Search Results (417)

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. Full article

Background/Objectives: New vaccines designed to combat infections such as Group B Streptococcus and respiratory syncytial virus will soon be accessible in Africa. While outbreak response vaccines are given to pregnant women, safety data for maternal vaccines in low- and middle-income countries (LMICs) are limited. This study explored Ugandan pregnant women’s knowledge, attitudes, and engagement in adverse event reporting and vaccine decision-making. Methods: This nested qualitative study was part of a national gap analysis of pharmacovigilance systems for maternal vaccines. Five Focus Group Discussions (FGDs), each involving eight participants, were held with pregnant and or breastfeeding women at four healthcare facilities and one research center. The data collected from these discussions were analyzed thematically using a manifest content analysis, conducted in Atlas.ti software version 9 for qualitative data analysis. Results: Women valued maternal vaccines, particularly tetanus, but reported confusion about schedules and hesitancy when informed of potential side effects. Many adverse events were normalized, therefore not reported, and most participants were unaware of national reporting mechanisms beyond informing healthcare providers. Barriers included inadequate information, dismissive or rushed provider interactions and reliance on family, peers, and informal care networks to manage side effects. Women expressed a strong desire to be informed and actively involved in decisions about pregnancy vaccines, including the introduction of new vaccines. Conclusions: Strengthening maternal vaccine safety monitoring requires clearer, balanced communication; simplified and well-publicized reporting tools; supportive provider–patient interactions; and integration of community and informal networks. Pregnant women should be engaged as active partners in pharmacovigilance and maternal vaccine introduction to build trust, improve adverse event reporting, and support vaccine uptake. Full article

Background: With the emergence of SARS-CoV-2 Omicron sub-variants exhibiting increased transmissibility and immune escape, booster immunization is recommended. Ideally, vaccination across all age groups, including children and adolescents, is critical to control viral spread and reduce variant emergence. The heterologous scheme consisting of two doses of SOBERANA^® 02 followed by a third dose of SOBERANA^® Plus, which are recombinant protein subunit vaccines constructed from the ancestral RBD, has proven safety, immunogenicity, and effectiveness in pediatric populations as primary series. This study evaluated the safety and immunogenicity of a SOBERANA^® Plus booster dose administered six months after primary vaccination in individuals aged 3–18 years. Methods: In this follow-up analysis of a phase I/II trial, 244 participants received the booster. Safety was monitored via active surveillance at 1 h, 24 h, and over 28 days post-vaccination. Humoral responses were assessed 28 days post-booster. Antibody responses to the SARS-CoV-2 nucleocapsid (N) protein were assessed in all collected serum samples. Results: Adverse events occurred in 18% of participants, predominantly local (85.2%) versus systemic (14.8%); no serious or severe adverse events were reported. All humoral response parameters increased significantly post-booster, including neutralizing antibodies against D614G (24.7-fold increase) and Omicron BA.1 (55.9-fold increase), with similar responses in N-negative and N-positive individuals. Importantly, cross-neutralizing activity against recent Omicron sub-variants (XBB.1.5 and EG.5.1) was also detected. Conclusions: A SOBERANA^® Plus booster is safe and significantly enhances cross-neutralizing immunity against evolving Omicron sub-variants in children and adolescents. These results highlight the potential of first-generation RBD-based vaccines to maintain broad immunity despite viral evolution. Full article

Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-COVID Syndrome (PCS) are chronic conditions that share relevant pathophysiological mechanisms. Conventional rehabilitation programs have often been associated with patient dissatisfaction and frequent adverse events (AEs), highlighting the need for safer and more effective clinical approaches. This study aims to compare the effects of a telerehabilitation program based on conscious movement with those of conventional low-intensity exercise in individuals with ME/CFS or PCS. Methods: This is a prospective, single-blind, three-arm, parallel, superiority randomized clinical trial. A total of 147 participants (aged 18–70) with ME/CFS or PCS will be recruited and randomly assigned to one of three groups: (a) conscious movement; (b) low-intensity exercise; or c) usual care. All interventions will be delivered via telehealth over 12 weeks, with weekly 45-min sessions combining health education and individually tailored exercises. Participants will be encouraged to practice daily using the provided materials. Adherence rates and potential AEs will be recorded. The primary outcome is the total score on the 14-item Chalder Fatigue Scale at 12 weeks (post-intervention). Secondary outcomes include heart rate variability, functional performance, pain intensity and interference, mental health, interoceptive awareness, quality of life, sleep quality and fear of movement. Measurements will be collected at baseline, post-intervention, and at 3-month follow-up. Discussion: Recent evidence suggests that both autonomic and cognitive activity modulate immune function. Conscious movement, which integrates exercise with interoception and mindfulness-based strategies, may provide greater benefits than low-intensity exercise alone. Study limitations should be considered when interpreting the results. Trial registration: Registered at ClinicalTrials.gov on 15 May 2025 (NCT06978582). Protocol version 4 (29 September 2025). Ethics Committee code: 2025-0180. Full article

Background and Clinical Significance: Targeted biologic therapies, especially monoclonal antibodies (mAbs) such as nivolumab and alemtuzumab, have revolutionized treatment for malignancies and autoimmune conditions but can cause rare immune-related adverse events (IRAEs), including orbitopathy. To date, only a handful of cases have described the treatment of thyroid eye disease secondary to mAbs, and even fewer have described how to treat refractory disease. Case Presentation: We are illustrating two cases in this report: a 73-year-old woman who developed thyroid eye disease (TED) after nivolumab therapy for melanoma, and a 36-year-old man who presented with TED following alemtuzumab treatment for multiple sclerosis. Both patients failed corticosteroid therapy but showed a significant improvement with teprotumumab, an anti-insulin-like growth factor (IGF)-1 receptor mAb. Conclusions: These cases highlight underrecognized orbital IRAEs linked to mAb therapy and demonstrate teprotumumab’s potential as an effective option for steroid-refractory thyroid orbitopathy. Clinicians should maintain an awareness of orbital complications in patients receiving mAbs to enable prompt diagnosis and intervention, minimizing visual morbidity. Further studies are needed to clarify the pathogenesis of mAb-associated orbitopathy and to establish evidence-based treatment protocols for these rare but impactful complications. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the management of several malignancies, including melanoma, non-small cell lung cancer, and urothelial carcinoma. However, these therapies frequently cause endocrine immune-related adverse events (irAEs), such as thyroid dysfunction, hypophysitis, or autoimmune diabetes, and may carry important prognostic implications. This systematic review and meta-analysis aimed to determine the incidence, spectrum, and clinical significance of endocrine irAEs across major tumor types. Methods: Following PRISMA guidelines and PROSPERO registration (CRD42025646504), we systematically searched PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus for studies reporting endocrine irAEs in ICI-treated patients. Random-effects meta-analyses estimated pooled hazard ratios (HRs) for overall (OS) and progression-free survival (PFS) and odds ratios (ORs) for adverse events. Subgroup and meta-regression analyses explored associations by cancer type, ICI class, and event severity. Results: Forty-three studies comprising 17,399 patients were included. Endocrine irAEs occurred in 11–30% of patients and were associated with improved OS (HR: 0.60, 95% CI: 0.54–0.67; p < 0.001) and PFS (HR: 0.61, 95% CI: 0.54–0.68; p < 0.001). Severe events were most frequent with pembrolizumab in melanoma and non-small cell lung cancer and with anti-programmed death-ligand 1 therapy in urothelial carcinoma. In exploratory meta-regression analyses accounting for cancer type, ICI subclass, and irAE severity, no statistically significant correlation was observed between the occurrence of endocrine irAEs (OR) and survival benefit (PFS HR: 0.20, 95% CI −0.10 to 0.51; p = 0.19; OS HR: 0.14, p > 0.05). Conclusions: The development of endocrine irAEs coincides with favorable long-term survival outcomes but may represent surrogate markers of immune activation rather than direct predictors of ICI efficacy. However, the lack of consistent ≥ 3-year follow-up across studies warrants cautious interpretation. Routine endocrine monitoring and interdisciplinary management are essential to optimize the safety and effectiveness of immunotherapy. Full article

This study aimed to assess the prevalence and reporting rate of adverse events following immunization (AEFIs) among healthcare professionals (HCPs) and students of health-related disciplines after COVID-19 vaccination. It was conducted at the beginning of the vaccination campaign in Poland (February 2021), when vaccines were only available to limited groups of recipients, mainly those related to healthcare. Questionnaires were distributed among HCPs in the Pomeranian voivodeship (N = 1063) and students at the Medical University of Gdańsk (N = 1506). The primary objective was to compare respondents’ self-reported AEFI notifications with official reports published by the National Sanitary Inspectorate. A total of 240 participants declared having reported at least one AEFI, whereas official reports from the same period indicated that only 194 individuals had reported AEFIs in the entire voivodeship. This translates into significant differences in notification rates (14.9% and 0.09%, respectively). A detailed breakdown into local and systemic AEFIs also revealed significant discrepancies with official reports (850 vs. 329 and 1137 vs. 46, respectively). The most common reasons for not reporting were managing the symptoms on one’s own and perceiving the symptoms as not severe enough to report. Underreporting of AEFIs is an issue that requires attention from both the scientific community and public health authorities, as it may hinder reliable vaccine safety assessment and contribute to increased vaccine hesitancy. Full article

Background: Influenza vaccines have been administered in Jiangsu Province. This study aimed to conduct a comprehensive retrospective analysis of influenza vaccine safety in the region from 2019 to 2023. Methods: Data were sourced from the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) and Jiangsu Provincial Electronic Immunization Registries System (JSEIRS) systems. A comprehensive retrospective analysis was performed to calculate the incidence rates of adverse events following immunization (AEFI) and to identify potential safety signals through disproportionality analysis. Results: Out of 4,906,905 administered doses, 2080 AEFI cases were reported, yielding an overall incidence rate of 42.39 per 1,000,000 doses. Significantly higher rates were observed in children aged 6–35 months (71.03 per 1,000,000) and among recipients of trivalent vaccines (52.79 per 1,000,000) compared to quadrivalent vaccines (36.03 per 1,000,000). The vast majority of AEFIs were mild, common adverse reactions (94.47%, predominantly fever and local reactions), occurring predominantly within one day post-vaccination, while disproportionality analysis identified expected signals for common adverse reactions and rare local purulent infections. Conclusions: Overall, the findings affirm the vaccine’s favorable safety profile, align with pre-marketing data, and underscore the critical role of continuous post-marketing surveillance in maintaining public confidence and monitoring the safety of both established and new vaccine formulations. Full article

Background: Acute respiratory infections (ARIs) pose a significant clinical challenge in paediatric populations, especially in children with comorbidities who may exhibit underlying immune dysregulation. Inosine pranobex (IP) is an immunomodulatory agent that enhances T-lymphocyte and Natural Killer (NK) cell function, offering a targeted therapeutic rationale for such cases. Objective: This study aimed to retrospectively describe the clinical characteristics, immunological profiles, and outcomes of paediatric patients with complex, PCR-confirmed viral ARIs and significant comorbidities, for whom adjunctive therapy with IP was initiated based on clinical judgment. Methods: This retrospective case series analysed data from 14 paediatric patients hospitalised at a specialised centre (National Institute of Paediatric Tuberculosis and Respiratory Diseases in Dolny Smokovec, Slovakia). Cases were selected based on PCR-confirmed viral ARI, a history of recurrent infections, significant comorbidities, and initiation of IP therapy. The indication for IP was guided by the treating physician in cases of severe, prolonged, or recurrent disease course, where immune dysregulation was suspected, often supported by prior immunophenotyping. Results: A frequent observation in this cohort was the presence of baseline cellular immune alterations with a frequent observation of baseline cellular immune alterations, most notably the depletion of natural killer (NK) cells. NK cell depletion was identified in half of the patients (7/14). Following the initiation of treatment regimens that included adjunctive IP, clinical stabilisation or improvement was observed in all 14 patients included in the study. The therapy was well tolerated, with no reported adverse events attributable to IP. Conclusions: This case series highlights the common presence of cellular immune alterations in children with complex ARIs. While the observational nature of this study precludes any conclusions about causality, the favourable clinical course, safety profile, and strong immunological rationale support the need for prospective controlled trials to evaluate the role of IP in this specific high-risk paediatric population. Full article

Background/Objectives: Teclistamab is a bispecific antibody targeting BCMA and CD3, approved for relapsed/refractory multiple myeloma. It is administered continuously until progression or intolerance; however, prolonged use may increase infections and treatment burden. This study compares continuous versus fixed-duration teclistamab to determine whether treatment discontinuation after response is feasible without compromising outcomes. Methods: A multicenter retrospective study was conducted on adults with relapsed/refractory multiple myeloma treated with teclistamab between August 2022 and May 2024. Patients received step-up dosing followed by weekly administration. Those who achieved ≥VGPR and discontinued therapy due to deep response, toxicity, or preference were assigned to the fixed-duration group. Outcomes included response rates, progression-free survival (PFS), overall survival (OS), and adverse events. Results: Eighty-eight patients were included (continuous: n = 72; fixed: n = 16). The fixed group had higher complete response rates (69% vs. 44%) and shorter median time to best response (1 vs. 2 months). Median PFS was 16 months for continuous dosing versus 13 months for fixed-duration. Twelve-month PFS was similar (65% vs. 66%). Twelve-month OS was 83% vs. 81% in the continuous and fixed groups, respectively. Cytokine release syndrome and neurotoxicity rates were similar. Infections were more frequent and severe in the fixed cohort (75% any grade; 69% grade ≥ 3). Conclusions: Fixed-duration teclistamab after deep response appears feasible in appropriately selected patients, with comparable early survival outcomes to continuous treatment. Prospective studies are needed to define selection criteria, immune recovery markers, and optimal discontinuation timing. Full article

Introduction: Cannabidiol (CBD) is widely available over the counter for presumed medical and recreational purposes. Despite its non-psychoactive nature, CBD exhibits intrinsic pharmacological activity that may lead to potential adverse drug events (ADEs) and drug–drug interactions (DDI) with common prescription medications through cytochrome P450 inhibition. Due to their largely unregulated nature and widespread advertising, consumers who use CBD products may not be aware of these potential negative drug interactions. The purpose of this study was to determine how frequently patients who use CBD products concurrently take prescription medication with known drug–drug interaction (DDI) potential, and to identify specific therapeutic classes most commonly involved. Methods: In this cross-sectional study, a survey was distributed to patients and family members in the adult and pediatric Emergency Departments of a Level 1 Trauma Center in eastern North Carolina. Respondents reported household CBD use and selected from a list of conditions for which they take prescription medications. Results: Of 681 eligible respondents, 254 (37.3%) reported CBD use in their household (CBDUIH). Among those with CBDUIH, 69.7% reported concurrent use of 1 or more medications with a potential DDI risk. The most common categories of prescriptions were antidepressants (64.4%) and antihypertensives (41.8%), followed by agents for diabetes, hyperlipidemia, and immune disorders. Conclusions: The majority of CBD users in this population are concurrently taking medications with DDI potential, highlighting the need for patient and provider education, and improved labeling of CBD-based products to accurately reflect risks. Further study of clinically significant interactions is needed to determine which medications within these common categories have the most substantial risk of DDI. Full article

Background and Aim: People with HIV (PWH) have historically been excluded from cancer immunotherapy trials due to concerns over immune dysregulation and safety. This systematic review evaluates the safety, efficacy, and immunologic outcomes of Programmed death-1 (PD-1) inhibitors in PWH diagnosed with non-small-cell lung cancer (NSCLC). Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, Web of Science, and Medline through January 2025. Studies were included if they reported outcomes of ICIs in PWH with NSCLC. Data extraction included progression-free survival (PFS), overall survival (OS), immune-related adverse events (irAEs), antitumor response, HIV viral control, and immunologic parameters. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. Results: Six cohort studies (n = 762 patients) met inclusion criteria. ICIs used included nivolumab, pembrolizumab, atezolizumab, and durvalumab, with treatment durations ranging from 3.1 to 5.4 months. Median PFS ranged from 3.0 to 6.3 months, and OS ranged from 10.0 to 66.0 months. Overall response rates (ORRs) varied from 13% to 75%, and disease control rates (DCRs) ranged from 47% to 62.5%. irAEs occurred in 25% to 75% of patients, with 6–20% experiencing grade 3–4 events. Corticosteroids were required in 13–29% of patients, and treatment discontinuation due to toxicity occurred in up to 30%. Most patients had controlled HIV, with CD4 counts typically above 300 cells/μL and undetectable viral loads. Conclusions: ICIs appear safe and effective in PWH with NSCLC, with toxicity and efficacy outcomes comparable to the general population. While immunotherapy should not be withheld based solely on HIV status, better standardization in reporting HIV-related variables is needed to optimize patient selection and management. Full article

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs), a revolutionary class of oncology therapeutics that enhance T cell-mediated antitumor immunity, are associated with various immune-related adverse events (IRAEs). While destructive thyroiditis and hypothyroidism are common, ICI-induced Graves’ disease (GD) is exceedingly rare, and the occurrence of concomitant Graves’ ophthalmopathy (GO) is even rarer. Case Presentation: A 57-year-old man with bladder cancer developed GO after receiving the first dose of the programmed death 1 (PD-1) inhibitor pembrolizumab. He presented with severe proptosis, extraocular muscle enlargement, hyperthyroidism, and significantly increased thyroid-stimulating hormone receptor autoantibodies (TRAb). Following the treatment with glucocorticoids and immunosuppressive therapy, his symptoms improved markedly but relapsed upon dosage reduction. To date, we have not identified any previous reports of GO with confirmed positive thyroid-related antibodies induced by pembrolizumab. Conclusions: This case offers valuable insights into the potential IRAEs, underscoring the importance of thorough clinical evaluation and early recognition to improve patient outcomes and quality of life. A literature review of ICI-induced GO was also performed, with further discussion of the potential pathogenic mechanisms, risk factors, and management strategies. Full article

Acute myocardial infarction (MI) is a major cardiovascular event and a leading cause of mortality worldwide. Beyond the initial ischemic injury, the inflammatory and immune responses play pivotal roles in both tissue damage and subsequent healing. While the anti-inflammatory strategies targeting neutrophil-driven injury have demonstrated potential in limiting early cardiac damage, growing evidence highlights the critical role of innate immune cells beyond the acute phase. Neutrophils, traditionally associated with tissue injury, also contribute to the resolution of inflammation and initiate key repair processes. Monocytes and macrophages follow a dynamic trajectory, transitioning from pro-inflammatory to reparative states, and play essential roles in debris clearance, angiogenesis, and scar formation. In the early inflammatory phase of acute MI, immune cells such as neutrophils and monocytes are rapidly recruited and activated. While they initially amplify inflammation through the release of pro-inflammatory mediators, their subsequent transition toward anti-inflammatory and reparative phenotypes helps limit tissue damage by clearing necrotic debris from the infarcted area and contributes to the resolution of inflammation. Accumulating evidence reveals a complex crosstalk between neutrophils and macrophages post-MI, with resident macrophages being involved in neutrophil recruitment, and neutrophil-derived signals participating in monocyte recruitment and macrophage polarization, thereby coordinating the spatial and temporal phases of cardiac repair. Understanding how neutrophil-derived mediators influence macrophage responses and whether macrophage-secreted factors reciprocally modulate neutrophil behavior opens promising pathways for developing targeted therapies to limit adverse remodeling following MI. Therefore, this review aims to (i) provide an overview of the roles of neutrophils and monocytes/macrophages in the pathophysiology of myocardial infarction, (ii) explore the mechanisms of communication, particularly via neutrophil-derived secreted factors, that influence monocyte/macrophage function and impact post-MI inflammation, repair, and remodeling, and (iii) highlight the potential therapies interfering with inflammation and neutrophil/macrophage cross-talk. Full article

Objectives: This phase 3 clinical trial aimed to evaluate the safety and immunogenicity of the Sabin inactivated poliovirus vaccine (sIPV) manufactured by Biominhai in healthy infants following a sequential immunization regimen. Methods: A total of 300 healthy infants aged 2 months were randomly divided into the test group (sIPV-sIPV-bOPV) and the control group (wIPV-wIPV-bOPV) according to the ratio of 1:1. Both groups were inoculated under “2IPV + 1bOPV” schedule. Safety was assessed alongside poliovirus antibody levels before and after vaccination. Results: The overall incidence of adverse reactions (AEs) in the test and control groups was 44% and 39%, respectively. AEs in both groups primarily occurred following the first dose, with approximately 30% classified as grade 1 in severity. No significant differences were observed between groups regarding the incidence, severity, and symptoms of AEs. Additionally, no vaccine-related serious adverse events (SAEs) were reported. At 30 days after the last dose, the seroconversion rates of neutralizing antibodies against poliovirus types I and III reached 100% in both groups, while type II rates at 99% for the test group and 95% for the control. Notably, the seroconversion rates for all types in the test group were non-inferior to those in the control group. The geometric mean titers (GMTs) of neutralizing antibodies against poliovirus for type I (8622.64 vs. 2687.65), type II (207.73 vs. 54.06), and type III (2121.74 vs. 1699.12) were significantly higher in the test group (p < 0.0001 for type I and II; p = 0.04 for type III). Conclusions: The study concluded that the trial vaccine sIPV following sequential immunization program demonstrates good safety and immunogenicity, showing non-inferiority to the control vaccine. Full article