Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reactivating T cell-mediated anti-tumor immunity. However, this enhanced immune activity can lead to immune-related adverse events (irAEs). This narrative review focuses on endocrine irAEs, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. It also explores infectious complications and their underlying mechanisms. These mechanisms include immune dysregulation resulting directly from ICI-induced T-cell activation and indirectly from the immunosuppressive therapies used to treat irAEs. Furthermore, potential role of endocrine irAEs in predisposing patients to infectious complications is analyzed. The objective is to provide non-oncology specialists with the clinical insight necessary to recognize and manage these complex side effects. This narrative review synthesizes current literature on the diagnosis, management, and pathophysiology of endocrine irAEs and infections associated with different classes of ICIs (anti-CTLA-4, anti-PD-1, and anti-PD-L1). Endocrine irAEs are common, with incidence varying by ICI type; combination therapies pose the highest risk. Thyroid dysfunction is the most frequent, followed by hypophysitis, which often leads to permanent secondary adrenal insufficiency. ICI-induced diabetes mellitus is a rare but serious complication, frequently presenting as diabetic ketoacidosis. ICIs are believed to induce a distinct array of infections resulting from immunological dysregulation, unrelated to immunosuppressive medication. The phenomenon is increasingly called ICI therapy-induced dysregulated immunity. Moreover, evidence suggests that endocrine irAEs can compromise immune function and lead to a significantly higher risk of bacterial and fungal infections. Identifying infections that imitate irAEs is particularly important because the therapy is significantly distinct. Greater interdisciplinary awareness is crucial for the early recognition and appropriate management of both the endocrine and infectious complications, ultimately improving the safety and outcomes for patients receiving immunotherapy.

Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study. Reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect flavivirus RNA in clinical samples (cerebrospinal fluid; CSF, urine). ELISA was used for IgM and IgG antibody detection in serum and CSF with confirmation of cross-reactive samples by virus neutralization test. WNV was detected more frequently (74.4%) than TBEV (25.6%). A statistically significant age difference was found between WNV patients (median 65 years) and TBEV patients (median 36 years). Comorbidities were more frequently detected in WNV patients (hypertension 56.3 vs. 18.2%; diabetes 31.3 vs. 0%). Meningitis was the most common clinical presentation in both TBE and WNV neuroinvasive disease (WNND; 63.6 and 59.4%, respectively). In addition, some rare clinical presentations of WNND were also detected (cerebellitis, polyradiculoneuritis). No significant differences in the frequency of clinical symptoms were observed between WNV and TBEV-infected patients (fever 93.7 vs. 100%; malaise 78.1 vs. 100%; headache 75.0 vs. 100%; nausea 50.0 vs. 63.6%; vomiting 34.4 vs. 54.6%). Comparative analysis of total and differential leukocyte blood count showed similar results. However, CSF pleocytosis was higher in TBE patients, with a significant difference in the neutrophil and lymphocyte count (WNND median 48.5% and 51.5%; TBE median 10.0 and 90.0%, respectively). The length of hospital stay was 12 days for WNND and 9 days for TBE. Phylogenetic analysis of detected WNV strains revealed the presence of WNV lineage 2 in eastern Croatia.

Background: Pancreatic stone protein (PSP) has emerged as a promising biomarker for the early diagnosis of sepsis, infectious diseases, and chronic inflammatory conditions, including cancer, diabetes, and inflammatory bowel disease. This review evaluates the role of PSP as a biomarker and functional protein, emphasizing its diagnostic and prognostic value. Methods: This review was conducted through a comprehensive literature search using the PubMed database, covering publications from the discovery of PSP in the 1980s up to 2025. The information was gathered into thematic sections to provide a comprehensive and structured review of PSP as a biomarker and functional protein in health and disease. Results: A total of 256 articles were reviewed and critically assessed, with 80 meeting the inclusion criteria and forming the basis of this review. The reviewed literature underscores PSP as a multifaceted protein involved in inflammation, immune modulation, tissue regeneration, and systemic infection. PSP shows promise as an early biomarker in critically ill patients. Conclusions: PSP is a clinically promising but not yet fully validated biomarker. To enable its routine clinical application, standardized diagnostic cutoffs, validation through multicenter trials, and integration with existing biomarker panels are required. Further research is warranted to fully establish its diagnostic and prognostic potential across diverse clinical settings.

Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine associated with acute and chronic inflammatory states. This prospective observational study aimed to investigate the prognostic roles of GDF-15 and routine clinical laboratory parameters in COVID-19 patients. Upon the admission of 95 adult hospitalized COVID-19 patients in Croatia, blood analysis was performed, and medical data were collected. The patients were categorized based on survival, ICU admission, and hospitalization duration. Logistic regression and ROC curve methods were employed for the statistical analysis. Logistic regression revealed two independent predictors of negative outcomes: CURB-65 score (OR = 2.55) and LDH (OR = 1.005); one predictor of ICU admission: LDH (OR = 1.004); and one predictor of prolonged hospitalization: the need for a high-flow nasal cannula (HFNC) upon admission (OR = 4.75). The ROC curve showed diagnostic indicators of negative outcomes: age, CURB-65 score, LDH, and GDF-15. The largest area under the curve (AUC = 0.767, specificity = 65.6, sensitivity = 83.9) was represented by GDF-15, with a cutoff value of 3528 pg/mL. For ICU admission, significant diagnostic indicators were LDH, CRP, and IL-6. Significant diagnostic indicators of prolonged hospitalization were CK, GGT, and oxygenation with an HFNC upon admission. This study reaffirms the significance of the commonly used laboratory parameters and clinical scores in evaluating COVID-19. Additionally, it introduces the potential for a new diagnostic approach and research concerning GDF-15 levels in this widespread disease.

Background: COVID-19 is a multisystem disorder associated with inflammatory, metabolic, electrolyte, and endocrine disturbances. However, the clinical relevance of dysnatremia and acute hormonal alterations remains uncertain, particularly when assessed alongside established clinical risk factors. Methods: This prospective cohort study included 252 adults hospitalized with confirmed COVID-19. Clinical, laboratory, hormonal, and metabolic parameters were assessed at admission, and their associations with disease severity, intensive care unit (ICU) admission, and in-hospital mortality were analyzed. Results: The median age was 73 years, 50.4% of patients were female, and severe or critical disease was present in 81.7%. Dysnatremia and/or endocrine alterations were detected in 55.2% of patients, including hyponatremia in 16.7%, while thyroid-function alterations were observed in 40.9%. Dysnatremia was associated with higher glucose levels and inflammatory-cell changes. Several hormonal and metabolic parameters showed statistically significant univariate associations with adverse outcomes; however, their discriminative performance was weak, with AUC values below clinically meaningful thresholds. After adjustment for major clinical confounders, dysnatremia and endocrine alterations were not independent predictors of disease severity, ICU admission, or mortality. Conclusions: These findings suggest that electrolyte and endocrine abnormalities in hospitalized COVID-19 patients primarily reflect systemic stress physiology and acute disease burden rather than functioning as independent prognostic biomarkers.