Semen analysis and reproductive hormones in boys with classical Hodgkin lymphoma treated according to the EuroNet-PHL-C2 protocol.

STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years. STUDY DESIGN, SIZE, DURATION: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy. LIMITATIONS, REASONS FOR CAUTION: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited. WIDER IMPLICATIONS OF THE FINDINGS: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Radiological evaluation of response in patients with locally advanced/metastatic soft tissue sarcoma treated with trabectedin.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83 months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7-4.6); median overall survival was 34.3 months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

Water sorption studies with mesoporous multivariate monoliths based on UiO-66.

Hierarchical linker thermolysis has been used to enhance the porosity of monolithic UiO-66-based metal-organic frameworks (MOFs) containing 30 wt% 2-aminoterephthalic acid (BDC-NH2) linker. In this multivariate (i.e. mixed-linker) MOF, the thermolabile BDC-NH2 linker decomposed at ∼350 °C, inducing mesopore formation. The nitrogen sorption of these monolithic MOFs was probed, and an increase in gas uptake of more than 200 cm3 g-1 was observed after activation by heating, together with an increase in pore volume and mean pore width, indicating the creation of mesopores. Water sorption studies were conducted on these monoliths to explore their performance in that context. Before heating, monoUiO-66-NH2-30%-B showed maximum water vapour uptake of 61.0 wt%, which exceeded that reported for either parent monolith, while the highly mesoporous monolith (monoUiO-66-NH2-30%-A) had a lower maximum water vapour uptake of 36.2 wt%. This work extends the idea of hierarchical linker thermolysis, which has been applied to powder MOFs, to monolithic MOFs for the first time and supports the theory that it can enhance pore sizes in these materials. It also demonstrates the importance of hydrophilic functional groups (in this case, NH2) for improving water uptake in materials.

The evidence base for the optimal antibiotic treatment duration of upper and lower respiratory tract infections: an umbrella review.

BACKGROUND: Many trials, reviews, and meta-analyses have been performed on the comparison of short versus long antibiotic treatment in respiratory tract infections, generally supporting shorter treatment. The aim of this umbrella review is to assess the soundness of the current evidence base for optimal antibiotic treatment duration. METHODS: A search in Ovid MEDLINE, Embase, and Clarivate Analytics Web of Science Core Collection was performed on May 1, 2024, without date and language restrictions. Systematic reviews addressing treatment durations in community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis were included. Studies from inpatient and outpatient settings were included; reviews in paediatric populations were excluded. Outcomes of interest were clinical and bacteriological cure, microbiological eradication, mortality, relapse rate, and adverse events. The quality of the reviews was assessed using the AMSTAR 2 tool, risk of bias of all included randomised controlled trials (RCTs) using the Cochrane risk-of-bias tool (version 1), and overall quality of evidence according to GRADE. FINDINGS: We identified 30 systematic reviews meeting the criteria; they were generally of a low to critically low quality. 21 reviews conducted a meta-analysis. For CAP outside the intensive care unit (ICU; 14 reviews, of which eight did a meta-analysis) and AECOPD (eight reviews, of which five did a meta-analysis), there was sufficient evidence supporting a treatment duration of 5 days; evidence for shorter durations is scarce. Evidence on non-ventilator-associated HAP is absent, despite identifying three reviews (of which one did a meta-analysis), since no trials were conducted exclusively in this population. For sinusitis the evidence appears to support a shorter regimen, but more evidence is needed in the population who actually require antibiotic treatment. For pharyngotonsillitis (eight reviews, of which six did a meta-analysis), sufficient evidence exists to support short-course cephalosporin but not short-course penicillin when dosed three times a day. INTERPRETATION: The available evidence for non-ICU CAP and AECOPD supports a short-course treatment duration of 5 days in patients who have clinically improved. Efforts of the scientific community should be directed at implementing this evidence in daily practice. High-quality RCTs are needed to underpin even shorter treatment durations for CAP and AECOPD, to establish the optimal treatment duration of HAP and acute sinusitis, and to evaluate shorter duration using an optimal penicillin dosing schedule in patients with pharyngotonsillitis. FUNDING: None.

Early screening for chronic liver disease: impact of a FIB-4 first integrated care pathway to identify patients with significant fibrosis.

Liver fibrosis is often undetected whereas it is the determinant of liver-related mortality. We evaluate a pathway based on the systematic calculation of FIB-4 to screen for advanced hepatic fibrosis. Systematic calculation of FIB-4 was implemented in the centralized laboratory of a French University Hospital in 4 pilot departments. If ≥ 2.67, the FIB-4 result was returned to the prescribers, for patients between 18 and 70 years of age, with an incentive to measure liver stiffness by vibration controlled transient elastography. During a 2-years period, a FIB-4 was calculated in 2963 patients and 135 were ≥ 2.67 (4.6%). After exclusion of patients with a known cause of elevated FIB-4, 47 patients (34.8%) were eligible for elastography. Forty patients underwent elastography, but only 15% (7/47) at the spontaneous request of the referring physician. Fifteen patients were identified with significant fibrosis, among which 8 attended the scheduled specialist consultation, all with a confirmed diagnosis of cirrhosis. A sequential pathway based on the systematic calculation of FIB-4 enables the identification of patients with significant unknown liver fibrosis, allowing to refer them to specialized care. Raising awareness is essential to improve the care pathway.

Verification and application of qPCR and viability-qPCR for Legionella monitoring in evaporative cooling systems complementing the conventional culture method.

To date, in many countries the only legally valid method for evaporative cooling system (ECS) monitoring is the culture method. However, a duration of up to 14 days and a risk of underestimation of Legionella concentrations are seen as limitations of cultivation methods. Rapid cultivation-independent methods are an important step towards a more practicable monitoring of ECS to quickly control interventions if elevated concentrations of Legionella are found. Two commercial kits for quantitative polymerase chain reaction (qPCR) and viability-qPCR (v-qPCR) were studied, comprising sample filtration and DNA extraction. Cryopreserved Legionella pneumophila were established as calibration standard with intact (ILC) and total Legionella count (TLC) determined by flow cytometry before conducting spiking experiments in commercial mineral water and artificial process water. Final assessment was carried out using real ECS samples. Recovery and robustness ranged from 86 to 108 % for qPCR with a drop to 40-60 % for v-qPCR when compared to direct extraction, possibly attributable to cell damage during sample concentration. All methods including culture did perform well regarding linearity with R2 ≥ 0.95 for most trials. Detected concentrations in comparison to spiked Legionella counts differed with culture averaging 25 ± 7 % of spiked ILC and v-qPCR being closest to spiked concentrations with 65-144 %. In comparison, qPCR was several fold above spiked TLC concentrations. For real ECS samples Legionella spp. were detected in concentrations above 103 GU/100 mL by v-qPCR in 70-92 % of samples, depending on the kit used. Most of these samples were either culture-negative or not evaluable on agar plates. This study showed that a cryopreserved bacterial standard based examination is applicable and can be used for future v-qPCR verification. For assessment of differences in results between culture and v-qPCR/qPCR in ECS samples expert knowledge about the operating mode and used analytical methods is required. Guidelines addressing this issue could be a solution.

Inherent uncertainty in pedestrian collision reconstruction: How evidence variability affects head kinematics and injury prediction.

Reconstructing individual cases from real-world collision data is used as a tool to better understand injury biomechanics and determine injury thresholds. However, real-world data tends to have inherent uncertainty within parameters, such as ranges of impact speed, pre-impact pedestrian stance or pedestrian anthropometric characteristics. The implications of this input parameter uncertainty on the conclusions made from case reconstruction about injury biomechanics and risk is not well investigated, with a 'best-fit' approach more frequently adopted, leaving uncertainty unexplored. This study explores the implications of uncertain parameters in real-world data on the biomechanical kinematic metrics related to head injury risk in reconstructed real-world pedestrian-car collisions. We selected six pedestrian-car cases involving seven pedestrians from the highly detailed GB Road Accident In-Depth Studies (RAIDS) database. The collisions were reconstructed from the images, damage measurements and dynamics available in RAIDS. For each case, we varied input parameters within uncertain ranges and report the range of head kinematic metrics from each case. This includes variations of reconstructed collision scenarios that fits within the constraints of the available evidence. We used a combination of multibody and finite element modelling in Madymo to test whether the effect of input data uncertainty is the same on the initial head-vehicle and latter head-ground impact phase. Finally, we assessed whether the predicted range of head kinematics correctly predicted the injuries sustained by the pedestrian. Varying the inputs resulted in a range of output head kinematic parameters. Real-world evidence such as CCTV footage enabled predicted simulated values to be further constrained, by ruling out unrealistic scenarios which do not fit the available evidence. We found that input data uncertainty had different implications for the initial head-vehicle and latter head-ground impact phase. There was a narrower distribution of kinematics associated with the head-vehicle impact (initial 400 ms of the collision) than in the latter head-ground impact. The mean head-vehicle kinematics were able to correctly predict the presence or absence of both subdural haematoma (using peak rotational acceleration) and skull vault fracture (using peak contact force) in all pedestrians presented. This study helps increase our understanding of the effects of uncertain parameters on head kinematics in pedestrian-car collision reconstructions. Extending this work to a broad range of pedestrian-vehicle collision reconstructions spanning broad population demographics will improve our understanding of injury mechanisms and risk, leading to more robust design of injury prevention measures.

Acute Health System-Level Interventions for Identification and Management of Domestic Abuse: Preliminary Interrupted Time Series Evaluation.

This preliminary interrupted time series analysis evaluated different interventions to improve identification of victim-survivors of domestic abuse in one U.K. National Health Service trust, focusing on emergency department, sexual health services and HIV care, and obstetrics and gynecology. This analysis demonstrated that while system-level interventions can improve identification of domestic abuse in clinical contexts, the exact nature of interventions most likely to be effective may vary in different clinical contexts. For example, none of the modeled interventions generated significant impacts in emergency department contexts, and estimates were close to the null in all cases, but routine inquiry demonstrated effectiveness in sexual health services, while implementation generated improved effectiveness in the obstetrics and gynecology setting.

A robust time-delay selection criterion applied to convergent cross mapping.

This work presents a heuristic for the selection of a time delay based on optimizing the global maximum of mutual information in orthonormal coordinates for embedding a dynamical system. This criterion is demonstrated to be more robust compared to methods that utilize a local minimum, as the global maximum is guaranteed to exist in the proposed coordinate system for any dynamical system. By contrast, methods using local minima can be ill-posed as a local minimum can be difficult to identify in the presence of noise or may simply not exist. The performance of the global maximum and local minimum methods are compared in the context of causality detection using convergent cross mapping using both a noisy Lorenz system and experimental data from an oscillating plasma source. The proposed heuristic for time lag selection is shown to be more consistent in the presence of noise and closer to an optimal uniform time lag selection.

Participation 1.5 years after mild traumatic brain injury in children and adolescents.

This longitudinal prospective cohort study examined participation between 6 months and 1.5 years after pediatric mild Traumatic Brain Injury (mTBI) in 68 children aged 6-18 years. Levels of participation in different settings remain mostly stable between 6 months and 1.5 years after mTBI, with a substantial proportion of children continuing to indicate less than full functioning. Future studies should examine risk factors and opportunities for early identification to prevent long-term negative consequences of pediatric mTBI regarding participation.

Changes in hand function and health state utility after cubital tunnel release using the United Kingdom Hand Registry.

This study aimed to analyse and contrast changes in health-related quality of life (HR-QoL) and hand symptoms in the first 6 months after surgical treatment for primary cubital tunnel syndrome. Data originated from the United Kingdom Hand Registry. HR-QoL was assessed using the generic EuroQol five-dimensional assessment tool (EQ-5D-5L) and hand symptoms using the Patient Evaluation Measure (PEM). In total, 281 patients were included in the statistical analysis. Cubital tunnel release resulted in clinically relevant relief of hand symptoms. However, no improvement in HR-QoL was detected by the EQ-5D-5L. As a result, current health economic models, such as those used by the National Institute for Health Care Excellence (NICE) in the UK, might conclude that cubital tunnel release is not cost-effective. This discrepancy requires exploration, and hand-specific preference-based measures might be needed for value-based healthcare in hand surgery.Level of evidence: III.

A low-cost, antimicrobial aloe-alginate hydrogel film containing Australian First Nations remedy 'lemon myrtle oil' (Backhousia citriodora) - Potential for incorporation into wound dressings.

Chronic wounds pose a global public health challenge, particularly in remote settings where access to specialised wound care and dressings can be limited and cost-prohibitive. First Nations communities in Australia are at a significantly higher risk for developing chronic wounds and this risk further increases for people living in remote regions. There is an urgent need to develop inexpensive but effective wound dressings to improve wound outcomes. Over the past decade, sodium alginate (SA)-based hydrogel polymers have emerged as a cost-effective and biocompatible component in wound dressings, and many have been successfully commercialised. In this study, we have developed and evaluated various prototypes of SA-based hydrogels with the addition of another low-cost component, aloe vera (AV) to further tailor the physicochemical properties of the hydrogel. Since the presence of microbes is a major contributor to the pathophysiology of chronic wounds, we also evaluated the antimicrobial activity of lemon myrtle oil (LMO) (Backhousia citriodora) incorporated into the hydrogel, a remedy used traditionally by First Nations Australians. Novel formulations of AV-SA-LMO hydrogel prototypes in the absence and presence of lemon myrtle oil (at a concentration of 5 µg/mL) were assessed for their physicochemical and antimicrobial properties and compared to a commercially available hydrogel-based dressing. The addition of lemon myrtle oil imparted viscoelastic behaviour for improved processability of AV-SA-LMO hydrogel prototypes, while increasing protein adhesion, enhancing physical properties, and demonstrating antimicrobial activity against the common wound-infecting microbes Staphylococcus epidermidis and Candida albicans. Fourier transmission infrared (FTIR) spectra confirmed the molecular structures of the hydrogel prototypes as predicted. The prototypes also demonstrated biocompatibility with the HaCaT human keratinocyte cell line. This study has provided preliminary evidence that a 25:75 aloe vera:sodium alginate hydrogel with 5 µg/mL lemon myrtle oil has comparable physicochemical characteristics to a commercial hydrogel-based wound dressing and antimicrobial properties against S. epidermidis and C. albicans.

Time resolved x-ray diffraction using the flexible imaging diffraction diagnostic for laser experiments (FIDDLE) at the National Ignition Facility (NIF): Preliminary assessment of diffraction precision.

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a new diagnostic at the National Ignition Facility (NIF) designed to observe in situ solid-solid phase changes at high pressures using time resolved x-ray diffraction. FIDDLE currently incorporates five Icarus ultrafast x-ray imager sensors that take 2 ns snapshots and can be tuned to collect X-rays for tens of ns. The platform utilizes the laser power at NIF for both the laser drive and the generation of 10 keV X-rays for ∼10 ns using a Ge backlighter foil. We aim to use FIDDLE to observe diffraction at different times during compression to probe the kinetics of phase changes. Pb undergoes two solid-solid phase transitions during ramp compression: from face centered cubic (FCC) to hexagonal close packed (HCP) and HCP to body centered cubic (BCC). Results will be reported on some of the first shots using the FIDDLE diagnostic at NIF on ramp compressed Pb to a peak pressure of ∼110 GPa and a single undriven CeO2 calibration shot. A discussion of the uncertainties in the observed diffraction is included.

A serum B-lymphocyte activation signature is a key distinguishing feature of the immune response in sarcoidosis compared to tuberculosis.

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).

Developing time-resolved x-ray diffraction diagnostics at the National Ignition Facility (invited).

As part of a program to measure phase transition timescales in materials under dynamic compression, we have designed new x-ray imaging diagnostics to record multiple x-ray diffraction measurements during a single laser-driven experiment. Our design places several ns-gated hybrid CMOS (hCMOS) sensors within a few cm of a laser-driven target. The sensors must be protected from an extremely harsh environment, including debris, electromagnetic pulses, and unconverted laser light. Another key challenge is reducing the x-ray background relative to the faint diffraction signal. Building on the success of our predecessor (Target Diffraction In Situ), we implemented a staged approach to platform development. First, we built a demonstration diagnostic (Gated Diffraction Development Diagnostic) with two hCMOS sensors to confirm we could adequately protect them from the harsh environment and also acquire acceptable diffraction data. This allowed the team to quickly assess the risks and address the most significant challenges. We also collected scientifically useful data during development. Leveraging what we learned, we recently developed a much more ambitious instrument (Flexible Imaging Diffraction Diagnostic for Laser Experiments) that can field up to eight hCMOS sensors in a flexible geometry and participate in back-to-back shots at the National Ignition Facility (NIF). The design also allows for future iterations, such as faster hCMOS sensors and an embedded x-ray streak camera. The enhanced capabilities of the new instrument required a much more complex design, and the unexpected issues encountered on the first few shots at NIF remind us that complexity has consequences. Our progress in addressing these challenges is described herein, as is our current focus on improving data quality by reducing x-ray background and quantifying the uncertainties of our diffraction measurements.

Surgical and Medical Management of Pediatric Spine Trauma.

Pediatric spine trauma is rare but presents unique challenges to clinical management. Special considerations include but are not limited to the need to minimize ionizing radiation in this patient population, anatomic immaturity, physiologic variants, and injuries seen only in the pediatric population. Here we review the epidemiology of pediatric spine trauma, presentation, diagnosis, and treatment of the most common injuries and discuss specific medical and surgical strategies for treatment.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

Interosseus Membrane Reconstruction Following a Forearm Injury: A Case Report.

Background Essex-Lopresti injuries are complex, frequently missed forearm/elbow injuries consisting of a fracture of the radial head with disruption of both the distal radioulnar joint (DRUJ) and the interosseous membrane (IOM). Ideal management of these injuries remains controversial, especially in relation to the IOM, due in part to underdiagnosis of IOM injury and incomplete understanding of the IOM role. Methods A 43-year-old man sustained an open radial shaft fracture with associated radial head subluxation, coronoid base fracture, and DRUJ injury with ulnar head subluxation. He was taken for surgery, where elbow instability with near complete disruption of the IOM was observed. Persistent gross rotational instability was noted following radius fixation, so braided suture and button reconstruction of the central band of the IOM was performed. This restored rotational and longitudinal stability to the radiocapitellar joint and DRUJ. Over 1 year out from the index surgery, the patient's elbow and DRUJ have remained stable, and he is back working as a laborer. Results While little literature exists on outcomes of acute IOM reconstruction in these injuries, recent biomechanical studies have shown the importance of the central band on rotational elbow stability. Conclusion This case supports the importance of the central band of the IOM by demonstrating the impact of its repair on the longitudinal and rotational stability of the elbow and DRUJ. IOM repair has the potential to improve our treatment of this complicated injury by better restoring forearm stability and function of the elbow, which future studies could help further elucidate.