Clinical Disease Research Articles

Efficacy of an inactivated EHDV-8 vaccine in preventing viraemia and clinical signs in experimentally infected cattle

Epizootic haemorrhagic disease (EHD), caused by the EHD virus (EHDV), is a vector-borne viral disease transmitted through Culicoides biting midges. EHDV comprises seven serotypes (1, 2, and 4–8), with EHDV-8 having recently emerged and spread in Europe over the last two years. Such event has raised concerns about the significant threat posed by EHDV-8 to livestock industry. In this study, an inactivated vaccine against EHDV-8 (vEHDV8-IZSAM) was developed. Safety and efficacy of the vaccine were evaluated in calves through clinical, serological, and virological monitoring following experimental challenge.The vaccine was proven safe, with only transient fever and localized reactions observed in a few animals, consistent with adjuvanted vaccine side effects. vEHDV8-IZSAM elicited a robust humoral response, as evidenced by the presence of neutralizing antibodies. After challenge with a virulent isolate, viraemia and clinical signs were evidenced in control animals but in none of the vaccinated animals.This study highlights the potential of vEHDV8-IZSAM as a safe and highly effective vaccine against EHDV-8 in cattle. It offers protection from clinical disease and effectively prevents viraemia. With the recent spread of EHDV-8 in European livestock, the use of an inactivated vaccine could be key in protecting animals from clinical disease and thus to mitigate the economic impact of the disease. Further investigations are warranted to assess the duration of the induced immunity and the applicability of this vaccine in real-world settings. Accordingly, joint efforts between public veterinary institutions and pharmaceutical companies are recommended to scale up vaccine production.

High Levels of Triggering Receptor Expressed in Myeloid Cells-Like Transcript-1 Positive, but Not Glycoprotein 1b+, Microparticles Are Associated With Poor Outcomes in Acute Respiratory Distress Syndrome.

To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with clinical outcomes and/or disease severity in acute respiratory distress syndrome (ARDS). Retrospective cohort study. ARDS Network clinical trials. A total of 564 patients were diagnosed with ARDS. None. Using flow cytometry, we demonstrated the presence of TLT-1+ platelet-derived microparticles (PMP) that bind fibrinogen in plasma samples from fresh donors. We retrospectively quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive microparticles in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA (Studies 01 and 03 lower versus higher tidal volume, ketoconazole treatment, and lisofylline treatment Clincial Trials) ARDS Network clinical trials and evaluated the relationship between these measures and clinical outcomes. No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa+ and TLT-1+ MPs (χ2p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT+ PMP in the 75th percentile. In all three cohorts, patients whose TLT+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors. Although both αIIbβIIIa+ and TLT+ microparticles (αIIbβIIIa, TLT-1) were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with Acute Physiology and Chronic Health Evaluation III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression.

Incidence of RSV in Adults: A Comprehensive Review of Observational Studies and Critical Gaps in Information.

We conducted a global comprehensive literature review of observational studies reporting RSV incidence in adults and determined current evidence gaps. PubMed and Embase were searched for English-language publications (2000-2022) and congress abstracts (2019-2021) reporting RSV incidence rates/cumulative incidence. Cross-sectional studies, case series, and other designs estimating only RSV frequency were excluded. The search included all geographic areas; data were extracted by age group and underlying condition where available. 528 potentially relevant records were identified, of which 37 primary studies were relevant to this review. Most evidence was from high-income regions. Approximately two-thirds of the studies reported RSV incidence in the hospital setting. Fifteen studies included or focused exclusively on RSV incidence in adult populations with underlying conditions. Studies varied in their measurement and presentation of incidence. RSV incidence estimates were highly variable within and between geographic regions. Overall, RSV incidence tended to increase with age and was highest in adults with underlying conditions. Estimates of RSV incidence are highly variable across populations and geographies. Further population-based studies with well-defined consistent case definitions and surveillance strategies are needed for accurate and comparable estimates of RSV incidence, particularly in the geographic regions identified by the gap analysis.

Slit2–Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice

BackgroundSepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated.MethodsThe animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays.ResultsThe C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1β, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1β and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection.ConclusionsIn this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.

Impact of Tafamidis on Delaying Clinical, Functional, and Structural Cardiac Changes in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy.

Background: This study aimed to evaluate the effect of treatment with tafamidis on clinical, laboratory, functional, and structural cardiovascular imaging parameters at the 12-month follow-up timepoint in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and to assess the response to treatment in terms of disease progression. Methods: Patients with ATTRwt-CM undergoing treatment with tafamidis for >12 months were included. The patients underwent a comprehensive evaluation (including echocardiography, cardiac magnetic resonance imaging, six-minute walking test, assessment of quality of life, and laboratory tests) at baseline and the 12-month follow-up timepoint. Disease progression was assessed using a set of tools proposed by an international panel of experts, evaluating three main domains (clinical, biochemical, and structural). Results: The study cohort consisted of 25 patients (mean age of 75.9 ± 6.1 years, with 92% males). At the 12-month follow-up timepoint, an improvement in quality of life calculated with the KCCQ overall score (64 ± 20 vs. 75 ± 20, p = 0.002) and a reduction in pulmonary artery pressure (34 ± 10 mmHg vs. 30 ± 5 mmHg, p-value = 0.008) and in native T1 time were observed (1162 ± 66 ms vs. 1116 ± 52 ms, p-value = 0.001). Clinical, biochemical, and structural disease progression was observed in 6 (24%), 13 (52%), and 7 (28%) patients, respectively. Overall disease progression was observed in two patients (8%). Conclusions: This study described the impact of tafamidis treatment on clinical, laboratory, and functional parameters. Disease progression, assessed using a multiparametric tool recommended by a recent position paper of experts, was observed in a minority of patients.

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma (aGC), it may lead to an adverse prognosis. Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients. AIM To determine the efficacy and safety of cetuximab (CET) combined with the FOLFOX4 regimen (infusional fluorouracil, folinic acid, and oxaliplatin) as first-line therapy for patients with aGC, who received evidence-based care (EBC). METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled. Of these, 60 in the research group (RG) received CET + FOLFOX4 as first-line therapy, whereas 57 in the control group (CG) received FOLFOX4. The efficacy [clinical response rate (RR) and disease control rate (DCR)], safety (liver and kidney dysfunction, leukopenia, thrombocytopenia, rash, and diarrhea), serum tumor marker expression [STMs; carbohydrate antigen (CA) 19-9, CA72-4, and carcinoembryonic antigen (CEA)], inflammatory indicators [interleukin (IL)-2 and IL-10], and quality of life (QOL) of the two groups were compared. RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG, with an equivalent safety profile between the two groups. RG exhibited notably reduced CA19-9, CA72-4, CEA, and IL-2 levels following treatment, which were lower than the pre-treatment levels and those in the CG. Post-treatment IL-10 was statistically increased in RG, higher than the pre-treatment level and the CG. Moreover, a significantly improved QOL was evident in the RG. CONCLUSION The CET + FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC. It facilitates the suppression of STMs, ameliorates the serum inflammatory microenvironment, and enhances QOL, without increased adverse drug effects.

Health professionals’ perceptions of prehabilitation before haematopoietic cell transplantation to optimise candidacy in older adults

PurposeHaematologic malignancies for the most part are diseases of the elderly. Haematopoietic stem cell transplantation (HSCT) remains the only potentially curative strategy for many patients but carries substantial morbidity and mortality risks, particularly in frail or co-morbid patients. Pre-transplant optimisation of key targets through prehabilitation may have significant clinical impact.MethodsWe utilised qualitative methodology (semi-structured interviews) to gain insights and understanding of the perceptions of medical, nursing and allied health professionals towards prehabilitation before haematopoietic cell transplantation to optimise candidacy in older adults. Thematic analysis was performed using a qualitative descriptive approach completed in duplicate by two researchers.ResultsBetween August and October 2023, eleven health professionals participated from four large cancer centres across the island of Ireland (n = 3 consultant haematologists, n = 7 specialist haematology nurses and n = 1 senior haematology physiotherapist). Four major themes were identified. The themes comprehensive biopsychosocial care and increasing demand for transplant in older patients highlight the unique challenges impacting older adults who receive HSCT. The multimodality pathways of care theme highlights the heterogeneity of treatment pathways across different clinical sites and disease types. This has implications for the prehabilitation: logistics and benefits theme, which indicated strong support for prehabilitation but emphasised that implementation must consider national reach and context.ConclusionsThere is broad national multidisciplinary interest in the development of prehabilitation programmes for patients being considered for transplant. Our results will inform the development of services in this area in consideration of national reach, malignancy-specific pathways and the unique factors associated with older age.

Genetic diversity of porcine circoviruses 2 and 3 circulating among wild boars in the Moscow Region of Russia.

Porcine circoviruses (PCVs) are widely distributed in swine herds. PCV2, the significant swine pathogen, causes infections characterized by growth and development disorders, skin lesions, and respiratory distress. PCV3 has been circulating worldwide and can be associated with various clinical signs and disease developments. Wild boars are the main reservoir of these pathogens in wildlife and can create an alarming threat to pig farming. In Russia, three PCV2 genotypes (PCV2a, PCV2b, and PCV2d) were identified in pig farms. Additionally, PCV3 was observed in pig herds during the monitoring studies in the country. However, data considering the circulation of PCVs in herds of wild boars in Russia is scant. For this purpose, we performed PCR assays of the samples from 30 wild boars hunted in the Moscow Region of Russia in 2021-2023. The ratios of wild boars positive for PCV2, PCV3, or coinfected were 50, 10, and 13.3%, respectively. Additionally, we sequenced 15 PCV2 and four PCV3 complete genomes and conducted phylogenetic analysis, which divided PCV2 isolates into two groups: PCV2d and PCV2b. The study showed a high infection rate of PCV2 among wild boars, with PCV2d dominance. Simultaneously, PCV3 also circulates among wild boars. The obtained results can provide a basis for the development of preventive measures to support infection transmission risks between farm and wild animals.

A Cross-sectional Analytical Study of Morphological Patterns of Acanthosis Nigricans and Its Association with Components of Metabolic Syndrome

Background: Acanthosis nigricans (AN) is a dermatosis that manifests as asymptomatic and symmetrical darkening, affecting the skin of intertriginous areas. It is a marker of insulin resistance and is usually associated with metabolic syndrome (MS). The present study was conducted to study the morphological patterns of AN and to assess its correlation with different components of MS. Methodology: Using the purposive sampling technique (1-year period), 100 patients fulfilling the case definition of AN were enrolled based on the inclusion and exclusion criteria. A detailed history and a cutaneous examination (color, texture, and sites of AN) were done. Anthropometric measurements and scoring of the AN were done. Investigations were reviewed. Data were recorded, and MS was diagnosed using the National Cholesterol Education Program’s Adult Panel III criteria. The data were analyzed using Microsoft Excel 13 software. Results: The mean age was 36.9 ± 10.1 years, with a male-to-female ratio of 1:1.38. The mean duration of AN was 18.8 ± 12.5 months. Seventy percent of cases had involvement of two or more sites. MS was present in 55% of cases of AN. Gender, duration of AN, site of AN, neck and axilla severity, and total cholesterol were not statistically significantly associated with MS (P &gt; 0.05). Its association with systolic and diastolic blood pressure, waist circumference, fasting blood sugar, and high triglyceride was found to be statistically significant (P &lt; 0.05). A low high-density lipoprotein level was found to be highly significant (P &lt; 0.01). On applying the Chi-square test, all five parameters of MS had a significant association with AN. Conclusion: Understanding the relationship between AN and MS is important, as patients with AN are at risk for all the components of MS individually and collectively.

TLR2 and TLR4 Polymorphisms Are Not Associated with Dental Caries in Polish Children.

The aim of the present study was to analyze the association of the TLR2 (Toll-like receptor 2 gene) 2258G>A (rs5743708), TLR4 (Toll-like receptor 4 gene) 896A>G (rs4986790), and TLR4 1196C>T (rs4986791) polymorphisms with dental caries in Polish children. The participants, 261 15-year-old children, were divided into two groups: 82 cases (i.e., children with DMFT (Decayed, Missing, and Filled Teeth) index >5, having either moderate or high caries experience, assigned as the "higher" caries experience group) and 179 controls (i.e., children with DMFT ≤ 5, having either low or very low caries experience, assigned as the "lower" caries experience group). Genomic DNA was isolated from buccal swabs, and genotyping was determined by means of real-time PCR (polymerase chain reaction). There were no significant differences in the genotype or allele distributions in all tested SNPs (single nucleotide polymorphisms) between children with "higher" caries experience and those with "lower" caries experience. TLR4 haplotype frequencies did not differ significantly between cases and controls. In an additional analysis with another case definition applied (subjects with DMFT ≥ 1 were assigned as "cases", whereas children with DMFT = 0 were assigned as "controls"), no significant differences in the TLR2 and TLR4 genotype, allele frequencies, and TLR4 haplotype frequencies were found between the case and the control groups. The results of the present study broaden our knowledge on the potential genetic factors that might affect caries risk and suggest that TLR2 rs5743708 and TLR4 rs4986790 and rs4986791 SNPs are not associated with dental caries susceptibility in Polish children.

An injectable subunit vaccine containing Elongation Factor Tu and Heat Shock Protein 70 partially protects American bison from Mycoplasma bovis infection.

Mycoplasma bovis (M. bovis) is the etiologic agent of high mortality epizootics of chronic respiratory disease in American bison (Bison bison). Despite the severity of the disease, no efficacious commercial vaccines have been licensed for the prevention of M. bovis infection in bison. Elongation factor thermal unstable (EFTu) and Heat Shock Protein 70 (Hsp70, DnaK) are highly conserved, constitutively expressed proteins that have previously been shown to provide protection against M. bovis infection in cattle. To assess the suitability of EFTu and Hsp70 as vaccine antigens in bison, the immune response to and protection conferred by an injectable, adjuvanted subunit vaccine comprised of recombinantly expressed EFTu and Hsp70 was evaluated. Vaccinates developed robust antibody and cellular immune responses against both EFTu and Hsp70 antigens. To assess vaccine efficacy, unvaccinated control and vaccinated bison were experimentally challenged with bovine herpes virus-1 (BHV-1) 4 days prior to intranasal infection with M. bovis. Vaccinated bison displayed reductions in joint infection, lung bacterial loads, and lung lesions compared to unvaccinated controls. Together, these results showed that this subunit vaccine reduced clinical disease and bacterial dissemination from the lungs in M. bovis challenged bison and support the further development of protein subunit vaccines against M. bovis for use in bison.

The nature and magnitude of cognitive impairment in narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia: a meta-analysis.

People with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) often report cognitive impairment which can be quite burdensome but is rarely evaluated in routine clinical practice. In this systematic review and meta-analysis, we assessed the nature and magnitude of cognitive impairment in NT1, NT2, and IH in studies conducted from January 2000 to October 2022. We classified cognitive tests assessing memory, executive function, and attention by cognitive domain. Between-group differences were analyzed as standardized mean differences (Cohen's d), and Cohen's d for individual tests were integrated according to cognitive domain and clinical disease group. Eighty-seven studies were screened for inclusion; 39 satisfied inclusion criteria, yielding 73 comparisons (k): NT1, k = 60; NT2, k = 8; IH, k = 5. Attention showed large impairment in people with NT1 (d = -0.90) and IH (d = -0.97), and moderate impairment in NT2 (d = -0.60). Executive function was moderately impaired in NT1 (d = -0.30) and NT2 (d = -0.38), and memory showed small impairments in NT1 (d = -0.33). A secondary meta-analysis identified sustained attention as the most impaired domain in NT1, NT2, and IH (d ≈ -0.5 to -1). These meta-analyses confirm that cognitive impairments are present in NT1, NT2, and IH, and provide quantitative confirmation of reports of cognitive difficulties made by patients and clinicians. These findings provide a basis for the future design of studies to determine whether cognitive impairments can improve with pharmacologic and nonpharmacologic treatments for narcolepsy and IH.

Isophorone-based crystallization-induced-emission sensors detect proteome aggregation in live cells and tissues with breast cancer

BackgroundProtein misfolding and aggregation can lead to various diseases. Recent studies have shed light on the aggregated protein in breast cancer pathology, which suggests that it is crucial to design chemical sensors that visualize protein aggregates in breast cancer, especially in clinical patient-derived samples. However, most reported sensors are constrained in cultured cell lines. ResultsIn this work, we present the development of two isophorone-based crystallization-induced-emission fluorophores for detecting proteome aggregation in breast cancer cell line and tissues biopsied from diseased patients, designated as A1 and A2. These probes exhibited viscosity sensitivity and recovered their fluorescence strongly at crystalline state. Moreover, A1 and A2 exhibit selective binding capacity and strong fluorescence for various aggregated proteins. Utilizing these probes, we detect protein aggregation in stressed breast cancer cells, xenograft mouse model of human breast cancer and clinical patient-derived samples. Notably, the fluorescence intensity of both probes light up in tumor tissues. SignificanceThe synthesized isophorone-based crystallization-induced-emission fluorophores, A1 and A2, enable sensitive detection of protein aggregation in breast cancer cells and tissues. In the future, aggregated proteins are expected to become indicators for early diagnosis and clinical disease monitoring of breast cancer.

The association between cystic fibrosis-related diabetes and periodontitis in adults: A pilot cross-sectional study.

Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been evaluated. The objective of this study was to assess if: 1) CFRD is associated with periodontitis among adults with CF, and 2) periodontitis prevalence differs by CF and diabetes status. This was a pilot cross-sectional study of the association between CFRD and periodontitis in adults with cystic fibrosis (CF) (N = 32). Historical non-CF controls (N = 57) from the U.S. National Health and Nutrition Examination Survey (NHANES) dataset were frequency matched to participants with CF on age, sex, diabetes status, and insulin use. We defined periodontitis using the U.S. Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition, as the presence of two or more interproximal sites with CAL ≥3 mm and two or more interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. Because NHANES periodontal data were only available for adults ages ≥30 years, our analysis that included non-CF controls focused on this age group (CF N = 19, non-CF N = 57). Based on CF and diabetes status, we formed four groups: CFRD, CF and no diabetes, non-CF with diabetes, and non-CF and no diabetes (healthy). We used the Fisher's exact test for hypotheses testing. There was no association between CFRD and periodontitis for participants with CF ages 22-63 years (CFRD 67% vs. CF no diabetes 53%, P = 0.49), this was also true for those ages ≥30 years (CFRD 78% vs. CF no diabetes 60%, P = 0.63). For the two CF groups, the prevalence of periodontitis was significantly higher than for healthy controls (CFRD 78% vs. healthy 7%, P<0.001; CF no diabetes 60% vs. healthy 7%, P = 0.001) and not significantly different than the prevalence for non-CF controls with diabetes (CFRD 78% vs. non-CF with diabetes 56%, P = 0.43; CF no diabetes 60% vs. non-CF with diabetes 56%, P = 0.99). Among participants with CF, CFRD was not associated with periodontitis. However, regardless of diabetes status, participants with CF had increased prevalence of periodontitis compared to healthy controls.

Exosomes, and the potential for exosome-based interventions against COVID-19.

Since late 2019, the world has been devastated by the coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with more than 760 million people affected and ∼seven million deaths reported. Although effective treatments for COVID-19 are currently limited, there has been a strong focus on developing new therapeutic approaches to address the morbidity and mortality linked to this disease. An approach that is currently being investigated is the use of exosome-based therapies. Exosomes are small, extracellular vesicles that play a role in many clinical diseases, including viral infections, infected cells release exosomes that can transmit viral components, such as miRNAs and proteins, and can also include receptors for viruses that facilitate viral entry into recipient cells. SARS-CoV-2 has the ability to impact the formation, secretion, and release of exosomes, thereby potentially facilitating or intensifying the transmission of the virus among cells, tissues and individuals. Therefore, designing synthetic exosomes that carry immunomodulatory cargo and antiviral compounds are proposed to be a promising strategy for the treatment of COVID-19 and other viral diseases. Moreover, exosomes generated from mesenchymal stem cells (MSC) might be employed as cell-free therapeutic agents, as MSC-derived exosomes can diminish the cytokine storm and reverse the suppression of host anti-viral defences associated with COVID-19, and boost the repair of lung damage linked to mitochondrial activity. The present article discusses the significance and roles of exosomes in COVID-19, and explores potential future applications of exosomes in combating this disease. Despite the challenges posed by COVID-19, exosome-based therapies could represent a promising avenue for improving patient outcomes and reducing the impact of this disease.

Diagnostic value of ultrasound-guided fine-needle aspiration cytology in the pathological natures of thyroid nodules: A retrospective study.

Thyroid nodules, a clinical disease with high incidence, include benign and malignant types. This study aims to evaluate the diagnostic value of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in determining the pathological nature of thyroid nodules and to conduct an in-depth analysis of its diagnostic efficacy across nodules of varying sizes. This retrospective study identified 116 patients undergoing thyroidectomy in Zibo Central hospital from January 2022 to March 2023, with 98 meeting the study's inclusion criteria. All patients received ultrasound and US-FNAC examinations before surgery to analyze the ultrasonic features of thyroid nodules. The diagnosis results of pathological natures obtained by US-FNAC were analyzed with the result of post-operative pathological examination as the gold standard. The patients were divided into four groups according to the median and quartile of nodular diameters to explore the diagnostic efficacy of US-FNAC for the pathological natures of thyroid nodules with various diameters and comprehensively evaluate its application value. The evaluation tool of diagnostic efficacy was the receiver operator characteristic (ROC) curve. A total of 98 puncture nodules were evaluated, with a diameter of 0.8-5.2 cm. Post-operative pathological examination showed 10 (10.20%) benign and 88 (89.80%) malignant lesions. The ultrasound examination showed 14 (14.29%) benign and 84 (85.71%) suspected malignant lesions. The US-FNAC results showed 2 cases (2.04%) of type I, 9 cases (9.18%) of type II, 3 cases (3.06%) of type III, 29 cases (29.59%) of type IV, 39 cases (39.80%) of type V, and 16 cases (16.33%) of type VI, including 9 (9.18%) benign and 84 (85.72%) malignant lesions and 5 (5.10%) uncertain pathological natures. According to the median and quartile of nodular diameters, specifically, 1.90 (1.60, 2.30) cm, 93 nodules with decided pathological natures were divided into groups Q1 (n = 24, ≤1.6 cm), Q2 (n = 26, 1.7-1.9 cm), Q3 (n = 24, 2.0-2.3 cm), and Q4 (n = 19, >2.3 cm). The results of ROC analysis showed that the area under the curve (AUC), sensitivity, and specificity of US-FNAC diagnosis were 0.894, 98.80%, and 80.00%, respectively. The AUCs of US-FNAC in groups Q1, Q2, Q3, and Q4 were 0.978, 1.000, 0.977, and 0.971. The AUCs of Q1 group, Q2 group, Q3 group and Q4 group were all > 0.9, and US-FNAC had high diagnostic efficiency for the pathological properties of thyroid nodules with different diameters. US-FNAC has a high diagnostic efficiency for the pathological properties of thyroid nodules. Whether the nodule diameter has an effect on the accuracy of this method requires more clinical evidence.

Characterization of gram-negative bloodstream infections in hospitalised Australian children and their clinical outcomes.

Gram-negative bloodstream infections (GNBSI) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSI in children that relate the clinical presentation, pathogen characteristics and outcomes. A 3-year prospective study of GNBSI in children aged <18 years was conducted in five Australian children's hospitals between 2019-2021. The clinical characteristics, disease severity and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. There were 931 GNBSI episodes involving 818 children. Median age was 3 years (IQR 0.6-8.5). 576/931 episodes (62%) were community onset though 661/931 (71%) occurred in children with comorbidities and a central venous catheter (CVC) was present in 558/931 (60%). CVC (145/931) and urinary tract (149/931) were the most common sources (16% each). 100/931 (11%) children required Intensive Care Unit (ICU) admission and a further 11% (105/931) developed GNBSI in ICU. 659/927 (71%) isolates were Enterobacterales of which 22% (138/630) were third generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes (ESBL) were confirmed in 65/138 (47%) 3GCR-Enterobacterales. Most common ESBL genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted OR 3.2, 95%CI 1.6-6.4). GNBSI in children are frequently healthcare-associated and affect children under 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritise future antimicrobial clinical trials.

Systemic lupus erythematous in men with interstitial lung pneumonia: a rare case report

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with unknown etiology and very diverse clinical manifestations, disease course, and prognosis. It is most common in African-American women, the prevalence being 4 per 1000 females. SLE predominantly affects young women, most presenting between 20 and 40 years of age. Male SLE is rare, with only one male patient reported per nine females. Pulmonary involvement in SLE is various. SLE-associated interstitial lung disease (ILD), while rare, is a predictor of poor prognosis. We report a 50-year-old male patient with complaints of shortness of breath, previously diagnosed with systemic lupus erythematous by examination of the antinuclear antibody (ANA) profile. The patient underwent a computed tomography (CT) scan of the thorax and the results showed interstitial lung pneumonia. The patient was given azathioprine and methylprednisolone therapy for Systemic lupus erythematous and ceftriaxone and acetylcysteine ​​for interstitial lung pneumonia.

Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade.

Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p<0.0001), lower eosinophil count (p<0.0001), lower serum IgE levels (p<0.0001)), lower IgG4-RD responder index (RI) scores (p<0.0001), and fewer affected organ numbers (p<0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.