Search Results (604)

Background/Objectives: Infections after stroke are a serious medical problem and have a significant impact on the outcome of stroke, but data regarding the Asian population are limited. This study aims to determine the bacterial and fungal profile of pathogenic organisms of infections after acute ischemic stroke (AIS). Methods: This is a retrospective study using the medical records of patients at least 18 years old who were hospitalized with AIS in a tertiary stroke hospital from 1 January 2018 to 31 December 2022. Demographic, patient-related, and other examination data were extracted from hospital medical records. Infections after AIS were defined as any infection that developed during the acute phase of ischemic stroke and was confirmed by microbiologic culture as the gold standard. Factors associated with infection were analyzed using multiple logistic regression. Results: Among 599 AIS patients with infection who underwent microbiologic culture, the prevalence of infection with an isolated pathogen was 21.4%, and most organisms were from sputum. Positive microbiologic culture revealed that bacteria such as K. pneumoniae, E. coli, A. baumannii, and S. aureus were the most common causes of infection, while fungi were rare. During the COVID-19 period, bacteria developed resistance to antimicrobials, including β-lactamase antibiotics for Gram-negative bacteria and methicillin for Gram-positive bacteria. Care in the intensive ward, including the stroke unit, reduced the risk of a positive microbiological culture in the COVID-19 and non-COVID-19 period. Urinary catheters promoted infections in the non-COVID-19 period, whereas steroids, total parenteral nutrition, and tracheostomy were negatively associated with infections after AIS in the COVID-19 period. Conclusions: The prevalence and factors associated with infection after stroke changed during the COVID-19 period. The risk of infection after stroke requires preventive measures such as early dysphagia screening. Full article

Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu—characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)—and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals. Full article

African swine fever (ASF) needs to be controlled, and prevention of the spread of African swine fever virus (ASFV) is dependent on enhanced surveillance and early disease detection. Commercial swine operations, especially in North America, Europe, and Asia, are characterized by comparatively large numbers of pigs, and sampling individual pigs, which represents the main strategy for current ASF surveillance, can be both costly and labor intensive. A study performed in Ghana was designed to estimate the diagnostic sensitivity of pen-based aggregate oral fluid testing for ASFV in infected pigs in a pen of 30 animals and to evaluate its utility as a tool to support surveillance of ASF in the US. This study was performed in three phases: (i) virus (Ghana ASFV24) amplification in a target host species to generate the challenge inoculum; (ii) titration of the inoculum (10% spleen homogenate) in target host species to determine the minimum dose inducing acute ASF in pigs with survival up to 5–6 days post-inoculation (dpi); and (iii) the main study, involving 186 pigs, consisting of 6 replicates of 30 pigs per pen and one seeder pig inoculated with wildtype ASFV (highly virulent genotype II) per pen. Daily sampling of aggregate oral fluids, uncoagulated blood, oropharyngeal swabs, fecal and water nipple swabs, and recording of rectal temperatures and clinical observations was carried out. The seeder pigs were each inoculated intramuscularly with 0.5 mL of the 10% spleen homogenate, which induced the desired clinical course of ASF in the pigs, with survival of up to 6 dpi. ASFV DNA was detected in the seeder pigs as early as 1 dpi and 2 dpi in the blood and oropharyngeal swabs, respectively. Transmission of ASFV from the seeder pigs to the contact pig population was detected via positive amplification of ASFV DNA in aggregate oral fluid samples at 3 days post-contact (dpc) in 4 out of 6 pens, and in all 6 pens, at 4 dpc. Testing of oropharyngeal swabs and blood samples from individual pigs revealed a variable number of ASFV-positive pigs between 3 and 5 dpc, with detection of 100% positivity between 6 and 18 dpc, the study endpoint. These findings demonstrate the potential utility of aggregate oral fluid sampling for sensitive and early detection of ASFV incursion into naïve swine herds. It also demonstrates that testing of environmental samples from the premises could further enhance overall ASF early detection and surveillance strategies. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression. Full article

During the COVID-19 pandemic, some studies suggested that transmission events could originate from schools. This study aimed to evaluate early-warning methods for identifying asymptomatic COVID-19 cases by implementing screening programs in schools. This study was conducted between September 2021 and May 2023, employing a rotation-screening plan for COVID-19 detection on a sample of students aged 14 to 19 years attending secondary schools in the regions of Tuscany, Veneto, Apulia and Friuli-Venezia Giulia. The schools were divided into two groups: experimental and control, with a ratio of 1:2. Two types of molecular salivary tests for SARS-CoV-2 were used to conduct the screening. This study included 16 experimental schools and 32 control schools. Out of 2527 subjects, 11,475 swabs were administrated, with 9177 tests deemed valid for analysis (a 20% loss of tests). Among these, 89 subjects (3.5%) tested positive. In control schools, 1895 subjects (6.5%) tested positive for SARS-CoV-2. This study recorded peaks in infections during the winter and autumn months, consistent with patterns observed in the general population. Beginning in September 2022, a shift occurred, with 2.6% of positive cases reported in the case schools compared to 0.3% in the control schools. Initially, most cases of COVID-19 were detected in the control schools; however, as the pandemic emergency phase concluded, cases were primarily identified through active screening in experimental schools. Although student participation in the active screening campaign was low during the project’s extension phase, this approach was efficacious in the early identification of positive cases. Full article

Background/Objectives: Heart transplantation (HTx) is a lifesaving procedure for end-stage heart failure patients; however, postoperative infections remain a major challenge due to immunosuppressive therapy and surgical complications. Traditional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) have limitations in distinguishing infections from systemic inflammatory response syndrome (SIRS). Emerging markers such as Presepsin and interleukin-6 (IL-6) may improve diagnostic accuracy. This study aimed to evaluate the kinetics and reliability of these four inflammatory biomarkers in heart transplant recipients in the immediate postoperative period. Methods: This retrospective observational study included 126 patients who underwent HTx at Policlinic of Bari between January 2022 and November 2024. Patients were categorized into infected (n = 26) and non-infected (n = 100) groups based on clinical and microbiological criteria. Biomarkers (CRP, PCT, Presepsin, and IL-6) were measured preoperatively and on postoperative days (PODs) 1, 2, 3, 4, 5, and 10. Statistical analyses included the Mann–Whitney U test and logistic regression to identify the independent predictors of infection. Results: CRP and PCT levels differed significantly between the groups only on day 10, limiting their use as early infection markers. In contrast, Presepsin levels were significantly elevated in infected patients from day 1 (p < 0.001), whereas IL-6 levels showed significant differences from day 3 onward. Presepsin showed the strongest association with infection in the early postoperative phase. Conclusions: Presepsin and IL-6 outperformed CRP and PCT in detecting early postoperative infections in heart transplant recipients. Their early elevation supports their use as reliable markers for guiding timely clinical intervention and improving patient outcomes. Further research is needed to validate these findings in larger cohorts and with different immunosuppressive regimens. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

To improve implant osseointegration while preventing infection, we developed a strontium (Sr)-doped Ti₃C₂T_x MXene coating on titanium, aiming to synergistically enhance bone integration and antibacterial performance. MXene is a family of two-dimensional transition-metal carbides/nitrides whose abundant surface terminations endow high hydrophilicity and bioactivity. The coating was fabricated via anodic electrophoretic deposition (40 V, 2 min) of Ti₃C₂T_x nanosheets, followed by SrCl₂ immersion to incorporate Sr²⁺. The coating morphology, phase composition, chemistry, hydrophilicity, mechanical stability, and Sr²⁺ release were characterized. In vitro bioactivity was assessed with rat bone marrow mesenchymal stem cells (BMSCs)—with respect to viability, proliferation, migration, alkaline phosphatase (ALP) staining, and Alizarin Red S mineralization—while the antibacterial efficacy was evaluated against Staphylococcus aureus (S. aureus) via live/dead staining, colony-forming-unit enumeration, and AlamarBlue assays. The Sr-doped MXene coating formed a uniform lamellar structure, lowered the water-contact angle to ~69°, and sustained Sr²⁺ release (0.36–1.37 ppm). Compared to undoped MXene, MXene/Sr enhanced BMSC proliferation on day 5, migration by 51%, ALP activity and mineralization by 47%, and reduced S. aureus viability by 49% within 24 h. Greater BMSCs activity accelerates early bone integration, whereas rapid bacterial suppression mitigates peri-implant infection—two critical requirements for implant success. Sr-doped Ti₃C₂T_x MXene thus offers a simple, dual-function surface-engineering strategy for dental and orthopedic implants. Full article

Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after a SARS-CoV-2 infection are missing. Therefore, in this study, we performed blood eosinophil, neutrophil, and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after the hospitalization of patients with severe SARS-CoV-2 infections. Blood cell counts were reported at seven different timepoints over the 30-day period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate a 95% drop in the blood eosinophil count by D1, with eosinophils displaying a phenotype defined as CD69/CD63/CD125^high and CCR3/CD44^low during the early phases of hospitalization. Conversely, by D7 the neutrophil count increased significantly and displayed an immature, activated, and immunosuppressive phenotype (i.e., 3% of CD10/CD16^low and CD10^lowCD177^high, 6.7% of CD11b^highCD62L^low, and 1.6% of CD16^highCD62L^low), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64^high and CD32^low monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with a likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils and the functions of the eosinophils and the monocytes, as well as these innate immune cell types, interplays need to be further investigated. Full article

This study aims to investigate the response of surface bacterial communities in Trachinotus ovatus to Cryptocaryon irritans infection at different stages of a single infection cycle (0~168 h). These samples were analyzed using high-throughput 16S rRNA sequencing. Alpha diversity analysis showed a reduction in the richness and diversity of skin microbiota during infection, with partial recovery post-detachment. Beta diversity analysis revealed distinct structural shifts in skin microbiota at early (24 h) and post-detachment (168 h) stages compared to other phases, while gill microbiota remained stable except during detachment. At the phylum level, Proteobacteria, Actinobacteriota, Bacteroidetes, and Firmicutes were dominant on the skin at different stages, whereas the gill microbiota was predominantly Proteobacteria (>90%). At the genus level, opportunistic pathogens, such as Vibrio and Nautella, increased in relative abundance on the skin with the infection progression, while gill microbiota composition barely changed. The hepatic bacterial load continued to increase with infection duration. These findings indicate that C. irritans alters microbiota composition on skin, facilitating pathogen invasion, thereby elevating the risk of secondary bacterial infections in T. ovatus. Full article

Early biomarkers are needed to predict the long-term persistence of rheumatical symptoms in patients infected with Chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to predict the risk of post-CHIK chronic rheumatism (pCHIK-CR) in adult patients of two prospective cohorts. We evaluated 46 febrile patients (median age: 33.5 years; IQR: 19 years; women: 50.0%) with CHIKV infection confirmed during the 2014–2015 outbreak in Santander, Colombia. The participants were classified by a rheumatologist as either cases (pCHIK-CR) or controls (WoRM, without rheumatical manifestations). We quantified serum levels of IL-4, IL-6, IL-8/CXCL-8, IL-27, CCL-2, CXCL-9, CXCL-10, and IgG using Luminex and ELISA assays during the acute and subacute phases of infection. Then, we evaluated the association of these immune factors with the case-control status using piecewise logistic regression adjusted for age and sex. There were non-linear associations between IL-8/CXCL-8, CXCL-9, and CXCL-10 with pCHIK-CR. Increases in the levels of IL-8/CXCL-8 (<35.7 pg/mL), CXCL-9 (≥6000 pg/mL), and CXCL-10 (≥36,800 pg/mL) were significantly associated with a reduced risk of pCHIK-CR (adjusted ORs: 0.85, 0.96, and 0.94, respectively). These results suggest that increases in IL-8/CXCL-8, CXCL-9, and CXCL-10 levels, measured in the early stages of CHIKV infection, may predict a chronic disease risk. This suggests the possibility that an early and strong immune response could contribute to enhancing CHIKV control and potentially reduce the risk of persistent joint symptoms. Given their expression patterns and timing, these three immune factors may be considered promising biomarker candidates for assessing the risk of chronic rheumatologic disease. These findings should be considered as exploratory and validated in additional cohort studies. Full article

Background/Objectives: Febrile neutropenia is a frequent and potentially life-threatening complication in pediatric oncology patients receiving chemotherapy. Due to profound immunosuppression, early diagnosis of infections remains a major clinical challenge. This review evaluates the diagnostic and prognostic utility of infection biomarkers in children with chemotherapy-induced severe neutropenia. Methods: We reviewed clinical studies that assessed the diagnostic performance of inflammatory biomarkers—including C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8, IL-10), and others—in pediatric febrile neutropenia. The review includes data on sensitivity, specificity, predictive value, and clinical applications. Results: CRP remains a common but nonspecific marker, often insufficient for early stratification. PCT showed consistently high negative predictive value and early responsiveness to bacterial infections. IL-6 and IL-10 demonstrated strong early diagnostic accuracy in the early phase (AUC > 0.80 in multiple studies) and were particularly useful in predicting septic shock when combined. IL-8, while less specific, may help rule out infection when levels are low. Emerging biomarkers such as presepsin, MR-proADM, and PSP showed promising diagnostic performance. Presepsin achieved near-perfect accuracy in some cohorts (AUC up to 0.996), outperforming CRP and PCT, though its ability to discriminate bacteremia at fever onset varied. MR-proADM demonstrated consistent AUCs above 0.75 and may support early sepsis identification. PSP was associated with significantly elevated levels in sepsis. Additional novel markers—including sTNFR-II, sIL-2R, IP-10, Flt-3L, MCP-1-a, and MBL—showed encouraging diagnostic profiles in individual studies, particularly due to high specificity, but require external validation. G-CSF also emerged as a promising candidate in multimarker models. In contrast, TNF-α and IL-1β displayed limited utility as standalone indicators. Conclusions: Biomarkers such as PCT, IL-6, Il-8, and IL-10 offer valuable tools for early infection detection and risk stratification in pediatric febrile neutropenia. Emerging markers—including presepsin, MR-proADM, and PSP—further enhance diagnostic precision and may support early identification of sepsis. Multimarker strategies, particularly those incorporating presepsin, IL-10, or MR-proADM, show potential to improve diagnostic performance beyond conventional markers. Further prospective validation is needed to optimize clinical implementation and guide personalized treatment decisions. Full article

Background: In just twenty years, three dangerous human coronaviruses—SARS-CoV, MERS-CoV, and SARS-CoV-2 have exposed critical gaps in early detection of emerging viral threats. Current diagnostics remain pathogen-focused, often missing the earliest phase of infection. A virus-agnostic, host-based diagnostic capable of detecting responses to viral intrusion is urgently needed. Methods: We hypothesized that the lungs act as biomechanical instruments, with infection altering tissue tension, wave propagation, and flow dynamics in ways detectable through subaudible vibroacoustic signals. In a matched case–control study, we enrolled 19 RT-PCR-confirmed COVID-19 inpatients and 16 matched controls across two Johns Hopkins hospitals. Multimodal data were collected, including passive vibroacoustic auscultation, lung ultrasound, peak expiratory flow, and laboratory markers. Machine learning models were trained to identify host-response biosignatures from anterior chest recordings. Results: 19 COVID-19 inpatients and 16 matched controls (mean BMI 32.4 kg/m², mean age 48.6 years) were successfully enrolled to the study. The top-performing, unoptimized, vibroacoustic-only model achieved an AUC of 0.84 (95% CI: 0.67–0.92). The host-covariate optimized model achieved an AUC of 1.0 (95% CI: 0.94–1.0), with 100% sensitivity (95% CI: 82–100%) and 99.6% specificity (95% CI: 85–100%). Vibroacoustic data from the anterior chest alone reliably distinguished COVID-19 cases from controls. Conclusions: This proof-of-concept study demonstrates that passive, noninvasive vibroacoustic biosignatures can detect host response to viral infection in a hospitalized population and supports further testing of this modality in broader populations. These findings support the development of scalable, host-based diagnostics to enable early, agnostic detection of future pandemic threats (ClinicalTrials.gov number: NCT04556149). Full article

Introduction: The health emergency caused by the pandemic led to severe health issues in populations across many countries worldwide, including widespread morbidity and significant mortality. Nevertheless, several countries succeeded in keeping infection rates remarkably low before the approval of vaccines and the initiation of vaccinations in early 2021. We aim to identify the success factors of health policies in managing the impact of the health emergency across a selection of countries, focusing on how they protected their populations. Our study presents outcomes of sustainable health policy measures, along with health and social system challenges, and economic responses during the global health emergency. We sometimes found it difficult to define what counted as a success factor in some countries. Method: Our study draws upon a selection of reports and documents published by various ministries and economic, social, and health authorities, which we collected online. We structured our study into three phases to frame and contextualize the impact of health policy measures and countermeasures as follows: (i) observations and content analysis; (ii) empirical support through illustrative examples; and (iii) development of a health emergency toolkit of assessment. The documents were not always easy to compare because they differed in format and detail. Results: Our study outlines ten success factors for sustainable health policy measures and countermeasures: (i) preparedness; (ii) control; (iii) precaution; (iv) proactive decision-making; (v) synchronization; (vi) adequate legislation; (vii) goal fulfillment; (viii) digital health technology; (ix) empirical evidence; (x) ethical and moral virtues. Sometimes we struggled to separate what was ethical guidance from what was simply practical advice. Conclusion: We argue that the relevance of the health emergency toolkit of assessment outlined in our study demonstrates clearly that the success factors related to sustainable health policy measures and countermeasures can be applied and adapted to the societal conditions of individual countries. These factors may form a foundation for the development of a health emergency toolkit of assessment for future health emergencies. We also maintain that these factors may serve as a platform for establishing sustainable plans across health, social, and economic domains, with clear guidelines for implementation, management, and control. It is our hope that future health systems will make use of these findings before the next crisis emerges. Full article