Degree Of Elevation Research Articles

Shape control tools for periodic Bézier curves

Bézier curves are an essential tool for curve design. Due to their properties, common operations such as translation, rotation, or scaling can be applied to the curve by simply modifying the control polygon of the curve. More flexibility, and thus more diverse types of curves, can be achieved by associating a weight with each control point, that is, by considering rational Bézier curves. As shown by Ramanantoanina and Hormann (2021), additional and more direct control over the curve shape can be achieved by exploiting the correspondence between the rational Bézier and the interpolating barycentric form and by exploring the effect of changing the degrees of freedom of the latter (interpolation points, weights, and nodes). In this paper, we explore similar editing possibilities for closed curves, in particular for the rational extension of the periodic Bézier curves that were introduced by Sánchez-Reyes (2009). We show how to convert back and forth between the periodic rational Bézier and the interpolating trigonometric barycentric form, derive a necessary condition to avoid poles of a trigonometric rational interpolant, and devise a general framework to perform degree elevation of periodic rational Bézier curves. We further discuss the editing possibilities given by the trigonometric barycentric form.

Stress-induced severe transient hypercortisolism with reversible bilateral adrenal enlargement after cardiogenic shock.

Acute illness-related stress can result in severe hypercortisolism and bilateral adrenal enlargement in certain patients. We report a case of stress-induced hypercortisolism and bilateral adrenal enlargement in a patient admitted for acute respiratory distress and cardiogenic shock. Bilateral adrenal enlargement and hypercortisolism found during hospitalization for acute illness resolved 3 weeks later following the resolution of acute illness. Acute illness can be a precipitating factor for stress-induced hypercortisolism and bilateral adrenal enlargement. We hypothesize that increased adrenocorticotrophic hormone mediated by corticotrophin-releasing hormone from physical stress resulted in significant adrenal hyperplasia and hypercortisolism. This mechanism is downregulated once acute illness resolves. Adrenal enlargement with abnormal adrenal function after stress is uncommon in humans; however, if present, it can have self-resolution after the acute illness is resolved. Stress induces enlargement of the adrenals, and the degree of cortisol elevation could be very massive. This process is acute, and the absence of cushingoid features is expected. Treatment efforts should be focused on treating the underlying condition.

Abnormal thyroid function: an unusual presentation of pituitary stalk interruption syndrome.

An 11-year-old girl with past medical history of septic shock and multi-organ failure at age 5 presented to her primary care doctor with concern for pallor of the lips. Laboratory studies demonstrated low free thyroxine (T4) and normal thyroid-stimulating hormone (TSH). A referral to endocrinology was made where the patient was evaluated, and laboratory evaluation was repeated. The patient was asymptomatic and clinically euthyroid with a height consistent with her mid-parental height and was in mid- to late-puberty. The repeated laboratory evaluation demonstrated a pattern suggestive of primary hypothyroidism with low free T4 and an elevated TSH. However, the magnitude of elevation of TSH was less than expected, given the degree of lowering of free T4; therefore, central hypothyroidism was considered. Workup was initiated, and laboratory studies and MRI imaging confirmed an underlying diagnosis of panhypopituitarism in the setting of pituitary stalk interruption syndrome. Pituitary stalk interruption syndrome is a rare but important cause of panhypopituitarism. Central hypothyroidism should be suspected in patients with low free thyroxine with an inappropriate degree of elevation of thyroid-stimulating hormone. Workup of central hypothyroidism should include multi-pituitary hormone assessment, and, if evident, MRI imaging should be done. Adrenal insufficiency should be suspected in a hypotensive, critically ill patient who is failing to improve on standard-of-care therapy.

Comparison of surgical treatment options in periprosthetic shoulder infections: a systematic review from 2016 to 2022.

Periprosthetic shoulder infection (PSI) management proves to be challenging because of patient morbidity, poor outcomes and need for reoperations. Different surgical treatment methods have been defined; however, a prominent method could not be determined. This systematic review investigated the most recent articles about various treatment modalities used in the surgical treatment of PSI to find the most effective method in terms of infection clearance and function. The keywords were searched using PubMed (MEDLINE), ScienceDirect (Elsevier), and Google Scholar databases on September 30, 2022. Studies which report on operative treatment and have longer than 2-year follow-up were included in this review. Of the 555 studies in total, 16 were reviewed. The absence of symptomatic persistent infection (PI) during follow-up was regarded as a satisfactory outcome. Functional outcomes were analyzed according to the reported mean pooled Constant and Murley Score (CMS) and shoulder forward elevation degree (FE) for each treatment group. A total of 339 patients (139 female, 197 male) with 342 shoulders from sixteen studies were included. The mean age of the patients was 67.5±3.8 years, mean follow-up duration was 53.3±19.5 months. In total, 217 shoulders were treated with two-stage revision, 59 were treated with one-stage revision, 37 were treated with definitive spacer, 23 were treated with debridement, antibiotics, and implant retention (DAIR), and 6 were treated with resection arthroplasty. The PI rate in whole treatment groups was 9.9%. The PI rate was significantly highest in the DAIR group (30.4%, P=0.001), while there was no significant difference between other treatment groups (P=0.23). CMS and FE were available for 156 and 190 shoulders, respectively. CMS was highest in the one-stage revision group (63.4±5.9, P=0.001), and FE was highest in the DAIR group (119.3°±28.5°, P=0.001). The revision surgeries (one-stage and two-stage revision) were more effective than the non-revision surgeries in functional outcomes. In terms of infection clearance, revision procedures were more successful. Surgeons should prefer revision methods over non-revision procedures when feasible.

The Impact of Teachers’ Inquiry-based Instruction Method on The Academic Performance of students in Kunar University, Afghanistan.

The motivation behind this study was to investigate the effect inquiry-based instruction methodologies had with respect to students’ achievement. Besides, the review recognized a university that showed elevated degrees of performance in the Sayed Jamaluddin Afghani university, Kunar province 2022. These recognized university lecturers, who were lined up with detailed victories, were welcome to take part in this review. The participants who partook in the review gave a record of the educational methodologies operated among those students who generally showed elevated degrees of achievement. The collected information permitted the researcher to sum up the picked techniques and besides report on the serious level of recurrence in which request-based methodologies were utilized. It was presumed that request-based educational methodologies were successful systems lined up with successful students.

Cardiovascular Effects of Excess Growth Hormone: How Real is the Threat?

Patients with acromegaly carry a high risk of developing cardiovascular diseases (CVD). In fact, CVD is the leading cause of mortality among this group of patients. The most frequent cardiovascular complications are heart failure (HF), valvular disease, hypertension, arrhythmias, and coronary artery disease (CAD). The pathophysiology centers on the family of growth hormone (GH). These hormones are involved in normal cardiac development and function; however, excess of insulin-like growth factor-1 (IGF-1), the principally active hormone, can also cause negative effects on the cardiovascular system. HF in acromegaly usually presents with biventricular enlargement and diastolic dysfunction and is strongly associated with the duration of GH excess rather than the degree of hormone elevation. There is a high prevalence of valvular disease affecting aortic and mitral valves among patients with longer disease duration. The development of hypertension in acromegaly may be attributed to the effects of chronic GH/IGF-1 excess on different organ systems, which act via several mechanisms. The aspect of arrhythmia and CAD complicating acromegaly are currently not fully understood.

COVID-19 Vaccination Certificates in the Darkweb

COVID-19 vaccines have been rolled out in many countries and with them a number of vaccination certificates. For instance, the EU is utilizing a digital certificate in the form of a QR-code that is digitally signed and can be easily validated throughout all EU countries. In this article, we document the current state of the COVID-19 vaccination certificate market in the darkweb with a focus on the EU Digital Green Certificate (DGC) . We investigate 17 marketplaces and 10 vendor shops that include vaccination certificates in their listings, and discover that a multitude of sellers in both types of platforms are advertising forging capabilities. According to their claims, it is possible to buy fake vaccination certificates issued in many countries worldwide. We demonstrate some examples of such sellers, including how they advertise their services, and we develop a taxonomy of EU COVID-19 certificate forging capabilities, describing the potential methods that the vendors are utilizing to generate certificates. We highlight two particular cases of vendor shops, with one of them showing an elevated degree of professionalism, showcasing forged valid certificates, the validity of which we verify using two different national mobile COVID-19 applications.

Exploring the ecosystem services bundles and influencing drivers at different scales in southern Jiangxi, China

Located in the hilly and mountainous central area of the national ecological security strategic pattern (described as “two ecological barriers and three green belts”), southern Jiangxi is an important ecological barrier in southeast China and a pilot area for the national mountains-rivers-forests-farmlands-lakes-grasslands restoration projects. In recent years, the rapid economic development of the southern Jiangxi region and the rapid changes in land use, agricultural intensification, and population urbanization have severely tested this ecosystem on which people depend for their survival. Currently, studies of ecosystems and their interactions from a single spatial perspective have sprung up, but only a few studies have comprehensively analyzed different spatial scales to facilitate the sustainable development of regional ecosystems. Multi-scale studies should be carried out to quantitatively understand the relationship between ecosystem services (ESs) and socio-natural drivers, in an attempt to find a suitable scale to assess regional ESs or to achieve complementary advantages by combining multi-scales so as to conduct hierarchical management of ESs. Therefore, to better understand the interplay between ESs and to achieve the goals of sustainable development, we quantitatively analyzed the evolutionary patterns, trade-offs, and synergies of ESs. In our analysis, we also looked at bundling ESs and their drivers for seven ecosystem services at the township and watershed scales for 2000–2020 in southern Jiangxi. Crop production, meat production, water yield, carbon storage, soil retention, habitat quality, and forest recreation services were specifically quantified, and redundancy analysis was used to explore the influence degree of precipitation, temperature, elevation, slope, GDP, and population density on ESs. The results showed that most ESs have increased in southern Jiangxi, indicating spatial and temporal heterogeneity. The scale effect of trade-off and synergy showed that the spatial variation was similar, but the amplitude of variation was different. Compared with the watershed scale, the overall bundle of ESs in southern Jiangxi is better identified and clustered at the township scale. In addition, Cluster 4 at the township scale and Cluster 3 at the watershed scale can comprehensively identify high-value areas of ecosystem services in the study area. The rapid growth of GDP and population density caused by rapid urbanization were the main driving factors of the difference in ESs between the two scales in southern Jiangxi. Our results provide recommendations for governance and restoration of regional ecosystem services and support for conducting a comprehensive analysis of spatio-temporal evolutionary mechanisms and interactions of ecosystem services at different scales.

An evaluation algorithm for [formula omitted]-Bézier triangular patches formed by convex combinations

An extension to triangular domains of the univariate q-Bernstein basis functions is introduced and analysed. Some recurrence relations and properties such as partition of unity and degree elevation are proved for them. It is also proved that they form a basis for the space of polynomials of total degree less than or equal to n on a triangle. In addition, it is presented a de Casteljau type evaluation algorithm whose steps are all linear convex combinations.

Lipidomic analysis of geopropolis of Brazilian stingless bees by LC-HRMS

Stingless bees (Meliponini) represent over than 500 species, found in tropical and sub-tropical regions of the world. They produce geopropolis, a resinous natural product containing bioactive compounds, which is commonly used in folk medicine. In the current study, LC-HRMS and bioinformatic tools were used to carry out for the first time the lipidomic analysis of geopropolis from indigenous Brazilian stingless bees. As a result, 61 compounds of several lipid classes were identified with elevated degree of confidence. Then, we demonstrated that lipids in geopropolis are not restricted to waxes and fatty acids; but fatty amides and amines, phenolic lipids, resorcinols, retinoids, abietanoids, diterpenoids, pentacyclic triterpenoids, prostaglandins, retinoids, and steroids were found. In addition, multivariate analysis, based on the lipidomic profile of extracts, reinforces the assumption that the species of stingless bees, as well as the geographical origin are relevant factors to affect geopropolis composition once that the lipidic profile allowed the discrimination of geopropolis in groups related to the geographical origin, bee specie or bee genus. The lipidic profile also suggest a selective forage habits of T. angustula, which seems to collect resins from more specific vegetal sources regardless geographic origin, while other stingless bees, such as M. marginata and M. quadrifasciata, are less selective and may adapt to collect resins from a wider variety of plants.

Titanium surface roughening with ultrasonic pulsating water jet

Biomedical industries are looking for natural ways of processing biocompatible materials to improve their biological performances. One untested option is the use of the water hammer effect in the form of water droplets; this can create surfaces with high degrees of capillary elevation whose structures resemble a trabecular structure. In this study, we analyzed the modified surface morphologies and integrity of the titanium alloy Ti6Al4V using water droplet impingement generated with an ultrasonic pulsating water jet at starting frequencies of f = 20 kHz and 40 kHz. The water droplets were distributed along a linear offset trajectory. Two transition methods for producing modified surface morphologies were compared, one with a single transition and another with an additional secondary transverse transition. The created surfaces were classified according to the area surface roughness parameters, Sa and Sz. The results were compared with a control group of samples exposed to a continuous jet with ff = 0 Hz. By setting the technological parameters of an ultrasonic pulsating water jet, the aim was to create surface properties that increased biological interactions during osseointegration. The results positively support the initial indications that the pulsating water jet surface treatment was a more advantageous alternative than other techniques based on using solid particles for surface erosion, whose artifacts can become lodged in the material and contaminate surfaces.

Flavoprotein fluorescence elevation is a marker of mitochondrial oxidative stress in patients with retinal disease.

Recent studies of glaucoma, age-related macular degeneration, and diabetic retinopathy have demonstrated that flavoprotein fluorescence (FPF) can be utilized non-invasively as an indicator of mitochondrial oxidative stress in the retina. However, a comprehensive assessment of the validity and reliability of FPF in differentiating between healthy and diseased eyes across multiple disease states is lacking. Here, we evaluate the sensitivity and specificity of FPF in discriminating between healthy and diseased eyes in four leading causes of visual impairment worldwide, one of which has not been previously evaluated using FPF. We also evaluate the association between FPF and visual acuity. A total of 88 eyes [21 eyes of 21 unaffected controls, 20 eyes from 20 retinal vein occlusion (RVO) patients, 20 eyes from 20 diabetic retinopathy (DR) patients, 17 eyes from 17 chronic exudative age-related macular degeneration (exudative AMD) patients, and 10 eyes from 10 central serous retinopathy (CSR) patients] were included in the present cross-sectional observational study. Eyes were imaged non-invasively using a specially configured fundus camera OcuMet Beacon® (OcuSciences, Ann Arbor, MI). The macula was illuminated using a narrow bandwidth blue light (455 - 470 nm) and fluorescence was recorded using a narrow notch filter to match the peak emission of flavoproteins from 520 to 540 nm. AUROC analysis was used to determine the sensitivity of FPF in discriminating between diseased eyes and healthy eyes. Nonparametric Kruskal-Wallis Tests with post-hoc Mann Whitney U tests with the Holm-Bonferroni correction were performed to assess differences in FPF intensity, FPF heterogeneity, and best corrected visual acuity (BCVA) between the five groups. Spearman rank correlation coefficients were calculated to assess the relationship between FPF and BCVA. AUROC analysis indicated that FPF intensity is highly sensitive for detecting disease, particularly for exudative AMD subjects (0.989; 95% CI = 0.963 - 1.000, p=3.0 x 107). A significant difference was detected between the FPF intensity, FPF heterogeneity, and BCVA in all four disease states compared to unaffected controls (Kruskal-Wallis Tests, p = 1.06 x 10-8, p = 0.002, p = 5.54 x 10-8, respectively). Compared to healthy controls, FPF intensity values were significantly higher in RVO, DR, exudative AMD, and CSR (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). Spearman rank correlation coefficient between FPF intensity and BCVA was ρ = 0.595 (p = 9.62 x 10-10). Despite variations in structural retinal findings, FPF was found to be highly sensitive for detecting retinal disease. Significant FPF elevation were seen in all four disease states, with the exudative AMD patients exhibiting the highest FPF values compared to DR, CSR, and RVO subjects. This is consistent with the hypothesis that there is elevated oxidative stress in all of these conditions as previously demonstrated by blood studies. FPF intensity is moderately correlated with the late-in disease-marker BCVA, which suggests that the degree of FPF elevation can be used as a metabolic indicator of disease severity.

A novel wireless oxygen gas sensor based on silver film loaded on a patch antenna

In this work, a patch antenna loaded with sensitive silver film was employed for the detection of oxygen gas at high concentrations. SEM micrographs demonstrate that the morphology of the Ag film presents an elevated degree of porosity, confirming that the film is suitable for adsorbing O2 gas molecules on its surface. Numerical simulation performed was validated, and the values of the far-field parameters showed that the investigated device works efficiently as an antenna. During the tests carried out, it was observed that the device responds sensitively to the presence of oxygen gas demonstrating shifts of the antenna resonant frequency to higher values as a function of the O2 concentration. The antenna sensitivity was calculated, presenting a value of 0.14 MHz/O2% for the frequency at 5.968 GHz, 0.23 MHz/O2% for frequency at 8.246 GHz, and 0.15 MHz/O2% for the frequency at 10.039 GHz. Results obtained indicate that the patch antenna tested could be used as a sensor of oxygen gas in environments with elevated concentrations of this gas, such as oxygen concentrators and other medical equipment. Because the device analyzed is an antenna, it would be possible transmitting the sensing information to another device which would make it a potential candidate for application in healthcare monitoring.

Food Allergens and Essential Oils in Moisturizers Marketed for Children in Japan.

Introduction Personal skincare leave-on products increase the risk of food allergies. Parents must be imparted with an elevated degree of cognizance regarding the allergenic nature of pediatric skincare products. Material and methods We aimed to examine the data inferred from the promotional material on labeling these products about their proclivity to elicit skin sensitization. This study investigated the relationship between food allergens and essential oil ingredients and highlighted marketing terms, product prices, and ratings of moisturizers for children that are sold on Amazon, Japan. We searched and recorded the product labels and website marketing terms, price (per gram or milliliter), the number of reviews, and allergens and investigated the relationship between the percentage of food allergens in those products and marketing terms, price, and the number of Amazon reviews. Results Among the 164 pediatric skincare products we included, 144 (87.8%) that were manufactured in Japan were the most common; 7 (4.3%), 15 (9.1%), 23 (14.0%), 24 (14.6%), and 54 (32.9%) contained the eight regulated food allergens, grain, nut, fruit, and essential oils, respectively. Marketing terms emphasizing "natural/organic" were more likely to contain grain allergens and essential oils and were more expensive with and without "organic" labeling, respectively, whereas those labeled with marketing terms emphasizing "hypoallergenic" were less likely to contain fruit allergens or essential oils. Products with fewer Amazon reviews were more likely to use the marketing term "natural/organic" and had a higher grain allergen content. Conclusion In Japan, 4.3% of children's skincare products sold on Amazon contain eight food allergens that should obligatorily be labeled when included in food products. In addition, more than 10% of these children's skin care products contain ingredients derived from nuts, while more than 30% contain fruit extracts or essential oils.

Traits plasticity of Sodom Apple (Calotropis procera) along the environmental gradient in the semi-arid environment.

Biomass and morphological characteristics of plant species provide essential insight into how well a species adapts to its environment. The study aims to evaluate how environmental variables (viz., altitude, slope, aspect degree, and soil properties) influence the morphological traits and biomass variability of Calotropis procera (Aiton) W.T. Aiton in a semi-arid environment. C. procera sample locations were divided into 39 permanent sites (5×5 = 25 m2). Slope, aspect degree, slope aspect, altitude, and soil variables (soil moisture, organic matter, nitrogen (N %), and phosphorus (P) gradients were used to quantify morphological parameters (height, diameters, canopy area, volume, and leave/branch biomass) and aboveground biomass. Environmental variables, i.e., altitude and aspect degree, were the most important factor influencing the biomass variation and affecting soil moisture content; however, they did not directly affect the total biomass of the species. The results also reveal significant plasticity in morphological traits exists concerning elevation and aspect degree at (p< 0.05). Plant volume was a better indicator of species' total biomass revealed from the regression model showing significant at p< 0.05. The study also reveals that soil properties such as soil moisture and Phosphorus have an important role in enhancing the productivity of the studied plant species. The results concluded that plants functional traits and biomass shows significant variation across the altitude and these parameters could be consider in the conservation of this native species.

Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life.

Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown. We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish "T2-high" asthma or OVA combined with ozone exposure (OVA + ozone) to induce "T2-low" asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed. Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma. The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.

Phosphate Recovery from Aqueous Solutions via Vivianite Crystallization: Interference of FeII Oxidation at Different DO Concentrations and pHs.

Vivianite (Fe3(PO4)2·8H2O) crystallization has attracted increasing attention as a promising approach for removing and recovering P from wastewaters. However, FeII is susceptible to oxygen with its oxidation inevitably influencing the crystallization of vivianite. In this study, the profile of vivianite crystallization in the presence of dissolved oxygen (DO) was investigated at pHs 5-7 in a continuous stirred-tank reactor. It is found that the influence of DO on vivianite crystallization was highly pH-related. At pH 5, the low rate of FeII oxidation at all of the investigated DO of 0-5 mg/L and the low degree of vivianite supersaturation resulted in slow crystallization with the product being highly crystalline vivianite, but the P removal efficiency was only 30-40%. The removal of P from the solution was substantially more effective (to >90%) in the DO-removed reactors at pH 6 and 7, whereas the efficiencies of P removal and especially recovery decreased by 10-20% when FeII oxidation became more severe at DO concentrations >2.5 mg/L (except at pH 6 with 2.5 mg/L DO). The elevated degree of vivianite supersaturation and enhanced rate and extent of FeII oxidation at the higher pHs led to decreases in the size and homogeneity of the products. At the same pH, amorphous ferric oxyhydroxide (AFO)─the product of FeII oxidation and FeIII hydrolysis─interferes with vivianite crystallization with the induction of aggregation of crystal fines by AFO, leading to increases in the size of the obtained solids.

A double-NURBS approach to the generation of trochoidal tool path

Trochoidal milling becomes a popular strategy in high-speed rough milling, thanks to its advantages in lowering cutting force (and tool wear) and increasing tool life. However, it also suffers from the disadvantages of low cutting efficiency and prolonged machining time due to its reduced cutter-workpiece engagement in the cutting area and the idle tool path in the non-cutting area. In this paper, a new trochoidal tool path generation method is proposed based on a double-NURBS curve. Unlike traditional circular trochoidal tool path that combines circular and linear paths to approximate the trochoidal path, the double-NURBS tool path can truly represent a trochoidal path with C2 continuity throughout the entire tool path. In the front cutting area, the control points of the NURBS are modified to increase the cutter-workpiece engagement angles; in the rear non-active area, the NURBS curve is modified to shorten the non-cutting distance and the machining time. Degree elevation of the NURBS circle from 2 to 3 maintains C2 continuity to ensure the machining is smooth throughout all transitions. Cutting force simulations and pocket machining experiments are carried out to validate that the proposed double-NURBS approach deliver the expected result and performance.

Drug-Induced Liver Injury in Tuberculosis: Mechanisms of Development and Diagnostic Methods

The review article discusses modern aspects of drug-induced liver injury (DILI) in patients with tuberculosis who are receiving etiotropic therapy. The main mechanisms of DILI, including toxic and idiosyncratic types, are described, as well as their pathogenetic, biochemical, and epidemiological differences. DILI can manifest as various clinicomorphological forms of liver damage, such as steatosis and steatohepatitis, acute and chronic hepatitis, mitochondrial cytopathy, cholestasis, sclerosing cholangitis, vascular injury, and others. The main diagnostic method for DILI is the detection of liver enzymes - transaminases and alkaline phosphatase - based on the degree of elevation and their ratio, which identify two main types of liver injury - hepatocellular and cholestatic - as well as a mixed variant. The article provides a scoring assessment of liver damage in a patient receiving chemotherapy to classify it as drug-induced liver injury.

Nonalcoholic Fatty Liver Disease Is a Risk Factor for Thiopurine Hepatotoxicity in Crohn's Disease.

Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD. In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a Cox-proportional hazards model. Of the 311 CD patients studied, 116 (37%) were treated with thiopurines, 54 (47%) of which were found to have NAFLD. At follow-up, there were 44 total cases of elevated liver enzymes in those treated with thiopurines. Multivariable analysis demonstrated that NAFLD was a predictor of elevated liver enzymes in patients with CD treated with thiopurines (HR 3.0, 95% CI 1.2-7.3, P = .018) independent of age, body mass index, hypertension, and type 2 diabetes. Steatosis severity by PDFF positively correlated with peak alanine aminotransferase (ALT) at follow-up. Kaplan-Meier analysis demonstrated poorer complication-free survival (log-rank 13.1, P < .001). NAFLD at baseline is a risk factor for thiopurine-induced hepatotoxicity in patients with CD. The degree of liver fat positively correlated with the degree of ALT elevation. These data suggest that evaluation for hepatic steatosis be considered in patients with liver enzyme elevations with thiopurine therapy.