Acute Phase Research Articles

The changes of coagulation profiles in Kawasaki disease and its associations with clinical classification, intravenous immunoglobulin responsiveness and coronary artery involvement

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = −0.72, FDP: r = −0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.

Optimizing serum electrolyte levels in stroke patients: a multimodal approach with soymilk supplementation

Introduction: Electrolyte imbalances are common in stroke patients and can significantly impact their overall health, potentially leading to severe complications and even fatal outcomes. In this study, we investigated the impact of combining multiple exercise training modalities (METM) with soymilk supplementation on serum electrolyte levels in stroke patients. Methods: In a single-blind, four-arm randomized clinical trial, 120 stroke patients were randomly assigned to one of the following groups: 1) the METM group, 2) the soymilk group, 3) the METM plus soymilk group, and 4) the control group. Changes in serum electrolyte levels were compared both within and across groups over four consecutive weeks. Results: Upon admission, 38.3% of the participants presented with hyponatremia, 26.7% hypokalemia, and 73.3% hypocalcemia. Over time, there was an overall improvement in serum electrolyte imbalances across all study groups compared to the baseline. Between-group comparisons revealed that the METM plus Soymilk group exhibited statistically significant improvements compared to the other groups with absolute reductions in the proportion of participants with hyponatremia, hypokalemia, and hypocalcemia by 43.3%, 33.3%, and 73.4%, respectively. Conclusions: The study findings substantiate the common occurrence of hyponatremia, hypokalemia, and hypocalcemia during the acute phase of stroke. Implementation of the METM alongside soymilk intake demonstrated potential in rectifying electrolyte imbalances among stroke patients, hinting at a promising intervention strategy.

A Review on Mastitis in Dairy Cows Research: Current Status and Future Perspectives

One of the most serious diseases affecting dairy cattle, causing significant losses both in breeding and economy, is mastitis, an inflammation of the mammary gland. Due to the economic importance of this issue, many research teams are striving to develop an easy-to-apply and, most importantly, effective method to prevent mastitis. The use of traditional methods for mastitis detecting and treating, as well as improvement in hygienic conditions, have not yielded the expected results in combating this disease combating. Currently, the main task is to find the tools that would allow for the rapid detection of mastitis and the improvement of udder health in cows while maintaining high milk production, which is essential for the profitability of dairy cattle farming. Accurate and rapid diagnostic tools, with the simultaneous capability of identifying pathogens, may help to reduce losses. Sufficient sensitivity and specificity for tests are required to minimize the number of false-positive and false-negative cases. Efforts are also being made to determine the optimal threshold value for detecting the disease at its earliest possible stage. The estimation of somatic cell count (SCC) as a phenotypic indicator of mastitis is widely used. A more precise parameter for accurately describing udder health is the differential somatic cell count (DSCC). The well-known California Mastitis Test (CMT) is an inexpensive, easy, and rapid method for mastitis detection useful on farms. The latest diagnostic methods for mastitis utilize tests based on the activity of N-acetyl-β-d-glucosaminidase (NAGase) or lactate dehydrogenase (LDH) as well as the determination of acute phase proteins (APPs) in blood serum and milk (such as haptoglobin, serum amyloid A, fibrinogen, and ceruloplasmin). Research also focuses on the genomic improvement of mastitis resistance in successive generations, and for this purpose, many quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs) have been identified. In recent years, immunotherapy has become an increasingly common area of research, including vaccinations, T/B cell immunotherapy, RNA immunotherapy, epigenetic immunotherapy, stem cell therapy, and native secretory factors. An important aspect of the control of mastitis is the implementation of strategies that focus primarily on preventing the disease through appropriate breeding and farm management practices. In the forthcoming years, a significant challenge will be the development of universal diagnostic and therapeutic strategies that can be effectively implemented as alternatives to antibiotic therapy. Future research should prioritize the advancement of preventive and therapeutic techniques, such as immunotherapies, bacteriocins, herbal therapy, and nanoparticle technology.

Treatment options applied to the preclinical studies using animal models for Chagas Disease: a systematic review and meta-analysis

Background Chagas disease (CD) is a neglected tropical disease endemic to Latin America, has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, by difficulty to obtain appropriate diagnoses and poor treatment, the search for novel therapeutic options remains. Methods In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines. Results Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies Conclusions This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD. Inplasy registration INPLASY202430101 (25/03/2024)

Left ventricular thrombus routine screening with contrast echocardiography in patients with anterior ST-elevation myocardial infarction: is it worth it?

BackgroundLeft ventricular (LV) thrombus has a higher incidence among patients with anterior ST-elevation myocardial infarction (STEMI) when compared to other types of acute myocardial infarction and is associated with worse prognosis. The management of LV thrombus diagnosis remains challenging. Contrast echocardiography (transthoracic echocardiography, TTE) has shown potential in improving the accuracy for its diagnosis, thereby influencing treatment strategies concerning antithrombotic/anticoagulation therapy. The aim of this study was to assess the effectiveness of contrast TTE as a routine screening method for detecting LV thrombus in the acute phase of anterior STEMI.MethodsA prospective, single center, randomized controlled trial was conducted among patients with anterior STEMI. The study group underwent contrast TTE, while the control group received a conventional approach. Demographical, clinical, and diagnostic data were collected. Thrombus detection rates were compared between groups.ResultsA total of 68 patients were included (32 in the study group and 36 in the control group). No substantial baseline differences were observed between groups. Thrombus detection rate was 25.0% in the study group and 13.9% in the control group, however these results did not reach statistical significance (P = 0.24). The prevalence of anterior/apical aneurysm was higher in the study group (46.9% vs. 22.2%, P = 0.03).ConclusionsConventional TTE may be adequate for diagnosing LV thrombus in the acute phase of anterior STEMI; however, further larger-scale and multicenter studies are necessary to obtain more robust and conclusive results. Ultrasound contrast may play a significant role in the detection of anterior/apical aneurysms, which are known risk factors for the subsequent development of thrombus.Trial registrationNCT06480929 (ClinicalTrials.gov, Retrospectively registered).

The Dynamics of NS1 Antigen and Platelet Levels in the Acute Phase of Dengue Hemorrhagic Fever

Introduction: Dengue hemorrhagic fever (DHF) is a significant global health concern, particularly in tropical and subtropical regions. The early diagnosis and effective management of DHF are crucial to reduce morbidity and mortality. The NS1 antigen and platelet count are two key laboratory parameters used in the diagnosis and monitoring of DHF. This study aimed to investigate the dynamics of NS1 antigen and platelet levels during the acute phase of DHF and their correlation with disease severity. Methods: A prospective cohort study was conducted at a tertiary care hospital in Central Java, Indonesia. Patients presenting with suspected DHF were enrolled and followed up during their hospitalization. Blood samples were collected at admission and at regular intervals to measure NS1 antigen levels and platelet counts. Clinical and laboratory data were collected to assess disease severity. Results: A total of 150 patients were included in the study. The majority of patients were adults (median age, 32 years) with a female predominance (58%). The median duration of fever at presentation was 4 days. NS1 antigen levels were significantly higher in patients with DHF compared to those with dengue fever (DF) (p < 0.001). Platelet counts were significantly lower in patients with DHF compared to those with DF (p < 0.001). NS1 antigen levels showed a negative correlation with platelet counts (r = -0.62, p < 0.001). The levels of NS1 antigen and platelet count were also significantly associated with disease severity. Conclusion: The dynamics of NS1 antigen and platelet levels during the acute phase of DHF provide valuable insights into disease pathogenesis and can aid in the early diagnosis and prediction of disease severity. The negative correlation between NS1 antigen and platelet levels suggests a potential role of NS1 in the development of thrombocytopenia in DHF. Further studies are needed to elucidate the exact mechanisms underlying these observations.

Nonreversed great saphenous vein grafts for vascular reconstruction after resection of lower-limb sarcoma

ObjectiveReversed great saphenous vein (GSV) graft is widely used for revascularization in limb-sparing surgery for sarcoma invading great vessels. However, a mismatch in caliber between the reverse graft and the cut end of the artery can threaten graft patency. Recently, we introduced the use of a venous valvulotome to allow non-reversed GSV graft. The purpose of this study was to evaluate the safety and versatility of this technique. DesignWe retrospectively compared long-term patency and limb salvage rates between non-reversed GSV and reversed GSV in patients undergoing limb-sparing surgery for sarcoma. MethodsThirty-seven patients were included, with 21 in the non-reversed GSV group and 16 in the reversed GSV group. Patient characteristics, surgical details, and complications were reviewed from the hospital records. The patency of reconstructed vessels was assessed by contrast-enhanced CT or MRI. Statistical analyses, including Kaplan–Meier survival analysis, were employed for comparisons. ResultsThe median follow-up was 38 months. Overall graft patency was 90.4% (19 of 21 patients) in the non-reversed GSV group and 81.2% (13 of 16) in the reversed RGSV group. In the non-reversed GSV group, there was one case of graft occlusion each in the acute phase and chronic phase, but limb circulation remained intact and all limbs were spared. ConclusionNon-reversed GSV grafting with a valvulotome offers a safe and versatile alternative to reversed GSV grafts in limb-sparing sarcoma surgery. It eliminates the need for vein reversal and minimizes diameter mismatch, potentially expanding the indication for autologous revascularization in previously ineligible cases.

Mild coronavirus disease 2019: Results of a multicentric prospective study on severe acute respiratory syndrome coronavirus 2 presence in semen fractions and cells and its effects on semen parameters.

Severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019, affects multiple organs. The virus enters cells through angiotensin-converting enzyme-2 and host factors present in genital organs, leading to concern over virus shedding in semen and reproductive function. To investigate severe acute respiratory syndrome coronavirus 2 in semen from patients with a mild infection, identify the seminal infected cells, and explore the effect of the infection on sex hormones and semen parameters. Prospective study of 54 men with mild severe acute respiratory syndrome coronavirus 2 infection. Semen was collected at 7, 15, 30, 60, 90, 180, and 365 days after symptom onset, and severe acute respiratory syndrome coronavirus 2 RNA was measured in serum, saliva, urine, and semen. The presence of infectious severe acute respiratory syndrome coronavirus 2 in semen was assessed using Vero cell culture. Infected semen cells were identified using immunofluorescence against severe acute respiratory syndrome coronavirus 2 nucleoprotein antigen and cell markers. Semen characteristics as well as testosterone, inhibin B, luteinizing hormone, and follicle-stimulating hormone levels were determined. 11% of patients had at least one severe acute respiratory syndrome coronavirus 2 RNA-positive semen. One patient had viral semen shedding up to day 90 after infection onset, with replication-competent virus isolated from semen and 40% cell fraction at day 7. After sperm preparation, 90% fraction was severe acute respiratory syndrome coronavirus 2 RNA-positive at days 7 and 15. The swim-up fraction was positive only on day 7. In semen, nucleoprotein antigen was detected mainly in exfoliated epithelial cells and less frequently in Sertoli cells. Sperm count and motile sperm count were lower at day 30 than at day 7. Round cells in semen were increased during the acute phase. At days 7 and 15, sperm count and motile sperm count were lower in severe acute respiratory syndrome coronavirus 2 RNA-positive semen compared with negative semen, while semen volume and follicle-stimulating hormone levels were increased. Long-term follow-up shows no evidence of a detrimental effect on hormonal or semen characteristics. 11% of patients with mild coronavirus disease 2019 who were not hospitalized had severe acute respiratory syndrome coronavirus 2 excretions in semen, which persisted for up to 90 days in one patient. No germ cells appeared infected by the virus, but the detection of nucleoprotein antigen-positive epithelial semen cells and Sertoli cells suggests genital tract infection. Albeit infrequent, semen may contain the replication-competent virus during the acute phase with potential risk of severe acute respiratory syndrome coronavirus 2 transmissions during sexual contact and assisted reproduction procedures. The effect of mild coronavirus disease 2019 on spermatogenesis and reproductive hormones was moderate and reversible.

In the Acute Phase of Anterior Cruciate Ligament Rupture: Quantitative Assessment of Matrix Changes and Correlation between Different States of Meniscus and Adjacent Cartilage.

Cartilage and meniscus are important structures that maintain the health of the knee joint. Early detection of changes in the internal components of cartilage and meniscus before morphological changes occur is essential to prevent and delay the development of osteoarthritis (OA). This study was designed to determine the changes in the matrix composition of morphologically intact cartilage and meniscus during the acute phase of an anterior cruciate ligament (ACL) rupture, as well as the effect of different states of meniscus (intact or tear) on adjacent cartilage during the acute phase. This cross-sectional study compared and analyzed 50 patients in the acute phase of ACL rupture who underwent surgical treatment and 66 age-, weight- and height-matched healthy volunteers from May 2022 to May 2023 at our institution. Mean T2 relaxation times and effect sizes in different regions of tibiofemoral articular cartilage and meniscus were compared between the two groups using the Mann-Whitney nonparametric t-test, and correlations between different meniscal states and adjacent cartilage were analyzed. Both in the lateral and medial compartments of the knee, T2 relaxation times were significantly higher in all subregions of cartilage and meniscus in the ACL rupture group (p < 0.05), and the site of injury was predominantly centered in the medial compartment (femur, p = 0.000; tibia, p = 0.000; anterior horn, p = 0.000). In the respective compartments, the posterior horn of the lateral meniscus showed a significant positive correlation with the mid-cartilage of the femoral and tibial (r = 0.566, p = 0.035; r = 0.611, p = 0.02); and the posterior horn of the medial meniscus showed a significant positive correlation with the posterior tibial cartilage (r = 0.668, p = 0.018). During the acute phase of ACL rupture, the internal composition of the cartilage and meniscus undergoes significant changes, even if the morphology is intact. More importantly, the state of the meniscus significantly affects the internal composition of the adjacent cartilage. This is an early warning sign of OA, which should be closely monitored and carefully managed in clinical practice.

Development of a new accurate lateral flow immunoassay for diagnosis of human leptospirosis.

The current diagnostic methods for leptospirosis diagnosis are technically complex and expensive, with limited applicability to specialized laboratories. Furthermore, they lack diagnostic accuracy in the acute stage of the disease, which coincides with a period when antibiotics are highly effective. New simple and accurate tests are mandatory to decentralize and improve diagnosis. Here, we introduced a new lateral flow immunoassay (Lepto-LF) for human leptospirosis. We conducted a double-blinded assay using 104 serum samples from patients with confirmed or discarded diagnosis for leptospirosis. The diagnostic performance of Lepto-LF was estimated across different ranges of days from onset of symptoms (dpo), considering the diagnostic algorithm as reference standard. Additionally, it was compared with the screening methods enzyme-linked immunosorbent assay (IgM-ELISA) and the slide agglutination test using temperature-resistant antigen (SATR). Lepto-LF exhibited perfect diagnostic performance with a Youden´s index J = 1 from 6 dpo in the acute phase. IgM-ELISA gave slightly lower accuracy with J = 0.91 and 95.5% of both sensitivity and specificity; while SATR showed a markedly inferior yield (J = 0.41, sensitivity = 95.5%, specificity = 45.5%). The performances remained consistent in the convalescence phase of the disease (> 10 dpo). Lepto-LF was found to be a reliable test for simple, rapid and early diagnosis of leptospirosis, resulting a promising tool for decentralizing leptospirosis diagnosis and enabling timely treatment of patients. In addition, Lepto-LF may be employed as confirmatory test, especially in remote areas and vulnerable contexts where the standard MAT is not available.

Discovering novel plasma biomarkers for ischemic stroke: Lipidomic and metabolomic analyses in an aged mouse model

Ischemic stroke remains a leading cause of mortality and long-term disability worldwide, necessitating efforts to identify biomarkers for diagnosis, prognosis, and treatment monitoring. The present study aimed to identify novel plasma biomarkers of neurodegeneration and inflammation in a mouse model of stroke induced by distal middle cerebral artery occlusion. Using targeted lipidomic and global untargeted metabolomic profiling of plasma collected from aged male mice 24 h after stroke and weekly thereafter for 7 weeks, we discovered distinct acute and chronic signatures. In the acute phase, we observed elevations in myelin-associated lipids, including sphingomyelin (SM) and hexosylceramide (HCER) lipid species, indicating brain lipid catabolism. In the chronic phase, we identified 12-hydroxyeicosatetraenoic acid (12-HETE) as a putative biomarker of prolonged inflammation, consistent with our previous observation of a biphasic pro-inflammatory response to ischemia in the mouse brain. These results provide insight into the metabolic alterations detectable in the plasma after stroke and highlight the potential of myelin degradation products and arachidonic acid derivatives as biomarkers of neurodegeneration and inflammation, respectively. These discoveries lay the groundwork for further validation in human studies and may improve stroke management strategies.

Multimodal mucosal and systemic immune characterization of a non-human primate trachoma model highlights the critical role of local immunity during acute phase disease.

Trachoma is a leading cause of infection-related blindness worldwide. This disease is caused by recurrent Chlamydia trachomatis (Ct) infections of the conjunctiva and develops in two phases: i) active (acute trachoma, characterized by follicular conjunctivitis), then long-term: ii) scarring (chronic trachoma, characterized by conjunctival fibrosis, corneal opacification and eyelid malposition). Scarring trachoma is driven by the number and severity of reinfections. The immune system plays a pivotal role in trachoma including exacerbation of the disease. Hence the immune system may also be key to developing a trachoma vaccine. Therefore, we characterized clinical and local immune response kinetics in a non-human primate model of acute conjunctival Ct infection and disease. The conjunctiva of non-human primate (NHP, Cynomolgus monkeys-Macaca fascicularis-) were inoculated with Ct (B/Tunis-864 strain, B serovar). Clinical ocular monitoring was performed using a standardized photographic grading system, and local immune responses were assessed using multi-parameter flow cytometry of conjunctival cells, tear fluid cytokines, immunoglobulins, and Ct quantification. Clinical findings were similar to those observed during acute trachoma in humans, with the development of typical follicular conjunctivitis from the 4th week post-exposure to the 11th week. Immunologic analysis indicated an early phase influx of T cells in the conjunctiva and elevated interleukins 4, 8, and 5, followed by a late phase monocytic influx accompanied with a decrease in other immune cells, and tear fluid cytokines returning to initial levels. Our NHP model accurately reproduces the clinical signs of acute trachoma, allowing for an accurate assessment of the local immune responses in infected eyes. A progressive immune response occurred for weeks after exposure to Ct, which subsided into a persistent innate immune response. An understanding of these local responses is the first step towards using the model to assess new vaccine and therapeutic strategies for disease prevention.

Clinical Associations of E148Q Heterozygosity: What to Expect From E148Q?

The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant. Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations. Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52. The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.

Long-term impacts of COVID-19 in patients with prior heart failure in Korea: A nationwide cohort study using the common data model.

Limited data are available on the long-term prognosis and monitoring period after coronavirus disease 2019 (COVID-19) infection in the population with prior heart failure (HF). We aimed to exam the association of COVID-19 with clinical prognosis in populations with prior HF and evaluate prognosis within 30 days and 30 days to 1 year after infection. Based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea from January 2018 to April 2022, 9,822,577 patients were selected and converted to the Observational Medical Outcomes Partnership-common data model by the Big Data Department of Health Insurance Review and Assessment Service of Korea. In the dataset, 1,565,274 patients exhibited diagnosis of HF based on the International Statistical Classification of Diseases and Related Health Problems 10 codes. They were divided into 2 groups according to COVID-19 infection, and propensity-score-matching analysis was performed. The clinical outcome was all-cause mortality. Among the 1,565,274 patients with an HF diagnosis, 1,152,975 patients were classified into the HF with the COVID-19 group and 412,299 patients in the HF without COVID-19 group. We created 200,780 matched pairs by propensity-score-matching analysis. Within 30 days of COVID-19, the HF with COVID-19 group had a higher risk of all-cause death compared with the HF without COVID-19 group (hazard ratio [HR]: 2.19, 95% confidence interval [CI]: 2.04-2.36, P < .01). Thirty days to 1 year after COVID-19 infection, the HF with COVID-19 group exhibited a higher risk of all-cause death (HR: 2.04, 95% CI: 1.83-2.27, P < .01). In populations with prior HF, COVID-19 is associated with a higher risk of all-cause mortality within 30 days and this risk remains augmented up to 1 year after the acute phase of COVID-19. Our findings suggest that greater attention may be crucial in populations with prior HF for a prolonged period after COVID-19 infection.

Prognostic significance of serum secreted frizzled-related protein 5 in patients with acute aortic dissection

BackgroundSecreted frizzled-related protein 5 (SFRP5) is a novel adipokine that has been found to be closely associated with metabolic and cardiovascular diseases. We investigated serum SFRP5 levels during the acute phase and their predictive value for the prognosis of acute aortic dissection (AAD). MethodsIn total, 152 AAD patients and 164 controls were enrolled in this study. Serum SFRP5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). AAD patients were divided into high-SFRP5 and low-SFRP5 groups based on the optimal cutoff value and followed up for prognosis. The primary endpoint was all-cause mortality, and the secondary endpoint focused on AAD-related events (including AAD-related mortality and unplanned reoperations). ResultsSerum SFRP5 levels were significantly higher in AAD patients than in non-AAD controls, regardless of whether they had Stanford type A or B AD. Multivariate logistic regression analysis revealed an independent association between SFRP5 and the presence of AAD (adjusted OR 1.267, 95 % CI 1.152–1.394; p < 0.001). The receiver operating characteristic curve demonstrated that the optimal cutoff value for SFRP5 to predict the presence of AAD was 10.26 ng/mL (AUC 0.7241, sensitivity 49.34 %, specificity 87.20 %). Notably, serum SFRP5 levels of patients in the death group were significantly higher than those in the survival group. Compared with patients in the low-SFRP5 group, those in the high-SFRP5 group exhibited a significantly increased risk of all-cause mortality (HR 9.540, 95 % CI 2.803–32.473; p < 0.001) and AAD-related events (HR 6.915, 95 % CI 2.361–20.254; p < 0.001) during the follow-up period. ConclusionSerum SFRP5 levels were significantly elevated in the acute phase of AAD, and high serum SFRP5 levels were independently associated with poor AAD prognosis. These results suggest that serum SFRP5 level during the acute phase may be an effective biomarker and therapeutic target for the prognosis of AAD.

Characterization of Inflammation/Immune-, Acute Phase-, Extracellular Matrix-, Adhesion-, and Serine Protease-Related Proteins in the Amniotic Fluid of Women With Early Preterm Prelabor Rupture of Membranes.

To determine whether altered concentrations of various inflammation/immune-, acute phase-, extracellular matrix-, adhesion-, and serine protease-related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM). This was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24-31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme-linked immunosorbent assay (ELISA): APRIL, DKK-3, Gal-3BP, IGFBP-2, IL-8, VDBP, lumican, MMP-2, MMP-8, SPARC, TGFBI, TGF-β1, E-selectin, ICAM-5, P-selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA. Multivariate logistic regression analyses revealed that (i) elevated APRIL, IL-8, MMP-8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF-β1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL-8 and MMP-8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL-6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates. ECM (lumican, SPRAC, TGFBI, and TGF-β1)- and serine protease (uPA)-associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL-8, MMP-8, and IL-6)-associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.

Airway extracellular LTA4H concentrations are governed by release from liver hepatocytes and changes in lung vascular permeability

Leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme, with dual activities critical in defining the scale of tissue inflammation and pathology. LTA4H classically operates intracellularly, primarily within myeloid cells, to generate pro-inflammatory leukotriene B4. However, LTA4H also operates extracellularly to degrade the bioactive collagen fragment proline-glycine-proline to limit neutrophilic inflammation and pathological tissue remodeling. While the dichotomous functions of LTA4H are dictated by location, the cellular source of extracellular enzyme remains unknown. We demonstrate that airway extracellular LTA4H concentrations are governed by the level of pulmonary vascular permeability and influx of an abundant repository of blood-borne enzyme. In turn, blood LTA4H originates from liver hepatocytes, being released constitutively but further upregulated during an acute phase response. These findings have implications for our understanding of how inflammation and repair are regulated and how perturbations to the LTA4H axis may manifest in pathologies of chronic diseases.

Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers

BackgroundPreeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. MethodsProteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver operating characteristics curve (AUC). ResultsA total of 1,307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Up-regulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC > 0.9 and P < 0.001, for all) as validated by MRM and ELISA. ConclusionsOur data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.

Effect of fluid resuscitation with albumin on mortality in patients with severe burns: A nationwide inpatient data analysis

The present study aimed to evaluate the effect of albumin administration on mortality in patients with severe burns. We retrospectively analyzed data from the Diagnosis Procedure Combination Database, a nationwide inpatient database in Japan. We identified patients in the database aged ≥15 years who were admitted with severe burns (burn index ≥15) from April 2014 to March 2021. We included patients who received albumin within 2 days of admission in the albumin group and those who did not in the control group. The outcome was the 28-day mortality. Eligible patients (n = 2,492) were categorized into an albumin group (n = 1,128) or a control group (n = 1,364). One-to-one propensity score matching generated 530 pairs of patients with and without albumin administration. The 28-day mortality did not differ significantly between the two groups (albumin vs. control, 21.7% vs. 22.8%; risk difference, -1.1%; 95% confidence interval, -6.1% to +3.9%). These results suggest that albumin administration within 2 days of admission in patients with severe burns may not be associated with mortality during the acute phase.

Customized Negative Pressure Wound Therapy: Innovative Design in Polyurethane Foam for Complex Burn Reconstruction.

The use of negative pressure wound therapy (NPWT) throughout the entire treatment of a burn patient boosts wound healing and recovery. Hand burns require specialized management that enhances wound healing and facilitates early physical rehabilitation. Thus, this article showcases a novel idea of NPWT foam customization that boosts recovery and rehabilitation in patients with hand burns. We present two patients with hand burns treated with NPWT using a customized foam design that allowed for early rehabilitation while providing and optimized recovery. In the two cases presented, the patients required two surgical stages; in the first surgery, debridement of the burns was performed and customized NPWT with instillation was applied, and in the second surgical stage, the bed was reconstructed with partial-thickness skin grafts, which were bolstered with customized conventional NPWT. The management, reconstruction, and rehabilitation were accomplished in under 2 weeks, achieving a remarkable 100% success rate in graft integration during the acute phase on the first attempt. This highlights the effectiveness of incorporating NPWT across all burn treatment phases, expediting recovery and ensuring optimal functional outcomes for patients. Surgeons can customize different NPWT foam shapes that facilitate its use on difficult-to-treat areas, allowing for a faster recovery and better rehabilitation outcomes.