Background Monoclonal antibodies (mAbs) effectively treat and prevent various diseases, but their clinical application is hindered by issues related to the route of administration and pharmacokinetics (PK). Intravenous (IV) administration is cumbersome, while subcutaneous (SC) administration is hampered by lower bioavailability and potential for immunogenicity. This study evaluated the efficacy of liposomal formulations in enhancing the subcutaneous (SC) delivery and PK of broadly neutralizing antibodies (bNAbs) directed against HIV. Methods mAbs were encapsulated in liposomes with and without PEGylation. The liposomes were characterized for particle size, polydispersity index, zeta potential, and release. Thereafter, mice were injected with free mAbs or liposome-encapsulated mAbs, and PK was evaluated. Results Liposomes exhibited sizes of 85-92 nm with negative surface charges. Encapsulation efficiencies were 61% for PEGylated and 58% for non-PEGylated liposomes. Stability testing over 16 weeks revealed that formulations remained stable at 4°C but showed leakage at 37°C. Cytotoxicity assays confirmed that the liposomal formulations did not affect cell viability or induce apoptosis in HMEC-1 cells. In vivo, PK studies in humanized FcRn mice indicated that the PEGylated formulations generally had higher half-life, Cmax, AUC, and MRT, and lower CL values compared to their non-PEGylated formulations of the same injection type. Both liposomal formulations showed improvements in bioavailability and extended half-life compared to free mAbs administered via SC and IV routes. Compared to the gold standard of IV free mAb injection, SC injection of antibodies encapsulated in PEGylated liposome had up to 80% higher bioavailability and 45% extension of half-life. Compared to the SC free mAb injection, the differences were even more pronounced, with liposomal SC injection having up to 113% higher bioavailability and 81% extension of half-life. Conclusion Overall, liposomal encapsulation effectively protected SC injected mAbs from degradation, facilitated sustained release, and improved PK profiles, suggesting a promising strategy for enhancing the therapeutic potential of mAbs in conditions that need repeated injections. Future work should further optimize liposomal formulations to increase loading capacity, stability, and release kinetics. STATEMENT OF SIGNIFICANCE: This study addresses a challenge in the administration of monoclonal antibodies (mAbs). Intravenous administration requires additional resources, including nursing staff, making it time-consuming and costly. Although subcutaneous (SC) administration offers a less expensive and more patient-friendly option, it suffers from lower bioavailability and potentially shorter half-life. In this study, we encapsulated mAbs in liposomal formulations specifically designed to enhance their pharmacokinetics by promoting efficient lymphatic transport. Compared with both SC and even IV administration of free antibodies, liposomal formulations of mAbs remarkably improve bioavailability and extend the half-life. This innovative approach combines the comfort of SC administration with enhanced pharmacokinetics, addressing the limitations of current SC delivery methods. Liposomal formulations have the ability to greatly improve SC mAb administration by reducing the amount of antibody needed to be administered, reducing the frequency of injections, and potentially protecting against immunogenicity.

Background: Women living with HIV (WLWH) are at increased risk of human papillomavirus (HPV)‐related cancers. Throughout Europe, there is great heterogeneity among guidelines for screening programmes, access to HPV testing and HPV vaccination. The aim of this systematic review is to summarize available data on screening and prevention measures for HPV‐related anogenital cancers in WLWH across the WHO European Region (WER).Methods: The systematic review followed the PRISMA guidelines and was registered on Prospero. PubMed, Embase and Web of Science databases were searched to identify available studies, written in English and published between 2011 and 2022. A metanalysis was conducted using random‐effects models to calculate pooled prevalence of HPV. Subgroup analyses were conducted according to country and HPV testing.Results: Thirty‐four articles involving 10 336 WLWH met the inclusion criteria. Studies were heterogenous in their methodology and presentation of results: 73.5% of studies focused on cervical cancer prevention, and only 4.4% on anal cancer; 76.5% of studies conducted HPV testing as a routine part of screening. The prevalence of high‐risk HPV was 30.5–33.9% depending on the detection method used. A total of 77% of WLWH had cervical cytology results reported. Six studies reported the positive association of CD4 cell count <200 cells/μL with HPV prevalence and cervical abnormalities. Anal HPV testing was conducted in <8% of participants. HPV vaccination was completed in 5.6% of women (106/1902) with known vaccination status. There was no information about the vaccination status of the majority of women in the analysed studies (8434/10336).Conclusion: Data about screening of HPV‐related anogenital cancer in WLWH in Europe are heterogenous and lacking, especially in relation to anal cancer. HPV DNA testing is not routinely done as part of screening for HPV‐related cancer; guidelines should include indications for when to use this test. Low CD4 count is a risk factor for HPV infection and cytological abnormalities. HPV vaccination data are poor and, when available, vaccination rates are very low among WLWH in Europe. This review concludes that significant improvements are required for data and also consistency on guidelines for HPV screening, prevention and vaccination in WLWH.

Objectives: This study aims to evaluate the use and efficacy of antibiotic-lock therapy (ALT) in the management of catheter-related bloodstream infections (CRBSIs), focusing on its impact on infection resolution, catheter retention, and clinical outcomes. Methods: Patients aged ≥18 years diagnosed with CRBSIs who had long-term indwelling catheters and for whom catheter replacement posed clinical challenges were enrolled in the retrospective study from January 2019 to December 2024. Participants were divided into two groups based on treatment: Group 1 received intravenous (IV) antibiotics combined with antibiotic-lock therapy (ALT), while Group 2 received IV antibiotics alone. Patient demographics, pathogen distribution, administered antibiotic regimens, duration of treatment, laboratory parameters, clinical outcomes, and mortality rates were evaluated. Results: A total of 54 patients were included, of whom 42.6% were female, and the mean age was 66.3 ± 15.4 years. Group 1 comprised 50% of the study population. The median treatment duration was 14 days. The most common pathogen was Coagulase-negative staphylococci, and 33.3% of CRBSIs were caused by Gram-negative bacteria (GNB). Group 1 demonstrated lower C-reactive protein levels at treatment 48/72 h of treatment (p = 0.013) and a reduced frequency of catheter revision (p < 0.0001) compared to Group 2. Overall, ALT achieved a success rate of 88.9%, with success rates of 86% for GNB infections and 90% for Gram-positive bacterial infections. Among patients receiving daily ALT, the success rate was 86%, while those receiving the therapy every three days had a success rate of 90%. Conclusions: Antimicrobial lock therapy can be considered a treatment option for managing CRBSIs, particularly in cases where removal of the implantable catheter is not feasible, allowing for salvage.

Background: Computed tomography (CT) evaluation systematics has become necessary to eliminate the difference of opinion among radiologists in evaluating COVID-19 CT findings. Introduction: The objectives of this study were to evaluate the efficiency of CO-RADS scoring system in our patients with COVID-19 as well as to examine its correlation with clinical and laboratory findings. Method: The CO-RADS category of all patients included in the study was determined by a radiologist who did not know the rtRT-PCR test result of the patients, according to the Covid-19 reporting and data system of Mathias Prokop et al. Results: A total of 1338 patients were included. CT findings were positive in 66.3%, with a mean CO-RADS score of 3,4 ± 1,7. 444 (33.1%) of the patients were in the CO-RADS 1-2, 894 (66.9%) were in the CO-RADS 3-5 group. There were positive correlations between CO-RADS score and age, CMI, hypertension, diabetes mellitus, chronic pulmonary diseases presence of symptoms, symptom duration, presence of cough, shortness of breath, malaise, CRP, and LDH, while CORADS score was negatively correlated with lymphocyte count. The results of the ROC analysis suggested that those with age ≥40 years, symptom duration >2 days, CMI score >1 and/or comorbid conditions were more likely to have a CO-RADS score of 3-5. Conclusion: The CO-RADS classification system is a CT findings assessment system that can be used to diagnose COVID-19 in patients with symptoms of cough, shortness of breath, myalgia and fatigue for more than two days.

Crimean-Congo hemorrhagic fever virus (CCHFV), a zoonotic agent in the Nairoviridae family (genus Orthonairovirus), is a high-priority pathogen. CCHFV infection causes Crimean-Congo hemorrhagic fever (CCHF), a human disease with case fatality rates of up to 40%. Serological surveillance of CCHFV in animals and humans is crucial for ecological studies and public health. We developed CCHFV mix-and-read assays utilizing split-NanoLuc technology (NanoBiT) to detect anti-CCHFV antibodies against the nucleoprotein (NP) stalk region and the GP38 glycoprotein. These species- and isotype-agnostic assays provide results in ∼30 min. Using serum samples from RT-PCR-confirmed CCHF cases collected during and after hospitalization, we investigated anti-NP and anti-GP38 antibody development. The performance of the mix-and-read assays was compared to the NP-based IDScreen® CCHF commercial assay using human sera, and cross-reactivity potential was evaluated using a diverse panel of anti-orthonairovirus antisera raised in mice. In human convalescent cases (n = 21), mix-and-read assay concordance between anti-GP38 and anti-NP antibody detection was 100%. Both mix-and-read assays and IDScreen® CCHF demonstrated identical sensitivity of 95.2% in convalescent patients. The specificity of the NP assay was 98.9%, and that of GP38 was 99.7%, both comparable to IDScreen® CCHF (specificity: 99.7%). Cross-reactivity against CCHF NP and GP38, regardless of assay type, was primarily observed in antisera raised against other orthonairoviruses within the Nairobi sheep disease genogroup. The simplicity and robust performance of the CCHFV mix-and-read assays make them ideal tools for supporting serological surveillance in humans and animals. Furthermore, the inclusion of the GP38 antigen alongside NP enhances the precise identification of retrospective CCHF cases, further strengthening broad surveillance efforts. CDC Emerging Infectious Disease Research Core Funds, funding for reagent, CDC personal, travel. Defence Threat Reduction Agency (HDTRA12210007): E.K. salary. Oak Ridge Institute for Science and Education (ORISE): E.K. salary and travel. National Institute of Allergy and Infectious Diseases (1R01AI180125-01A1): sample acquisition. Funding sources did not have a role in the writing or decision to submit the publication.