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Abstract Heteroresistance (HR) in bacteria describes a subpopulational phenomenon of antibiotic resistant cells of a generally susceptible population. Here, we investigated the molecular mechanisms and phenotypic characteristics underlying HR to ceftazidime (CAZ) in a clinical Enterobacter cloacae complex strain (ECC). We identified a plasmid-borne gene duplication-amplification (GDA) event of a region harbouring an ampC gene encoding a β-lactamase bla DHA-1 as the key determinant of HR. Individual colonies exhibited variations in the copy number of the genes resulting in resistance level variation which correlated with growth onset (lag times) and growth rates in the presence of CAZ. GDA copy number heterogeneity occurred within single resistant colonies, demonstrating heterogeneity of GDA on the single-cell level. The interdependence between GDA, lag time and antibiotic treatment and the strong plasticity underlying HR underlines the high risk for misdetection of antimicrobial HR and subsequent treatment failure.

Summary:. Liposuction is a common procedure for patients with lymphedema with nonpitting adipose tissue hypertrophy. However, routinely, the lipoaspirate is discarded. Experimental studies have shown that adipose-derived stem cells in fat may enhance the regenerative and lymphangiogenic effects of the fat. Recent evidence has shown that lymphedema fat is enriched in adipose-derived stem cell populations, thus making it an interesting regenerative option. This article introduces a novel surgical technique using the lipoaspirate of a patient with lymphedema for regenerative purposes. A 42-year-old woman developed lymphedema 18 months after mastectomy and axillary lymph node dissection surgery. The patient underwent upper limb liposuction and latissimus dorsi flap reconstruction of the breast. Lipofilling of the flap and axillary area after scar release was performed using suctioned lymphedema fat. The results showed a sustained reduction in the volume of the lymphedema arm, an improved lymphatic transport index, decreased fluid extravasation, and new lymphatics in the upper arm. At 64-month follow-up, the patient had good breast symmetry, had minimal swelling of the lymphedema arm, and rarely used compression garments. This report is the first to use lymphedema fat for regenerative purposes, differentiating it from existing literature that uses healthy fat. In conclusion, successful dual-effect fat grafting with lymphedema fat presents a promising avenue for further investigation. This innovative approach addresses breast cancer-related lymphedema and offers potential benefits in regenerative and lymphangiogenic effects without the need for microsurgical expertise. This case report emphasizes the importance of exploring this novel option for future research and clinical applications.

Aims: Older adults with hip fractures are at high risk of experiencing complications after surgery, but estimates of the rate of specific complications vary by study design and follow-up period. The aim of this systematic review was to determine the prevalence of complications in older adults after hip fracture surgery., Methods: MEDLINE, Embase, CINAHL, and CENTRAL databases were searched from inception until 30 June 2023. Studies were included if they reported prevalence data of complications in an unselected, consecutive population of older adults (aged ≥ 60 years) undergoing hip fracture surgery., Results: A total of 95 studies representing 2,521,300 patients were included. For surgery-specific complications, the 30-day prevalence of reoperation was 2.31%, surgical site infection 1.69%, and deep surgical site infection 0.98%; the 365-day prevalence of prosthesis dislocation was 1.11%, fixation failure 1.77%, and periprosthetic or peri-implant fracture 2.23%. For general complications, the 30-day prevalence of acute kidney injury was 1.21%, blood transfusion 25.55%, cerebrovascular accident 0.79%, lower respiratory tract infection 4.08%, myocardial infarction 1.98%, urinary tract infection 7.01%, and venous thromboembolism 2.15%., Conclusion: Complications are prevalent in older adults who have had surgery for a hip fracture. Studies reporting complications after hip fracture surgery varied widely in terms of quality, and we advocate for the routine monitoring of complications in registries and clinical trials to improve the quality of evidence., Competing Interests: E. L. Goh reports an institutional research grant from National Institute for Health and Care Research (NIHR) which enabled research for this study. M. L. Costa's employer, the University of Oxford, receives research grant funding from NIHR and Wellcome for research into musculoskeletal trauma. D. Metcalfe reports an institutional research grant from NIHR and an institutional programme grant from the Kadoorie Charitable Foundation, neither of which are related to this study., (© 2025 Goh et al.)

Background: The chronic lymphocytic leukemia treatment strategies have transitioned from chemotherapy and chemoimmunotherapy to chemotherapy-free regimens. Frequentist network meta-analysis allows for direct and indirect comparisons between different treatments., Methods: Randomized controlled trials assessing first-line treatments were included. Outcomes were progression-free survival (PFS), overall survival, undetectable minimal residual disease, objective response rate, and adverse events. Studies with comparable characteristics also underwent subgroup analysis, stratifying by age, comorbidities, IGHV status, and cytogenetic abnormalities., Results: A total of 30 eligible trials involved 12 818 patients, and 30 treatments were included. Acalabrutinib demonstrated a PFS advantage over ibrutinib and obinutuzumab-venetoclax in patients aged older than 65 years or with unmutated IGHV. In younger patients with comorbidities, acalabrutinib-obinutuzumab had superior PFS compared with ibrutinib-obinutuzumab, ibrutinib-venetoclax, and obinutuzumab-venetoclax. For older patients with comorbidities, acalabrutinib and acalabrutinib-obinutuzumab outperformed obinutuzumab-venetoclax without statistically difference between them. Minimal residual disease-guided ibrutinib-venetoclax surpassed obinutuzumab-venetoclax in patients without comorbidities. Ibrutinib-obinutuzumab exhibited extended PFS benefits compared with obinutuzumab-venetoclax in patients with mutated IGHV or with del(17p) and/or TP53 mutations. Ibrutinib-venetoclax and ibrutinib-obinutuzumab had lower neutropenia rates than obinutuzumab-venetoclax. Ibrutinib-venetoclax had fewer infections than acalabrutinib and acalabrutinib-obinutuzumab. Acalabrutinib-obinutuzumab caused less diarrhea than ibrutinib-venetoclax but more headaches than ibrutinib-obinutuzumab and obinutuzumab-venetoclax. Obinutuzumab-venetoclax had lower hypertension rates than ibrutinib-obinutuzumab. Ibrutinib-venetoclax had fewer arthralgia than acalabrutinib-obinutuzumab. For any grade secondary primary neoplasms, ibrutinib-venetoclax and obinutuzumab-venetoclax was less than acalabrutinib-obinutuzumab., Conclusion: Tailored chemotherapy-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different adverse events spectra., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Recurrent coarctation of the aorta (re-CoA) is a well-known although not fully understood complication after surgical repair, typically occurring in 10%-20% of cases within months after discharge., Objectives: To (1) characterize geometry of the aortic arch and blood flow from pre-discharge magnetic resonance imaging (MRI) in neonates after CoA repair; and (2) compare these measures between patients that developed re-CoA within 12 months after repair and patients who did not., Methods: Neonates needing CoA repair, without associated major congenital heart defects, were included. Transthoracic echocardiography (echo) and 4D phase-contrast MRI were performed prior to discharge after CoA repair to assess 3D arch geometry, flow velocity and flow pattern in the distal aortic arch corresponding to the area at risk for re-CoA. Arch geometry was assessed by measuring angles of the aortic arch and its branches using 3D patient-specific geometries segmented from MRI. Continuous data are presented as median and interquartile range., Results: The median age at CoA surgery was 9 days. Four out of the included 28 patients (14%) developed re-CoA within the first 12 months after surgery. Re-CoA was associated with repair technique (lateral thoracotomy 100% vs. 33%, p  = 0.02), higher postoperative isthmic flow velocity by echocardiography (1.9 [0. 9] m/s vs. 1.25 [0.5] m/s, p  = 0.04) and postoperative crenel aortic arch (100% vs. 21%, p  = 0.007) with a larger distance between the first and last branching points (12.6 [3.1] mm vs. 7.3 [7.0] mm; p  = 0.01). A smaller angle between the ascending aorta and the brachiocephalic artery (89 [58]° vs. 122 [37]°, p  = 0.05) and between the proximal aortic arch and the left carotid artery (75° vs. 97 [37]°, p  = 0.04), with a more pronounced caliber change between the ascending aorta and the proximal (1.85 vs. 0.86 [0.76]; p  = 0.03) and distal aortic arch (2.19 [2.42] vs. 1.01 [0.94]; p  = 0.03) were observed in re-CoA patients. Patients who developed re-CoA had more left-handed helical flow in systole ( p  = 0.045), more right-handed helical flow in diastole ( p  = 0.02), and less vortical flow ( p  = 0.05)., Conclusion: Subtle changes in aortic arch geometry and flow pattern early after neonatal CoA repair may contribute to the risk of re-CoA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2025 Fricke, Christierson, Heiberg, Sjöberg, Hedström, Steiner, Weismann, Töger and Liuba.)