Search Results (241)

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). Methods: A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. Results: CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. Conclusions: CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials. Full article

Staphylococcus aureus (S. aureus) is a major cause of opportunistic infections in humans and animals, leading to severe systemic diseases. The rise of MDR strains associated with animal carriage poses significant health challenges, underscoring the need to investigate animal-derived S. aureus. Objectives: This study examined the genotypic relatedness and phenotypic profiles of antimicrobial resistance in S. aureus, previously sampled from nostril swabs of healthy horses from two geographically distant Brazilian states (Northeast and South), separated by over 3700 km. The study also sought to confirm the presence of methicillin-resistant (MRSA) and borderline oxacillin-resistant (BORSA) strains and to characterize the isolates through molecular typing using PCR. Methods: Among 123 screened staphylococci, 21 isolates were confirmed as S. aureus via biochemical tests and PCR targeting species-specific genes (femA, nuc, coa). Results: REP-PCR analysis generated genotypic profiles, revealing four antimicrobial resistance patterns, with MDR observed in ten isolates. Six isolates exhibited cefoxitin resistance, suggesting methicillin resistance, despite the absence of the mecA gene. REP-PCR demonstrated high discriminatory power, grouping the isolates into five major clusters. Conclusions: The genotyping indicated no clustering by geographical origin, highlighting significant genetic diversity among S. aureus strains colonizing horses’ nostrils in Brazil. These findings highlight the widespread and varied nature of S. aureus among horses, contributing to a deeper understanding of its epidemiology and resistance profiles in animals across diverse regions. Ultimately, this genetic diversity can pose a public health risk that the epidemiological surveillance services must investigate. Full article

Background: Prehabilitation programs improve postoperative outcomes in vulnerable patients undergoing major surgery. However, current screening tools such as the Malnutrition Universal Screening Tool (MUST) may lack the sensitivity needed to identify those who would benefit most. Muscle quality assessed by Computed Tomography (CT), specifically muscle radiodensity in Hounsfield Units (HUs), has emerged as a promising alternative for risk stratification. Objective: To evaluate the prognostic performance of CT-derived muscle radiodensity in predicting adverse postoperative outcomes in colorectal cancer patients, and to compare it with the performance of the MUST score. Methods: This single-center cross-sectional study included 201 patients with non-metastatic colon cancer undergoing elective laparoscopic resection. Patients were stratified based on enrollment in a multimodal prehabilitation program, either within an Enhanced Recovery After Surgery (ERAS) protocol or a non-ERAS pathway. Nutritional status was assessed using MUST, SARC-F questionnaire (strength, assistance with walking, rise from a chair, climb stairs, and falls), and the Global Leadership Initiative on Malnutrition (GLIM) criteria. CT scans at the L3 level were analyzed using automated segmentation to extract muscle area and radiodensity. Postoperative complications and hospital stay were compared across nutritional screening tools and CT-derived metrics. Results: MUST shows limited sensitivity (<27%) for predicting complications and prolonged hospitalization. In contrast, CT-derived muscle radiodensity demonstrates higher discriminative power (AUC 0.62–0.69), especially using a 37 HU threshold. In the non-ERAS group, patients with HU ≤ 37 had significantly more complications (33% vs. 15%, p = 0.036), longer surgeries, and more severe events (Clavien–Dindo ≥ 3). Conclusions: Opportunistic CT-based assessment of muscle radiodensity outperforms traditional screening tools in identifying patients at risk of poor postoperative outcomes, and may enhance patient selection for prehabilitation strategies like the ERAS program. Full article

Background. To meet the WHO’s viral hepatitis elimination goal by 2030, the Minister of Health (Italy) introduced free HCV screening among people born between 1969 and 1989 and those at greater risk (people in the care of the addiction services and detained). Aims. To estimate the following: (i) the prevalence of HCV in hospitalized patients born before 1969 not included in the free HCV screening, (ii) the prevalence of transaminase values outside the range, and (iii) the HBV prevalence in a subgroup of patients. Methods. Anti-HCV antibodies and transaminase values were prospectively evaluated in patients born before 1969 and admitted to the Santa Maria alle Scotte Hospital in Siena. The first screening (October 2021–July 2022) was conducted in the Internal Medicine Division (cohort 0), and the second one (May 2024–October 2024) in Internal Medicine, Gastroenterology, and Geriatric Units (cohorts 1–3), including clinical features and HBV markers in a subgroup of patients. Results. Overall, 774 subjects underwent HCV screening. In the first screening period, 1.4% (8/567) of patients were anti-HCV+, of whom 0.7% were HCV RNA+ (4/567). In the second, 3.9% of patients (8/207) were anti-HCV+ and 0.9% were viremic (2/207). Overall, HCV prevalence was 0.8%. Of 96 patients in the gastroenterology cohort, 8 patients were at risk for occult HBV infection (8.3%). Conclusions. Our study demonstrates a chronic HCV infection prevalence of 0.8% in hospitalised patients born before 1969 and a prevalence of 8.3% of people at risk for occult HBV infection in a subgroup of patients residing in South-Eastern Tuscany, confirming that an opportunistic screening can identify the unrecognized people affected by viral hepatitis. Full article

Background: Opportunistic screening is one major screening approach for esophageal squamous cell carcinoma (ESCC). We aimed to develop a score-based risk stratification model to assess the risk of ESCC and precancerous lesions in opportunistic screening and to validate it in an external population. Methods: The study was a secondary analysis of a published esophageal cancer screening trial. The trial was conducted in 39 secondary or tertiary hospitals in China, with 14,597 individuals including 71 high-grade intraepithelial neoplasia (HGIN) and 182 ESCC, enrolled for opportunistic screening. Additionally, questionnaires and endoscopy were performed. The primary outcome was histology-confirmed high-grade esophageal lesions, including HGIN and ESCC. The predictors were selected using univariable and multivariable logistic regression. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC). Results: The score-based prediction model contained 8 variables on a 21-point scale. The model demonstrated an AUROC of 0.833 (95% CI, 0.803–0.862) and 0.828 (95% CI, 0.793–0.864) for detecting high-grade lesions in the training and validation cohorts, respectively. Using the cut-off score determined in the training cohort (≥9), the sensitivity reached 70.0% (95% CI, 50.6–85.3%), 81.3% (95% CI, 63.6–92.8%), and 81.1% (95% CI, 64.9–92.0%) in the validation cohort for detecting HGIN, early ESCC, and advanced ESCC, respectively, at a specificity of 76.4% (95%CI, 75.4–77.4%). The score-based model exhibited satisfactory calibration in the calibration plots. The model could result in 75.6% fewer individuals subjected to endoscopy. Conclusions: This score-based model demonstrated superior discrimination for esophageal high-grade lesions. It has the potential to inform referral decisions in an opportunistic screening setting. Full article

Aerococcus urinaeequi is an opportunistic pathogen that has been isolated from humans, pigs, and chickens, but with no reports in geese until now. This research aimed to isolate and identify A. urinaeequi from four geese, and establish a specific PCR detection method for A. urinaeequi. Strain E1 was identified as A. urnaeequi through a combination of Gram staining (Gram-positive coccus), colony morphology (α-hemolysis), and whole genome sequencing analysis. Comparative genomics was used to analyze the genome sequences of five reference strains of A. urinaeequi to screen for a species-specific genomic region (401 bp). Based on this region, specific primers were designed to establish the PCR detection method for A. urnaeequi, and the specificity and sensitivity of this assay were tested. The results showed that the target sequence was specifically amplified only for the genome of A. urinaeequi, and that the minimum nucleic acid detection concentration was 7.08 × 10⁻³ ng/μL. The mouse infection model indicated that the target fragment could be amplified from the tissue samples of dead mice in the challenge groups, verifying the applicability of PCR for clinical sample detection. Specific sequences of A. urinaeequi were detected in the lungs of three pigs using the PCR method, confirmed to be consistent through whole genome sequencing, and previously identified as A. urinaeequi or A. viridans by 16S rRNA sequencing. For the detection of fecal samples from geese, canines, and felines using the PCR method, the highest positive rate was 36.9% (31/84) of geese, followed by 21.7% (20/90) of felines, and finally 6.9% (16/230) of canines. A strain of A. urinaeequi was isolated and identified in geese for the first time, and a species-specific PCR detection method for A. urinaeequi was established with high specificity and sensitivity, which could well distinguish the bacterial species A. urinaeequi from its phylogenetically related species, A. viridans. Full article

Objectives: The aim of this study was to develop AI-based predictive models to assess the risk of osteoporosis in postmenopausal women using panoramic radiographs (OPTs). Methods: A total of 301 panoramic radiographs (OPTs) from postmenopausal women were collected and labeled based on DXA-assessed bone mineral density. Of these, 245 OPTs from the Hospital of San Giovanni Rotondo were used for model training and internal testing, while 56 OPTs from the University of Parma served as an external validation set. A mandibular region of interest (ROI) was defined on each image. Predictive models were developed using classical radiomics, deep radiomics, and convolutional neural networks (CNNs), evaluated based on AUC, accuracy, sensitivity, and specificity. Results: Among the tested approaches, classical radiomics showed limited predictive ability (AUC = 0.514), whereas deep radiomics using DenseNet-121 features combined with logistic regression achieved the best performance in this group (AUC = 0.722). For end-to-end CNNs, ResNet-50 using a hybrid feature extraction strategy achieved the highest AUC in external validation (AUC = 0.786), with a sensitivity of 90.5%. While internal testing yielded high performance metrics, external validation revealed reduced generalizability, highlighting the challenges of translating AI models into clinical practice. Conclusions: AI-based models show potential for opportunistic osteoporosis screening from OPT images. Although the results are promising, particularly those obtained with deep radiomics and transfer learning strategies, further refinement and validation in larger and more diverse populations are essential before clinical application. These models could support the early, non-invasive identification of at-risk patients, complementing current diagnostic pathways. Full article

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population. Full article

A backyard cat with symptoms of otitis was transferred to a veterinary clinic in Central Greece. A sample was obtained and P. aeruginosa was isolated. The strain exhibited an extensively drug-resistant (XDR) profile, as it was non-susceptible to all tested agents except colistin. DNA extraction and whole-genome sequencing (WGS) were performed using a robotic extractor and Ion Torrent technology, respectively. The genome was assembled and screened for resistance and virulence determinants. The isolate belonged to the high-risk clone ST308 with a total of 67 antibiotic resistance genes (ARGs) and 221 virulence factor-related genes being identified. No plasmids were detected. The metallo-beta-lactamase (MBL) bla_NDM-1 gene and 46 efflux pumps were included in the strain’s resistome. Both ARGs conferring tolerance to disinfecting agents and biofilm-related genes were identified, associated with the ability of this clone to adapt and persist in healthcare facilities. This case highlights the risk of relevant bacterial clones spreading in the community and even being transmitted to companion animals, causing challenging opportunistic infections to susceptible individuals, while others may become carriers, further spreading the clones to their owners, other animals and the environment. Full article

Pneumocystis jirovecii is an opportunistic fungus that causes severe pneumonia in immunosuppressed individuals. While Pneumocystis colonization, a subclinical form of infection, has been studied in different populations, its implications during pregnancy remain poorly understood. Given the immune modulation of pregnancy, maternal colonization or infection may contribute to vertical transmission and neonatal respiratory complications. This scoping review aims to map the existing evidence on Pneumocystis colonization/infection during pregnancy, identifying knowledge gaps, prevalence, risk factors, and potential neonatal outcomes. A systematic literature search was conducted in three databases following PRISMA-ScR guidelines. A total of 26 studies were included, covering Pneumocystis pneumonia cases (n = 19) and Pneumocystis colonization (n = 7). The review found that most Pneumocystis pneumonia cases in pregnant women were associated with HIV before antiretroviral therapy. More recent cases were related to hematologic malignancies. Pneumocystis colonization rates varied widely (5.4–46.5%). Evidence of vertical transmission was observed, but neonatal impact remains underexplored. This review highlights the need for HIV screening in pregnant women and the need to include Pneumocystis in the diagnosis of pregnant women with pneumonia. Increased awareness and research on Pneumocystis in pregnancy are necessary to improve maternal and neonatal outcomes. Future studies should focus on vertical transmission and neonatal respiratory health. Full article

The gastrointestinal microbiota of medicinal leeches is particularly interesting due to their blood-feeding habits, increasing medical use, and risk of pathogen transmission. Three groups of Hirudo verbana were used to study the leech microbiota: farmed leeches fasting for a long time, farmed leeches recently fed with bovine blood, and wild specimens fed with amphibian blood. The microbiota of the leeches’ mouth, pharynx, crop, and intestine was analyzed. Metasequencing analyses were performed using amplification of the 16S rRNA V3-V4 region on a NovaSeq Illumina platform. The relative abundance of bacterial microbiota included environmental bacteria from the families Rhizobiaceae, Comamonadaceae, Sphingobacteriaceae, Phreatobacteraceae, Myxococcaceae, Chitinophagaceae, Rhodospirillaceae, and Bdellovibrionaceae, as well as symbiotic/probiotic bacteria such as Mucinivorans, Aeromonas, Vagococcus, Lactobacillales, and Morganella. Significant differences were found in the different regions of the digestive system among the three groups of leeches, and environmental bacteria were present in all groups to varying degrees. A negative correlation was found between the dominant environmental and the symbiotic/probiotic bacteria. In contrast, a positive correlation was found between environmental and symbiotic/probiotic bacteria, indicating their association with host factors. Microbiota diversity, abundance, and bacterial correlations may be influenced by factors such as the leech’s fasting state, blood meal source, and environmental conditions. The identified opportunistic pathogens, such as Rickettsia, Anaplasma, and Treponema, identified for the first time in H. verbana, should be taken into consideration when using this leech in hirudotherapy. Our results show that extensive screening for opportunistic and pathogenic agents should be performed on leeches intended for medical use. Long-fasting leeches and leeches cultured in specialized farms are recommended for hirudotherapy. Full article

Background/Objectives: Ulcerative colitis (UC) and Crohn’s disease (CD) are the usual clinical forms of inflammatory bowel disease (IBD). Changes in the oral microbiota, especially the presence of emerging fungi and herpesviruses, have been shown to worsen the clinical aspects of IBD. The aim of this study was to screen for emerging pathogens in the oral yeast microbiota and the presence of herpesvirus in IBD patients. Methods: Oral swabs of seven UC or CD patients were collected. The samples were plated on Sabouraud Dextrose Agar and subcultured on CHROMagar Candida and CHROMagar Candida Plus. Polyphasic taxonomy was applied and identified using molecular tools, such as MALDI-TOF MS and ITS partial sequencing. Multiplex qPCR was used to identify the herpesvirus. Results: The mean age was 38.67 ± 14.06 years, 57.14% were female, and two had diabetes. The CD patients presented with Rhodotorula mucilaginosa, Candida orthopsilosis and Kodamaea jinghongensis, while the UC patients presented with Cutaneotrichosporon dermatis, Candida glabrata, Candida lusitanea and Candida tropicalis. Two UC individuals had at least one herpesvirus. In the first individual, a co-detection of Herpes Simplex Virus 1 (HSV-1) and C. lusitaniae was observed. The second presented with co-infections of Epstein–Barr virus (EBV), Human Herpesvirus 7 (HHV-7) and C. tropicalis. Conclusions: We identified rarely described yeasts and co-infections in IBD patients, highlighting the need to identify emerging pathogens in the oral microbiota, as they may contribute to opportunistic infections. Full article

Objective: The aim of this scoping review was to evaluate whether artificial intelligence integrated into breast cancer screening work strategies could help resolve some diagnostic issues that still remain. Methods: PubMed, Web of Science, and Scopus were consulted. The literature research was updated to 28 May 2024. The PRISMA method of selecting articles was used. The articles were classified according to the type of publication (meta-analysis, trial, prospective, and retrospective studies); moreover, retrospective studies were based on citizen recruitment (organized screening vs. spontaneous screening and a combination of both). Results: Meta-analyses showed that AI had an effective reduction in the radiologists’ reading time of radiological images, with a variation from 17 to 91%. Furthermore, they highlighted how the use of artificial intelligence software improved the diagnostic accuracy. Systematic review speculated that AI could reduce false negatives and positives and detect subtle abnormalities missed by human observers. DR with AI results from organized screening showed a higher recall rate, specificity, and PPV. Data from opportunistic screening found that AI could reduce interval cancer with a corresponding reduction in serious outcome. Nevertheless, the analysis of this review suggests that the study of breast density and interval cancer still requires numerous applications. Conclusions: Artificial intelligence appears to be a promising technology for health, with consequences that can have a major impact on healthcare systems. Where screening is opportunistic and involves only one human reader, the use of AI can increase diagnostic performance enough to equal that of double human reading. Full article

Quorum sensing (QS) is a molecular communication mechanism among bacterial cells. It is critical in regulating virulence factors, motility, antibiotic resistance, and biofilm formation. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen linked to healthcare-associated infections, food poisoning, and biofilm formation. Treating infections caused by pathogenic bacteria has become a challenge due to the development of multi-antibiotic resistance upon continuous exposure of bacteria to antibiotics. An alternative strategy to conventional antimicrobials to decrease the bacterial pathogenicity is QS inhibition, also known as quorum quenching. Using plant-derived compounds is an environmentally friendly strategy to block the bacterial QS and inhibit bacterial growth. Portulaca oleracea is a popular plant in different countries and is also used in traditional medicine. It is widely consumed raw in salads and as garnishes, though it can be cooked as a vegetarian dish. This study evaluates the antimicrobial activity of the methanolic extract of P. oleracea and its effectiveness in blocking or attenuating the QS of P. aeruginosa. The agar well diffusion method used for screening the antibacterial activity showed a significant growth inhibition of P. aeruginosa by the extract at 500 mg/mL with a minimum inhibitory concentration of 31.25 mg/mL. A bioindicator bacterium, Chromobacterium violaceum CV026, was used to determine the effect of the methanolic extract on the QS of P. aeruginosa. The results indicated a significant reduction in biofilm formation, pyocyanin production, and LasA staphylolytic activity. The phytochemical analysis by Gas Chromatography–Mass Spectrometry showed that the methanolic extract contained several phenols, alkaloids, esters, and other compounds previously reported to have antibacterial and antioxidant effects. These findings highlight the effectiveness of P. oleracea methanolic extract in attenuating the QS and virulence factors of P. aeruginosa. This study suggests that P. oleracea is an important source of natural antimicrobials and its use would be beneficial in food and pharmaceutical applications. Full article

Background/Objectives: Opportunistic diabetes screening in dental clinics is an innovative strategy with significant public health implications. Methods: This prospective observational study assessed diabetes risk and referral compliance among periodontitis patients using the Finnish Diabetes Risk Score (FINDRISC) and capillary fasting blood glucose (cFBG). Patients with FINDRISC ≥ 11 and/or cFBG ≥ 5.6 mmol/L were classified as high-risk and referred for further medical evaluation, with compliance tracked through medical practitioner feedback. Results: A total of 142 participants were recruited by 20 general dental practitioners (GDPs). Of these, 36.4% (n = 47) had a FINDRISC ≥ 11, with a mean score of 7.7 ± 4.5, and 26.3% (n = 34/129) had cFBG levels ≥ 5.6 mmol/L. There was no significant difference between periodontal status and FINDRISC (p = 0.291) or between periodontal status and cFBG (p = 0.129). Overall, 54 patients (41.8%) were referred for follow-up, with 33 (61.1%) completing the process. Among those who completed referrals, 10 (30.3%) were diagnosed with prediabetes and seven (21.2%) with diabetes. Non-compliance was more common among patients from lower socioeconomic backgrounds. Conclusions: This study shows the feasibility of integrating diabetes risk screening into private dental practice and its potential to identify high-risk individuals. Shared care models and policy adaptations are essential to improve interdisciplinary collaboration and overcome referral compliance barriers. Full article