Search

Patients with non-infectious systemic inflammation may suffer from one of many diseases, including hyperinflammation (HI), autoinflammatory disorders (AID), and systemic autoimmune disease (AI). Despite their clinical overlap, the pathophysiology and patient management differ between these disorders. We aimed to investigate blood biomarkers able to discriminate between patient groups. We included 44 patients with active clinical and/or genetic systemic inflammatory disease (9 HI, 27 AID, 8 systemic AI) and 16 healthy controls. We quantified 55 serum proteins and combined multiple machine learning algorithms to identify five proteins (CCL26, CXCL10, ICAM-1, IL-27, and SAA) that maximally separated patient groups. High ICAM-1 was associated with HI. AID was characterized by an increase in SAA and decrease in CXCL10 levels. A trend for higher CXCL10 and statistically lower SAA was observed in patients with systemic AI. Principal component analysis and unsupervised hierarchical clustering confirmed separation of disease groups. Logistic regression modelling revealed a high statistical significance for HI (P = 0.001), AID, and systemic AI (P < 0.0001). Predictive accuracy was excellent for systemic AI (AUC 0.94) and AID (0.91) and good for HI (0.81). Further research is needed to validate findings in a larger prospective cohort. Results will contribute to a better understanding of the pathophysiology of systemic inflammatory disorders and can improve diagnosis and patient management., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study of sensitive and specific biomarkers, such as blood inflammatory cytokines, could provide an answer to the challenges faced in the differential diagnosis of patients with systemic inflammation. Limited data exist on the impact of age on serum levels of inflammatory cytokines. We collected serum samples of 42 healthy children and young adults (1 month to 21 years). Serum levels of interleukin 1 receptor antagonist (IL-1Ra), IL-1β, IL-6, IL-18, tumor necrosis factor-alpha (TNF-α), CXCL9, and CXCL10 were measured. Data were analyzed for three different age groups (<6, 6-17, and 18-21 years). IL-18, TNF-α, and CXCL9 values varied significantly according to age group. Median values of IL-18 and TNF-α decline with age, whereas CXCL9 and CXCL10 are lowest at 6-17 years. IL-1Ra is stable among age groups. In the majority of cases, IL-1β and IL-6 are not measurable above the lower limit of quantification. A scoping literature review revealed highly variable data on IL-1Ra, IL-18, TNF-α, and CXCL10. For CXCL9, pediatric reference data are scarce. In conclusion, we report an age-dependent signature of multiple inflammatory cytokines measured in the serum of healthy children and young adults, suggesting the need to use age-specific reference values in future pediatric studies.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome., Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified., Results: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes., Conclusions: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Systems thinking has emerged in recent years as a promising approach to understanding and acting on the prevention and amelioration of non-communicable disease. However, the evidence on inequities in non-communicable diseases and their risks factors, particularly diet, has not been examined from a systems perspective. We report on an approach to developing a system oriented policy actor perspective on the multiple causes of inequities in healthy eating., Methods: Collaborative conceptual modelling workshops were held in 2015 with an expert group of representatives from government, non-government health organisations and academia in Australia. The expert group built a systems model using a system dynamics theoretical perspective. The model developed from individual mind maps to pair blended maps, before being finalised as a causal loop diagram., Results: The work of the expert stakeholders generated a comprehensive causal loop diagram of the determinants of inequity in healthy eating (the HE2 Diagram). This complex dynamic system has seven sub-systems: (1) food supply and environment; (2) transport; (3) housing and the built environment; (4) employment; (5) social protection; (6) health literacy; and (7) food preferences., Discussion: The HE2 causal loop diagram illustrates the complexity of determinants of inequities in healthy eating. This approach, both the process of construction and the final visualisation, can provide the basis for planning the prevention and amelioration of inequities in healthy eating that engages with multiple levels of causes and existing policies and programs.

Poor diet may represent one pathway through which lower socioeconomic position (SEP) leads to adverse health outcomes. This study examined the associations between SEP and diet quality, its components, energy, and nutrients in a nationally representative sample of Australians. Dietary data from two 24-h recalls collected during the cross-sectional Australian Health Survey 2011-13 ( n = 4875; aged ≥ 19 years) were analysed. Diet quality was evaluated using the Dietary Guidelines Index (DGI). SEP was assessed by index of area-level socioeconomic disadvantage, education level, and household income. Linear regression analyses investigated the associations between measures of SEP and dietary intakes. Across all of the SEP indicators, compared with the least disadvantaged group, the most disadvantaged group had 2.5-4.5 units lower DGI. A greater area-level disadvantage was associated with higher carbohydrate and total sugars intake. Lower education was associated with higher trans fat, carbohydrate, and total sugars intake and lower poly-unsaturated fat and fibre intake. Lower income was associated with lower total energy and protein intake and higher carbohydrate and trans fat intake. Lower SEP was generally associated with poorer diet quality and nutrient intakes, highlighting dietary inequities among Australian adults, and a need to develop policy that addresses these inequities., Competing Interests: The authors declare no conflict of interest.

This study aimed to examine the changes in typical portion sizes of commonly consumed discretionary foods among Australian adults from 1995 to 2011-2012. Data of adults (age ≥19 years) from the 1995 Australian National Nutrition Survey and 2011-2012 National Nutrition and Physical Activity Survey were used. Typical portion sizes (median portion) of fourteen discretionary foods that contributed the most to energy intake were determined. Ten out of fourteen food categories demonstrated a significant change in kJ per typical portion from 1995 to 2011-2012 ( p ≤ 0.001). kJ per typical portion increased for pizza, cake, sausage, cereal bar, processed meat, ice cream and wine, with pizza and cake demonstrating the largest increases (+570 kJ and +950 kJ in 2011-2012, respectively; both +66% above 1995). In contrast, kJ per typical portion of pastry, snack food and potato fries decreased by 10-40% over time, and did not change for biscuit, chocolate, sugar-sweetened beverage and beer. Similar changes were observed for grams per typical portion consumed. Temporal trends in typical portion sizes were similar according to age group, gender and socioeconomic status. The findings suggest that population-wide strategies that enable consumers to choose smaller portions of discretionary foods are needed to reduce the excess consumption of these products., Competing Interests: The authors declare no conflict of interest. No financial support to declare.

Objective: To elucidate the difficulty of cytologically differentiating high grade squamous intraepithelial lesion (SIL) with extension into the endocervical clefts from adenocarcinoma in situ (AIS). Criteria for the cytologic diagnosis of AIS have been delineated. However, it may sometimes be difficult to differentiate between AIS and carcinoma in situ (CIS)., Study Design: We reviewed cervical smears initially diagnosed as glandular intraepithelial neoplasia (GIN) with or without associated SIL CIN; in total, slides from 10 patients were studied. The final diagnosis in two cases was SIL plus GIN, in three cases high grade SIL (HSIL) (CIN 3) plus tubal metaplasia and in five cases HSIL without GIN., Results: The cervical smears from the last five cases showed, besides features diagnostic of HSIL, the presence of large, crowded sheets with feathering, consisting of fusiform cells with an oval, bare, hyperchromatic nucleus, reminiscent of AIS. At one end of these sheets, normal endocervical cells were sometimes present. In all these cases the cone biopsy revealed HSIL with extension into the endocervical clefts., Conclusion: In retrospect, differential diagnosis with AIS is possible in most cases if diagnostic criteria are strictly applied. Indeed, contrary to AIS, feathering is often restricted to one end of the crowded sheets. Moreover, none of these crowded sheets contains glandular openings, and strips and rosettes with pseudostratification are absent.

We reviewed the few published cases of male urethral squamous cell carcinoma after urethroplasty. A new case report is added. Considering the known facts we conclude that urethral cancer following urethroplasty, performed to cure urethral stricture, is a rare complication. One must be aware of possible evolution to malignancy when this surgical procedure is not fully successful, i.e. in the case of recurring urinary obstruction or disturbed wound healing. Alarming symptoms are fistulization, abscess formation, ulceration and induration. Histopathological examination is needed, firstly before urethroplasty to exclude already existing malignant changes of the urethral mucosa and secondly whenever suspicion is raised after surgery. It is of utmost importance to diagnose a urethral carcinoma as early as possible because the cure rate in advanced stage is minimal.