Blood Bilirubin Research Articles

Impact of missing values on the ability of the acute physiology and chronic health evaluation III and Japan risk of death models to predict mortality

PurposeThis study assessed model performance of the Acute Physiology and Chronic Health Evaluation (APACHE) III and Japan Risk of Death (JROD) when degraded by the number and category of missing variables. We also examined the impact of missing data on predicted mortality for facilities with missing physiological variables. MethodsWe obtained data from the Japanese Intensive care PAtient Database (JIPAD). We calculated observed and predicted mortality rates using the APACHE III and JROD and the standardized mortality ratio (SMR) by the number and category of missing variables. Smoothed spline curves were calculated for the SMR to the missing proportion of the facility. ResultsA total of 61,357 patients from 57 ICUs were included between April 2015 and March 2019. The APACHE III and JROD SMRs increased as the number of missing values increased. The SMR in the APACHE III model was elevated in facilities with a larger proportion of missing in each of the APS categories, arterial blood gas, albumin, glucose, and bilirubin. Facilities with a high proportion of missing albumin data preserved their SMRs in only the JROD model. ConclusionAn increased number of missing physiological variables resulted in falsely low predicted mortality rates and high SMRs.

Treatment of refractory or relapsed myelodysplastic neoplasms with luspatercept: a multicenter Chinese study.

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67years: range 29 to 80years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84g/L, and patients had significantly higher hemoglobin concentrations after 12weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

OS09.6.A A MULTICENTER, PHASE I/II, OPEN-LABEL STUDY OF INTRATHECAL PEMETREXED FOR LEPTOMENINGEAL METASTASES FROM SOLID TUMOR (PMLM, NCT 05289908)

Abstract BACKGROUND There has never been a dose-escalation study on intrathecal pemetrexed (IP) with vitamin supplementation. This phase I/II study was to evaluate the maximum-tolerated dosage (MTD) of IP with vitamin supplementation and the antitumor activity for leptomeningeal metastases (LM) from solid tumors. MATERIAL AND METHODS Phase I study followed the classic 3 + 3 design, with the dose of IP escalated from 15 mg. Phase II followed the Simon 2-stage design with the recommended dose determined in phase I. IP was administered twice per week for 2 weeks (induction therapy), followed by once per week for 4 weeks (consolidation therapy). Clinically stable or improved patients continued IP once a month (maintenance therapy). Vitamin B12 (1000 μg) and folic acid (400 μg, q.d.) were given at the beginning of treatment. Primary end points were MTD in phase I and clinical response rate (CRR) in phase I/II. All patients were assessed to investigate safety, CRR and overall survival (OS). RESULTS Between Feb 2022 and Jan 2023, 34 patients (male: 16; female: 18; age: 45-68 years; median: 56 years) were enrolled, including non-small lung cancer (20), small-cell lung cancer (3), breast cancer (8), others (3). Thirty-three patients had a confirmed LM diagnosis (positive CSF cytology). Remaining one had probable diagnosis (positive neuroimaging with typical clinical signs). Ten patients were enrolled in phase I. Three of 4 patients receiving IP at 15 mg completed induction and consolidation treatment without dose limiting toxicity (DLT). The dose was escalated to 20 mg. Two DLT (1 grade 4 hematologic toxicity and 1 grade 5 arachnoiditis) occurred in 6 patients at 20 mg. The MTD was determined to be 15 mg. Then 24 patients were enrolled in phase II and given 15 mg of IP. 82.4% (28/34) and 58.8% (20/34) patients completed induction and consolidation therapy, respectively. 41.2% (14/34) patients received maintenance therapy. Adverse events (AEs) rate was 73.5% (25/34). 50% (17/34) patients showed grade ≥ 3 AEs, including myelosuppression (11), elevation of hepatic aminotransferases (EHA) (5), elevation of blood bilirubin (EBB) (1), arachnoiditis (1), radiculitis (1), fatigue (1) and nausea (1). The overall CRR was 41.2% (14/34) by neuro-oncology proposal criteria, including 10 (29.4%) with improved neurological dysfunction, 11 (32.4%) with CSF cytological response and 4 (11.8%) with neuroimaging improvement. In a total of 28 patients receiving IP at 15 mg, 50% (14/28) patients showed grade ≥ 3 AEs, including myelosuppression (9), EHA (10), fatigue (1) and nausea (1). The CRR was 46.4% (13/28) in patients at 15 mg IP. Median survival was 7.6 (range 0.3-13.7) months in phase I, while has not yet been achieved in phase II until March 15, 2023. CONCLUSION MTD of IP was 15 mg with folic acid and vitamin B12 supplementation. IP is an optimal therapeutic option for LM from solid tumors.

N-acetylcysteine vs placebo as adjunctive treatment in paediatric leukaemia: A single blind, randomized controlled trial

Background: Acute lymphoblastic leukaemia (ALL) accounts for about 25% of all cancer types in children. Many chemotherapeutic agents have been shown to be related to increased oxidative stress and hepatotoxicity which affect the survival rate. N-acetylcysteine (NAC) has been used as adjunctive treatment in malignancy. Objectives: To analyse the effect of NAC administration towards blood oxidant, transaminase enzyme, and bilirubin level in ALL children undergoing induction phase of chemotherapy. Method: This is a single-blind placebo-controlled randomized clinical trial carried out from August to December 2020 in Cipto Mangunkusumo National Hospital, Jakarta, Indonesia. Subjects were randomized consecutively into 2 groups treated with NAC or placebo. Inclusion criteria were newly diagnosed ALL-standard risk (SR) children undergoing chemotherapy induction. Exclusion criteria were subjects contraindicated to NAC, already diagnosed with liver dysfunction, and already taken antioxidants. Data were analysed using SPSS 21. Normality test was conducted followed by data analysis with unpaired t-test. Results: A total of 18 subjects were included in study and 2 of them were excluded. Malondialdehyde levels showed an increase of 0.17nmoL in the NAC group and a decrease of 0.19nmoL in the placebo group. Aspartate transaminase (AST) level increased in mean of 11.40 U/L in the NAC group compared to placebo group 5.67 U/L. Alanine transaminase (ALT) level in the NAC group showed an increase in mean of 23.24 U/L compared to placebo group which showed a decrease in mean of 3.5 U/L. Bilirubin level in the NAC group showed an increase of 0.7 mg/dL compared to placebo group 0.17 mg/dL. There was no significant difference in MDA levels, AST, ALT, and bilirubin levels in the 2 groups (p=0. 186; p=0.638; p=0.164; p=0.352, respectively). Conclusions: Higher malondialdehyde level was shown as a trend in subjects in both groups before chemotherapy was done. N-acetyl cysteine administration showed no significant difference in reducing MDA levels, transaminase enzymes, and bilirubin levels in ALL-SR patients compared to placebo.

SpeCamX: mobile app that turns unmodified smartphones into multispectral imagers.

We present the development of SpeCamX, a mobile application that enables an unmodified smartphone into a multispectral imager. Multispectral imaging provides detailed spectral information about objects or scenes, but its accessibility has been limited due to its specialized requirements for the device. SpeCamX overcomes this limitation by utilizing the RGB photographs captured by smartphones and converting them into multispectral images spanning a range of 420 to 680 nm without a need for internal modifications or external attachments. The app also includes plugin functions for extracting medical information from the resulting multispectral data cube. In a clinical study, SpeCamX was used to implement an augmented smartphone bilirubinometer, predicting blood bilirubin levels (BBL) with superior performance in accuracy, efficiency and stability compared to default smartphone cameras. This innovative technology democratizes multispectral imaging, making it accessible to a wider audience and opening new possibilities for both medical and non-medical applications.

A CASE STUDY ON AYURVEDIC MANAGEMENT OF KAMALA W.S.R. TO JAUNDICE

Jaundice is a yellow pigmentation of the skin, the conjunctival membrane over the sclera and other mucous membrane caused by hyperbilirubinemia (increase level of bilirubin in blood). Today’s lifestyle with unhygienic and poor dietary habit specially in children which are responsible factor to promote hepatic damage which clinically reflect as kamala. This paper discusses patients seen in the OPD of Kaumarbhritya department, Uttaranchal ayurvedic hospital Dehradun. In this case 15-year female patient having kamala who was suffering from yellowish discolouration of skin, icterus, yellowish discolouration of urine, pain in abdomen, weakness, vomiting (3-4 times in a day), anxiety and anorexia in the last 5 days. The patient was treated with shaman chikitsa. Patients got significant results as per the values of bilirubin with symptomatic relief in complaints within 15 days of treatment. Kamala can be successfully managed by shamana chikitsa the effect of ayurvedic treatment was assessed in relation to improvement in overall clinical sign and symptoms &amp; biochemical investigations further study will be needed as per different assessment criteria.

Investigating the Impact of Eight Weeks of Aerobic Training on Liver Enzymes and Hematological Profile in Children with Leukemia

Objectives: The objective of the evaluation was to study and determine the impact of eight weeks of aerobic training (AT) on liver enzymes and changes in hematological profile in children with leukemia.Methods: This is a semi-experimental and applied study. Statistical samples include 24 children aged 7 to 10 years that referred to hospital and were divided randomly into two control (n=12) and experimental (n=12) groups. Eight-week AT with 40 to 70 percent of heart rate reserve, three sessions per week, no exercise training program was observed in the controls during the study. We measure Liver enzymes such as Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), Hemoglobin (Hb), White Blood Cells (WBC), platelets (PLT), and bilirubin. Data analysis using a paired t-test and analysis of covariance was performed with software SPSS version 20.Results: The results showed that moderate-intensity AT has a significant effect on hemoglobin and liver enzyme levels and a significant increase in Hb (p&lt;0.05) and significant reduction the ALT and AST (p&lt;0.05) whereas there was no significant influence on WBC, ALT, and bilirubin (p&gt;0.05).Conclusion: AT may accelerate the oxygen supply and reduce liver damage caused by medications in children diagnosed with leukemia without having corrupting effect on PLT, bilirubin, and safety factors.

Anti-Nephrotoxic effect of green synthesized Actiniopteris radiata silver nanoparticles (AR-AgNPs) against gentamicin induced nephrotoxicity

A study on green synthesized silver nanoparticles (AgNPs) using aqueous extract of Actiniopteris radiata and investigated the effect of A. radiata biosynthesized silver nanoparticles (AR-AgNPs) against gentamicin induced nephrotoxicity. The surface plasmon resonance (SPR) peak at 440 nm in UV–visible absorbance spectrum reveals the presence of AgNPs. DLS analysis shows that the distribution of size is normal and the average size of AgNPs converges about 100 nm. SEM revealed the consistent shape, uniform distribution, and closely packed characteristics of NPs whereas EDX confirms the presence of metallic silver with a strong peak at 3 keV. The N–H and O–H stretching vibrations are observed in the FTIR spectrum around 3450 and 3423 cm−1. Gentamicin induced changes in serum parameters resulted in a significant increase in the level of serum urea, creatinine, bilurubin and uric acids. AgNPs even at modest doses (250 mg/kg), significantly reverted the level of serum markers. The gentamicin-induced AR-AgNP in mice with the levels of CAT, GPx, SOD and TBARS ensured the protection against the oxidative damage in mice which clearly implies that enhancing the antioxidant defense mechanism. Nephrotoxicity of gentamicin induced mice were demonstrated by significantly elevated levels of blood urea, serum creatinine, bilirubin, and uric acids. The exposure of AR-Ag nanoparticles leads to a substantial decrease in blood urea and serum creatinine levels and enhanced the antioxidant and anti-nephrotoxic activity.

Bilirubin and Redox Stress in Age-Related Brain Diseases.

Cellular redox status has a crucial role in brain physiology, as well as in pathologic conditions. Physiologic senescence, by dysregulating cellular redox homeostasis and decreasing antioxidant defenses, enhances the central nervous system's susceptibility to diseases. The reduction of free radical accumulation through lifestyle changes, and the supplementation of antioxidants as a prophylactic and therapeutic approach to increase brain health, are strongly suggested. Bilirubin is a powerful endogenous antioxidant, with more and more recognized roles as a biomarker of disease resistance, a predictor of all-cause mortality, and a molecule that may promote health in adults. The alteration of the expression and activity of the enzymes involved in bilirubin production, as well as an altered blood bilirubin level, are often reported in neurologic conditions and neurodegenerative diseases (together denoted NCDs) in aging. These changes may predict or contribute both positively and negatively to the diseases. Understanding the role of bilirubin in the onset and progression of NCDs will be functional to consider the benefits vs. the drawbacks and to hypothesize the best strategies for its manipulation for therapeutic purposes.

Spectral and temporal detection of blood bilirubin level using a point-of-care device.

Bilirubin is a biomarker for liver inflammation used to assess liver functions. Its concentration in the blood has been measured using a range of techniques both in clinical and point-of-care settings. Existing point-of-care devices utilize a spectral approach, namely dual-wavelength absorption measurement, to assess the blood bilirubin concentration. This work examines a novel temporal approach based on the photodegradation of bilirubin in the blood sample. It demonstrates that combining photodegradation characteristics with dual-wavelength measurement produces a more accurate technique for measuring blood bilirubin concentration. Tracking the evolution of absorbed light as a function of time represents a low-cost and simple way of improving the accuracy of point-of-care devices for bilirubin measurements.Clinical Relevance - This work demonstrates a facile and cheap bilirubin monitoring approach that may allow bilirubin monitoring applications in homes after a patient is discharged from a hospital, which may decrease the burden on patients, families, and clinicians.

Atrazine residue in waters of Ijebu-North local government, Nigeria: implications on human health, hematological, and biochemical parameters

Knowledge and implications of atrazine in waters from rural areas in Nigeria remain diminutive. Meanwhile, recent findings have shown presence of atrazine residue in water bodies. Atrazine level in six communities (Mamu, Oru, Ilaporu, Awa, Ijebu Igbo, and Ago-Iwoye) of Ijebu North local government, Ogun State, Nigeria using 69 hand-dug wells (HDWs), 40 boreholes (BHs) and four streams are monitored. Value of atrazine recorded was employed to appraise the implication on some hematological and biochemical parameters in relation to human health through dermal and ingestion contact using male albino rats. Highest atrazine of 0.08 mg/L was found in HDW of Ago-Iwoye out of 41 hand dug wells assessed, alongside 22 BH and four streams tested positive to atrazine, while the Oru documented lowest concentration with 0.01 mg/L. Ingestion and dermal hazard index (HI) were lower in adults than children and below acceptable limits in each community. Atrazine concentration at 0.01, 0.03, 0.04, and 0.08 mg/L in waters may not induce significant alteration in the hematological and some biochemical parameters of the exposed animal, while concentration at 0.04 and 0.08 mg/L might alter the blood glucose, albumin, and bilirubin. This is the first study to report atrazine in rural community waters in relation to human health in Nigeria.

The Practice of Pancreatoduodenectomy in India: A Nation-Wide Survey.

Introduction The way pancreatoduodenectomy (PD) is performed can vary a lot around the world, and there is no agreed-upon standard approach. To learn more about how PD is practised in India, a survey was conducted among Indian surgeons to gather information about their current practices. Methods A survey was created and shared with surgeons in India who practicepancreatic surgery. It had 33 questions that aimed to capture information about different aspects of PD practice. These questions covered topics such as the surgeons' education and experience, how they evaluated patients before surgery, what they considered during the operation, and how they managed patients after surgery. Results A total of 129 surgeons were sent the survey, and 110 of them completed it. The results showed that 40.9% of the surgeons had less than five years of experience, and 36.4% of them performed more than 15 PDs in a year. When deciding whether to perform preoperative biliary drainage, 60% of surgeons based their decision on the level of bilirubin in the patient's blood, while the rest considered other specific indications. The majority of surgeons (72.7%) looked at the trend of albumin levels to assess the patient's nutritional status before surgery. Venous infiltration was seen as a reason for neoadjuvant therapy by 76.4% of the participants, whereas 95.5% considered upfront surgery in cases of venous abutment. When it came to the type of PD, 40% preferred classical PD, 40.9% preferred pylorus-resecting PD (PRPD), and the rest chose pylorus-preserving PD (PPPD). Pancreatojejunostomy (PJ) was the preferred method for 77.3% of surgeons, while 6.3% preferred pancreatogastrostomy (PG). About 65.5% of surgeons used octreotide selectively during the operation when the duct diameter was small. Nearly all surgeons (94.5%) preferred to secure feeding access during PD, and all of them placed intraperitoneal drains. As for postoperative care, 37.3% of surgeons attempted early oral feeding within 48 hours, while 28.2% preferred to wait at least 48 hours before initiating oral feeds. Conclusions The survey revealed significant differences in how PD is practised among surgeons in India, highlighting the heterogeneity in their approaches and preferences.

The effect of acetaminophen on the structural and functional state of the large intestine and intestinal microflora

Objective. To assess the condition of the microbial-tissue complex of the large intestine when hepatotoxic concentrations of acetaminophen are administrated to the body of animals.Materials and methods. The experiments were performed on 24 white outbred rats weighing 180–220 g, which were divided into three groups. The control group received 2% starch solution enterally, the first experimental group was enterally administered with acetaminophen in starch solution at a dose of 1500 mg per kilogram of body weight, five times a day with one day interval; and the second experimental group was administered with acetaminophen at a dose of 2500 mg per kilogram of body weight the same way. Free amino acids and their nitrogen-containing metabolites were determined by high-performance liquid chromatography in samples of the microbial-tissue complex (MTC) of the large intestine previously frozen at -70 °C. For microbiological study, the aseptically isolated MTC was immediately sent to a microbiological laboratory for identification of the content of the main representatives of the intestinal microflora. Samples of the wall of the ascending colon were subjected to histological and electron microscopic examination. The hepatotoxic effect of acetaminophen was evaluated by registering the activity of enzymes and the content of total bilirubin in blood plasma.Results. Enteral administration of hepatotoxic amounts of acetaminophen to rats increases the concentrations of free amino acids and their nitrogen-containing derivatives in the microbial-tissue complex of the large intestine. At the same time, the concentrations of essential amino acids are significantly increased. Morphological changes in the cells of the epithelium of the large intestine and the structure of mitochondria have been shown.Conclusions. Toxic doses of acetaminophen have a significant impact on the indicators of the microbial-tissue complex of the large intestine. There are changes in biochemical parameters of amino acid metabolism: increased levels of substitutable amino acids and changes in the colonocytes (size and shape of mitochondria, the height of the brush border, the volume of the goblet cells), indicating decreased ability of the cells to use amino acids to support the functioning of the Krebs cycle. This is also confirmed by significantly increased concentrations of essential amino acids, which are mainly used for protein synthesis. The dysbiosis caused by acetaminophen further contributes to the damage to the large intestine. The negative effect of acetaminophen is confirmed by the dose-dependent changes we found in the microbial-tissue complex.

Evaluation of Tribulus terrestris effect on kidney and liver function in healthy mice

This research aims to evaluate the pharmacological efficacy of aqueous spine extracts of Tribulus terrestris (TT) on liver and kidney function through physiological, biochemical, haematological, and histological assessments. Tribulus terrestris is renowned for its therapeutic benefits in traditional medicine practices in China, India, Pakistan, and Sudan for treating various chronic ailments. The study employed 5 weight per volume percentage (% w/v) of TT aqueous spines extract. BALB/c mice, both male and female, aged 4-6 weeks, were maintained in controlled ecological conditions (temperature: 22-24°C, humidity: 50-70%, light/dark cycle: 12-h). The mice were divided into two groups: the control group received normal tap water throughout the experimental period, while the other group was administered 5% (w/v) TT spines solution for 15 days. The outcomes of BALB/c mice treated with 5% Tribulus terrestris were compared with the control group after 15 days, revealing no significant difference in the drug's efficacy. The physiological results indicated reduced body weight, food intake, and adverse effects in the biochemical profile, including urinary and serum electrolyte levels, liver function tests, increased random blood glucosem, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin (BIL), cholesterol (CHO), high-density lipoprotein (HDL), and triglycerides (TRI). Similarly, kidney function tests showed increased Urinary Nitrogen and creatinine plasma levels, with low blood urea nitrogen (BUN), urinary creatinine, and glomerular filtration rate (GFR). However, no significant difference was observed in haematological profile readings. In conclusion, the findings suggest that the aqueous spine extract of Tribulus terrestris does not demonstrate beneficial effects on liver and kidney function, indicating that this study supports the notion that the plant cannot be utilized as a medicinal remedy.

Gut–liver axis and the impact of probiotics on neonatal jaundice symptoms: a review

Neonatal jaundice, which can affect up to 60% of term and 80% of preterm babies, can have a serious detrimental effect on their health. The effects of microbiota on neonatal bilirubin are poorly understood, which creates a critical knowledge gap about how they affect the neonate's blood bilirubin levels and how the gut delicately balances close contact with the host. Prebiotics and probiotics have a significant impact on the management of hyperbilirubinemia, but their effectiveness is still being debated. To offer a compelling novel therapeutic approach for newborn hyperbilirubinemia, a thorough understanding of the process is required.

Hierarchical decision model for in vitro bilirubin content prediction from absorption spectrum of whole blood.

Bilirubin forms by the breakdown of heme proteins in the liver, but a newborn's sluggish liver can lead to elevated serum bilirubin levels that cross the blood-brain barrier and result in kernicterus. Earlier studies have used the 400 to 500nm optical wavelength range to characterize the bilirubin content. There is not a universally established correlation among other wavelengths and the amount of bilirubin in clinical whole blood samples. We demonstrated that the amount of bilirubin could be quantified with accuracy in a label-free, self-referenced manner using only a few wavelengths, viz. 468, 492, 500, 560, 605, 645, 660, and 675nm, wherein band-averaged absorption measurements are used. We addressed the above problem by conducting a preliminary study containing 50 neonates through an absorption spectrum measurement of whole blood in 3 to samples from the neonates. We constructed a hierarchical decision method that first grossly divides the 30 neonates of the training set into and bilirubin level cohorts. A subsequent boundary condition further divides the group into two and bilirubin level cohorts. A finer measure later predicted the bilirubin content of each of these groups as low (), medium (10 to ), and high (). Using this hierarchical decision model statistical approach, we quantified the amount of bilirubin in the 20 testing set samples with 82% accuracy. We formulated a biostatistical model in which we automated the spectrometric determination of total bilirubin in the whole blood for patients of neonatal hyperbilirubinemia.

Significance of portal venous blood flow as a factor to determine liver function in patients with decompensated cirrhosis due to hepatitis C virus infection following achievement of sustained viral response by sofosbuvir plus velpatasvir.

To determine the outcomes concerning portal venous blood flow and portosystemic shunts in patients with decompensated cirrhosis due to hepatitis C virus (HCV) infection who achieved sustained viral response (SVR) following antiviral therapy. Portal hypertension-related events and liver function were evaluated in 24 patients achieving SVR following sofosbuvir plus velpatasvir therapy. Serum albumin level (median; g/dL) increased from 2.9 at baseline to 3.5 at 12weeks after the end of treatment (EOT) (p=0.005), while liver volumes (cm3 ) decreased from 1260 to 1150 (p=0.0002). Portal hypertension-related events developed in 10 patients (41.7%), and the cumulative occurrence rates after the EOT were 29.2%, 33.3%, and 46.1% at 24, 48, and 96weeks, respectively. Multivariate logistic regression analysis revealed that the maximal diameter of the shunts (p=0.0235) was associated with the development of the events, with a cut-off value of 8.3mm (p=0.0105). Meanwhile, multiple linear regression analysis revealed that portal venous blood flow, liver volume, serum albumin, and bilirubin levels at baseline were associated with serum albumin levels at 12weeks after EOT (p=0.0019, p=0.0154, p=0.0010, and p=0.0350, respectively). In patients with decompensated cirrhosis due to HCV infection, the baseline portal venous blood flow and liver volume and function were predictive of liver function following SVR, while the maximal diameter of portosystemic shunts predicted the occurrence of portal hypertension-related events.

Preparation of chitin/MXene/poly(L-arginine) composite aerogel spheres for specific adsorption of bilirubin

Currently, hemoperfusion is clinically the most rapid and effective treatment for removing toxins from the blood. The core of hemoperfusion is the sorbent inside the hemoperfusion device. Due to the complex composition of the blood, adsorbents tend to adsorb substances such as proteins in the blood (non-specific adsorption) while adsorbing toxins. Hyperbilirubinemia is caused by excessive levels of bilirubin in the human blood, causing irreversible damage to the patient's brain and nervous system, and even leading to death. High adsorption and high biocompatibility adsorbents with specific bilirubin adsorption are urgently needed to treat hyperbilirubinemia. Herein, poly(L-arginine) (PLA) which can specifically adsorb bilirubin, was introduced into chitin/MXene (Ch/MX) composite aerogel spheres. Ch/MX/PLA prepared by supercritical CO2 technology had higher mechanical properties than Ch/MX and can withstand 50,000 times its own weight. The in vitro simulated hemoperfusion test showed that the adsorption capacity of Ch/MX/PLA was as high as 596.31 mg/g, which was 15.38 % higher than that of Ch/MX. Binary and ternary competitive adsorption tests showed that Ch/MX/PLA also had good adsorption capacity in the presence of a variety of interfering molecules. In addition, hemolysis rate testing and CCK-8 testing confirmed that Ch/MX/PLA had better biocompatibility and hemocompatibility. Ch/MX/PLA can meet the required properties of clinical hemoperfusion sorbents and has the ability to produce mass production. It has good application potential in the clinical treatment of hyperbilirubinemia.

HH2853, an EZH1/2 inhibitor, in patients with epithelioid sarcoma: Preliminary results from the phase 1 part of a first-in-human phase I/II study.

11562 Background: Epithelioid sarcoma (ES) is a rare and aggressive subtype of soft-tissue sarcoma. Over 90% of tumors have lost INI1 expression, leading to oncogenic dependence on the transcriptional repressor EZH2. Tazemetostat (an EZH2 inhibitor) has been approved by FDA for clinical use in ES. HH2853 is a novel selective EZH1/2 dual inhibitor, which has demonstrated superior anti-tumor efficacy to tazemetostat in INI1-loss preclinical models. Methods: This is a first-in-human, open-label, multi-center, Phase (Ph) I/II study in patients (pts) with relapsed/refractory non-Hodgkin lymphomas or advanced solid tumors. Ph I is composed of two parts: dose escalation and dose extension part. Local pathologically documented, advanced recurrent or metastatic ES pts who received prior systemic anti-tumor therapies or have no standard therapy are eligible. HH2853 was administered orally twice daily (BID) on a continuous 28-day treatment cycle. Safety and clinical activity of HH2853 were assessed in pts with ES from the Ph I part. Results: Between Dec 2, 2021 and Nov 7, 2022, 32 pts with pre-treated ES were enrolled to three dose levels (400, 600, and 800 mg BID) from 4 sites in China. Median prior lines of therapy was two. 12 (37.5%) pts received ≥3 lines of prior therapies. 30 (93.8%) pts had documented loss of INI1 expression by local immunohistochemical analysis. There were 18 (56.3%) pts with proximal subtype. As of Jan 4, 2023, at a median treatment duration of 124 days, the most common treatment-related adverse events (TRAE) were diarrhea (59.4%), blood bilirubin increased (43.8%), white blood cell count (WBC) decreased (34.4%), rash (31.3%), anemia (25.0%), hypokalemia (21.9%), and platelet count (PLT) decreased (21.9%). TRAEs of ≥Grade 3 included diarrhea, WBC decreased, anemia, hypokalemia, and neutrophil count decreased (6.2%, each), and blood bilirubin increased, PLT decreased, blood creatine phosphokinase increased, and hyperglycemia (3.1%, each). TRAEs leading to dose interruption or reduction were reported in 21.9% and 12.5% pts, respectively. No TRAE led to dose discontinuation or death. Tumor responses were observed from 400 to 800 mg BID. Overall response rate (ORR) was 15.6% (5/32) per investigator assessment according to RECIST 1.1. Three pts had unconfirmed response waiting to be confirmed at the next scheduled assessment, expecting to bring the total ORR to 25% [95% CI 11.5 – 43.4]. Median time to response was 1.9 months. One patient with complete response (CR) has responded for 222 days from the initial response. Disease control rate (DCR) (DCR = CR + partial response + stable disease at 6 weeks) was 78.1% [95% CI 60-90.7]. Conclusions: HH2853 showed an acceptable safety profile and promising anti-tumor activity in heavily pretreated ES pts with a wide therapeutic window, providing evidence for further investigation. Clinical trial information: NCT04390737 .

A first-in-human study of MIL95, an anti-CD47 monoclonal antibody (mAb), in patients with advanced solid tumors and lymphomas.

e14513 Background: CD47 provides a potent “do not eat me” signal that allows the tumor to escape removal by the innate immune system. MIL95 is a humanized, anti-CD47 lgG4 monoclonal antibody and that mediated blockade of CD47 can induce macrophage phagocytosis of cancer cells. To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIL95, we conducted a first-in-human phase 1 trial in pts with advanced solid tumors and lymphomas (Protocol number MIL95-CT101, Beijing Mabworks Biotech Co. Ltd.) at 5 clinical study sites in China. Currently the study is still ongoing. Methods: We enrolled pts aged 18 years or older with advanced solid tumors and lymphomas whose disease had progressed after standard systemic treatments. Pts were required to ECOG PS score of 0-1 and adequate organ functions. Pts were enrolled in this two-part dose-escalation study: Part A, to determine a priming dose at 0.1, 0.3, 0.8, 1 mg/kg; Part B, to determine optimal weekly maintenance dose at 3, 10, 20, 30, 45 mg/kg. Dose escalation was performed using an accelerated titration followed by traditional 3+3 design during a 14-day (Part A) or 28-day (Part B) dose-limiting toxicity (DLT) observation period. Results: As of 18 Dec 2022, 24 pts (median age 54.5 years; 37.5% male; 54.2% ECOG PS 1) were treated: 8 in part A, 16 in part B. The common tumor types were lymphomas (25.0%) and breast (25.0%), lung (12.5%) cancers. MIL95 toxicity was manageable, no DLT was observed, and dose escalation was ongoing at 45mg/kg. The most common treatment-related adverse events (TRAEs) occurring in ≥10% of pts were anemia (37.5%), blood bilirubin increased (37.5%), leukopenia (20.8%), pyrexia (16.7%), and fatigue (16.7%). Most toxicities were Grade 1 or 2. Five pts had ≥Grade 3 TRAEs (Grade 3 anemia in 2 pts, Grade 3 decreased appetite in 1 pt, Grade 3 enteritis infectious in 1 pt, Grade 4 platelet count decreased in 1 pt). 4 pts had SD as a best response, with 1 pt (Cholangiocarcinoma at dose 20 mg/kg) on study for &gt;5 months. Conclusions: MIL95 was well tolerated at 1 mg/kg priming dose following by maintenance doses of up to 45 mg/kg weekly. Further antitumor activity may need to be combined with other therapies. Clinical trial information: NCT04651348 .