We report a case of severe hypercalcaemia after a single cycle of a combination therapy of ipilimumab and nivolumab. Initial evaluation ruled out common causes, including bone metastases, parathyroid hormone/parathyroid hormone-related protein elevation and paraproteinaemia. Her serum 1,25-dihydroxyvitamin D (calcitriol) levels were significantly elevated following the first immunotherapy cycle. Hypercalcaemia responded only to glucocorticoid therapy, with normalisation of serum calcium and calcitriol levels. Recurrence of hypercalcaemia after glucocorticoid discontinuation and subsequent resolution with glucocorticoid re-initiation strongly supported a calcitriol-mediated mechanism, most likely as an immune-related effect of ipilimumab and nivolumab.

Accumulating evidence has pointed out that the altered expression of long non-coding RNAs (lncRNAs) is involved in the physiopathology of breast cancer (BC). However, the role of lncRNAs in BC progression remains poorly understood. Here, we evaluated cDNA microarray data from a previous study from our group to investigate the effects of SPARC expression on the transcriptome of MCF7 cells before and after treatment with docetaxel. We analyzed our gene expression data to identify differentially expressed long non-coding RNAs (DELncRNAs). In combination with in silico analysis, we selected a group of DELncRNAs with potential prognostic and predictive value for BC patients with tumors of different intrinsic subtypes. Overall, we identified 260 DELncRNAs comparing MCF7 cells with different expressions of SPARC after docetaxel treatment. Nine DELncRNAs (LOC646762, FLJ13224, CASC2, LOC100130691, MGC12916, LOC100190986, LOC283856, KIAA0125, and MIR155HG) showed significant associations with BC survival on the KM Plotter platform. Of these 9 DELncRNAs, MIR155HG, LOC283856, LOC100190986, and KIAA0125 were significantly correlated with recurrence-free survival and overall survival rates of BC patients, suggesting they could help predict the outcome of BC patients as prognostic factors. Moreover, in silico analysis showed that these DELncRNAs were able to predict BC patients' responses to different treatment protocols.

When, ∼20 years ago, investigators first determined that components of the genome considered nonfunctional had, in fact, gene regulatory capacity, they probably had no idea of their potential in controlling cell fate and were forced to revise and somehow reorganize their view of the molecular biology. Indeed, it is currently well documented how a class of small non-coding RNAs, microRNAs, are conserved among the species, expressed in different tissues and cell types and involved in almost every biological process, including cell cycle, growth, apoptosis, differentiation and stress response, exerting a finely tuned regulation of gene expression by targeting multiple molecules. As a consequence of the widespread range of processes they are able to influence, it is not surprising that miRNA deregulation is a hallmark of several pathological conditions, including cancer. Indeed, the aberrant expression of these tiny molecules in human tumors is not just a casual association, but they can exert a causal role, as oncogenes or tumor suppressors, in every step of tumor development, from occurrence to progression. An increasing body of evidence has indeed proved the importance of miRNAs in cancer, suggesting their possible use as diagnostic, prognostic and predictive biomarkers and leading to exploit miRNA-based anticancer therapies, either alone or in combination with current targeted therapies, with the goal to improve disease response and increase cure rates. Here, we review our current knowledge about miRNA involvement in cancer.

Chronic liver disease (CLD) represents a major global public health challenge, necessitating a systematic understanding of its complex immunopathological mechanisms. This review comprehensively summarizes the groundbreaking applications of cutting-edge technologies-including single-cell sequencing, spatial transcriptomics, and organoid models-in chronic liver disease immunology research: Single-cell sequencing resolves immune cell heterogeneity at unprecedented resolution, identifies rare cell subsets, and reveals dynamic changes and regulatory networks through multi-omics integration; Spatial transcriptomics complements this by mapping immune-stromal interactions within structural contexts such as the portal tract, fibrotic septa, and tumor niches, uncovering spatially organized immune evasion mechanisms and microenvironmental remodeling; Organoid technology constructs humanized liver-immune models that recapitulate disease-specific features-such as fibrosis, steatohepatitis, and hepatocellular carcinoma-enabling mechanistic validation, drug screening, and individualized therapeutic exploration. The synergistic integration of multi-omics profiling, spatial mapping, and organoid modeling is driving a paradigm shift in chronic liver disease immunology-transitioning from static cellular descriptions to spatiotemporal mechanism decoding, and from population-level insights to individualized pathophysiology and treatment prediction. These advanced approaches establish a technological foundation for building precision immunotherapeutic strategies tailored to spatiotemporal regulation of the liver immune microenvironment.

Multiple myeloma (MM) is an intractable hematologic malignancy characterized by clonal growth of malignant plasma cells in the bone marrow. Recent studies have highlighted the role of N6-methyladenosine (m6A) RNA modifications in MM progression; however, the function of the m6A demethylase fat mass and obesity-associated protein (FTO) remains unclear. This study aims to explore the mechanisms by which FTO-mediated m6A demethylation of Serpin Family F Member 1 (SERPINF1) impacts MM progression. SERPINF1 and FTO expressions were assessed via real-time quantitative polymerase chain reaction (RT-qPCR). The impact of such expressions on MM was evaluated using CCK-8, EdU, transwell, and tumor xenograft model assays. Key molecules involved in the Wnt/β-catenin pathway were assessed via Western blotting. The relationship between SERPINF1 and FTO was determined through correlation analysis, methylated RNA immunoprecipitation, luciferase, RT-qPCR, Western blotting, RNA immunoprecipitation, and actinomycin D treatment assays. Finally, the effect of their interaction on MM was assessed through rescue experiments. SERPINF1 expression was reduced in MM samples. SERPINF1 overexpression suppressed the malignant traits of MM cells and reduced the levels of β-catenin, c-Myc, and cyclin D1. In vivo experiments revealed that SERPINF1 overexpression suppressed tumor growth in xenograft models. Mechanistically, FTO expression was upregulated in MM and SERPINF1 expression was negatively regulated by demethylating its m6A sites via IGF2BP1. Rescue experiments demonstrated that SERPINF1 overexpression reversed FTO-induced oncogenic phenotypes. These findings suggest that FTO-mediated m6A demethylation suppressed SERPINF1 expression in MM, whereas SERPINF1 overexpression inhibited tumor progression via the Wnt/β-catenin pathway.

To create a prognostic scale for overall survival in grade 4 astrocytomas based on molecular biological data.

After morphological confirmation of WHO grade 4 astrocytoma (2021 WHO classification criteria), 175 patients were classified as GBM (grade 4) without IDH1 mutations; IDH1 mutation was detected in 25 patients (12.5%; G4 astrocytoma). Molecular biological analysis of IDH1 gene mutations and MGMT promoter methylation was performed in 194 (97%) patients.

To study concomitant significance of IDH1 mutation and MGMT promoter methylation in grade 4 gliomas, we created the IDH1/MGMT index(0 - IDH1+/MGMT+; 1 - IDH1/MGMT (+/-); 2 - IDH1-/MGMT-). This predictor was digitized in 194 patients who underwent molecular analysis. The most informative classification matrix according to overall survival was as follows: IDH1/MGMT index (OR=1.712; p=0.0004), REP (OR=1.971; p=0.0001), functional status before microsurgery at the lowest possible level (OR=1.797; p=0.001). Simple summation of numerical indicators for factors 1-3 in each patient allowed us to identify 5 prognostic classes: class 1 (0-1 points), class 2 (2 points), class 3 (3 points), class 4 (4 points), class 5 (5 points). Log-rank criterion for Kaplan-Meier survival curves revealed significant differences between classes (χ²=55.780; p<0.001). The median survival rates were 71.5, 42.3, 23.6, 17.4 and 8.1 months, respectively. Significant differences in survival were noted between almost all neighboring classes: classes 1-2 (χ²=3.21; p=0.073), classes 2-3 (χ²=5.77; p=0.016), classes 3-4 (χ²=6.03; p=0.014), classes 4-5 (χ²=11.97; p=0.0005). In "classes 1-3" in prognostic scale, median overall survival was 44.98 months (n=53; 95% CI: 20.5-69.4) for 3 Gy fractionation regimen and only 23.23 months (n=78; 95% CI: 17.3-29.1; χ²=9.28; p=0.002) for 2 Gy regimen. There were other results for classes 4-5. Median overall survival for 3 and 2 Gy fractionation regimens was low: 17.41 (n=28; 95% Cl: 13.8-21.0) and 15.83 months (n=41; 95% Cl: 11.7-20.0; -2=0.59; p=0.442), respectively.

The new prognostic scale for overall survival, based on molecular data, allows not only to predict further course of disease, but also to recommend irradiation 3 Gy for patients in classes 1-3 as an alternative to radiotherapy.

Epistaxis is common during pregnancy due to physiological changes, yet its clinical significance regarding obstetric outcomes is poorly understood. This study investigated the associations between epistaxis during pregnancy and maternal and neonatal outcomes.

We conducted a retrospective case-control study (2013-2022) at a single tertiary medical center. The study group included 104 pregnant women presenting with epistaxis, matched with 1924 controls based on age, ethnicity, and preexisting comorbidities. Multivariable logistic regression was used to identify independent predictors of adverse outcomes, including blood transfusion and preterm labor.

Women with epistaxis experienced significantly higher rates of third-trimester vaginal bleeding (7.7% vs. 1.1%; p < 0.001), preterm labor (15.4% vs. 8.7%; p = 0.022), and blood transfusion requirements (4.8% vs. 1.6%; p = 0.014). In a multivariable model, third-trimester epistaxis emerged as an independent predictor for blood transfusion (OR 4.96, 95% CI 1.47- 14.38; p = 0.005), even after adjusting for delivery mode and initial hemoglobin levels. While univariate analysis associated epistaxis with preterm labor, this relationship did not remain significant in the multivariable model (p = 0.254). Most epistaxis episodes (81.7%) were mild and resolved spontaneously.

Epistaxis during pregnancy, particularly in the third trimester, is independently associated with a nearly fivefold increase in the odds of requiring a blood transfusion. While typically considered benign, epistaxis may serve as a clinical marker for systemic vascular susceptibility. These findings suggest that pregnant women presenting with epistaxis may benefit from enhanced clinical surveillance and interdisciplinary coordination to manage potential peripartum hemorrhagic complications.

Long Covid (LC) is a multisystem condition leading to a wide range of symptoms and often requiring treatment by several different clinical specialties. Patients with LC have reported difficulties in accessing care and a lack of coordination of their care, particularly in a hospital setting.

To determine the extent to which the intensity and continuity of hospital care changes for patients after they receive an LC diagnosis.

Retrospective observational cohort study using a linked primary and secondary care dataset.

Routine healthcare data from North West London Integrated Care System of patients with a recorded diagnosis of LC who had attended a secondary care hospital Trust from 1 January 2019 to 30 September 2023.

The intensity of utilisation of secondary care was calculated, and the continuity of care with respect to hospitals and specialties was computed using the sequential continuity score (SeCon) before the Covid-19 pandemic, before and after an LC diagnosis.

5611 out of 6270 (90.1%) patients diagnosed with LC had a recorded secondary care interaction in the study period. Intensity of secondary care utilisation increased markedly in outpatient, inpatient and Emergency Department pathways after a diagnosis of LC but peaked in the week of diagnosis. Average hospital SeCon fell significantly after an LC diagnosis from 1.00 to 0.83, while specialty SeCon remained unchanged from after diagnosis (0.40) and before the pandemic (0.44). A notable shift in specialty activity was observed with a focus on respiratory medicine as a major hub in a densely connected patient-sharing network with cardiology and other medical and surgical specialties.

A recorded LC diagnosis was associated with increases in the intensity of hospital activity and a reduction in hospital-level care continuity, but no change in specialty continuity, which remains low.

Collectively, this indicates a significant need to support LC patients as they navigate fragmented secondary care pathways.

This study was co-designed with, conducted with and written in conjunction with people with long Covid.

To identify the prevalence and factors associated with symptoms of depression, anxiety, and stress among university students in Minas Gerais after the COVID-19 pandemic.

A cross-sectional study was conducted with students from four federal universities in Minas Gerais. Data collection was carried out online. To identify associated factors, a structured questionnaire was administered, encompassing sociodemographic, clinical, and academic variables, as well as the Depression, Anxiety, and Stress Scale (DASS-21). To determine the risk and protective factors associated with the investigated symptoms, a multivariate logistic regression analysis was performed, with a 5% significance level.

A total of 2,333 students participated in the study, comprising 75.6% (n=1,764) females and 24.4% (n=569) males, aged 18 to 62 years. The prevalence of symptoms was 77.2% (n=1,802) for depression, 76.8% (n=1,790) for anxiety, and 77.3% (n=1,803) for stress. Identified risk factors for all three outcomes were female sex (p-value<0.050), overload with academic routine after the pandemic (p-value<0.001), and the impact of the pandemic on academic performance (p-value<0.001) and future professional outlook (p-value<0.001). Family income equal to or above four minimum wages was a protective factor against symptoms of depression, anxiety, and stress (p-value<0.001). Receiving a student scholarship was specifically a protective factor for symptoms of anxiety (p-value 0.046).

A large proportion of university students in Minas Gerais presented symptoms of depression, anxiety, and stress after the COVID-19 pandemic. The implementation of psychosocial policies and interventions grounded in the identified protective factors is necessary.

To present the experience report of the Health Surveillance Department of Goiânia, Goiás, in conducting four seroepidemiological surveys aimed at estimating the seroprevalence of SARS-CoV-2 infection in 2020, describing the operational and methodological stages as well as the challenges encountered.

This is an experience report on the organization and implementation of four household-based seroepidemiological surveys conducted amid the rising COVID-19 transmission in 2020. The municipal health surveillance team conducted the activities by administering standardized questionnaires and collecting venous blood samples for serological testing.

In each survey, approximately 300 public health professionals visited around 2,500 households in a single day. In total, 10,147 individuals aged 5 years and older were recruited. The main challenges involved resource and field team organization, methodological design, laboratory support, and community participation. These obstacles were overcome through external partnerships, method standardization, and a systematized organizational structure.

The experience demonstrated that, despite operational constraints, municipal health surveillance can conduct large-scale seroepidemiological surveys within a short time frame. Intersectoral mobilization and process systematization facilitated the overcoming of challenges, resulting in a replicable strategy for other communicable diseases in emergency contexts.