Klebsiella spp. are pathobionts associated with acute infections, including pneumonia and infections in the urinary tract and bloodstream, often acquired in health-care settings. They represent a global threat owing to the prevalence of multidrug-resistant strains. Moreover, Klebsiella spp., similarly to other members of the human gut microbiota, can contribute to the pathogenesis of non-communicable disorders. In this Review, we describe the taxonomical and molecular characteristics of the Klebsiella genus, as well as its epidemiology and impact as an infectious agent. We also review current evidence that associates Klebsiella spp. with different non-communicable disorders, including chronic inflammatory and metabolic disorders and cancer. We discuss different approaches to target Klebsiella spp., including tailored antibiotics, faecal microbiota transplantation, live biotherapeutic products and bacteriophages. Finally, we discuss the importance of preventative measures, such as epidemiological surveillance, infection control practices and lifestyle interventions, to reduce the spread of Klebsiella spp. in health-care settings and the broader community.
Susceptibility to infection after solid organ transplantation (SOT) reflects interactions among epidemiologic exposures, allograft-specific factors, pharmacologic immunosuppression and host innate and adaptive immune functions. Substantial variability in susceptibility to viral, bacterial, and fungal infections occurs among recipients despite comparable immunosuppressive regimens. Accumulating evidence demonstrates that allelic variation, including single nucleotide polymorphisms, occurs in genes involved in multiple aspects of innate immune function and influence infectious risk after SOT. These genes encode pattern recognition receptors, complement components, phagocyte and natural killer cells functions, soluble opsonins, and cytokines. These variants are associated with altered susceptibility to bacterial, invasive fungal, and viral infections including cytomegalovirus, Epstein-Barr virus, BK polyomavirus, and hepatitis viruses. The contribution of allelic variation to infectious susceptibility remains incompletely defined. Identification of high-risk genotypes may enable individualized infectious surveillance, tailored antimicrobial prophylaxis, and host-directed interventions to advance precision transplantation.
Urinary tract infections (UTIs) in men, though less frequent than in women, represent a significant clinical challenge due to their increasing incidence with age and distinct microbiological profiles. This expert review analyzed data of urine cultures in men with community-acquired UTIs, collected from emergency departments of 15 french hospitals, from the private laboratory group Atoutbio (21 sites in Meurthe-et-Moselle and the Vosges French departments, alongside primary care records from the AntibioClic tool and the PRIMO database, to characterize the bacterial epidemiology of community-acquired male UTIs in France. Escherichia coli (39-40%) dominated, followed by Enterococcus faecalis (13-15%), Klebsiella pneumoniae (6-8%), and Proteus mirabilis (5-6%). Resistance rates were as follows amoxicillin (47-53.5%), amoxicillin-clavulanate (24-35.7%), trimethoprim-sulfamethoxazole (25.4-31.5%), and fluoroquinolones (16.3-20.2%). Resistance to third-generation cephalosporins (6.6-9.3%) and mecillinam (6.8-8.9%) was lower, while fosfomycin (1.4-1.5%) and nitrofurantoin (0.4-0.7%) retained high susceptibility. Extended-spectrum β-lactamase (ESBL)-producing E. coli ranged from 2 to 8.4%, with carbapenemase producers remaining rare (0.1%). Resistance was higher in men >65 years, particularly in nursing homes, where 3GC resistance reached 15-18%. « Emerging uropathogens » (Aerococcus urinae 1-1.1%, Actinotignum schaalii 0.1-0.4%) were rare. This study highlights the greater microbial diversity in male UTIs compared to women and underscores the need for systematic urine culture, susceptibility testing, and empirical therapy tailored to resistance patterns, age, and risk factors.
To describe the clinical effectiveness and safety of dalbavancin (DAL) for the treatment of Vascular Graft and Endograft Infections (VGEI). A retrospective, single-center observational study was conducted at a tertiary-care university hospital in Rome from January 2020 to December 2024, including all consecutive patients diagnosed with VGEI who received at least one dose of DAL. Cases were identified through the hospital electronic medical record database. VGEIs were diagnosed using MAGIC criteria. Primary outcomes were clinical and radiological response at the end of treatment (EOT) and at six-month follow-up. Thirteen patients were included (median age: 76 years; 92% of males; median Charlson Comorbidity Index 5). Aortic vessels were involved in 61.5% of cases, peripheral vessel in 38.5%. Microbiological identification was achieved in 84.6% of cases, with Staphylococcus aureus (MSSA and MRSA) being the most frequent pathogen. Surgical explant was performed in 53.8% of patients, predominantly for peripheral VGEIs. DAL was used to facilitate early discharge (69.2%) or as suppressive antibiotic therapy (30.8%). No adverse events related to DAL were reported. Clinical success was achieved in 84.6% of patients at EOT and maintained in 61.5% at six-month follow-up. DAL appears to be an effective and well-tolerated option for the management of VGEI, particularly in frail patients or those not eligible for surgery, both to facilitate early discharge and as long-term SAT. Further prospective studies are needed to confirm these findings.
Sexually transmitted infections (STIs) are continuing to rise in high-income countries, particularly among young adults. Increasing access to timely STI/HIV testing and treatment is key to reducing transmission. Web-accessed STI testing services have emerged as a pragmatic solution to improving access and uptake. However, these web-accessed alternatives do not always provide equivalent quality to in-person services. The scientific body of evidence around their development is limited and often not reported in detail, offering little guidance about design best practice. Translating a traditionally in-person service to a web-accessed one is a complex process that requires input from multiple stakeholders, including end users, clinical experts, and software developers, to support user acceptability, clinical safety, and technical feasibility. This manuscript outlines the evidence-based approach for establishing the clinical pathway for Test it, a statewide, publicly funded, web-accessed STI testing service targeting 16- to 29-year-olds in Victoria, Australia. We present the ten steps of the web-accessed clinical pathway and describe the iterative consultation and problem-solving process used to define them.
Malaria remains a major public health challenge in Ethiopia, with Plasmodium falciparum and Plasmodium vivax accounting for most malaria cases. Continuous monitoring of antimalarial drug efficacy and safety is essential to ensure effective case management and to detect early signs of emerging drug resistance. In addition, understanding gametocyte clearance following treatment is important because persistent gametocytaemia can sustain malaria transmission. This study assessed the therapeutic efficacy, safety, and gametocyte clearance following antimalarial treatment among patients with uncomplicated P. falciparum and P. vivax malaria in Northeast Ethiopia. A prospective observational study was conducted from November 2024 to January 2026 among 159 patients with uncomplicated malaria, including 81 P. falciparum and 78 P. vivax infections. Patients received treatment according to national guidelines, with artemether-lumefantrine for P. falciparum and chloroquine for P. vivax, while a subset also received a single low dose of primaquine. Participants were followed for 28 days to assess therapeutic outcomes, fever clearance, asexual parasite clearance, haemoglobin recovery, gametocyte clearance and adverse events. Data were analysed using SPSS version 26.0. Kaplan-Meier survival analysis was used to evaluate fever, parasite, and gametocyte clearance. Statistical significance was considered at p < 0.05. Therapeutic efficacy was high in both species, with adequate clinical and parasitological response rates of 88.9% among P. falciparum patients and 97.4% among P. vivax patients. Fever and asexual parasite clearance occurred more rapidly in P. vivax than in P. falciparum, with median fever clearance times of 2 and 3 days and median parasite clearance times of 2 and 4 days, respectively. Haemoglobin levels improved throughout follow-up in both groups, although P. falciparum infections were associated with lower baseline haemoglobin levels. Antimalarial treatments were generally well tolerated, with most adverse events being mild and no treatment discontinuations recorded. A transient increase in gametocyte carriage on day 3 was observed more frequently among participants who did not receive primaquine. Primaquine significantly accelerated gametocyte clearance, reducing the median clearance time from 11 to 7 days in P. falciparum and from 7 to 4 days in P. vivax. Higher baseline gametocyte density was associated with slower gametocyte clearance, particularly among P. falciparum patients. First-line antimalarial treatments remain highly effective and well tolerated for the management of uncomplicated P. falciparum and P. vivax malaria in Northeast Ethiopia. However, post-treatment gametocyte persistence may contribute to ongoing transmission, particularly in P. falciparum infections. The addition of low-dose primaquine significantly enhanced gametocyte clearance in both species, highlighting its potential role in reducing transmission and supporting malaria elimination efforts.
The workshop on 'Reactive and therapy induced BM changes linked to systemic infectious and non-infectious disorders including MAS/HLH' of the 22nd meeting of the European Association for Haematopathology held in Dubrovnik, 2024, included 58 cases. These encompassed a broad range of infections, autoimmune disorders, malignancies and therapy-effects, or a combination of these factors, of which 28 had an associated Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS). Histoplasmosis, the infection mostly associated with HLH, showed a wide variability of BM changes, with or without focal lesions. Leishmaniasis, less often associated with HLH, induced BM changes that mimic myelodysplastic syndrome. BM changes after COVID-19 infection included myeloid and megakaryocytic hypoplasia, erythroid hyperplasia, dyserythropoiesis, hemophagocytosis, and possibly ring granulomas. Other infectious causes included viruses (HHV-8, EBV, Parvovirus B19), mycobacterial infections, and human granulocytic anaplasmosis. HLH may arise in association with the full spectrum of EBV-related disorders, including acute infection, systemic chronic active EBV disease, viral reactivation, and EBV-associated malignancies. BM changes associated with autoimmune diseases included plasmacytosis, myeloid hyperplasia and hemophagocytosis, with or without meeting the criteria of MAS/HLH, the latter often triggered by a secondary infection or exacerbation of the disease. Haematologic malignancies (EBV-positive and negative) with HLH encompassed B-cell, T-/NK-cell, and myeloid neoplasms. In addition, the workshop included therapy-induced BM changes, such as differentiation syndrome, lenalidomide-associated B-ALL, therapy-related dysplasia, gelatinous transformation, CAR-T-induced BM hypoplasia, and CAR-T-associated HLH. Finally, the workshop demonstrated the presence of T-cell expansions in a variety of conditions, which should not be misinterpreted as T-cell malignancy.
Congenital human cytomegalovirus (HCMV) infection, caused by maternal transmission, is a leading cause of congenital disabilities and poses a substantial global disease burden. Historically, HCMV vaccine development has centered on protecting seronegative women. However, accumulating evidence indicates that the majority of HCMV infections in newborns stem from non-primary infections (reinfection or reactivation). Although HCMV shedding may have diagnostic value, the relationship between viral shedding and host immune status in seropositive individuals remains poorly elucidated. A total of 142 HCMV-seropositive women of reproductive age were enrolled from the Reproductive Medicine Clinic of Taizhou People's Hospital, Jiangsu Province, China. Serum samples and cervical secretions were collected, and antibody levels and HCMV DNA loads were detected, respectively. Serum IgG binding to postfusion glycoprotein B (gB), cell-surface-expressed gB, and pentameric complex (PC) was significantly associated with HCMV shedding in cervical secretions. In contrast, no significant associations were observed between cervical shedding and Serum IgG binding to prefusion gB or the structural antigen pp150, nor with neutralizing antibody (NAb) titers against Towne and ADR131 strains in MRC-5 cells or ADR131 strain in ARPE-19 cells. These findings advance the current understanding of the interplay between viral shedding and humoral immunity in HCMV-seropositive individuals. Importantly, they provide novel evidence supporting site-specific HCMV shedding as a potential biomarker for reinfection/reactivation, and a potential exploratory surrogate marker for subsequent vaccine endpoint validation. This study thus offers new insights for the development of HCMV vaccines targeting seropositive populations.
Although people living in malaria-endemic areas experience repeated infections with Plasmodium, the role of regulatory T (Treg) cells in recurrent malaria remains poorly understood. During a primary infection with Plasmodium, Treg cells suppress protective immunity by inhibiting germinal center (GC) reactions, thereby impeding the control of parasitemia. In contrast, memory Treg (mTreg) cells remaining after the clearance of initial Plasmodium infection acquire protective functions after recall. Longitudinal studies in humans and mice show that mTreg cells undergo antigen-driven expansion and inflammation-induced epigenetic reprogramming during reinfection to transition from FOXP3+ immunosuppressive cells to BCL6+ follicular T helper (TFH) cell-like effectors. These mTreg cell-derived TFH-like cells enhance GC responses and the generation of antibodies specific to Plasmodium, ultimately facilitating Plasmodium control. Precluding such mTreg-to-TFH cell differentiation abolished protection. Our findings reveal a previously unrecognized adaptive plasticity in canonical mTreg cells that enables a context-dependent functional switch from immunoregulatory to protective effectors during recurrent infections.
Host defense against invasive bacterial infections of the skin is essential for survival. It involves a complex yet incompletely understood process of microbial recognition followed by innate and adaptive systems for communication between resident and recruited cells to mount an effective defense. Stromal fibroblasts have not been classically considered immunocytes but are gaining recognition for their critical role in inflammation. Here, we identify fibroblast-derived C-C motif chemokine ligand 2 (CCL2) as a key mediator of host defense against invasive Staphylococcus aureus infection. Single-cell RNA sequencing revealed that fibroblasts are a predominant source of CCL2 under steady-state conditions in both human and mouse skin. The use of mice with a conditional deletion of CCL2 in fibroblasts demonstrated that the expression of CCL2 by fibroblasts alters macrophage cytokine production and antigen-presentation-associated responses and is important for monocyte recruitment. Additionally, we revealed a novel role for fibroblast-derived CCL2 in promoting fibroblast-to-adipocyte differentiation via ERK and p38 signaling, leading to reactive adipogenesis and enhanced production of the antimicrobial peptide cathelicidin. In mice with targeted deletion of Ccl2 in fibroblasts, these host immune responses are impaired, and S. aureus infection of the skin is greatly increased. These findings highlight fibroblast-derived CCL2 as a critical regulator of immunity and suggest its broader implications in inflammatory and infectious diseases.
Fecal Sludge (FS) is a well-known reservoir for multiple pathogenic organisms and antimicrobial-resistant E. coli. Contaminated drinking water (DW) is the primary route through which fecal-oral diseases are spread. This study examined the prevalence of Extended-spectrum beta-lactamase (ESBL)-producing E. coli in FS and adjacent DW samples collected within the Rohingya Camps. The DW and treated FS samples were screened for thermotolerant E. coli and the isolates were characterized for their ESBL-production ability, presence of major antibiotic resistance (AMR) genes, pathogenic genes, biofilm formation ability and phylogenetic clustering. Among the samples, 88.1% FS and 40.2% DW contained E. coli. From the selected isolates, 32.3% of FS and 12.5% of DW were ESBL-positive. Subsequently, 113 ESBL-FS and 56 ESBL-DW isolates were characterized based on their concurrent presence. Upon screening, blaCTX-M (81.1%) was the most prevalent AMR gene, followed by blaTEM (23.7%) and blaNDM-1 (14.8%). Enteroaggregative E. coli (EAEC) (17.2%) and enterotoxigenic E. coli (ETEC) (12.4%) were the most prevalent diarrheagenic pathotypes and 4.7% were extra-intestinal pathogenic E. coli (ExPEC) strains. Antimicrobial susceptibility testing (AST) revealed that 98.2% of isolates were multidrug-resistant. At 25 °C, 34.3% of isolates formed strong biofilm. The ERIC (Enterobacterial Repetitive Intergenic Consensus sequences) phylogenetic clustering generated 16 clusters at a 70% similarity index. The detection of pathogenic isolates highlights the risk of severe infections within susceptible populations and a high percentage of multidrug resistance limits the treatment options.
The two-year armed conflict in the Tigray Region of Northern Ethiopia (2020-2022) created a humanitarian crisis marked by widespread sexual violence, healthcare disruption, and displacement of health personnel. However, reliable epidemiological evidence on the contribution of conflict-related sexual violence to HIV transmission remains scarce. This study addresses this gap by quantifying the impact of conflict-related rape on HIV incidence and prevalence in Tigray. A dynamic risk equation model was developed to capture HIV transmission during conflict. In this framework, conflict intensity influences key transmission drivers, including rape prevalence, number of perpetrators, trauma severity, reduced post-exposure prophylaxis (PEP) use, and healthcare service degradation. Data from the Central Statistics Agency of Ethiopia, UNAIDS regional estimates, World Health Organization, Ethiopian Public Health Institute, and relevant literature were used. Uncertainty analyses were conducted, complemented by global sensitivity analysis and numerical simulations. This model-based study indicates that mass rape could cause a median of 122 (interquartile range, IQR: 13-681) new HIV infections, indicating conflict-related mass rape could cause a median increase of 13.8% (IQR: 1.9%-62.5%), while the median increase in prevalence could be 0.002% (IQR: 0.00027%-0.0089%). These results suggest the increase in incidence due to rape is epidemiologically notable though the effect on population prevalence is small, reflecting that escalating conflict intensity characterized by increased rape frequency, declining health system capacity, and reduced PEP coverage further amplifies HIV transmission. Integrated strategies, including prevention of sexual violence, timely PEP access, and mobile health services, are essential to mitigate HIV transmission. Humanitarian agencies and conflicting parties should act on both public health and human rights grounds.
Objective: To analyze the epidemiological and clinical characteristics of pertussis in children diagnosed at the Affiliated Children's Hospital of Fudan University in Shanghai in 2024, as well as the antimicrobial resistance patterns of Bordetella pertussis. Methods: Demographic information and vaccination status were collected from the pertussis cases confirmed by nucleic acid testing at the Children's Hospital of Fudan University in 2024. Clinical data from all hospitalized pertussis cases and a portion of outpatient pertussis cases were collected to analyze their clinical characteristics. Bordetella pertussis was isolated from nasopharyngeal swab specimens of some cases, and antimicrobial susceptibility was tested. Results: Among the 9 899 cases diagnosed in 2024, 5 272 were males and 4 627 were females. The peak epidemic season occurred from April to July. Children aged 4-10 years accounted for 7 744 cases (78.2%). Among 6 947 cases with available vaccination records, 6 676 (96.1%) had completed the full course of pertussis vaccination. A total of 2 085 pertussis patients were included for analysis of clinical characteristics, including 1 779 outpatient cases and all 306 hospitalized cases. The incidence rates of paroxysmal cough, whoop, cyanosis, apnea, fever, and white blood cell counts ≥20×10⁹/L in hospitalized patients were 94.8%, 35.0%, 24.2%, 21.6%, 44.8%, and 26.1%, respectively, all significantly higher than those in outpatient cases (75.0%, 14.6%, 1.7%, 1.3%, 23.5%, and 4.0%; all P<0.001). The proportions of complications and co-infections in hospitalized patients were 64.1% and 70.6%, respectively, also significantly higher than those in outpatient cases (19.3% and 13.8%; both P<0.001). Among both outpatient and hospitalized patients, infants under 7 months were more prone to whoop, cyanosis, apnea, post-tussive vomiting, and peripheral white blood cell counts≥20×10⁹/L compared to those older than 7 months, with statistical significance (all P<0.001). The hospitalization rates were highest among infants aged 0~2 months at 64.8% (83/128). The median length of hospital stay [M (Q1, Q3)] was 3.5 (2.5, 5.5) days, and the median hospitalization cost [M (Q1, Q3)] was RMB 8 351.6 (6 934.6, 12 086.4) among hospitalized cases. There were 14 severe cases (4.6 %), including 2 deaths. Twelve severe cases were unvaccinated, of which 9 were infants aged 0~2 months. The average length of hospital stay for severe cases was (30.7±17.7) days, with a median average cost [M (Q1, Q3)] of RMB 107 996.2 (42 066.9, 133 530.9). Based on minimum inhibitory concentration (MIC) testing of 166 Bordetella pertussis isolates, 165 (99.4%) exhibited high-level resistance to azithromycin (MIC>256.000 μg/ml). The isolates remained susceptible in vitro to trimethoprim-sulfamethoxazole, levofloxacin, ceftazidime, cefoperazone-sulbactam, and doxycycline. Conclusion: Children aged 4-10 years are the primary affected group during the 2024 pertussis outbreak in Shanghai. Unvaccinated infants under 2 months of age are at high risk for severe disease. Empirical use of macrolides for pertussis treatment is not recommended. 目的： 分析2024年上海市复旦大学附属儿科医院诊断的儿童百日咳的流行病学和临床特征，以及百日咳鲍特菌的耐药模式。 方法： 收集2024年复旦大学附属儿科医院核酸检测确诊的百日咳患者的人口学信息和疫苗接种信息；同时收集2024年全部住院和部分门诊确诊百日咳患者的临床资料，分析其临床特点。采集部分患者的鼻咽拭子标本进行百日咳鲍特菌培养和药物敏感性检测。 结果： 2024年共确诊9 899 例百日咳患者，其中男5 272例，女4 627例；4~7月为流行高峰季节；78.2%的患者为4~10岁儿童（7 744例）；有疫苗接种信息的6 947例患者中，6 676例（96.1%）完成全程百日咳疫苗接种。共2 085例百日咳患者分析其临床特点，包括1 779例门诊和306 例住院患者。其中住院患者痉挛性咳嗽、鸡鸣样尾声、青紫发作、呼吸暂停、发热、外周血白细胞计数≥20×109/L的发生率分别为94.8%、35.0%、24.2%、21.6%、44.8%、26.1%，均高于门诊患者的75.0%、14.6%、1.7%、1.3%、23.5%、4.0%（均P<0.001）；住院患者合并并发症、混合感染的比例分别为64.1%、70.6%，均高于门诊患者的19.3%、13.8%（均P<0.001）。门诊和住院患者中，7月龄以下婴幼儿较7月龄以上均更易发生鸡鸣样尾声、青紫发作、呼吸暂停、咳嗽后呕吐、外周血白细胞计数≥20×109/L，统计学有差异（均P<0.001）。0~2月龄婴幼儿住院率较高为64.8%（83/128）；住院患者住院天数M（Q1，Q3）为3.5（2.5，5.5）d，住院医疗费用M（Q1，Q3）为8 351.6（6 934.6，12 086.4）元。14例（4.6%）为重症，其中2例死亡；12例未接种疫苗，其中9例为0~2月龄婴儿；重症患者平均住院日为（30.7±17.7）d，住院医疗费用M（Q1，Q3）为107 996.2（42 066.9，133 530.9）元。166株百日咳鲍特菌分离株的最低抑菌浓度检测，165株（99.4%）对阿奇霉素高水平耐药（MIC>256.000 μg/ml），对甲氧苄啶-磺胺甲恶唑、左氧氟沙星、头孢他啶、头孢哌酮/舒巴坦、多西环素体外敏感。 结论： 4~10岁儿童是2024年上海地区百日咳暴发时期的主要发病人群，2月龄以下未接种疫苗婴儿是重症病例高危人群。不推荐经验使用大环内酯类药物治疗百日咳。.
Fungal infections, especially in people with weakened immune systems, are a significant global health burden. Accurate identification of fungal morphology from microscopic images is a critical step in guiding timely antifungal treatment decisions. However, manual morphological assessment remains highly dependent on expert mycologists and is prone to inter-observer variability. In this study, we propose a hybrid deep learning framework that integrates the ConvNeXtV2-Base architecture with a Multi-Head Attention-based Multiple Instance Learning module for automated classification of microscopic fungal morphology images. The framework was evaluated on the open-access DeFungi dataset, consisting of 3696 microscopic images representing five clinically meaningful fungal morphology classes. In comparative experiments, classical vision transformer (ViT) models achieved 91.20% accuracy, while MIL-enhanced ViT models reached 93.99%. The proposed ConvNeXtV2-Base + MIL hybrid method outperformed all evaluated architectures, achieving 98.90% classification accuracy. These results establish a new benchmark for automated fungal morphology classification and highlight the potential of AI-assisted decision-support tools to aid expert mycologists in morphology-based assessment workflows.
Urolithiasis is increasingly common, with rising rates driven by obesity, diabetes and metabolic syndrome. Patients with cancer have additional, unique risks of stone formation owing to effects on fluid and electrolyte balance, systemic cancer therapies, tumour lysis syndrome and anatomical alterations after urinary diversion or nephrectomy. Moreover, urolithiasis itself has been linked to increased rates of renal cell carcinoma, urothelial carcinoma and bladder cancer, potentially mediated by chronic inflammation, recurrent infections and shared metabolic or environmental factors. Management in this setting is complex and must be individualized. Percutaneous nephrolithotomy achieves the highest stone-free rates in patients with altered urinary tract anatomy, whereas retrograde intrarenal surgery and shock wave lithotripsy have more selective roles. Preventive strategies focus on thorough metabolic evaluation, hydration optimization and addressing cancer-specific risk factors such as hypercalcaemia, acidosis and chronic urinary stasis. Despite these insights, data on the epidemiology, mechanistic underpinnings and optimal management of urolithiasis in patients with cancer remain limited. Prospective studies are needed to clarify causal relationships, refine preventive strategies and develop evidence-based treatment algorithms for this growing and complex population.
This investigation aimed to evaluate the efficacy and safety of intra-articular dimethyl itaconate (DI) combined with systemic vancomycin (Van) for the treatment of periprosthetic joint infections (PJI) induced by Staphylococcus aureus. The fifty rats were divided into five groups: Control (Con), PJI, PJI + DI, PJI + Van, and PJI + Van + DI. After three weeks, systemic and local inflammation, osteolysis, bone histomorphometry, bacterial load, and biofilm formation were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclast inhibition by DI and vancomycin, and Alizarin Red staining was used to assess its effect on osteogenic differentiation. In vivo, the combination therapy demonstrated superior mitigation of bone loss and intra-articular synovial inflammation compared to Van monotherapy. Furthermore, the co-administration of DI and vancomycin effectively facilitated bacterial and biofilm clearance within the joint, further alleviating the dysregulation between bone resorption and remodelling. Compared to the DI and vancomycin monotherapy group, the Van + DI group showed reduced bacterial counts in implants, bone tissue, and soft-tissue. However, intra-articular DI alone was insufficient for complete eradication of S. aureus-induced PJI. Safety assessments indicated that neither DI monotherapy nor its combination with vancomycin elicited hepatic or renal toxicity in rats. In vitro, it was validated that DI exerts a promotive effect on osteoblast function while concurrently inhibiting osteoclast formation. Intra-articular injection of DI combined with systemic vancomycin appears to be a safe and effective therapeutic strategy for PJI in our current rat model.
The absence of maternal immune rejection of a haploidentical fetus remains unexplained. We hypothesize that the presence of different HLA antigens on trophoblasts and maternal cells via killer cell immunoglobulin-like receptors (KIRs) provides two-way tuning (education, licensing) of decidual natural killer cells (dNK) with the appearance of alloreactive (HvG) and autoreactive (HvH) dNK. Disturbances in dNKHvG and dNKHvH representation may lead to abnormalities in placental development and pregnancy pathology. Our data show that recurrent pregnancy loss is not associated with specific HLA and KIR genotypes in mother and fetus, although the peculiarities of tuning involving KIR3DL2 may affect pregnancy outcome. Mathematical modeling shows the dependence of dNKHvG and dNKHvH representation on the probability of random KIR gene expression. The new description of NK cell involvement in the immune response in the placenta via two-way tuning is applicable to all cases where there are target cells with normal and different "guest" HLA expression (viral infections, tumors).
The popularity of domestic cats (Felis catus) as companion animals is undisputed. However, the human-feline proximity poses potential health risks due to zoonotic disease transmission as well as physical injuries from bites and scratches. It is alarming to note that epidemiological data supports the prevalence and colonisation of Staphylococcus spp., including methicillin resistant Staphylococcus aureus (MRSA) in the oral cavity of cats. Considering the problem of antibiotic resistance globally, this review collates recent findings on the role of cats as reservoirs of antibiotic resistant pathogenic Staphylococcus spp. and examines the clinical implications of staphylococcal infections in cats. It provides an in-depth study into the link between pathogenesis and antibiotic resistance. In the context of "one health" the pathogenesis mechanisms enabling persistence and virulence such as colonisation, invasion, toxin and enzyme production, and immune evasion are also discussed. A mechanistic overview of promotion of antibiotic resistance in bacteria is provided, focusing on genetic adaptations such as target modification, efflux pumps, and gene acquisition. Patterns of antimicrobial resistance (AMR) among cat-derived isolates are critically assessed, outlining emerging trends and their implications for therapeutic strategies. Zoonotic concerns, vis-a-vis the impact of resistant Staphylococcus spp. on human health are addressed. The threats posed by rising antibiotic resistance, such as compromised treatment outcomes and the heightened risk of transmission across species are reviewed and strategies for mitigation, including preventive methods, ongoing surveillance, and the adoption of alternative non-antibiotic measures such as probiotics, bacteriophage therapy, and antimicrobial peptides, are suggested herein.
Gastrointestinal graft-versus-host disease (GI-GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), often requiring invasive endoscopy for diagnosis. Fecal calprotectin (FC) offers a non-invasive marker of intestinal inflammation, but its utility in GI-GVHD needs clarification. In this prospective observational study of 165 adult allo-HSCT recipients, FC was measured on days +7, +14, and +21 post-transplant, at GI-GVHD onset, and 7 days post-treatment, alongside clinical, endoscopic, and histological data. GI-GVHD developed in 52.7% of patients, with histological confirmation in 90.3% of cases. FC lacked predictive value on day +7 (AUC = 0.50) but showed moderate-to-high accuracy on days +14 (AUC = 0.69) and +21 (AUC = 0.77), with an optimal day +21 cutoff of 52.5 µg/g (sensitivity 75%, specificity 87%). At diagnosis, median FC was 120 µg/g, correlating with endoscopic severity (r = 0.31; p = 0.02) but not clinical or histological grades. FC declined significantly post-treatment (120 to 51.5 µg/g; p = 0.04), though concurrent infections elevated levels without compromising discriminative ability. FC serves as a dynamic biomarker for predicting, diagnosing, and monitoring GI-GVHD, but requires integrated clinical interpretation due to limited specificity amid other inflammations.
To explore what works for whom, how and why when implementing women's sexual and reproductive health interventions in prisons to understand the barriers and facilitators to implementation and to generate recommendations for policymakers. Realist review using the Realist And Meta-narrative Evidence Synthesis: Evolving Standards guidelines. We systematically searched Ovid MEDLINE, Global Health, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the American Psychological Association (APA) PsycINFO databases and hand-searched unpublished literature and reference lists, January-June 2025. Primary studies of implementing women's sexual and/or reproductive health interventions, including those addressing sexually transmitted infections, cervical health, breast screening, contraception and women's health holistically. Study populations included people in prisons that detain women in high-income countries. We extracted and analysed data relating to implementation processes using a grounded theory approach and retroductive inference to articulate cross-case Intervention-Context-Actor-Mechanism-Outcome configurations (ICAMOCs) and refine programme theory. We discussed findings in relation to existing theories from the literature to elicit recommendations for policymakers. Of 4617 deduplicated records, 26 met the inclusion criteria. Ten ICAMOCs were constructed from cross-case analyses, grouped into three themes: (1) planning (teaming, team leadership, assessing needs and capacity, tailoring and planning), (2) doing (piloting, standardisation and support, trauma-informed engagement and peer advocacy) and (3) sustaining (evaluation-adaptation cycles). The ICAMOCs indicated three overarching mechanisms as being key to effective implementation, namely, perceived utility of the intervention, motivation and empowerment. For women's sexual and reproductive health interventions to be effective in prisons, everyone involved in implementation needs to perceive the intervention's benefit and be both motivated and empowered to take action. We recommend policymakers build a resilient and empowered delivery workforce, invest in research partnerships to increase awareness and understanding and promote trauma-informed approaches to women's healthcare in prisons.