Disease Severity Index Research Articles

Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT‐V Study

ABSTRACTBackgroundThe accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH.AimsIn the US multicentre SHUNT‐V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy.MethodsSubjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut‐off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%.ResultsSHUNT‐V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child–Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%–100% for LEV and 97.3%–100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%–35% of EGDs could have been avoided with 0%–3.7% of LEV and 0%–2.7% of all significant PH lesions missed.ConclusionsHepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal‐systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child–Pugh A cirrhosis.Trial Registration: The SHUNT‐V study was registered at ClinicalTrials.gov (NCT03583996)

Efficacy of L-arabinose in managing cucumber Fusarium wilt and the underlying mechanism of action.

Cucumber Fusarium wilt (CFW), triggered by Fusarium oxysporum f. sp. cucumerinum, leads to substantial yield reductions in global cucumber (Cucumis sativus L.) production. Common management strategies for CFW include soil fumigation, grafting, and crop rotation. However, these methods have limitations regarding safety and efficacy stability, necessitating the development of new, cost-effective, and eco-friendly control strategies. Our prior research demonstrated that L-arabinose, an inexpensive and safe sugar commonly used in food and beverages, effectively suppressed bacterial wilt in tomatoes. This study explores the potential of L-arabinose in managing CFW and investigates its mechanism of action. Soil applications of L-arabinose, ranging from 0.00001 to 0.01%, effectively suppressed CFW. The most significant suppressive effect was observed at 0.01%, reducing the disease severity index by 67.5% compared to the control treatment. Microscopic examination of transverse root sections showed that pathogen hyphae colonized the epidermis but seldom penetrated the cortical layer of roots in L-arabinose-treated seedlings. In contrast, the entire root tissue of control seedlings was colonized by the pathogen. Quantitative real-time PCR revealed a significant increase in the expression of defense-related genes dependent on salicylic acid, jasmonic acid, and ethylene in L-arabinose-treated plants compared to control plants, 6 and 10 days post pathogen inoculation. This study demonstrated that soil application of L-arabinose can effectively suppress CFW by priming root tissues for multiple defense signaling pathways. Therefore, L-arabinose holds potential as a new fungicide for managing CFW. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Plasma neurofilament light chain in fibromyalgia: A case control study exploring correlation with clinical and cognitive features.

Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β-amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests. Plasma NFL levels were assessed in 33 FM patients and compared with 22 age-matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short-term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses. NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration. Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration. Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach.

Addressing data quality issues to assess clinical and epidemiological risk factors for COVID-19 among documented cases in Liberia: a single-centre, retrospective, observational study

IntroductionIdentification of risk factors for severe COVID-19 can help to inform case management in resource-constrained settings. We aimed to rigorously but retroactively address data issues to identify risk factors for...

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited. This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD. We conducted a retrospective multicenter study involving adult patients with moderate-to-severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. This first Spanish series assessing abrocitinib in real-world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well-tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD.

Allelopathic interactions of Carthamus oxyacantha, Macrophomina phaseolina and maize: Implications for the use of Carthamus oxyacantha as a natural disease management strategy in maize.

Fungicides are used to control phytopathogens but all these fungicides have deleterious effects. Allelopathic interactions can be harnessed as a natural way to control the pathogens but there are no reports that show the allelopathic interactions of donor plant, recipient crop, as well as the target plant pathogen and the material used for inoculum production. So, in the present study, the suitability of Carthamus oxyacantha M. Bieb. was assessed against Macrophomina phaseolina, the cause of charcoal rot in maize. Among the various treatments in pot experiment, a negative control, 3 concentrations of inoculum (1.2×105, 2.4×105, and 3.6×105 colony forming units (CFU) mL-1, 3 concentrations (0.5, 1.0, and 1.5% w/w) of C. oxyacantha along with an autoclaved M. phaseolina (Mp) and C. oxyacantha alone were included to investigate their allelopathic effects on maize, not investigated earlier. Maximum suppression of the disease was observed by 1.5% (w/w) concentration of C. oxyacantha. Soil amendment with C. oxyacantha significantly suppressed the disease incidence (DI) and disease severity index (DSI) in charcoal rot of maize up to 40 and 55%, respectively over the strongest level of inoculum (Mp3). C. oxyacantha not only reduced area under disease incidence progress curve (AUDIPC) and area under disease severity progress curve (AUDSPC), but also improved the morphological, biochemical and physiological parameters of maize. The maximum increase of 48, 65, and 75% in values of shoot length (SL), shoot dry mass (SDM), and root dry mass (RDM), respectively was observed by application of the highest concentration of C. oxyacantha in the treatment Mp1+Co3, over infested control (Mp1). Photosynthetic pigments, such as chlorophyll a, chlorophyll b and carotenoids were increased to 58, 64, and 46%, respectively over Mp1, by the application of C. oxyacantha. Carbon assimilation rate (A), stomatal conductance (gs), rate of transpiration (E), and internal carbon dioxide concentration (Ci) were significantly increased to 58, 48, 48, and 20%, respectively over infested control (Mp3), by application of C. oxyacantha concentration 1.5 (w/w). Moreover, defense enzymes like superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities were boosted up to 27, 28, and 28% over Mp3, respectively. Positive allelopathy of C. oxyacantha towards maize and negative allelopathy towards M. phaseolina makes C. oxyacantha a suitable candidate for charcoal rot disease control in maize.

Association of thyroid hormones with the severity of chronic kidney disease: a cross-sectional observational study at Tabuk, Saudi Arabia.

The interplay between chronic kidney disease (CKD) and thyroid dysfunction is becoming more evident in the biomedical community. However, the intricacies of their relationship warrant deeper investigation to understand the clinical implications fully. This study aims to systematically evaluate the correlation between thyroid hormone levels, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and markers of renal disease severity. These markers include serum creatinine, urea, and parathyroid hormone (PTH) levels in individuals diagnosed with CK). We conducted a cross-sectional observational study involving a cohort of 86 participants with CKD recruited from the renal clinic at King Fahad Hospital in Tabuk. Biochemical parameters, encompassing plasma electrolytes and thyroid hormone concentrations, were quantitatively assessed. These measurements were performed with the aid of a Roche Cobas E411 analyzer. The Pearson correlation coefficient was employed to delineate the strength and direction of the associations between the thyroid function markers and renal disease indicators. The statistical analysis highlighted a generally weak correlation between the concentrations of thyroid hormones and the indicators of renal disease severity, with Pearson correlation coefficients between -0.319 and 0.815. Critically, no significant correlation was found between creatinine and thyroid hormones (TSH, T3, T4), nor was any substantial correlation between urea and thyroid hormones. Conversely, a robust positive correlation was noted between the levels of parathyroid hormone and serum creatinine (r=0.718, p<0.001). The data suggests that thyroid hormone levels have a minimal correlation with the severity of renal disease markers. In contrast, the pronounced correlation between PTH and creatinine underscores the importance of considering PTH as a significant factor in managing and therapeutic intervention of CKD complications. These initial findings catalyze further research to thoroughly investigate the pathophysiological relationships and potential therapeutic targets concerning thyroid dysfunction in patients with renal impairment.

Identification and Functional Analysis of Git3 G Protein-Coupled Receptors in Ganoderma boninense PER71

G protein-coupled receptors (GPCRs) are integral components of eukaryotic heterotrimeric G proteins, playing crucial roles in detecting extracellular signals and initiating the activity of signaling proteins within cells to activate cellular responses to these signals. The objectives of this study are to identify and characterize the function of Git3, a Class III GPCR protein, in the oil palm pathogen Ganoderma boninense. To identify the potential genes encoded for GPCR in this fungus, intensive data mining on the genome and transcriptome data has been carried out. A total of six classes of GPCRs have been identified. These include Class II pheromone detectors, Class III carbon detectors, Class IV nitrogen detectors, Class VII proteins similar to glycosyltransferase, Class VIII proteins similar to hemolysin, and Class X protein receptors. Among these, the Class III protein Git3, postulated to be involved in glucose sensing and fungal pathogenicity, was selected for gene knockdown using RNA interference (RNAi). A plasmid, designated pUChph-GIT3, was constructed, to target git3 silencing by incorporating a hygromycin resistance gene cassette and antisense sequences of git3. Transformation of G. boninense PER71 with pUChph-GIT3 produced five potential Δgit3 gene-silenced mutants. PCR analysis confirmed the integration of the RNAi expression cassette into the fungal genome. Quantitative PCR (qPCR) analysis revealed significant reductions in git3 expression in three G. boninense mutants, M42, M66, and M5 by 47%, 23%, and 13%, respectively. The Disease Severity Index (DSI) indicated slower disease progression in oil palm plantlets infected with Δgit3 mutants compared to those infected with wild-type G. boninense PER71. In conclusion, this study successfully isolated and characterized the git3 GPCR from G. boninense and demonstrated that it might play a role during the early stages of infection, as the mutants were able to slow the progression of infection in oil palm plantlets.

Variation in Morphological Characteristic and Growth Rate of Isolated Dikaryotic Ganoderma boninense Mycelia on Nutrient Medium and Rubberwood Block: A Cue for Their Virulency

Undeniably, the formation of new Ganoderma variants within the plantation rapidly declines the life expectancy of oil palm trees. The produced variants induce severe infection on the palm, largely impeding disease management approaches to prevent infection. Selection of the high virulent of Ganoderma spp. affiliated with stem rot disease is crucial for assessing the planting material to identify either resistant or tolerant oil palm cultivars and optimise treatment strategies in line with species varieties. So far, the genetic diversity and virulency of these Ganoderma species in the IOI Group estate have not yet been explored. About seven basidocarps were collected from Ganoderma-infected palms and identified as Ganoderma boninense. The cultural traits of these nine isolates, including P4.1E and PER71 showed distinct phenotypical variations on potato dextrose agar (PDA). Though sequence analysis revealed four PM09C isolates were 100 per cent identical, incompatible reactions were observed among isolates, similar to other isolates from different fields. The mycelia rate expansion on the nutrient medium had a significantly correlated relationship to the disease incidence (DI) (r = 0.750), disease severity index (DSI) (r = 0.690) and death rate (DR) (r = 0.732). Overall, these findings contribute to the understanding of Ganoderma species in the estate and provide valuable insights for developing targeted management strategies in evaluating tolerant planting material for future replanting. Keywords: Ganoderma, oil palm, basal stem rot, genetic diversity, virulency.

Inoculation of Bacillus velezensis Bv-116 and its bio-organic fertilizer serve as an environmental friendly biocontrol strategy against cucumber Fusarium wilt.

The aim of this study was to evaluate the effects of Bacillus velezensis Bv-116 and its bio-organic fertilizer on the control of cucumber Fusarium wilt caused by Fusarium oxysporum f. sp. Cucumerinum (FOC), the promotion of growth of cucumber seedlings, and the soil microbial community. B. velezensis Bv-116 exhibited an inhibition rate of 84.93% against FOC, as well as broad-spectrum inhibitory activities against other soil-borne plant pathogenic fungi. Fermentation products of B. velezensis Bv-116 destroyed the cell structure of FOC and inhibited the growth of FOC mycelium. These products were identified as volatile antimicrobial gases, proteases and cellulases. In the greenhouse pot experiment, both B. velezensis Bv-116 and its bio-organic fertilizer exhibited significant promoting effects on cucumber growth, and a significant reduction in the incidence and disease severity index of cucumber wilt (p < 0.05). Analysis of the microbial community structure of cucumber rhizosphere soil revealed that inoculation of B. velezensis Bv-116 and its bio-organic fertilizer increased the abundance of genera with biocontrol capabilities against plant pathogens. In addition, inoculation of the bio-organic fertilizer reversed the excessive proliferation of Fusarium and Acidobacteria. Our results suggest the potential of inoculating B. velezensis Bv-116 and its bio-organic fertilizer as an environmentally friendly biocontrol strategy against cucumber wilt.

Assessing the Correlation Between Retinal Arteriolar Bifurcation Parameters and Coronary Atherosclerosis.

The aim of this study was to examine the relationship between the morphological parameters of retinal arteriolar bifurcations and coronary artery disease (CAD). In this cross-sectional observational study, fundus photography was conducted on 444 participants to capture retinal arteriolar bifurcations. A total of 731 fundus photographs yielded 9625 measurable bifurcations. Analyzed bifurcation parameters included the diameters of the parent vessel (d0), the larger branch (d1), and the smaller branch (d2), as well as the angles (θ1) and (θ2) representing the orientation of each branch in relation to the parent vessel, respectively. Additionally, theoretical optimal angles ( ) and ( ), calculated from the measured parameters, provided a benchmark for ideal bifurcation geometry. The study assessed the variation in these parameters across different levels of coronary atherosclerosis severity. After adjusting for anatomical characteristics including the asymmetry ratio, area ratio, and distance to the optic disc, we observed that patients with severe coronary artery stenosis had significant deviations from the theoretical optimal bifurcation angles, with a decrease in ( ) and an increase in ( ) compared to those with moderate stenosis. The findings suggest a clear alteration in retinal arteriolar bifurcation morphology among patients with severe CAD, which could potentially serve as an indicator of disease severity.

Reduced Sense of Smell in Patients with Severe Chronic Rhinosinusitis and its Implications for Diagnosis and Management: A Narrative Review.

Reduced sense of smell is a common symptom in patients with chronic rhinosinusitis (CRS). Although it is often under-diagnosed by healthcare providers, reduced sense of smell can have a substantial negative impact on patient's quality of life as measured by health-related quality of life (HRQoL) assessments and patient-reported outcomes. This narrative review describes current smell loss diagnosis and management guidelines in CRS, and the relationship between smell loss and CRS. Reduced sense of smell can be an indication of CRS disease severity in patients with (CRSwNP) and without nasal polyps (CRSsNP), and recovery of smell can be an indicator of successful CRS treatment. The current first-line therapeutic options for smell loss are intranasal corticosteroids and nasal irrigation, and second-line therapeutic options include systemic steroids and surgery. Shared decision-making between patient, caregiver, and healthcare provider is important when choosing the most appropriate CRS treatment option. Emerging biologic therapies that target type 2 inflammation signaling pathways, such as dupilumab, omalizumab, and mepolizumab, have been shown to improve smell and taste in randomized controlled trials of patients with CRSwNP.A graphical abstract and video abstract are available with this article.

Facilitating effects of plant extracts on soil health and replanted Panax ginseng growth in recession soil.

Plant extracts have been shown to be effective agricultural strategies for improving soil fertility and quality, and promoting plant growth in soil degradation remediation. The application of plant extracts improves the material cycle of soil microecology, such as the decomposition of nitrogen, phosphorus, and potassium, while increasing plant resistance. However, there is currently no experiment to demonstrate whether plant extracts have a promoting effect on the growth of ginseng and the mechanism of action. Pot experiments were carried out to investigate the effects of extracts, namely Rubia cordifolia (RC), Schisandra chinensis (SC), and Euphorbia humifusa (EH) on soil properties, enzyme activities, and plant physiological characteristics were evaluated. Results showed that compared with CK, plant extract-related treatments increased soil Organic carbon (OC), Available nitrogen (AN), Available phosphorus (AP) contents, and Soil urease activity. (S-UE), Soil sucrase activity (Soil sucrase), Soil acid phosphatase activity. (S-ACP). Meanwhile, plant extract-related treatments significantly increased plant physiological properties and TP (Total protein) content, and decreased the content of MDA (malondialdehyde) by 15.70% -36.59% and PRO (proline) by 30.13% -148.44%. Furthermore, plant extract-related treatments also significantly promote plant growth and reduce plant incidence, the fresh weight of ginseng increased by 27.80% -52.08%, ginseng root activity increased by 45.13% -90.07%, and ginseng incidence rate decreased by 20.00% -46.67%. Through correlation analysis between fresh weight of ginseng and root parameters and soil index, fresh weight is significantly positively correlated with root diameter, fiber root number, root activity, total protein (TP), catalytic activity (CAT) and superoxide dismutase activity (SOD), H, soil urea activity (S-UE), soil sucrose activity (S-SC), soil acid phosphate activity (S-ACP), and soil laccase activity (SL); The fresh weight was significantly negatively correlated with incidence rate, disease severity index, and malondialdehyde content (MDA). In summary, plant extract-related treatments improve soil quality and promote ginseng growth, further enhancing soil health and plant disease resistance. These findings provide new insights into ginseng cultivation and soil health management and highlight a new approach that can be applied to a wider range of agricultural practices and environmental sustainability.

Influence of Wheat Cultivars, Infection Level, and Climate after Anthesis on Efficacy of Fungicide for Control of Fusarium Head Blight in the Huang-Huai-Hai Plain of China

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, causes significant losses in grain yield and quality of wheat (Triticum aestivum) by inducing floret sterility. Grains become contaminated with mycotoxins, especially deoxynivalenol (DON), making them unsuitable for consumption. To clarify the impact of wheat cultivar resistance, infection level, and climate after anthesis on the efficacy of a fungicide for the control of FHB, we treated two moderately susceptible cultivars and 11 susceptible cultivars with fungicide (48% phenamacril + tebuconazole) at anthesis over two years. FHB incidence (INC), disease severity index (DSI), Fusarium-damaged kernels, DON contamination, thousand-kernel weight, and yield were evaluated under artificially inoculated and naturally infected field trials in 2018 and 2021. The results of multi-factor variance analysis show that the control efficacy with respect to INC and DSI is affected by cultivar, fungicide, infection level, and climatic conditions including the average daily temperature, average daily relative humidity, and total rainfall from anthesis to 21 days after anthesis (p &lt; 0.01). Notably, cultivar resistance (deviance = 13.34, 9.55, and 11.22) is more important than fungicide (deviance = 5.77, 6.66, and 6.69) to control the efficacy of INC, DSI, and DON. The results also suggest that infection level appears to be more important than cultivars and fungicide to control the efficacy of INC, and more important than fungicide to control the efficacy of DSI. Total rainfall is more important than other climatic factors. Our results reveal that fungicide is more effective in moderately susceptible cultivars (‘Zhengmai 9023’ and ‘Xinong 979’, 89.5%~98.9%) and some susceptible cultivars than in other susceptible cultivars (‘Zhengmai 7698’ and ‘Zhoumai 27’, 51.9%~67.2%). Thus, integrating cultivar resistance with fungicide application can be an effective strategy for the management of FHB and DON in winter wheat in the Huang-huai-hai Plain of China.

Anti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity. Four cohorts of pre-liver transplant PSC patients were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HC) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Olink® inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity. A total of 137 PSC patients (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD) and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HC) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared to PSC alone (p<0.0001 and 0.003) and HC (p<0.0001 and p<0.0001). However, anti-αvβ6 levels in PSC alone were not increased compared to HC. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity including alkaline phosphatase level (r=0.32, p=0.004), the revised Mayo PSC risk score (r=0.25, p=0.02) and liver stiffness measurement (r=0.43, p=0.008) after adjusting for age, gender, race/ethnicity and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling. Anti-αvβ6 autoantibodies identify a subset of PSC patients with concomitant IBD.

The Role of Serum Level of Col2a1 and Hyaluoronic Acid in Diagnosis of Knee Osteoarthritis

Osteoarthritis (OA) is a complex condition in which affected tissues experience changes in metabolism, structure, biochemistry, and function. This condition arises when chondrocytes fail to balance the synthesis and degradation of extracellular components like proteoglycans and collagens, leading to inflammation of the synovial membrane and joint capsule. Aim of the study: This study was designed to evaluate the serum levels of Type II Collagen alpha 1 (coll2a1) and Hyaluronic Acid (HA) in diagnosis of early stage of knee osteoarthritis in Iraqi patients Subjects and Methods: This case- control study was carried out at Department of Biochemistry, College of Medicine, University of Baghdad and at Rheumatology Department , Baghdad Hospital / Medical City, during the period from September 2022 to March 2023. It included ninety volunteer males and females subdivided into subgroups: Group 1consisted of 50 patients who have had early stages of knee osteoarthritis (KOA) and group 2 involved 40 apparently healthy subjects who served as control group. The diagnosis of KOA was made by a consultant rheumatologist using American College of Rheumatology (ACR) criteria. Moreover, patients were sub- classified according to their BMI (normal weight, overweight and obese) and KOA severity (grad1 and grad 2). Investigations included serum measurements of Human serum coll2a1( type II collagen alpha I) and Human serum HA (Hyaluronic Acid) in all patients and controls by ELISA technique. Results: The mean (±SD) values of Coll2a1, HA, of KOA patients were significantly higher than those of controls (for all, p &lt;0.01). There was significant positive correlation between. The mean value of serum hyaluronic acid was significantly increased in grad 2 KOA when compared with grad 1 KOA patients (p &lt; 0.004). The results found that fibulin-3 has the highest receiver operator characteristic (ROC) and area under curve (AUC=89.2% ) at cutoff (7.50 ng/ml) with sensitivity 80.0 and specificity 80.0 in diagnosis of KOA. Also, serum Coll2a1 has high diagnostic utility (AUC=88.6%) at cutoff (286.00 pg/ml) with sensitivity 82.0 and specificity 80.0 . Conclusion: Assessing non-invasive serum levels of coll2a1 (with a cutoff of 286.00 pg/ml) offers a new biochemical marker for diagnosing the early stages of knee osteoarthritis (KOA) potentially before changes become visible on X-rays. Additionally, measuring serum hyaluronic acid levels could serve as an indicator of disease severity, helping to differentiate between various grades of KOA.

Evaluation of a New Diabetes Mellitus Index Based on Measurements Using the Scheimpflug Analyzer Corvis ST.

Chronic hyperglycemia causes changes in corneal biomechanics that can be measured with the Scheimpflug Analyzer Corvis ST. The diagnostic reliability of the new diabetes mellitus (DM) index developed based on this should be evaluated. In a prospective cross-sectional study, the index was initially developed using data from 81 patients with DM and 75 healthy subjects based on logistic regression analysis. The reliability of the DM index was subsequently assessed using data from another 61 patients and 37 healthy individuals. In addition, the dependence of the DM index on indicators of disease severity was analyzed. The index initially achieved a sensitivity of 79% and specificity of 80% with a cutoff value of 0.58. The evaluation showed a sensitivity of 67% and specificity of 76% with an optimized cutoff of 0.51 (area under the curve = 0.737, P < 0.001). The DM index correlated weakly with the severity of diabetic retinopathy (r = 0.209, P = 0.014). It was increased in the presence of diabetic maculopathy (P = 0.037) and in type 1 DM compared with patients with type 2 disease (P = 0.039). In this first evaluation, the new DM index achieved sufficiently good sensitivity and specificity and was weakly associated with disease-specific factors. With further improvements, it could complement the diagnostic options in DM with a simple, rapid, and noninvasive assessment method.

Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP). To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC). In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated. UC patients had 4- and 3.7-times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (-0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (-0.64), albumin (-0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (-0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05. Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.

The Pulmonary Artery Pulsatility Index Provides No Additional Prognostic Information in Pediatric Pulmonary Arterial Hypertension.

The pulmonary artery pulsatility index (PAPi, calculated as (SPAP - DPAP)/mRAP) has been suggested as a measure of right ventricular-vascular coupling (RVVC) and as a prognostic parameter in cardiovascular conditions, particularly right ventricular failure. This retrospective study investigated the relationship between the PAPi and its components with disease severity parameters, the RVVC, and clinical outcomes in children with pulmonary arterial hypertension (PAH). We analyzed data from 111 children from the Dutch National Registry with PAH. The PAPi (median 6.0 [3.9-8.3]) was calculated from heart catheterization data and the RVVC was determined as the TAPSE/sPAP ratio via echocardiography (0.25 ± 0.12 mm/mmHg). Disease severity was characterized by clinical, hemodynamic, and laboratory data. Cox proportional hazard modeling assessed the PAPi's predictive value for transplant-free survival. There was no correlation between the RVVC and PAPi (R = -0.208, p = 0.111, n = 60). The PAPi correlated negatively with uric acid (R = -0.387, p < 0.001) but not with other disease severity parameters. Mean right atrial pressure correlated with multiple disease severity indicators. Transplant-free survival rates at 1, 3, and 5 years were 87%, 79%, and 73%, respectively. Neither the PAPi nor its components correlated with transplant-free survival. In conclusion, the PAPi does not correlate with the RVVC and this study could not demonstrate any prognostic value of the PAPi regarding disease severity or outcomes in children with PAH, challenging its utility in this population.

Exploring the relationship between cycle threshold values and oral manifestations in COVID-19: a comprehensive overview.

This cross-sectional study aimed to compare oral manifestations between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-positive and SARS-CoV-2-negative patients and to examine associations between oral symptoms, Ct values of E and N SARS-CoV-2 viral genes, and the implications of low Ct values indicating a high viral load, which is a predictive factor for the outcome of COVID-19. A total of 353 participating patients were aged ≥18 years with clinical manifestations of COVID-19 infection and tested for SARS-CoV-2 carriage at the medical center, by reverse transcriptase polymerase chain reaction (RT-PCR). All patients filled out an anonymous digital questionnaire regarding oral and general symptoms and overall medical health. Results: A significant association was found between SARS-CoV-2 carriage and dry mouth, unpleasant taste and changes in taste (p < 0.001); for example, 37.4% of the 147 SARS-CoV-2- positive participants had a dry mouth, compared to 18.9% of the 206 SARS-CoV-2- negative participants. Oral blisters were experienced by patients with an E gene Ct value of 10-20 (50%) or 21-30 (50%) (p = 0.041). Bad breath, dry mouth, unpleasant taste and changes in taste were mostly present in participants whose Ct values of both E and N genes were between 21 and 30. Conclusions: This study found significant associations between low Ct values of E and N SARS-CoV-2 viral genes and high viral load, indicating that Ct values can serve as predictive factors for COVID-19 outcomes. The findings suggest that while oral symptoms are present, the Ct values and associated high viral loads are more critical indicators of disease severity and prognosis.