Disease Severity Research Articles

Factors Associated with Upper Extremity Functionality After Mini-Open Release Surgery for Treatment of Carpal Tunnel Syndrome

Aim: The objective of this study was to investigate the correlation between upper extremity functionality, pain intensity, muscle strength, and symptom severity among patients diagnosed with carpal tunnel syndrome (CTS) who underwent mini-open release surgery. Material and Method: This retrospective study entailed the review of medical records of 70 patients diagnosed with CTS who underwent mini-open release surgery between January 2021 and January 2023. Data were collected from preoperative assessments and routine follow-up evaluations conducted at 3 months post-surgery. Upper extremity functionality was assessed utilizing the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, pain severity was determined using the Visual Analog Scale (VAS), muscle strength was evaluated through hand grip strength, and disease severity was measured using the Boston Carpal Tunnel Questionnaire (BCTQ). Results: A statistically significant improvement was observed in DASH questionnaire scores, VAS scores, hand grip strength, and BCTQ scores at the 3-month follow-up compared to preoperative values (p

Upregulation of psoriasin/S100A7 correlates with clinical severity in patients with oral lichen planus

ObjectivesThe aim of this study was to: (1) investigate the expression patterns of antimicrobial peptides (AMPs), specifically psoriasin (S100A7) and calgranulin A and B (S100A8/A9), in patients with oral lichen planus (OLP) compared to healthy individuals; (2) evaluate the oral health-related quality of life (OHrQoL) in OLP patients versus healthy controls; (3) investigate the impact of clinical severity of OLP on OHrQoL; and (4) assess the influence of AMP expression on clinical severity and OHrQoL in OLP patients.Materials and methodsOral mucosal biopsies (n = 38) were collected from healthy individuals (n = 17) and patients with OLP (n = 21). Levels of AMPs (S100A7, S100A8, S100A9) and pro-inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) were assessed by RT-qPCR. AMP protein localization was identified by indirect immunofluorescence analysis. OHrQoL was assessed using the OHIP-G14 questionnaire, and clinical severity was evaluated with the Oral Disease Severity Score (ODSS). Correlations between OLP manifestation, OHrQoL, and AMP expression were evaluated.Results(1) S100A7 (p < 0.001), IL-8 (p < 0.001), and TNFα (p < 0.001) mRNA levels were significantly upregulated in OLP tissue compared to healthy tissue, while S100A8 (p < 0.001) and S100A9 (p < 0.001) mRNA levels were downregulated. Immunofluorescence staining revealed an enhanced expression of S100A7 and decreased protein expression of S100A9 in OLP tissue. (2) OLP patients (9.58 ± 8.32) reported significantly higher OHIP-G14 scores compared to healthy individuals (0.67 ± 0.87; p < 0.001), particularly in the categories “physical pain” (p < 0.001) and “psychological discomfort” (p = 0.025). (3,4) Clinical severity (25.21 ± 9.77) of OLP correlated positively with OHrQoL (ρ = 0.497) and psoriasin expression (ρ = 0.402).ConclusionsThis study demonstrated differential expression patterns of AMPs in OLP and highlighted the correlation between the clinical manifestation of OLP and OHrQoL. Further research approaches should address the role of psoriasin in the risk of malignant transformation of OLP.Clinical relevancePsoriasin is a putative biomarker to monitor disease severity including malignant transformation of OLP lesions. OHIP-G14 scores can be useful to monitor OHrQoL in OLP patients.

Management and Long-Term Outcomes of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Drug reaction with eosinophilia and systemic symptoms (DReSS) is known to cause mortality and long-term sequelae in the pediatric population, however there are no established clinical practice guidelines for the management of pediatric DReSS. We conducted a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the currently available data on treatment, mortality, and long-term sequelae of DReSS in children (aged 0-18 years). Data from 644 individuals revealed that various treatment strategies are being used in the management of pediatric DReSS, and strategies were often used in combination. The diversity in treatment approaches cannot be solely attributed to age or disease severity and reflects the lack of evidence-based management guidelines for DReSS. Children are also at risk of developing autoimmune sequelae following DReSS, most commonly thyroid disease and type 1 diabetes mellitus. We found that the eventual development of autoimmune disease was more often associated with DReSS caused by antibiotics, especially minocycline and sulfamethoxazole, in comparison with individuals who did not develop sequelae. In this study, we identify strengths and weaknesses in the currently available literature and highlight that future prospective studies with structured and long-term follow-up of children with DReSS are needed to better understand potential risk factors for mortality and development of sequelae after DReSS.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism

IntroductionCoronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles.MethodsAdult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID).ResultsTwo women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2).ConclusionGene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid’s ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.

Winter Durum Wheat Disease Severity Detection with Field Spectroscopy in Phenotyping Experiment at Leaf and Canopy Level

Accurate disease severity assessment is critical for plant breeders, as it directly impacts crop yield. While hyperspectral remote sensing has shown promise for disease severity assessment in breeding experiments, most studies have focused on either leaf or canopy levels, neglecting the valuable insights gained from a combined approach. Moreover, many studies have centered on experiments involving a single disease and a few genotypes. However, this approach needs to accurately represent the challenges encountered in field conditions, where multiple diseases could occur simultaneously. To address these gaps, our current study analyses a combination of diseases, yellow rust, brown rust, and yellow leaf spots, collectively evaluated as the percentage of the diseased leaf area relative to the total leaf area (DA) at both leaf and canopy levels, using hyperspectral data from an ASD field spectrometer. We quantitatively estimate overall disease severity across fifty-two winter durum wheat genotypes categorized into early (medium milk) and late (late milk) groups based on the phenophase. Chlorophyll content (CC) within each group is studied concerning infection response, and a correlation analysis is conducted for each group with nine vegetation indices (VI) known for their sensitivity to rust and leaf spot infection in wheat. Subsequent parametric (linear and polynomial) and nonparametric (partial least squares and kernel ridge) regression analyses were performed using all available spectral bands. We found a significant reduction in Leaf CC (&gt;30%) in the late group and Canopy CC (&lt;10%) for both groups. YROI and LRDSI_1 are the VIs that exhibited notable and strong negative correlations with Leaf CC in the late group, with a Pearson coefficient of −0.73 and −0.72, respectively. Interestingly, spectral signatures between the early and late disease groups at both leaf and canopy levels exhibit opposite trends. The regression analysis showed we could retrieve leaf CC only for the late group, with R2 of 0.63 and 0.42 for the cross-validation and test datasets, respectively. Canopy CC retrieval required separate models for each group: the late group achieved R2 of 0.61 and 0.37 (cross-validation and test), while the early group achieved R2 of 0.48 and 0.50. Similar trends were observed for canopy DA, with separate models for early and late groups achieving comparable R2 values of 0.53 and 0.51 (cross-validation) and 0.35 and 0.36 (test), respectively. All of our models had medium accuracy and tended to overfit. In this study, we analyzed the spectral response mechanism associated with durum wheat diseases, offering a novel crop disease severity assessment approach. Additionally, our findings serve as a foundation for detecting resistant wheat varieties, which is the most economical and environmentally friendly management strategy for wheat leaf diseases on a large scale in the future.

Comparative analysis of dynamic transcriptomes reveals specific COVID-19 features and pathogenesis of immunocompromised populations.

A majority of previous studies focused on the characterization of coronavirus infectious disease 2019 (COVID-19) disease severity in people with normal immunity, while the characterization of COVID-19 in immunocompromised populations is still limited. Our study profiles changes in the transcriptome landscape post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hematological tumor patients and non-tumor individuals. Furthermore, our integrative and comparative systems biology analysis of the interactome, complexome, and transcriptome provides new insights into the tumor-specific pathogenesis of COVID-19. Our findings confirm that SARS-CoV-2 potentially tends to target more non-functional host proteins to indirectly affect host immune responses in hematological tumor patients. The identified unique genes, complexes, functions/pathways, and expression patterns post-SARS-CoV-2 infection in patients with hematological tumors increase our understanding of how SARS-CoV-2 manipulates the host molecular mechanism. Our observed differential genes/complexes and clinical indicators of normal/long infection and deceased COVID-19 patients provide clues for understanding the mechanism of COVID-19 progression in hematological tumors. Finally, our study provides an important data resource that supports the increasing value of the application of publicly accessible data sets to public health.

Role of ethanolamine utilization and bacterial microcompartment formation in Listeria monocytogenes intracellular infection.

Ethanolamine (EA) affects the colonization and pathogenicity of certain human bacterial pathogens in the gastrointestinal tract. However, EA can also affect the intracellular survival and replication of host cell invasive bacteria such as Listeria monocytogenes (LMO) and Salmonella enterica serovar Typhimurium (S. Typhimurium). The EA utilization (eut) genes can be categorized as regulatory, enzymatic, or structural, and previous work in LMO showed that loss of genes encoding functions for the enzymatic breakdown of EA inhibited LMO intracellular replication. In this work, we sought to further characterize the role of EA utilization during LMO infection of host cells. Unlike what was previously observed for S. Typhimurium, in LMO, an EA regulator mutant (ΔeutV) was equally deficient in intracellular replication compared to an EA metabolism mutant (ΔeutB), and this was consistent across Caco-2, RAW 264.7, and THP-1 cell lines. The structural genes encode proteins that self-assemble into bacterial microcompartments (BMCs) that encase the enzymes necessary for EA metabolism. For the first time, native EUT BMCs were fluorescently tagged, and EUT BMC formation was observed in vitro and in vivo. Interestingly, BMC formation was observed in bacteria infecting Caco-2 cells, but not the macrophage cell lines. Finally, the cellular immune response of Caco-2 cells to infection with eut mutants was examined, and it was discovered that ΔeutB and ΔeutV mutants similarly elevated the expression of inflammatory cytokines. In conclusion, EA sensing and utilization during LMO intracellular infection are important for optimal LMO replication and immune evasion but are not always concomitant with BMC formation.IMPORTANCEListeria monocytogenes (LMO) is a bacterial pathogen that can cause severe disease in immunocompromised individuals when consumed in contaminated food. It can replicate inside of mammalian cells, escaping detection by the immune system. Therefore, understanding the features of this human pathogen that contribute to its infectiousness and intracellular lifestyle is important. In this work we demonstrate that genes encoding both regulators and enzymes of EA metabolism are important for optimal growth inside mammalian cells. Moreover, the formation of specialized compartments to enable EA metabolism were visualized by tagging with a fluorescent protein and found to form when LMO infects some mammalian cell types, but not others. Interestingly, the formation of the compartments was associated with features consistent with an early stage of the intracellular infection. By characterizing bacterial metabolic pathways that contribute to survival in host environments, we hope to positively impact knowledge and facilitate new treatment strategies.

RESIDUAL CARDIOVASCULAR RISK AND SEVERITY OF CORONARY DISEASE

Abstract Background The presence of residual risk in patients with a history of atherosclerotic cardiovascular disease (ASCVD) is a cause of additional cardiovascular events. The aim of this study is to correlate residual cardiovascular risk with the severity of coronary disease. Methods We enrolled 52 patients hospitalized with a diagnosis of acute coronary syndrome from September to October 2023 at the Clinical and Rehabilitation Cardiology of the San Filippo Neri Hospital. All patients were treated with percutaneous and/or surgical coronary revascularization and had a history of ASCVD. Thirty of these patients had a single–vessel coronary disease and 22 had a multivessel coronary disease. We analyzed the main cardiovascular risk factors and the received therapies in both groups. Results Triglyceride levels were significantly higher in the group with a multivessel coronary disease (132.94 ± 65.41 mg/dl vs 94.06 ± 37.63 mg/dl; p=0.01) as well as the levels of glycated hemoglobin (50.91 ± 15.23 mmol/mol vs 42.92 ± 6.65 mmol/mol; p=0.01) and high–sensitivity C–reactive protein (hs–CRP, 1.25 ± 1.48 mg/dl vs 0.65 ± 0.46 mg/dl; p=0.04). We found no significant differences between the two groups for the other main cardiovascular risk factors and the therapies. Conclusions Our data show that higher levels of triglycerides, glycated hemoglobin and hs–CRP, an inflammatory biomarker, are associated with a more extensive coronary disease. This finding suggests that a better metabolic control, in terms of glycated hemoglobin and triglyceride levels, and inflammation could contribute to the reduction of coronary disease extension.

LIFETIME MANAGEMENT OF AORTIC STENOSIS IN EXTREME SETTING

Abstract A 51–year–old male patient returned to our attention due to symptomatic severe aortic stenosis. Despite the severity of the aortic valve disease, he had been previously turned down from aortic valve replacement by us because of lack of symptoms and very unfavorable anatomy. Indeed he had been irradiated at the age of 3 due to Hodgkin’s Lymphoma and presented with porcelain aorta, small ascending aorta and aortic annulus. The patient returned to us with a 3–month history of progressive dyspnea (NYHA class IIa) and one episode of lipothymia during physical exercise. Physical examination, hematologic and biochemical investigations at admission were normal. Our trans–thoracic echocardiogram confirmed a trileaflet aortic valve (AV) that was severely stenotic and calcified with a mean gradient of 60 mmHg and an AV area of 0.5 cm2 (0.3 cm2/m2), in presence of good left ventricular systolic function with an ejection fraction (EF) of 60%. CT excluded coronary disease but, confirmed severe calcified aortic stenosis and porcelain aorta with small calcific sino–tubular junction and ascending aorta and protruding LVOT calcium. (Ascending aorta 19 mm; STJ 19 mm). The heart–team judged the patient not suitable for AVR and decided to perform a high–risk TAVI, leaving apical conduit as the last resort. From a technical standpoint, the LVOT calcium and the short and narrow STJ were high risk features for rupture with balloon expandable devices. On the other hand the short and narrow STJ with the narrow ascending aorta would represent a serious issue for the expansion of self–expanding devices and an even more troublesome feature for future coronary access and coronary occlusion in the setting of TAVI–in–TAVI down the road. Given the patient’s young age, a balloon expandable SAPIEN ultra 23 mm was chosen to be implanted with a two–step inflation to minimize the risk of STJ rupture. The prosthesis was partially expanded until anchoring was achieved on the aortic leaflets then, on continuous pacing, the balloon was rapidly collapsed, pushed down deeper under the STJ and fully inflated to achieve prosthesis’ inflow expansion. Intra–procedural and post–procedural course were uneventful and the patient was discharged home in 5th Day. Transthoracic echocardiogram at the dismission reveal a trans–aortic mean gradient of 18 mmhg, the absence of significant paravalvular leaks and a preserved ejection fraction. Pre–discharge CT scan confirmed feasibility of future TAVI–in–TAVI in case of need.

"UNUSUAL" ATRIAL FLUTTER: A CASE REPORT

Abstract A 64–years old male patient was admitted in the Emergency Department with signs of heart failure in a setting of dilated hypokinetic cardiomyopathy with severe depression of left ventricular ejection fraction and no severe coronary artery disease. In the previous medical history: systemic arterial hypertension, obesity, dysthyroidism due to amiodarone, history of atrial fibrillation treated by transcatheter ablation in the left atrium with pulmonary veins isolation (PVI) and the creation of an anterior line in 2010. The ECG documented an atrial flutter rhythm 2:1 probably typical (Fig. 1). An indication was therefore made for hospitalization in Cardiology. After the restoration of a good hemodynamic state, given the persistence of the atrial tachyarrhythmia, an indication for transcatheter ablation was formulated. The electrophysiological study highlighted an activation sequence suggestive of typical common flutter (cranial–caudal right atrial activation; proximal–distal left atrial activation). We then proceeded to ablate the cavo–tricuspid isthmus without interrupting the arrhythmia. Therefore, left and right atrial electroanatomical mapping was performed which confirmed the right isthmic block and documented the left origin of the flutter, showing conduction gaps in the ostia of the pulmonary veins and in the previous anterior ablation line between the mitral annulus and the right superior pulmonary vein (RSPV) (Fig 2,3). Ablation of these gaps effectively stopped the arrhythmia. At the end of the procedure, after stimulation via atrial bursts of up to 200 msec there was no induction of arrhythmias. One month after the procedure, there was an improvement in the contractile function of the left ventricle. Discussion: This clinical case offers us an example of how the analysis of the surface ECG alone is not sufficient to adequately describe the complexity of the arrhythmic substrate characterizing an arrhythmia such as atrial flutter or atrial fibrillation. The electrophysiological study through electroanatomical reconstruction of endocavitary activation proves indispensable for the correct identification and consequent treatment of these complex arrhythmias, with clear clinical benefits for the patient.

REVASCULARIZATION WITHOUT DES: A CASE REPORT ABOUT METALLIC–LESS REVASCULARIZATION TECHNIQUES

Abstract Rational 56 years old patient, admitted to our service for myocardial infarction without ST elevation. In medical history he had dyslipidaemia, hypertension and familiarity for cardiovascular disease, without previous cardiological problems. The patient went to the ER for chest pain, started after his work shift. When admitted to the ER, the patient was still symptomatic for chest pain, with resolution after 3 hours after somministration of analgesics, with normal pressure and heart rate. An ECG was performed, without relevant findings, at the blood exams significative movement of cardiac troponins. At the echocardiogram apical hypokinesia of left ventricle with preserved ejection fraction. Technical Resolution Coronarography was performed, with evidence of severe diffuse atheromatic disease of the left anterior descending artery (LAD) at the proximal segment and sub–occlusive stenosis at the middle segment. Due to the diffuseness of the atherosclerotic disease on the LAD, which would have required a complete stenting of the artery, which using classical Drug Eluted Stents would have led to a complete metallization of the artery, in such a young patient who does not have medical history suggesting a progression of the atheromatic disease, metallic–less techniques were chosen. The two lesions were pre–dilatated with a non–compliant (NC) balloon. The proximal lesion was treated with a bioresorbable scaffold (BVS) Magmaris 3x25 mm, post–dilatated with a NC balloon, without complications. The distal segment was treated with a Drug Eluting Balloon (DEB) Pantera Lux 2.5x20 mm, expanded for 90 seconds, with evidence of focal dissection, not flow limiting.At the clinical follow–up performed at one and three months, the patient was asymptomatic for angina, without any cardiovascular event. Clinical Implications When facing coronaropathy in a young patient, it is a good option to treat the coronary with techniques that do not leave metallic material in the arteries, which exposes young patients to a higher rate of complications if compared to older patients. When it is preferred to use this kind of techniques, the options can be DEB or BVS. As seen in this case report, often the DEB can lead to complications. It’s well–known that every DEB complication needs a DES to fix it. However, little is proven and studied about the use of BVS on de–novo lesions and on coronary injuries as complications of “conventional” PCI, as well as those derived from DEB delivery.

THE “BACK TO THE FUTURE” OF CARDIOTHORACIC SURGERY: HIGH–RISK INTERVENTIONAL PROCEDURE TURNED DOWN TO CONVENTIONAL CARDIAC SURGERY

Abstract Background Structural interventional cardiology has been introduced at the beginning of our century to address high–risk patient suffering from severe aortic stenosis. Since then several technique and technology have been proposed to address an increasing population of patients and mitral valve diseases have been also addressed. While several authors are pushing up the indications for structural interventional procedures, however, we are experiencing some situations were conventional surgery is considered an alternative to high risk interventional procedures. Here we present a peculiar case of “back to the future” in cardiothoracic surgery. Case Description A 76 yo female patient, was referred to our Division from a peripheral Hospital suffering from severe aortic stenosis and coronary artery diseases. Medical history of the patient included persistent AF, COPD, arterial peripheral vascular disease, moderate chronic renal insufficiency and moderate dilatation of ascending aorta. Patient was previously assessed by another Centre and a percutaneous treatment (PTCA+TAVI) was proposed. Due to further admission for cardiac failure–related symptoms, however, patient was urgently referred to our Division. Fig 1 and 2 summarized clinical findings. “Heart team” evaluation, based also on the product specialist evaluation, considered the patient not suitable for interventional procedure due to the high risk of sub–optimal medium–term prognosis. Due to further clinical deterioration an extremely high–risk surgical procedure was mandatory. Results Surgical procedure included a sutureless aortic valve replacement, a MV plasty, a double coronary graft + a cpmbined carotid endoarterectomy. Postoperative course was free from significant complications and the patient was discharged to rehabilitation clinic on 15th postoperative days. Conclusion Despite interventional procedure are continuing to increase either as number of procedure either as complexity of diseases treated, conventional cardiac surgery remains still the only option for treatment in many clinical scenario. As a sort of “back to the future” situation, patient originally referred for interventional procedures are turned down due to the high risk of sub–optimal results. In such condition conventional cardiac surgery, performed with high level of accuracy could represent the last and only treatment option for high risk patients.

Increased frequencies of highly activated regulatory T cells skewed to a T helper 1-like phenotype with reduced suppressive capacity in dengue patients.

According to the World Health Organization, dengue is the fastest-spreading, epidemic-prone infectious disease. The extent of dengue virus infections increased over the years, mainly driven by globalization-including travel and trade-and environmental changes. Dengue is an immunopathology caused by an imbalanced immune response to a secondary heterotypic infection. As regulatory T cells (Tregs) are essential in maintaining immune homeostasis and dampening excessive immune activation, this study addressed the role of Tregs in dengue immunopathology. We show that Tregs from dengue patients are highly activated, skewed to a Th1-like Treg phenotype and less suppressive compared to healthy donor Tregs. Our data suggest that Tregs fail to resolve ongoing inflammation during dengue infection and hence contribute to the immunopathology of severe dengue disease. These data clarify the role of Tregs in dengue immunopathogenesis, emphasizing the need to develop T cell-based vaccines for dengue.

Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness

Critical illness and sepsis may cause organ failure and are recognized as mortality drivers in hospitalized patients. Neuropilin-1 (NRP-1) is a multifaceted transmembrane protein involved in the primary immune response and is expressed in immune cells such as T and dendritic cells. The soluble form of NRP-1 (sNRP-1) acts as an antagonist to NRP-1 by scavenging its ligands. The aim of this study was to determine the value of sNRP-1 as a biomarker in critical illness and sepsis. We enrolled 180 critically ill patients admitted to a medical intensive care unit and measured serum sNRP-1 concentrations at admission, comparing them to 48 healthy individuals. Critically ill and septic patients showed higher levels of sNRP-1 compared to healthy controls (median of 2.47 vs. 1.70 nmol/L, p &lt; 0.001). Moreover, sNRP-1 was also elevated in patients with sepsis compared to other critical illness (2.60 vs. 2.13 nmol/L, p = 0.01), irrespective of disease severity or organ failure. In critically ill patients, sNRP-1 is positively correlated with markers of kidney and hepatic dysfunction. Most notably, critically ill patients not surviving in the long term (one year after admission) showed higher concentrations of sNRP-1 at the time of ICU admission (p = 0.036), with this association being dependent on the presence of organ failure. Critically ill and septic patients exhibit higher serum concentrations of circulating sNRP-1, which correlates to organ failure, particularly hepatic and kidney dysfunction.

Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review

The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions. Here we review many emerging NMOSD biomarkers including markers of cellular damage, neutrophil-to-lymphocyte ratio, complement, and cytokines, with a focus on how each biomarker can potentially be used for initial diagnosis, relapse surveillance, disability prediction, and treatment monitoring.

Optimizing maintenance therapy in responders to abrocitinib induction: A post hoc analysis of JADE REGIMEN.

Treatment optimization may require dosing flexibility. The Phase 3 JADE REGIMEN trial (NCT03627767) evaluated maintenance of abrocitinib 200 mg-induced response in patients with moderate-to-severe atopic dermatitis (AD) randomly assigned to subsequent maintenance with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg) or placebo. Maintenance with continuous-dose abrocitinib was associated with a stronger prevention of disease flares, but also with a higher occurrence of adverse events, compared with the reduced dose. This post hoc analysis of JADE REGIMEN aimed to identify predictors of not flaring during the maintenance period and to generate tools that can be used to assess probability of not flaring. Data were analysed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 mg or 100 mg) or placebo in the 40-week maintenance period. Demographic and baseline disease characteristics and level of response to induction were evaluated for association with not flaring using logistic regression. Parameters with a significant (p < 0.15) interaction with the treatment arm were fitted into a multivariable regression model, which was used to assess probability of not flaring. Lower percentage body surface area affected at baseline (p = 0.09), absence of prior exposure to systemic agents (p = 0.02) and greater percentage change in EASI from baseline to randomization (p < 0.001) were identified as predictors of not flaring with abrocitinib. In both abrocitinib arms, percentage change in EASI from baseline to end of induction (Week 12) was the major contributor to the probability of not flaring in the maintenance period. Maintenance of response using reduced-dose abrocitinib 100 mg may be feasible for patients with lower baseline disease severity and strong response to abrocitinib 200 mg induction treatment.

Identification of Curvularia eragrostidis (Henn.) J.A.Mey. the Leaf Spot Pathogen of Oil Palm (Elaeis guineensis Jacq.) and It’s Control by False Elder (Peronema canescens Jack) Leaf Extract

Oil palm is the main vegetable oil-producing crop in Indonesia. Leaf spot disease is one of the major diseases that attacks oil palm seedlings at all seedling stages. In Indonesia, leaf spot disease in oil palm nurseries is most commonly caused by the genus Curvularia with an infection intensity of up to 60–70%. The control of leaf spot disease usually uses chemical fungicides but its continuous use can cause the development of resistant pathogen fungi and have a long-term negative impact on the environment. False elder (Peronema canescens Jack) leaves have bioactivity as an antimicrobial control disease caused by fungal infections. In this study, Curvularia was isolated from oil palm seedlings infected with leaf spot disease from oil palm nurseries in South Sumatra. Effectiveness testing of P. canescens leaves conducted by a Completely Randomized Design method with five treatments and three replications. The fungi that caused leaf spot disease in oil palm were identified as Curvularia eragrostidis. P. canescens leaf water extract at 25% concentration was very ineffective to quite effective in controlling disease severity based on the average number of spots and diameter of spots in oil palm with the values 36.25–59.50% and 12.50–27.78%. P. canescens leaf water extract could reduce the average number of spots and diameter of spots started on day 30 after being sprayed three times with P. canescens leaf water extract so that it could be used as an alternative to control C. eragrostidis leaf spot disease in oil palm that is more friendly to the environment.

Evaluating cardiovascular risk in metabolic steatosis with precision medicine non-invasive approaches: insights from a cohort study.

Metabolic associated steatotic liver disease (MASLD) is the most common liver condition. It is associated with increased liver-related morbidity and mortality, and also with high risk of cardiovascular events (CVD), representing itself an independent risk factor for it. This makes MASLD a presentation of high interest for internal medicine, also because of its association with metabolic syndrome (MetS). It is crucial to assess its risks in a noninvasive way. With the aim of finding specific risk profiles for CVD development in MASLD by performing a noninvasive assessment of: (1) preclinical signs of endothelial dysfunction (ED); (2) clinical assessment of CVD risk by Framingham Heart Risk Score (FHRs); (3) genomic characterization of MASLD associated polymorphisms; (4) specific untargeted metabolomic profiles, we enrolled 466 MASLD patients non-invasively classified in 4 group of liver fibrosis severity (group-A: low-fibrosis risk, group-B: high-fibrosis risk, group-C: MASLD-cirrhosis, group-D: MASLD-HCC) and 73 healthy controls. FHRs was similar in controls and low-fibrosis group and significantly higher in high-fibrosis patients, cirrhosis, and HCC, increasing among classes. At a multivariable regression, FHRs wasassociated with liver disease severity and diabetes. 38.2% of patients had altered EndoPAT,resembling ED.Patients with high FHRs (> 40%) and ED had different metabolomics compared to those without ED. Our study reveals that a deep, non-invasive characterization of MASLD patients through precision medicine approaches (untargeted metabolomics, SNPs, ED assessment) was able to show a peculiar pattern in MASLD patients with increased CVD risk, mostly correlated with liver disease severity.

Cannabinoid Modulation of Monoamine Levels in Mouse Brain: Unveiling Neurochemical Dynamics through an Innovative High-performance Liquid Chromatography-Fluorescence Detection Bioanalysis

AbstractHomeostasis of monoaminergic pathways is compromised in aging and neurodegenerative/neurological diseases such as Alzheimer’s disease and depression. On the other hand, their modulation has also been linked to the mechanism of action of several drugs. Therefore, monitoring the levels of noradrenaline (NA), adrenaline (AD), dopamine (DA), and serotonin (5-HT), as well as those of tryptophan (TRYP), the precursor of 5-HT, and DA metabolites, namely 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), is fundamental for assessing disease severity and progression. This work aimed to develop and validate the first High-Performance Liquid Chromatography (HPLC) coupled with fluorescence detector (FLD) method that simultaneously and accurately quantifies NA, AD, DA, DOPAC, HVA, 5-HT and TRYP in mouse brain and prefrontal cortex (PFC) matrices. Previous sample preparation by protein precipitation was required to extract the compounds. Calibration curves were plotted using the background subtraction approach to reduce the interference of the endogenous analytes. Intra and inter-day accuracy and precision were within the ranges defined by ICH (The International Council for Harmonisation) guideline for bioanalytical method validation. Following validation, the impact of cannabidiol (CBD), cannabigerol (CBG), and cannabidivarin (CBDV) was explored in mice brains post-administration, revealing significant alterations in specific neurotransmitter levels upon cannabinoid exposure and shedding light on the complex modulation of neurochemical dynamics by cannabinoids. This research highlights the fit-for-purpose of the HPLC-FLD method and provides insights into potential mechanisms underlying phytocannabinoid actions in the central nervous system (CNS).

Blood calprotectin as a biomarker for infection and sepsis – the prospective CASCADE trial

BackgroundEarly in the host-response to infection, neutrophils release calprotectin, triggering several immune signalling cascades. In acute infection management, identifying infected patients and stratifying these by risk of deterioration into sepsis, are crucial tasks. Recruiting a heterogenous population of patients with suspected infections from the emergency department, early in the care-path, the CASCADE trial aimed to evaluate the accuracy of blood calprotectin for detecting bacterial infections, estimating disease severity, and predicting clinical deterioration.MethodsIn a prospective, observational trial from February 2021 to August 2022, 395 patients (n = 194 clinically suspected infection; n = 201 controls) were enrolled. Blood samples were collected at enrolment. The accuracy of calprotectin to identify bacterial infections, and to predict and identify sepsis and mortality was analysed. These endpoints were determined by a panel of experts.ResultsThe Area Under the Receiver Operating Characteristic (AUROC) of calprotectin for detecting bacterial infections was 0.90. For sepsis within 72 h, calprotectin’s AUROC was 0.83. For 30-day mortality it was 0.78. In patients with diabetes, calprotectin had an AUROC of 0.94 for identifying bacterial infection.ConclusionsCalprotectin showed notable accuracy for all endpoints. Using calprotectin in the emergency department could improve diagnosis and management of severe infections, in combination with current biomarkers.Clinical trial registration numberDRKS00020521