bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIBIAL OSTEOMYELITIS REQUIRING RECONSTRUCTION WITH A FREE FLAP: A SINGLE-CENTRE REVIEW OF OUTCOMES
Authors: Valand Poonam , Hotchen Andrew , Frank Florian , McNally Martin , Ramsden Alex 
Published: November 2024

AimTo report outcomes of soft tissue reconstruction using free tissue transfer for the treatment of tibial osteomyelitis as part of a single-stage, ortho-plastic procedure.MethodPatients who underwent ortho-plastic reconstructive surgery to excise tibial osteomyelitis in combination with free tissue transfer in one stage were included. Patients underwent surgery between 2015 and 2024 in a single specialist centre within the UK. Baseline patient information, demographics, and infection information was recorded. Adverse outcomes were defined as (i) flap salvage required, (ii) flap failure and (iii) recurrence of infection. Patient reported quality of life was measured using the EuroQol EQ-5D-5L index score. Pre-operative QoL was compared to QoL at 1 year with a control group of 53 similar patients who underwent surgical treatment for tibial osteomyelitis without a free flap (local flap or primary closure).ResultsNinety-three patients were eligible for inclusion, with a mean age of 52 years (range 18–90). 77/93 (82.8%) had a free muscle flap with the remainder (17.2%) receiving a fasciocutaneous flap. The donor tissue was defined as 57 gracilis, 6 latissimus dorsi, 14 hemi-latissimus dorsi, and 16 anterolateral thigh. The recipient area of the tibia was distal 1/3 in 52 cases, middle 1/3 in 27 cases and proximal 1/3 in 12 cases. The average flap ischaemic time was 70 minutes (range 28 to 125).Seven patients (7.5%) required urgent flap salvage at a median time of 1.0 day (range 0.5 – 4.0). Of these, 4 (4.3%) went on to have total flap failure, of which 2 patients underwent below knee amputation subsequently. Flap failure was due to either arterial (n=2) or venous (n=2) anastomotic thrombus. There were 3 (3.2%) episodes of confirmed infection recurrence within the first year after the index procedure.EQ-index scores at 1-year post-operatively were significantly improved when compared to pre-operative scores (p=0.008). At 1-year post-operatively, EQ-index scores in patients who underwent free flap was similar compared to local flaps (p=0.410) and in those who underwent primary closure for tibial osteomyelitis (p=0.070).ConclusionsMicrosurgical single stage surgery can achieve high flap survival rate (95.7%). Free flaps fail early due to anastomotic thrombus with no late failures seen. Free tissue transfer does not appear to give inferior QoL compared to matched patients with local flaps or direct closure in tibial osteomyelitis.
GENOMIC CHARACTERIZATION AND CLINICAL EVALUATION OF PERIPROSTHETIC JOINT INFECTIONS CAUSED BY CUTIBACTERIUM ACNES
Authors: Liew-Littorin Clara , Davidsson Sabina , Nilsdotter-Augustinsson Åsa , Brueggemann Holger , Söderquist Bo 
Published: November 2024

AimCutibacterium acnes is a major skin commensal that may also act as an opportunistic pathogen. Findings of C. acnes in tissue cultures obtained during arthroplasty revision surgery are difficult to interpret, since they may represent true infection or contamination. This study investigated whether C. acnes isolates obtained from prosthetic joint infections (PJIs) were related and shared common genomic traits that might correlate with clinical courses and patient outcomes.MethodC. acnes isolates from revision surgery of patients with PJIs of the hip, shoulder, and knee were characterized using molecular methods to determine sequence type (ST) and the presence of virulence determinants (CAMP factors, dermatan sulfate-binding adhesion 1, hyaluronidase lyase, and linear plasmid). A standardized review of the patients’ medical charts was performed.ResultsThe study included 37 patients with C. acnes culture-positive tissue samples where multiple isolates of C. acnes belonged to the same ST. Most of the isolates belonged to phylotype IA1. Phylogenetic analysis of virulence determinants revealed no shared pattern among PJI isolates. Seven patients had a polymicrobial infection. Exchange revision was performed in 70% of the patients, and >50% of all patients received antibiotic treatment for ≥3 months. Failure was noted in seven patients, all of whom had shoulder PJIs.ConclusionsNo specific ST or any identifiable unique feature among virulence determinants were found among C. acnes isolated from PJIs of hips and shoulders. The majority of all included patients had low inflammatory markers and were treated successfully, even when the infection consisted of a polymicrobial infection.
INFECTION AFTER PRIMARY TOTAL HIP ARTHROPLASTY: A COMPARISON OF TIME TRENDS IN TWO NATIONAL HEALTH REGISTERS IN NORWAY FROM 2013 TO 2022
Authors: Karlsen Øystein Espeland , Eriksen-Volle Hanne-Merete , Furnes Ove , Dale Håvard , Westberg Marianne 
Published: November 2024

AimTwo types of national registers surveil infections after primary total hip arthroplasty (THA) in Norway: The National surveillance system for surgical site infections (NOIS) that surveil all primary THAs 30 days postoperatively for surgical site infections (SSI), and the Norwegian Arthroplasty Register (NAR) that follow all THAs until any surgical reoperation/revision or the death of the patient. Since these registers report on the same THAs we assessed correspondence between and time trends for the two registers in period 2013 to 2022. All reported THAs were included.MethodThe THAs were matched on a group level according to sex, age and ASA-class. In addition to descriptive statistics, adjusted Cox regression analyses were performed with adjustment for sex, age group (<45, 45-54, 55-64, 65-74, 75-84, >85 years) and ASA-class (1, 2, 3, 4 and missing). Changes in annual incidence and adjusted hazard rate (aHR) was calculated. Endpoints in the NOIS were 30-Days SSI and 30-Days reoperation for SSI. Endpoints in the NAR were 30-Days and 1-Year reoperation for periprosthetic joint infection (PJI).ResultsThe NOIS had registered 87,923 THAs with 1,393 (1.58%) SSIs and 765 (0.87%) reoperations for SSI within 30 postoperatively. The NAR had registered 91,194 THAs with 725 (0.80%) reoperations for infection after 30 days, and 1,019 (1.21%) reoperations for infections after one year. The distribution of sex, age and ASA-class was near identical in the two registers. There was a mean annual reduction in risk of both SSI (aHR 0.92 (95% CI 0.90-0.93)) and reoperation for SSI (0.95(0.92-0.97)) and PJI (30-Days: 0.96 (0.94-0.99), 1-Year: 0.95-0.99)) over the period 2013-2022.ConclusionsThe NOIS and the NAR have excellent completeness and the registrations in both registers may be considered representative for the Norwegian population. Not all SSI are reoperated. The incidence and risk of SSI (NOIS) and reoperation for PJI (NAR) is declining and may reflect a true reduction in incidence of PJI after primary THA.
EXTERNAL VALIDATION OF THE JS-BACH CLASSIFICATION FOR PREDICTING OUTCOME IN PERIPROSTHETIC JOINT INFECTIONS: A COHORT OF 653 PATIENTS
Authors: Kristensen Nicolai , Manning Laurens , Lange Jeppe , Davis Joshua 
Published: November 2024

AimPeriprosthetic Joint Infection (PJI) is a devastating complication in hip and knee joint arthroplasty. The “JS BACH” classification system was developed in 2021 to stratify the complexity of PJI, and more importantly, to act as a tool to guide referrals to specialist centers. The “JS BACH” classification has not been validated in an external cohort. This study aimed to do so using a large prospective cohort from Australia and New Zealand.MethodWe applied the JS-BACH classification to the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort. This prospective study of newly diagnosed PJI collected 2-year outcome data from 653 participants enrolled in 27 hospitals. The definition of PJI treatment failure at 24 months was any of the following: death, clinical or microbiological signs of infection, destination prosthesis removed, or ongoing antibiotic use.ResultsIndividual cases were classified as per JS-BACH into “1 - uncomplicated” (n = 268), “2 - complex” (n = 330), and “3 - limited options” (n = 55). This cohort was similar to the original JS-BACH population in terms of baseline characteristics. However, there was a difference in complexity, with more DAIR procedures, fewer revision procedures, and a higher proportion of uncomplicated patients in the PIANO cohort.The risk of treatment failure correlated strongly with the JS-BACH category, with odds ratios (95% CI [confidence interval]) for category 2 versus 1 of 1.75 (1.24 to 2.47) and for category 3 versus 1 of 7.12 (3.42 to 16.02).ConclusionsDespite the PIANO study population being less complicated than the original derivation cohort, the JS-BACH classification showed a clear association with treatment failure in this large external cohort.
INFECTION ERADICATION AFTER PREFABRICATED OR INDIVIDUAL SPACERS IN TWO-STAGE REVISION: TEN YEARS’ EXPERIENCE AT A TERTIARY ACADEMIC CENTRE
Authors: Lallinger Vincent , Goeggelmann Anja , Schlossmacher Benjamin , Heine Niels , von Eisenhart-Rothe Rüdiger , Lazic Igor 
Published: November 2024

AimIn Two-Stage Revision, utilizing temporary antibiotic spacers is widely accepted. These spacers are available prefabricated or can be individually moulded intraoperatively. In this study, we analysed the efficacy of prefabricated and individual spacers in infection eradication of periprosthetic joint infection in knee and hip arthroplasties.MethodAll spacers implanted at a tertiary academic center during two-stage exchanges between June 2010 and December 2019 were retrospectively analysed. Among 249 patients, 167 cases (minimum follow-up ≥ 12 months) were included. Commercial spacers contained vancomycin and gentamycin, while individual spacers contained vancomycin alone. Subgroup analysis by manufacturers was conducted using non-parametric methods including Mann-Whitney U and Kruskal-Wallis tests. Survival analysis utilized Kaplan-Meier curves, and categorical data were analyzed using the Chi² test. Statistical significance was defined as p < 0.05.ResultsOf the 167 patients included, a prefabricated spacer was implanted in 105 cases (62.9%) and an individual spacer was implanted in 62 cases (37.1%). In 106 cases, infection healing according to the Delphi consensus was achieved with a mean follow-up of 37.8 months [12;99]. Infection persistence was seen in 31.4% of the preformed spacers and in 45.2% of the individual spacers, with no statistically significant difference (p = 0.09). (Results are shown in the illustration). In the multivariate analysis, preoperative anemia (p = 0.02 OR 2.25 CI-95% 1.2-4.4 p = 0.01) and diagnosed paraneoplastic disease (p = 0.01 OR 3.0 CI-95% 1.4-6.7 p = 0.01) were found to be risk factors for failure.ConclusionsTwo-stage Revisions are successfully suitable options for the treatment of PJI. In this study, infection eradication was independent of the type of spacer. Anemia and paraneoplastic diseases were found to be risk factors of failure.
RADIOIMMUNOTHERAPY COMBATING METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS AND ITS BIOFILM IN VITRO
Authors: Ye Zijian , van der Wildt Berend , Vogely Charles , Weinans Harry , Poot Alex , van der Wal Bart 
Published: November 2024

AimProsthetic joint infections (PJI) remain a great challenge in orthopedic surgery with a high mortality rate. It is particularly complicated by biofilms and infections caused by Methicillin-resistant Staphylococcus aureus (MRSA). It concurrently shields bacteria from host immune responses and confers resistance to antibiotics. This study aims to investigate the efficacy of radioimmunotherapy as an innovative therapeutic modality to address the challenges posed by MRSA and its biofilm.MethodWe induced specific monoclonal antibodies 4497-IgG1 as carriers, which target wall teichoic acids (WTA) existing on MRSA and its biofilm. Radionuclides actiniumr-225 (225Ac, α-emitter) and lutetium-177 (177Lu, β-emitter) were conjugated with mAbs using DOTA as chelator. Quality control was assessed using thin layer chromatography and immunoreactivity assays. 225Ac- and 177Lu-labelled 4497-IgG1 were employed to evaluate the susceptibility of MRSA and its biofilm to the radioimmunotherapy in vitro. Planktonic MRSA and biofilms, at concentrations of 108 and 107 CFU/mL, were incubated at 37°C for 60 minutes in PBS containing either 225Ac-mAb (0 - 14.8 kBq) or 177Lu-mAb (0 - 14.8 MBq). Radiolabelled dunituximab and free radionuclides serve as isotype-matched negative control. The bacterial viability and metabolic activity were subsequently quantified using CFU and XTT assays.ResultsThe radiochemical purity of the 225Ac-mAbs and 177Lu-mAbs complex were determined to be 95.4% and 96.16%. Immunoreactivity fractions of them were measured at 81.8% and 80.8%. 225Ac-mAbs and 177Lu-mAbs exhibited significant and dose-dependent antimicrobial effects on both planktonic MRSA and biofilm. 225Ac- and 177Lu-4497IgG1 at doses of 7.4 kBq and 7.4 MBq resulted in more than 4-log reduction in bacterial counts. In biofilms, 2-log reduction at the highest 225Ac radioactivity of 14,8kBq. The 177Lu complex showed a strong dose-dependent effect, with a reduction of up to 4-log. The XTT assay confirmed these findings, showing a decrease in metabolic activity corresponding to a decrease in bacterial counts, and a slight increase in metabolic activity at the lower dose.ConclusionsOur study demonstrates the efficacy of 225Ac and 177Lu-labelled 4497-IgG1 antibodies in mediating dose-dependent bactericidal effects against planktonic MRSA and biofilms in vitro. This indicates that radioimmunotherapy could be a potential targeted therapeutic strategy against MRSA and its biofilm. Further research in preclinical and clinical settings is warranted to validate and refine these findings on biofilm-associated implant infections.
Short-term stability of a microcell optical reference based on the Rb atom two-photon transition at 778  nm
Authors: Callejo Martin , Mursa Andrei , Vicarini Rémy , Klinger Emmanuel , Tanguy Quentin , Millo Jacques , Passilly Nicolas , Boudot Rodolphe 
Published: November 2024

We report on the development and short-term stability characterization of an optical frequency reference based on the spectroscopy of the rubidium two-photon transition at 778 nm in a microfabricated vapor cell. When compared against a 778 nm reference signal extracted from a frequency-doubled cavity-stabilized telecom laser, the short-term stability of the microcell frequency standard is 3.5×10−13τ−1/2 until 200 s, in good agreement with a phase noise level of +43dBrad2/Hz at 1 Hz offset frequency. The two main contributions to the short-term stability of the microcell reference are currently the photon shot noise and the intermodulation effect induced by the laser frequency noise. Retaining a relevant margin of progress, these results show the interest of this spectroscopic approach for the demonstration of high-stability miniaturized optical vapor cell clocks. Such clocks are poised to be highly beneficial for applications in navigation, communications, and metrology.
Community-based intervention for monitoring of salt intake in hypertensive patients: A cluster randomized controlled trial
Authors: Sonuch Pitchaporn , Aekplakorn Wichai , Pomsanthia Nophatee , Boonyagarn Natthida , Makkawan Siripak , Thongchai Suchada , Tosamran Wasinee , Kunjang Ananthaya , Kantachuvesiri Surasak 
Published: November 2024

Background
Excessive sodium intake is associated with high blood pressure and an increased risk of cardiovascular disease. However, reducing dietary salt has been challenging due to a lack of awareness and a high threshold in detecting saltiness.

Objectives
The goal of this study is to evaluate the effectiveness of a combined intervention (intensive dietary education, food reformulation, environmental changes to facilitate salt reduction, and salt meter utilization), in comparison to standard education only, on salt intake and blood pressure.

Methods
A cluster randomized-controlled trial was conducted on 219 hypertensive adults aged 18 to 70 years in Uthaithani, Thailand. Participants were randomized 1:1 into the intervention group (n = 111) and the control group (n = 108).

Results
There were no differences in baseline characteristics between groups. The mean systolic and diastolic blood pressure was 143.6 and 82.1 mmHg and 142.2 and 81.4 mmHg in the intervention group, and the control group, respectively. The median 24-hour urinary sodium excretion was 3565 and 3312 mg/day, in the intervention and the control group, respectively. After 12 weeks, the change in systolic blood pressure was -13.5 versus -9.5 mmHg (P = 0.030) and diastolic blood pressure was -6.4 versus -4.8 mmHg (P = 0.164) in the intervention and control groups, respectively. Moreover, a reduction in 24-hour urine sodium excretion was observed [-575 versus -299 mg/day in the intervention and control groups, respectively (P = 0.194)]. The change in 24-hour urine sodium excretion was statistically significant and reduced from baseline in the intervention group (P = 0.004). The dietary salt intake was significantly improved and was statistically different between groups (P = 0.035).

Conclusions
The combined intervention significantly decreased systolic blood pressure and showed a trend towards reduced urine sodium excretion in hypertensive patients. These comprehensive approaches may be beneficial in reducing blood pressure and salt intake in the community.

Clinical trial registration
This trial was registered at Clinicaltrials.gov with the identifier NCT05397054. https://classic.clinicaltrials.gov/ct2/show/NCT05397054
Prevalence of endoepicardial asynchrony and breakthrough patterns in a bilayer computational model of heterogeneous endoepicardial dissociation in the left atrium
Authors: Zakeri Zafarghandi Elham , Jacquemet Vincent 
Published: November 2024

Background
Transmural propagation and endoepicardial delays in activation observed in patients with atrial fibrillation are hypothesized to be associated with structural remodeling and endoepicardial dissociation. We aim to explore in a computational model how the distribution of delays and the rate of endo- and epicardial breakthrough activation patterns are affected by fibrosis and heterogeneous layer dissociation.

Methods
A bilayer interconnected cable model of the left atrium was used to simulate a total of 4,800 episodes of atrial fibrillation on 960 different arrhythmogenic substrates with up to 30% epicardium-only diffuse fibrosis. Endoepicardial connections were heterogeneously distributed following random spatial patterns (characteristic length scale from 1.6 to 11.4 mm). Intermediate nodes were introduced in the transmural connections to enable the simulation of weaker coupling. This heterogeneous interlayer dissociation divided the atrial bilayer into connected and disconnected regions (from 27 to 48,000 connected regions). Activation time series were extracted in both layers to compute endoepicardial delays and detect breakthrough patterns.

Results
Because of epicardial fibrosis, fibrillatory waves were driven by the endocardium, which generated endoepicardial delays. The delays in the connected regions (up to 10 ms, but generally < 5 ms) were prolonged by higher fibrosis density and weaker coupling. Disconnected regions allowed longer delays (> 15 ms) and promoted the occurrence of breakthroughs. These breakthroughs had short lifespan (< 10–20 ms) and were more prevalent with higher fibrosis density and heterogeneous dissociation (larger disconnected regions). Severe remodeling (< 500 connected regions) was needed to produce clinically reported rates (> 0.1 breakthrough/cycle/cm2).

Conclusion
Heterogeneous endoepicardial dissociation aggravates activation delays and increases the prevalence of epicardial breakthroughs.
Spatial distributions of CD8 and Ki67 cells in the tumor microenvironment independently predict breast cancer-specific survival in patients with ER+HER2– and triple-negative breast carcinoma
Authors: Zilenaite-Petrulaitiene Dovile , Rasmusson Allan , Valkiuniene Ruta Barbora , Laurinaviciene Aida , Petkevicius Linas , Laurinavicius Arvydas 
Published: November 2024

Introduction
Breast cancer (BC) presents diverse malignancies with varying biological and clinical behaviors, driven by an interplay between cancer cells and tumor microenvironment. Deciphering these interactions is crucial for personalized diagnostics and treatment. This study explores the prognostic impact of tumor proliferation and immune response patterns, assessed by computational pathology indicators, on breast cancer-specific survival (BCSS) models in estrogen receptor-positive HER2-negative (ER+HER2–) and triple-negative BC (TNBC) patients.

Materials and methods
Whole-slide images of tumor surgical excision samples from 252 ER+HER2– patients and 63 TNBC patients stained for estrogen and progesterone receptors, Ki67, HER2, and CD8 were analyzed. Digital image analysis (DIA) was performed for tumor tissue segmentation and quantification of immunohistochemistry (IHC) markers; the DIA outputs were subsampled by hexagonal grids to assess the spatial distributions of Ki67-positive tumor cells and CD8-positive (CD8+) cell infiltrates, expressed as Ki67-entropy and CD8-immunogradient indicators, respectively. Prognostic models for BCSS were generated using multivariable Cox regression analysis, integrating clinicopathological and computational IHC indicators.

Results
In the ER+HER2– BC, multivariable Cox regression revealed that high CD8+ density within the tumor interface zone (IZ) (HR: 0.26, p = 0.0056), low immunodrop indicator of CD8+ density (HR: 2.93, p = 0.0051), and low Ki67-entropy (HR: 5.95, p = 0.0.0061) were independent predictors of better BCSS, while lymph node involvement predicted worse BCSS (HR: 3.30, p = 0.0013). In TNBC, increased CD8+ density in the IZ stroma (HR: 0.19, p = 0.0119) and Ki67-entropy (HR: 3.31, p = 0.0250) were independent predictors of worse BCSS. Combining these independent indicators enhanced prognostic stratification in both BC subtypes.

Conclusions
Computational biomarkers, representing spatial properties of the tumor proliferation and immune cell infiltrates, provided independent prognostic information beyond conventional IHC markers in BC. Integrating Ki67-entropy and CD8-immunogradient indicators into prognostic models can improve patient stratification with regard to BCSS.