various serological testing platforms, such as ELISA and ECLIA, for TTI testing. Specifically, low signal/cutoff ratios ≤6.5 obtained with ECLIA are highly indicative of false-positive results.

Quality of epicardial adipose tissue predicts major adverse cerebral and cardiovascular events following transcatheter aortic valve implantation.

Epicardial adipose tissue (EAT) have been shown to be associated with several heart disease, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). It is reported that the quality of EAT, represented by fat attenuation determined using computed tomography (CT) imaging, can detect the histologically-assessed remodeled EAT. We tested the hypothesis that quality of EAT would predict major adverse cerebral and cardiovascular events (MACCE) following transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS). A total of 125 consecutive severe AS patients who underwent TAVI were enrolled (39 male, mean 85.4 ± 4.0years). Using CT imaging before TAVI, we measured the average CT fat attenuation of EAT (EAT attenuation) and investigated the association with MACCE. During the mean follow up period of 567 ± 371days, 21 cases of MACCE were observed. Patients with MACCE had greater levels of EAT attenuation compared to those without (- 74 ± 3.7 Hounsfield Units (HU) vs - 77 ± 5.5 HU, p = 0.010). Based on the ROC curves, the high EAT attenuation was defined as > - 74.3 HU. According to this cut-off index, 44 patients were classified into the high EAT attenuation group (28 female, mean age 87 ± 3.6years), whereas 81 patients were classified into the low EAT attenuation group (13 female, 85 ± 4.1years). Kaplan-Meier survival curve demonstrated that the patients in the high EAT attenuation group showed greater prevalence of MACCE (log-rank 6.64, p = 0.010). Cox proportional hazards regression analysis revealed that EAT attenuation and Logistic EuroSCORE were independently associated with the incidence of MACCE. Our results suggest that quality of EAT, assessed by EAT attenuation detected by CT imaging, can predict the cerebral and cardiovascular events after TAVI in patients with AS.

Predictive value of angiopoietin-like protein 8 in metabolic dysfunction-associated fatty liver disease and its progression: A case-control study.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rapidly increasing, currently affecting approximately 25% of the global population. Liver fibrosis represents a crucial stage in the development of MAFLD, with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma. Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers. However, imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints. Consequently, it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis. To investigate the predictive value of angiopoietin-like protein 8 (ANGPTL8) in MAFLD and its progression. We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department, Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology, during September 2021-July 2022. Using abdominal ultrasonography and MAFLD diagnostic criteria, among the 160 patients, 80 patients (50%) were diagnosed with MAFLD. The MAFLD group was divided into the liver fibrosis group (n = 23) and non-liver fibrosis group (n = 57) by using a cut-off fibrosis-4 index ≥ 1.45. Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression. Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression. Compared with non-MAFLD patients, MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose (TyG) index (both P < 0.05). Serum ANGPTL8 (r = 0.576, P < 0.001) and TyG index (r = 0.473, P < 0.001) were positively correlated with MAFLD. Serum ANGPTL8 was a risk factor for MAFLD [odds ratio (OR): 1.123, 95% confidence interval (CI): 1.066-1.184, P < 0.001). Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD [area under the curve (AUC): 0.832 and 0.886, respectively; both P < 0.05]. Compared with MAFLD patients without fibrosis, those with fibrosis had higher serum ANGPTL8 and TyG index (both P < 0.05), and both parameters were positively correlated with MAFLD-associated fibrosis. Elevated serum ANGPTL8 (OR: 1.093, 95%CI: 1.044-1.144, P < 0.001) and TyG index (OR: 2.383, 95%CI: 1.199-4.736, P < 0.013) were risk factors for MAFLD-associated fibrosis. Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD-associated fibrosis (AUC: 0.812 and 0.835, respectively; both P < 0.05). The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD. They can serve as predictors for the risk of MAFLD and liver fibrosis, with the ANGPTL8 + TyG index potentially exhibiting even higher predictive value.

Clinical Implications of Serum Mac-2 Binding Protein in Patients After Living Donor Liver Transplantation for Biliary Atresia

Background: Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histological findings in patients after LDLT for biliary atresia (BA) Methods: Patients aged <19 years who underwent LDLT for BA at our institution and followed for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathological findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathological fibrosis scores and PV stenosis findings Results: The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 COI(Cut Off Index) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (p=0.016) and F1 (p=0.012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n=5) and 0.72 COI in patients without PV complications (n=51) (p=0.0001) Conclusions: M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients

Introduction: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. Methods: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. Results: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. Discussion/Conclusion: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Tacrolimus treatment in women with repeated implantation failures.

Tacrolimus is an immunosuppressive drug that works as a calcineurin inhibitor to improve the reproductive outcomes for women who have experienced multiple implantation failures (RIF) and show elevated type 1 helper T (Th1)/Th2 cell ratios. In the first part of this review, we indicate how we re-evaluated the cut-off index for selecting the participants in a tacrolimus regimen via transferred euploid blastocysts. In the second part, we cite cases where tacrolimus has improved the live birth rate for women who have experienced recurrent pregnancy losses (PRL) and we introduce the utility of tacrolimus treatment to prevent obstetrical complications. After reconsideration of the cut-off index (Th1/Th2 ≥ 11.8), however, the pregnancy rates of women with tacrolimus were significantly higher than those of women without tacrolimus. The PRL women treated with tacrolimus showed significantly lower rates of biochemical pregnancy, but higher live-birth rates compared with women who were not treated with tacrolimus. Moreover, prior severe obstetrical complications could be controlled via the administration of tacrolimus during pregnancy. Tacrolimus has become indispensable in the field of solid-organ transplantation, and in the near future, it should become an essential agent in the reproductive field, as well.