Thermally Active Medium-Density Fiberboard (MDF) with the Addition of Phase Change Materials for Furniture and Interior Design.

No matter where we reside, the issue of greenhouse gas emissions impacts us all. Their influence has a disastrous effect on the earth's climate, producing global warming and many other irreversible environmental impacts, even though it is occasionally invisible to the independent eye. Phase change materials (PCMs) can store and release heat when it is abundant during the day (e.g., from solar radiation), for use at night, or on chilly days when buildings need to be heated. As a consequence, buildings use less energy to heat and cool, which lowers greenhouse gas emissions. Consequently, research on thermally active medium-density fiberboard (MDF) with PCMs is presented in this work. MDF is useful for interior design and furniture manufacturing. The boards were created using pine (Pinus sylvestris L.) and spruce (Picea abies L.) fibers, urea-formaldehyde resin, and PCM powder, with a phase transition temperature of 22 °C, a density of 785 kg m-3, a latent heat capacity of 160 kJ kg-1, a volumetric heat capacity of 126 MJ m-3, a specific heat capacity of 2.2 kJ kgK-1, a thermal conductivity of 0.18 W mK-1, and a maximum operating temperature of 200 °C. Before resination, the wood fibers were divided into two outer layers (16%) and an interior layer (68% by weight). Throughout the resination process, the PCM particles were solely integrated into the inner layer fibers. The mats were created by hand. A hydraulic press (AKE, Mariannelund, Sweden) was used to press the boards, and its operating parameters were 180 °C, 20 s/mm of nominal thickness, and 2.5 MPa for the maximum unit pressing pressure. Five variants of MDF with a PCM additive were developed: 0%, 5%, 10%, 30%, and 50%. According to the study, scores at the MOR, MOE, IB, and screw withdrawal resistance (SWR) tests decreased when PCM content was added, for example, MOE from 3176 to 1057 N mm-2, MOR from 41.2 to 11.5 N mm-2, and IB from 0.78 to 0.27 N mm-2. However, the results of the thickness swelling and water absorption tests indicate that the PCM particles do not exhibit a substantial capacity to absorb water, retaining the dimensional stability of the MDF boards. The thickness swelling positively decreased with the PCM content increase from 15.1 to 7.38% after 24 h of soaking. The panel's thermal characteristics improved with the increasing PCM concentration, according to the data. The density profiles of all the variations under consideration had a somewhat U-shaped appearance; however, the version with a 50% PCM content had a flatter form and no obvious layer compaction on the panel surface. Therefore, certain mechanical and physical characteristics of the manufactured panels can be enhanced by a well-chosen PCM addition.

Investigation of the Potential of Repurposing Medium-Density Fiberboard Waste as an Adsorbent for Heavy Metal Ion Removal.

Medium-density fiberboard (MDF) waste generation has increased steadily over the past decades, and therefore, the investigation of novel methods to recycle this waste is very important. The potential of repurposing MDF waste as an adsorbent for the treatment of Cd(II), Cu(II), Pb(II), and Zn(II) ions in water was investigated using MDF offcuts. The highest adsorption potential in single-metal ion solution systems was observed for Pb(II) ions. The experimental data of Pb(II) ions fit well with the Freundlich isotherm and pseudo-second-order kinetic models. Complexation and electrostatic interactions were identified as the adsorption mechanisms. The adsorption behavior of multi-metal ion adsorption systems was investigated by introducing Cd(II) ions as a competitive metal ion. The presence of the Cd(II) ions reduced the adsorption potential of Pb(II) ions, yet the preference for the Pb(II) ions remained. Regeneration studies were performed by using 0.1 M HCl as a regeneration agent for both systems. Even though a significant amount of adsorbed metal ions were recovered, the adsorption potential of the MDF was reduced in the subsequent adsorption cycles. Based on these results, MDF fines have the potential to be used as an economical adsorbent for remediation of wastewater containing heavy metal ions.

Non-cirrhotic Ascites: A Case of Severe Alcoholic Hepatitis.

This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation excluded alternative etiologies, pinpointing sinusoidal non-cirrhotic portal hypertension. Present therapeutic modalities for AH, including steroids and pentoxifylline, offer limited efficacy, necessitating ongoing investigation. Liver transplantation may be contemplated in refractory cases. This case underscores the intricate nature of AH presentations and the challenges in their management, emphasizing the imperative need for continued research to delineate optimal therapeutic strategies. Early intervention remains pivotal in addressing AH complications, underscoring the need for heightened clinical vigilance and proactive treatment approaches in such cases.

Sustainable and economical alternatives to fragment capture materials in explosive and ballistic trials.

Strawboard has been utilised as a fragmentation capture material since the 1960s, mainly employed to capture fragments from explosives and explosive devices from arena trials of munitions. As this material has historically been calibrated to a known standard, it has a proven record of allowing research establishments to ascertain the velocity of a fragment based on the depth of penetration of the strawboard. During the time of calibration, strawboard was used as a common building material which was both widely available and relatively affordable; however, due to the recent economic crisis and geopolitical supply issues, this is no longer the case. Building on initial testing, this paper investigates alternatives to strawboard to determine if a cheaper, more readily available material can be used instead. The alternatives are compared and judged based on the NATO ARSP-03 guideline for capture material which includes metrics such as price and attainability, as well as assessing environmental impact and its ability to be used as a viable alternative to strawboard in an explosive environment. Based on these NATO guidelines, explosive fragmentation and ballistic experiments were conducted, and ten materials were tested based on the following criteria: Handling, Density, Flammability, Calibration, Cost and Availability. Medium Density Fibreboard (MDF) was found to be a suitable alternative to strawboard. The data demonstrates that it provides the same capture performance as strawboard at approximately a quarter of the cost and is far more readily available. Other materials also showed potential and further testing should be undertaken to validate these materials as alternatives to MDF.

Effect of Multidirectional Forging and Aging Treatment on Wear Properties of ZK61 Alloy.

This study investigated the effects of multidirectional forging (MDF) and aging treatments on the wear properties of ZK61 magnesium alloy. Dry sliding wear tests were performed on homogenized, MDF, and aged samples using a friction wear machine to analyze the surface morphology by scanning electron microscopy (SEM) and white light interferometry, as well as the hardness and tensile mechanical properties. The ZK61 magnesium alloy has higher sliding wear properties after MDF due to higher strength, hardness, and work hardening. Grain refinement affects the wear resistance of the material, but aging increases the hardness and tensile strength and decreases the wear resistance.

Possibilities for Efficient Furniture Construction Made of Thin and Ultra-Thin Materials by Using Mitre Joints.

One of the biggest challenges for designers and manufacturers of furniture is to reduce the thickness of conventional furniture materials such as particleboard (PB), medium-density fibreboard (MDF) and plywood. Designing furniture based on thin (less than 16 mm) and ultra-thin materials (less than 10 mm) is desirable for aesthetic reasons and because of the substantial material savings. However, the use of thin and ultra-thin materials reduces the strength of the furniture, especially the strength and deformation resistance of the joints. This study aimed to establish the possibilities for efficient furniture construction made of thin and ultra-thin materials using mitre joints. For this purpose, 14 types of L-type joints were tested: 12 glued and 2 detachable. The joints were made of eight wood-based panels and one non-wood panel. The bending moments and the stiffness coefficient under compression were determined. The obtained results show that the mitre joints made of laminated material with high-pressure laminate (HPL), 8 mm thick, MDF achieved the highest bending moment, and the highest stiffness coefficient was achieved by joints made of 10 mm thick compact HPL. Compact HPL joints were significantly affected by the type of adhesive used. Detachable joints had a relatively high bending strength but very low stiffness.

Automated atrial fibrillation and ventricular fibrillation recognition using a multi-angle dual-channel fusion network.

Atrial fibrillation (AFIB) and ventricular fibrillation (VFIB) are two common cardiovascular diseases that cause numerous deaths worldwide. Medical staff usually adopt long-term ECGs as a tool to diagnose AFIB and VFIB. However, since ECG changes are occasionally subtle and similar, visual observation of ECG changes is challenging. To address this issue, we proposed a multi-angle dual-channel fusion network (MDF-Net) to automatically recognize AFIB and VFIB heartbeats in this work. MDF-Net can be seen as the fusion of a task-related component analysis (TRCA)-principal component analysis (PCA) network (TRPC-Net), a canonical correlation analysis (CCA)-PCA network (CPC-Net), and the linear support vector machine-weighted softmax with average (LS-WSA) method. TRPC-Net and CPC-Net are employed to extract deep task-related and correlation features, respectively, from two-lead ECGs, by which multi-angle feature-level information fusion is realized. Since the convolution kernels of the above methods can be directly extracted through TRCA, CCA and PCA technologies, their training time is faster than that of convolutional neural networks. Finally, LS-WSA is employed to fuse the above features at the decision level, by which the classification results are obtained. In distinguishing AFIB and VFIB heartbeats, the proposed method achieved accuracies of 99.39 % and 97.17 % in intra- and inter-patient experiments, respectively. In addition, this method performed well on noisy data and extremely imbalanced data, in which abnormal heatbeats are much less than normal heartbeats. Our proposed method has the potential to be used as a diagnostic tool in the clinic.

Quantification of fragmentation capture materials and an assessment of the viability of economical alternatives: a preliminary study.

High pressure, high-temperature events need to be quantified experimentally. Where fragmentation occurs, i.e. against personal protective equipment, there is a requirement for both a reliable and repeatable measurement of numerous experimental metrics. Typically, the most critical is calculating the energy absorbed by the target material, to characterize target performance. This is achieved by detonating a device and capturing a proportion of the fragmentation in a suitable material that can achieve successful recovery of all fragmentation produced. Therefore, allowing the estimation of the target's response using the depth of penetration within the capture material which allows the calculation of energy absorption. The current standardized fragmentation capture material used within the UK is known as strawboard. Although effective, this material is both expensive and limited in its availability. This study explores the classification of strawboard to provide a suitable baseline to compare against medium density fibreboard (MDF) and flooring underlay, which represent two more economically friendly alternatives on the openmarket. It was found that the uniformity of response for the MDF material was better than that of strawboard, due to its reproducibility between batches and velocity ranges. To further explore this phenomena, high explosive trials were conducted, further demonstrating MDF to be a viable, reliable and cheaper alternative. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'.

Improving pathway prediction accuracy of constraints-based metabolic network models by treating enzymes as microcompartments.

Metabolic network models have become increasingly precise and accurate as the most widespread and practical digital representations of living cells. The prediction functions were significantly expanded by integrating cellular resources and abiotic constraints in recent years. However, if unreasonable modeling methods were adopted due to a lack of consideration of biological knowledge, the conflicts between stoichiometric and other constraints, such as thermodynamic feasibility and enzyme resource availability, would lead to distorted predictions. In this work, we investigated a prediction anomaly of EcoETM, a constraints-based metabolic network model, and introduced the idea of enzyme compartmentalization into the analysis process. Through rational combination of reactions, we avoid the false prediction of pathway feasibility caused by the unrealistic assumption of free intermediate metabolites. This allowed us to correct the pathway structures of l-serine and l-tryptophan. A specific analysis explains the application method of the EcoETM-like model and demonstrates its potential and value in correcting the prediction results in pathway structure by resolving the conflict between different constraints and incorporating the evolved roles of enzymes as reaction compartments. Notably, this work also reveals the trade-off between product yield and thermodynamic feasibility. Our work is of great value for the structural improvement of constraints-based models.

The Use of a Radial Basis Function Neural Network and Fuzzy Modelling in the Assessment of Surface Roughness in the MDF Milling Process.

Wood-based composites are increasingly used in the industry not only because of the shortage of solid wood, but above all because of the better properties, such as high strength and aesthetic appearance compared to wood. Medium-density fiberboard (MDF) is a wood-based composite that is widely used in the furniture industry. In this work, an attempt was made to predict the surface roughness of the machined MDF in the milling process based on acceleration signals from an industrial piezoelectric sensor installed in the cutting zone. The surface roughness parameter Sq was adopted for the evaluation and measurement of surface roughness. The surface roughness prediction was performed using a radial basis function (RBF) artificial neural network (ANN) and a Takagi-Sugeno--Kang (TSK) fuzzy model with subtractive clustering. In the research, as inputs to the ANNs and fuzzy model, the kinematic parameters of the cutting process and selected measures of the acceleration signal were adopted. At the output, the values of the surface roughness parameter Sq were obtained. The results of the experiments show that the surface roughness is influenced not only by the kinematic parameters of the cutting, but also by the vibrations generated during the milling process. Therefore, by combining information on the cutting kinematics parameters and vibration, the accuracy of the surface roughness prediction in the milling process of MDF can be improved. The use of TSK fuzzy modelling based on the subtractive clustering method for integrating the information from many acceleration signal measurements in the examined range of cutting conditions meant the surface roughness was predicted with high accuracy and high reliability. With the help of two tested artificial intelligence tools, it is possible to estimate the surface roughness of the workpiece with only a small error. When using a radial neural network, the root mean square error for estimating the value of the Sq parameter was 0.379 µm, while the estimation error based on fuzzy logic was 0.198 µm. The surface of the sample made with the cutting parameters vc = 76 m/min and vf = 1200 mm/min is characterized by a less concentrated distribution of ordinate densities, compared to the surface of the sample cut with lower feed rates but at the same cutting speed. The most concentrated distribution of ordinate density (for the cutting speed vc = 76 m/min) is characterized by the surface, where the feed rate value was vf = 200 mm/min, with 90% of the material concentrated in the profile height of 28.2 µm. When using an RBF neural network, the RMSE of estimating the value of the Sq parameter was 0.379 µm, while the estimation error based on fuzzy logic was 0.198 µm.

Gasification of MDF residue in an updraft fixed bed gasifier to produce heat and power via an ORC turbine.

Biomass, which is a renewable resource, is regarded as an essential energy source due to its accessibility and abundance. In this study, the gasification of wood-based biomass wastes from the medium density fiberboard (MDF) facility was carried out and investigated utilizing an updraft fixed bed gasifier. The feeding capacity of the upstream gasifier is 2100 kg/h. MDF wastes are loaded into the system with feeding capacities of 1500, 1750 and 2100 kg/h. As a reference, the system has also been tested with oak wood chips at a maximum rate of 2100 kg/h. Produced syngas production rate to biomass waste is approximately 2.5 Nm3/kg. The measured gas compositions are CO, CO2, CH4, H2, O2 and N2. Test results with 2100 kg/hMDF wastes have similar gas composition compared to the test results with oak wood chips. The quality of the syngas produced by gasification is directly related to the fuel. It has been observed that the efficiency of the gasification process can be directly or indirectly impacted by the properties of the fuel, such as the moisture content, chemical compositions, and size. The temperature of the produced gas is approximately 430 °C, and it isdirectly combusted with tars and soot it contains to ensure that no chemical energy is lost. The thermal gasification system converts approximately 88% by weight of MDF residue to syngas. The calorific value of produced syngas is obtained between 6.0 and 7.0 MJ/Nm3. The hot syngas containing tars produced from the gasifier was directly burned in the thermal oil heater retrofitted to vortex syngas burner to recover thermal energy, which was then utilized in the production of energy via an ORC turbine. The thermal oil heater has a thermal capacity of 7MWh and the power generation capacity of the ORC turbine is 955 kW of electricity.

Preparation and Properties of Medium-Density Fiberboards Bonded with Vanillin Crosslinked Chitosan.

An eco-friendly medium-density fiberboard (MDF) was prepared using vanillin (V) crosslinked chitosan (CS) adhesive through a hot-pressing process. The cross-linking mechanism and the effect of different proportions of added chitosan/vanillin on the mechanical properties and dimensional stability of MDF were investigated. The results showed that vanillin and chitosan are crosslinked to form a three-dimensional network structure due to the Schiff base reaction between the aldehyde group of vanillin and the amino group of chitosan. At the same time, when the mass ratio between vanillin/chitosan was 2:1, MDF obtained the best mechanical properties, the maximum modulus of rupture (MOR) of 20.64 MPa, the mean modulus of elasticity (MOE) of 3005 MPa, the mean internal bonding (IB) of 0.86 MPa, and the mean thickness swelling (TS) of 14.7%. Therefore, the MDF bonded with V-crosslinked CS can be a promising candidate for environmentally-friendly wood-based panels.

Using Mercury Stable Isotopes to Quantify Bidirectional Water-Atmosphere Hg(0) Exchange Fluxes and Explore Controlling Factors.

In this study, exchange fluxes and Hg isotope fractionation during water-atmosphere Hg(0) exchange were investigated at three lakes in China. Water-atmosphere exchange was overall characterized by net Hg(0) emissions, with lake-specific mean exchange fluxes ranging from 0.9 to 1.8 ng m-2 h-1, which produced negative δ202Hg (mean: -1.61 to -0.03‰) and Δ199Hg (-0.34 to -0.16‰) values. Emission-controlled experiments conducted using Hg-free air over the water surface at Hongfeng lake (HFL) showed negative δ202Hg and Δ199Hg in Hg(0) emitted from water, and similar values were observed between daytime (mean δ202Hg: -0.95‰, Δ199Hg: -0.25‰) and nighttime (δ202Hg: -1.00‰, Δ199Hg: -0.26‰). Results of the Hg isotope suggest that Hg(0) emission from water is mainly controlled by photochemical Hg(0) production in water. Deposition-controlled experiments at HFL showed that heavier Hg(0) isotopes (mean ε202Hg: -0.38‰) preferentially deposited to water, likely indicating an important role of aqueous Hg(0) oxidation played during the deposition process. A Δ200Hg mixing model showed that lake-specific mean emission fluxes from water surfaces were 2.1-4.1 ng m-2 h-1 and deposition fluxes to water surfaces were 1.2-2.3 ng m-2 h-1 at the three lakes. Results from the this study indicate that atmospheric Hg(0) deposition to water surfaces indeed plays an important role in Hg cycling between atmosphere and water bodies.

An optimized IL-12-Fc expands its therapeutic window, achieving strong activity against mouse tumors at tolerable drug doses.

BACKGROUND: Interleukin-12 (IL-12) has emerged as one of the most potent cytokines for tumor immunotherapy due to its ability to induce interferon γ (IFNγ) and polarize Th1 responses. Clinical use of IL-12 has been limited by a short half-life and narrow therapeutic index. METHODS: We generated a monovalent, half-life-extended IL-12-Fc fusion protein, mDF6006, engineered to retain the high potency of native IL-12 while significantly expanding its therapeutic window. In vitro and in vivo activity of mDF6006 was tested against murine tumors. To translate our findings, we developed a fully human version of IL-12-Fc, designated DF6002, which we characterized in vitro on human cells and in vivo in cynomolgus monkeys in preparation for clinical trials. FINDINGS: The extended half-life of mDF6006 modified the pharmacodynamic profile of IL-12 to one that was better tolerated systemically while vastly amplifying its efficacy. Mechanistically, mDF6006 led to greater and more sustained IFNγ production than recombinant IL-12 without inducing high, toxic peak serum concentrations of IFNγ. We showed that mDF6006's expanded therapeutic window allowed for potent anti-tumor activity as single agent against large immune checkpoint blockade-resistant tumors. Furthermore, the favorable benefit-risk profile of mDF6006 enabled effective combination with PD-1 blockade. Fully human DF6002, similarly, demonstrated an extended half-life and a protracted IFNγ profile in non-human primates. CONCLUSION: An optimized IL-12-Fc fusion protein increased the therapeutic window of IL-12, enhancing anti-tumor activity without concomitantly increasing toxicity. FUNDING: This research was funded by Dragonfly Therapeutics.

Acute Kidney Injury (AKI) at Admission Predicts Mortality in Patients With Severe Alcoholic Hepatitis (SAH).

Background & aims: Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia. Materials and methods: This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI. Results: 309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria (P < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days (P < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI. Conclusions: Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days. Lay summary: SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.

MERISTEM-DEFECTIVE regulates the balance between stemness and differentiation in the root meristem through RNA splicing control.

Plants respond to environmental stresses through controlled stem cell maintenance and meristem activity. One level of gene regulation is RNA alternative splicing. However, the mechanistic link between stress, meristem function and RNA splicing is poorly understood. The MERISTEM-DEFECTIVE (MDF) Arabidopsis gene encodes an SR-related family protein, required for meristem function and leaf vascularization, and is the likely orthologue of the human SART1 and yeast Snu66 splicing factors. MDF is required for the correct splicing and expression of key transcripts associated with root meristem function. We identified RSZ33 and ACC1, both known to regulate cell patterning, as splicing targets required for MDF function in the meristem. MDF expression is modulated by osmotic and cold stress, associated with differential splicing and specific isoform accumulation and shuttling between nucleus and cytosol, and acts in part via a splicing target SR34. We propose a model in which MDF controls splicing in the root meristem to promote stemness and to repress stress response, cell differentiation and cell death pathways.

An efficient method for qualitation and quantitation of multi-components of the herbal medicine Qingjin Yiqi Granules.

Qingjin Yiqi Granules (QJYQ) is a Traditional Chinese Medicines (TCMs) prescription for the patients with post-COVID-19 condition. It is essential to carry out the quality evaluation of QJYQ. A comprehensive investigation was conducted by establishing deep-learning assisted mass defect filter (deep-learning MDF) mode for qualitative analysis, ultra-high performance liquid chromatography and scheduled multiple reaction monitoring method (UHPLC-sMRM) for precise quantitation to evaluate the quality of QJYQ. Firstly, a deep-learning MDF was used to classify and characterize the whole phytochemical components of QJYQ based on the mass spectrum (MS) data of ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Secondly, the highly sensitive UHPLC-sMRM data-acquisition method was established to quantify the multi-ingredients of QJYQ. Totally, nine major types of phytochemical compounds in QJYQ were intelligently classified and 163 phytochemicals were initially identified. Furthermore, fifty components were rapidly quantified. The comprehensive evaluation strategy established in this study would provide an effective tool for accurately evaluating the quality of QJYQ as a whole.

Epidemiology and Disease Burden of Alcohol Associated Liver Disease.

Consumption of alcohol in excess leads to substantial medical, economic, and societal burdens. Approximately 5.3% of all global deaths may be attributed to alcohol consumption. Moreover, the burden of alcohol associated liver disease (ALD) accounts for 5.1% of all disease and injury worldwide. Alcohol use disorder (AUD) affects men more than women globally with significant years of life loss to disability in low, middle and well-developed countries. Precise data on global estimates of alcohol related steatosis, alcohol related hepatitis, and alcohol related cirrhosis have been challenging to obtain. In the United States (US), alcohol related steatosis has been estimated at 4.3% based on NHANES data which has remained stable over 14 years. However, alcohol-related fibrotic liver disease has increased over the same period. In those with AUD, the prevalence of alcohol related hepatitis has been estimated at 10-35%. Globally, the prevalence of alcohol-associated cirrhosis has been estimated at 23.6 million individuals for compensated cirrhosis and 2.46 million for those with decompensated cirrhosis. The contribution of ALD to global mortality and disease burden of liver related deaths is substantial. In 2016 liver disease related to AUD contributed to 50% of the estimated liver disease deaths for age groups 15 years and above. Data from the US report high cost burdens associated with those admitted with alcohol-related liver complications. Finally, the recent COVID-19 pandemic has been associated with marked increase in alcohol consumption worldwide and will likely increase the burden of ALD.

Emerging Pharmacotherapies in Alcohol-Associated Hepatitis.

The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis. Conclusion: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.

Outnumbered: Control Prothrombin Time in Maddrey's Discriminant Function Impacts Steroid Use but Not Mortality in Alcoholic Hepatitis.

BACKGROUND AND AIMS: In alcoholic hepatitis (AH), increases in the total bilirubin (TB) and the prothrombin time (PT), which are included in the Maddrey's discriminant function (MDF) and the model for end-stage liver disease (MELD), are associated with poor outcomes. However, the impact of which control PT in the MDF to use compared to the MELD on the outcomes in AH is unknown. Our aim is to determine whether the choice of the control PT used in the MDF calculations has any impact on steroid use and survival when compared to the MELD in those with AH. METHODS: Through retrospective chart review, we analyzed 882 subjects who were admitted from 2012 to 2020 with acute AH. Their MDF was calculated [(TB + 4.6 × (PT-control)] using the following three different control PTs: 12, 13.5, and 14.8 s, and was compared to the MELD. The primary outcomes were steroid use and 30-day survival. RESULTS: When it was stratified by the control PT, the percentage of MDF ≥ 32 (the threshold for steroids) decreased with increasing control PT (70%, 61%, and 52%, respectively), along with decreased steroid use (91%, 84%, and 75%, respectively). Those who received steroids were not shown to have improved 30-day survival compared to those who did not receive steroids (p = 0.41). The ability of the MDF for each control PT threshold to predict 30-day survival was similar (AUROC 0.735), and was lower compared to the MELD (0.767). CONCLUSION: While the choice of PT control in the MDF impacted the use of steroids in AH, the use of steroids and the choice of PT control used did not impact the overall survival. Regardless of which control PT was used in the MDF, the MELD was better at predicting 30-day survival. Important information: Background: Treatment with steroids is indicated in alcoholic hepatitis (AH) with Maddrey discriminant function (MDF) ≥ 32 and the model for end-stage liver disease (MELD) ≥ 20. The impact that the control prothrombin time (PT) value that is used in MDF has on steroid use and survival in AH is poorly understood. FINDINGS: The choice of control PT that is used when calculating the MDF impacts the use of steroids but does not impact mortality. The MELD was better than the MDF at any control PT used in predicting survival in acute AH. IMPLICATIONS FOR PATIENT CARE: Providers should be aware that higher control PT's have an effect on treatment decisions but should not generally impact survival in this population. The MELD appears to better predict 30-day survival in this population.