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Chryseobacterium spp. are Gram-negative, opportunistic pathogens antibiotic-resistant commonly found in the environment. The aim of this study was to investigate potential sources of Chryseobacterium infections in healthcare settings by comparing clinical and environmental isolates using phenotypic and genotypic analyses. Between June and July 2023, six cases of infection with Chryseobacterium spp. were identified in a hospital in Apulia, southern Italy. Environmental sampling (air, surfaces and water) was performed in parallel with routine clinical investigations. Isolates were subjected to antibiotic susceptibility testing and genotypic analysis using Sanger and Next-Generation Sequencing. Five cases of Chryseobacterium spp. infection were recorded in the Gastroenterology Department (Pavilion A) and one in the Vertebral Surgery Department (Pavilion B). C. indologenes was identified in blood and tracheal aspirate samples using MALDI-TOF MS. Environmental analysis carried out in the pavilions A and B isolated C. indologenes from sink tap in Pavilion B. Subsequently, genome sequencing revealed that Chryseobacterium strains misidentified as C. indologenes were more closely related to C. arthrosphaerae . Genetic analysis confirmed the cluster hypothesis involving four patients from the pavilion A, while no genetic link was found between the environmental and clinical strains. Innovative molecular methods in clinical and environmental investigations have allowed more accurate identification of the etiologic agent and possibly tracing the source of infection in the nosocomial setting. Control measures, such as patient isolation and room disinfection, have prevented the spread of infection.

Probiotic administration has become common practice in neonatal intensive care units (NICUs) to prevent necrotizing enterocolitis (NEC) and promote gut health in preterm infants. While probiotics are generally considered safe, rare cases of probiotic-related sepsis have been reported. We present a case of Lactobacillus rhamnosus sepsis in a preterm infant, highlighting the challenges involved in its diagnosis. The infant developed symptoms of sepsis on the 13th day of probiotic treatment. Laboratory analyses, including MALDI-TOF, BioFire BCID2 panel, and whole-genome sequencing (WGS), helped confirm the diagnosis and the presence of Lactobacillus rhamnosus. In this case, accurately identifying the Lactobacillus rhamnosus strain proved challenging, as initial analyses using the Vitek 2 system yielded incorrect identifications. This highlights the limitations of automated systems in distinguishing closely related species, reinforcing the need for advanced molecular techniques to achieve precise strain identification and confirm a probiotic-related infection. Given these diagnostic complexities, it is crucial for clinicians to maintain a high index of suspicion for probiotic-related infections in cases of unexplained sepsis, as this awareness can prompt further diagnostic investigations to ensure accurate pathogen identification. The infant responded to ampicillin therapy, showing clinical improvement within 10 days and was discharged in good health at 67 days of life. This case underscores the importance of advanced molecular diagnostic methods to confirm probiotic-related infections and highlights the need for caution in administering probiotics to vulnerable populations, such as preterm infants. Clinicians must maintain a high index of suspicion for probiotic-associated sepsis in unexplained cases of infection and tailor antibiotic therapy based on susceptibility profiles. These findings emphasize the need for rigorous monitoring, appropriate probiotic strain selection, and optimized safety protocols in NICUs to mitigate potential risks.

Background Bone infections such as chronic fungal erosive osteomyelitis are uncommon forms of bone infection. The endemic dimorphic fungus Coccidioides impact generally immunocompromised patients. These infections frequently have no symptoms and the clinical signs remain undetected, allowing the infection to worsen over weeks or months. Mycotic arthritis is one of the rarest clinical symptoms; it is hard to distinguish from other types of arthritis, which slows down the diagnosis procedure. Case presentation In order to demonstrate the beginning and progression of radiological abnormalities in a case of aggressive fungal osteomyelitis, we provide the case of a 31-year-old male patient here. The man showed signs of extensive bone erosion and inflammatory involvement in his right knee and right hallux phalanx, although he had no prior history of immunodeficiency. The infection resulting from Coccidioides Immitis in his right knee and in his hallux was the reason for the injuries. Conclusions While an acute, benign, and self-eradicating lung infection is the predominant presentation for most cases of coccidioidomycosis, a small percentage of patients experience a devastating extrapulmonary condition, which can include arthritis. The pathogenic mechanism of bone involvement is unknown, and it often remains untreated. Here, we discuss radiographic evidence of particular bone inflammation during the early phase and later phases of the disease, since management of this chronic condition remains a challenge. We propose that imaging may mimic osseous neoplasia in persistent fungal diseases, such as coccidioidomycosis.

Background Alzheimer's disease (AD) is one of the most common causes of dementia in old people. Neuronal deficits such as loss of memory, language and problem-solving are severely compromised in affected patients. The molecular features of AD are Aβ deposits in plaques or in oligomeric structures and neurofibrillary tau tangles in brain. However, the challenge is that Aβ is only one piece of the puzzle, and recent findings continue to support the hypothesis that their presence is not sufficient to predict decline along the AD outcome. In this regard, metabolomic-based techniques are acquiring a growing interest for either the early diagnosis of diseases or the therapy monitoring. Mass spectrometry is one the most common analytical platforms used for detection, quantification, and characterization of metabolic biomarkers. In the past years, both targeted and untargeted strategies have been applied to identify possible interesting compounds. Aim of review The overall goal of this review is to guide the reader through the most recent studies in which LC–MS-based metabolomics has been proposed as a powerful tool for the identification of new diagnostic biomarkers in AD. To this aim, herein studies spanning the period 2009–2020 have been reported. Advantages and disadvantages of targeted vs untargeted metabolomic approaches have been outlined and critically discussed.

SummaryBackgroundAdding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy. MethodsMITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III–IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m 2; standard group) intravenously every 3 weeks for six to eight cycles or avelumab (10 mg/kg intravenously) added to carboplatin and paclitaxel (experimental group) every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity. Patients, treating clinicians, and those assessing radiological examinations were not masked to study treatment. The primary endpoint was investigator-assessed progression-free survival, measured in the intention-to-treat (ITT) population. Patients who received at least one dose of study drug were included in the safety analysis. Experimental group superiority was tested with 80% power and one-tailed α 0·20. This trial is registered with ClinicalTrials.gov ( NCT03503786) and EudraCT (2016–004403–31). FindingsFrom April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2–29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7–12·1) in the standard group and 9·6 months (7·2–17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65–0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3–4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]). InterpretationAdding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted. FundingPfizer.

Bovine tuberculosis (BTB), caused by , is a chronic infectious disease of major veterinary and public health concern. It affects a broad range of domestic and wild animals, including water buffalo, and poses a risk to humans due to its zoonotic nature. The economic consequences of BTB, arising from production losses and trade restrictions, further underline its global importance. While cattle immune responses to BTB are well characterized, the immune mechanisms in buffalo remain poorly understood, despite their increasing role as livestock in endemic regions. Given that buffaloes and cattle, although closely related, display notable immunological differences, comparative studies are essential. This study aimed to investigate and compare antigen-specific cytokine responses in CD4 T lymphocytes from buffaloes and cattle exposed to or infected with . A multicolor flow cytometry assay was established to enable high-resolution analysis of cytokine-expressing CD4 T cells. Blood samples were obtained from 35 buffaloes (17 IGRA-positive from BTB outbreak farms and 18 IGRA-negative, including animals from both outbreak and Officially Tuberculosis-Free [OTF] herds) and 10 cattle (6 IGRA-positive from a BTB outbreak farm and 4 IGRA-negative from an OTF herd). Following six hours of in vitro stimulation with PPD-B or PBS, intracellular cytokine staining was performed. This approach allowed simultaneous quantification of single and polyfunctional CD4 T cell subsets producing IFN-γ, TNF-α, and IL-17A. Data were analyzed using factor analysis of mixed data (FAMD) to explore species- and infection-related immune response patterns. The multicolor flow cytometry approach successfully identified distinct cytokine-producing CD4⁺ T cell populations in both species. Overlapping immune profiles were observed between buffaloes and cattle; however, specific subsets-including IL-17A , IFN-γ IL-17A , and TNF-α IL-17A cells-contributed to interspecies differences. Importantly, the frequency of IFN-γ and TNF-α producing CD4 T cells correlated with IGRA test status, enabling discrimination between infected/exposed and non-infected animals. These results demonstrate the ability of cytokine expression patterns to reflect both infection status and host species. The findings indicate that buffaloes and cattle share broadly similar antigen-specific cytokine responses, although subtle differences in CD4⁺ T cell subsets exist. The study highlights the value of multicolor flow cytometry as a high-resolution tool for dissecting immune responses in veterinary immunology. These insights enhance understanding of buffalo immune mechanisms against BTB and may contribute to improved disease control strategies.

Background Colorectal cancer (CRC) encompasses tumors arising in the colon (CC) and rectum (RC), often treated as a single disease despite emerging evidence of biological divergence. Understanding the molecular differences between CC and RC is critical for improving diagnosis, prognosis, and therapeutic strategies. Methods We performed an integrated genomic and transcriptomic analysis of CC and RC data from The Cancer Genome Atlas (TCGA) to investigate their degree of similarity and observed that these tumors present distinct molecular profiles, which suggest an evolution through divergent pathways. Comparative analyses included copy number alterations (CNAs), somatic mutations, driver gene prediction, differential gene expression, pathway enrichment, and survival analysis. Results Chromosomal analyses revealed that 43% of focal and 77% of large-scale CNAs were specific of CC, while 10.5% and 57% were specific of RC with 8% of mutant genes unique to CC and 0.18% to RC. CC and RC presented distinct profiles of gene mutations, with CC showing significantly higher tumor mutational burden (0.51 muts/Mb vs 0.28 muts/Mb in RC). Distinct mutational signatures were identified, with CC characterized by a higher frequency of PIK3CA , BRAF , and DNAH1 mutations, while RC showed enrichment for TP53 and NRAS mutations. Importantly, analysis of predicted non-canonical driver genes identified ACVR1B , LTBP4 , SETD1A as CC-specific drivers and C4BPA , EHD1 as RC-specific drivers, underscoring divergent oncogenic mechanisms. However, the most substantial divergence was observed in transcriptomic profiling, with 56% and 33% of DEGs (in CC and RC, respectively) that were tumor-type specific. Notably, RC tumors segregated into two distinct transcriptional subtypes (Cluster 1 and Cluster 2), with Cluster 1 showed a more heterogeneous Consensus Molecular Subtypes (CMS) distribution, while Cluster 2 enriched in CMS4 (mesenchymal) and CMS3 (metabolic) consensus molecular subtypes. Accordingly, Gene Set Enrichment Analysis revealed CC-specific upregulation of Wnt, MYC, and mTOR signaling pathways, and RC-specific enrichment of GPCR and neuronal development pathways. On the other hand, pseudogene expression was significantly higher in CC, suggesting differential mechanisms of transcriptional dysregulation. Finally, we identified an RC-specific multigene survival signature as a prognostic model involving upregulation of C2CD4B , HSPD1P1 , LINC01356 , CBX3P9 , GATA2-AS1 and downregulation of ATP5F1EP2 , HSP90AB3P and SNRPFP1 . Conclusions Collectively, our findings provide robust molecular evidence that CC and RC follow divergent oncogenic pathways, emphasizing the need for site-specific biomarker development and therapeutic targeting in colorectal cancer.

Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD). The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD. We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro \"Cuore Mio\" pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment. The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged. We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease.

This letter describes a cohort of 100 children younger than 18 years of age with RT-PCR–confirmed Covid-19 who were assessed in 17 pediatric emergency departments in Italy. The descriptive results are compared with previously published results involving children in China and the United States.

Bubaline alphaherpesvirus-1 (BuAHV-1) and Bovine alphaherpesvirus-1 (BoAHV-1) are respiratory viruses that can cause an infection known as “Infectious Bovine Rhinotracheitis” (IBR) in both water buffalo and bovine species. As the main disease control strategy, vaccination can protect animals from clinical disease through the development of specific humoral and cell-mediated immune responses. In the present study, the time-related circulatory kinetics of hematological profile and bubaline monocyte subsets have been investigated in vaccinated buffalo calves after challenge infections with BuAHV-1. Thirteen buffalo calves were selected and grouped into the VAX-1 group, which received an IBR-live-attenuated gE-/tk-deleted marker vaccine; the VAX-2 group, which received an IBR-inactivated gE-deleted marker vaccine; the CNT group, which remained an unvaccinated control. Fifty-five days after the first vaccination, the animals were infected with 5 × 105.00 TCID50/mL of wild-type BuAHV-1 strain via the intranasal route. Whole blood samples were collected at 0, 2, 4, 7, 10, 15, 30, and 63 days post-challenge (PCDs) for the analysis of hematological profiles and the enumeration of monocyte subsets via flow cytometry. The analysis of leukocyte compositions revealed that neutrophils were the main leukocyte population, with a relative increase during the acute infection. On the other hand, a general decrease in the proportion of lymphocytes was observed early in the post-infection, both for the VAX-1 and VAX-2 groups, while in the CNT group, the decrease was observed later at +30 and +63 PCDs. An overall infection-induced increase in blood total monocytes was observed in all groups. The rise was especially marked in the animals vaccinated with an IBR-live-attenuated gE-/tK-deleted marker vaccine (VAX-1 group). A multicolor flow cytometry panel was used to identify the bubaline monocyte subpopulations (classical = cM; intermediate = intM; and non-classical = ncM) and to investigate their variations during BuAHV-1 infection. Our results showed an early increase in cMs followed by a second wave of intMs. This increase was observed mainly after stimulation with live-attenuated viruses in the VAX-1 group compared with the animals vaccinated with the inactivated vaccine or the non-vaccinated animal group. In summary, the present study characterized, for the first time, the hematological profile and distribution of blood monocyte subsets in vaccinated and non-vaccinated water buffalo in response to experimental infection with BuAHV-1. Although not experimentally proven, our results support the hypothesis of a linear developmental relationship between monocyte subsets.