Kočani General Hospital

Introduction: Ultrasound examination is a widely accepted method for developmental hip dysplasia screening, diagnosis and treatment monitoring. The Graf technique, routinely used in the Republic of North Macedonia is reliable and reproducible when performed in a precise and standardized manner, but it can be challenging when used by inexperienced ultrasonographers. We analyzed the relationship between findings of ultrasound scans obtained by the Graf method and femoral head coverage (FHC), in order to examine its usefulness in infant hip screening. Material and methods: Hip sonograms of 105 infants aged 0 to 6 months were examined. Measurements of alpha and beta angles according to Graf were performed and FHC was calculated as d*/D ratio. Multiple regression analysis was performed to examine the relationship between FHC, alpha and beta angles and infant age. Results: Two hips in a single patient were abnormal (grade 2c and D) according to Graf technique, with incidence of 0.95%. Seven hips (3.3%) had FHC below 50%, including the 2c and D hips and five hips with Ib grade according to Graf. FHC increased for 0.71% for each degree increase of alpha angle and decreased for 0.68% for each degree increase of beta angle. Infant age did not influence FHC. Conclusion: There was a positive correlation between alpha angle and FHC and negative correlation between beta angle and FHC. FHC above 50% is strongly indicative of normal hip morphology. FHC can be used in addition to the Graf method for assessment of infant hips.

Acquisition of multiple carbapenemase genes by Klebsiella pneumoniae (Kp) is an emerging public health threat. Here, we aim to elucidate the population structure of Kp blood isolates carrying two different carbapenemase genes and identify the mechanism facilitating their dissemination. The study was conducted in a tertiary healthcare center between 2014 and 2022. Twenty-four patients with bacteremia caused by Kp carrying two different carbapenemase genes were identified. All 24 blood isolates were analyzed by short-read genome sequences supplemented by long reads in a selected number of isolates. All isolates carried blaKPC (23 blaKPC-2, 1 blaKPC-3) and blaVIM-1 genes, along with a variety of antimicrobial resistance determinants. The isolates were clustered in six clonal lineages (ST39, ST147, ST323, ST258, ST3035, and ST340). Long-read genome sequences demonstrated that each carbapenemase gene was located in a separate group of plasmids: the blaKPC-2 on a fusion of IncFIB(pQil) and IncFII(K) plasmids, the blaKPC-3 on IncX3, the blaVIM-1 on IncC, or a fusion of the IncFIB(pNDM-Mar) and IncHI1B(pNDM-MAR) plasmids. Comparison of plasmid content of eight isolates carrying a single carbapenemase gene from a previous study with eight isolates carrying two carbapenemase genes from the present study, matched by clonal lineages, revealed that the second carbapenemase gene was acquired by addition of another plasmid. Identical plasmids were found within the same lineage and across lineages. These findings suggest that dissemination of carbapenemase genes in our hospital setting was driven by multiple plasmids across a variety of highly efficient clones.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with a poor prognosis. We conducted a retrospective study across six institutions in Miyazaki Prefecture, Japan, to assess the efficacy of tucidinostat in patients with relapsed/refractory ATL who had not undergone transplantation. Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated as key outcomes. ORR and DCR reached 54.2% and 91.7%, respectively. The median PFS was 3.95 months, and OS was 8.04 months, which were not inferior to the results of a phase IIb study. The influential factors for PFS were age ≥ 75 years and high soluble IL-2 receptor (sIL-2R) levels above 5000 U/mL at the start of treatment. Favorable patients without these factors achieved a PFS of 11.4 months. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.

Allergic diseases are common and affect a large proportion of the population. Interleukin-13 (IL-13)-expressing follicular helper T (TFH13) cells are a newly identified population of TFH cells that have been associated with high-affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of TFH13 cells are unknown. Here, we examined the developmental signals for TFH13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar TFH13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based TFH13-diphtheria toxin receptor model to perturb these cells, we found that TFH13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by TFH13 cells to amplify allergic responses. Thus, TFH13 cells orchestrate multiple features of allergic inflammation. TFH cells that express IL-13 are associated with high-affinity IgE responses, but factors controlling their development, transcriptional programming and exact function have remained unclear. Here, Chandrakar et al. find that the transcription factor JunB is required for TFH13 cell maintenance and that TFH13 cells producing IL-21 drive broad germinal center responses to allergen-specific IgG and IgE.

This cohort study examines the safety and efficacy of rituximab for patients with pempigus foliaceus.