18F-fluorodeoxyglucose positron emission tomography for the assessment of endo-bronchial involvement in granulomatosis with polyangiitis.

Bronchial stenosis is an uncommon but potentially life-threatening complication of granulomatosis with polyangiitis (GPA). The development of lower respiratory tract stenoses in patients with GPA is thought to be the result of persistent inflammation of the cartilaginous tissue. New assessment methods for this severe GPA complication are highly needed. Herein, we show the value of 18F-fluorodeoxyglycose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis, prediction of progression to bronchial stenosis and response to treatment of endobronchial involvement in a patient with GPA.

Alanine response to low energy synchrotron x-ray radiation.

Objective. The radiation response of alanine is very well characterized in the MV photon energy range where it can be used to determine the dose delivered with an accuracy better than 1%, making it suitable as a secondary standard detector in cancer radiation therapy. This is not the case in the very low energy keV x-ray range where the alanine response is affected by large uncertainties and is strongly dependent on the x-ray beam energy. This motivated the study undertaken here.Approach. Alanine pellets with a nominal thickness of 0.5 mm and diameter of 5 mm were irradiated with monoenergetic x-rays at the Diamond Light Source synchrotron, to quantify their response in the 8-20 keV range relative to60Co radiation. The absorbed dose to graphite was measured with a small portable graphite calorimeter, and the DOSRZnrc code in the EGSnrc Monte Carlo package was used to calculate conversion factors between the measured dose to graphite and the absorbed dose to water delivered to the alanine pellets. GafChromic EBT3 films were used to measure the beam profile for modelling in the MC simulations.Main results. The relative responses measured in this energy range were found to range from 0.616 to 0.643, with a combined relative expanded uncertainty of 3.4%-3.5% (k= 2), where the majority of the uncertainty originated from the uncertainty in the alanine readout, due to the small size of the pellets used.Significance. The measured values were in good agreement with previously published data in the overlapping region of x-ray energies, while this work extended the dataset to lower energies. By measuring the response to monoenergetic x-rays, the response to a more complex broad-spectrum x-ray source can be inferred if the spectrum is known, meaning that this work supports the establishment of alanine as a secondary standard dosimeter for low-energy x-ray sources.

Does policy that provides choice in athletic footwear affect musculoskeletal injury risk in US Coast Guard recruits?

INTRODUCTION: Musculoskeletal injuries (MSKIs) are ubiquitous during initial entry military training, with overuse injuries the most common. A common injury mechanism is running, an activity that is integral to US Coast Guard (USCG) training and a requirement for graduation. The purpose of this study was to assess the effects of a policy that allowed for athletic footwear choice on risk of lower quarter MSKI in USCG recruits. METHODS: A retrospective cohort study was performed that included 1230 recruits (1040 men, 190 women) who trained under a policy that allowed self-selection of athletic footwear and 2951 recruits (2329 men, 622 women) who trained under a policy that mandated use of prescribed uniform athletic shoes and served as controls. Demographic data and physical performance were derived from administrative records. Injury data were abstracted from a medical tracking database. Unadjusted risk calculations and multivariable logistic regression assessing the effects of group, age, sex, height, body mass and 2.4 km run times on MSKI were performed. RESULTS: Ankle-foot, leg, knee and lumbopelvic-hip complex injuries were ubiquitous in both groups (experimental: 13.13 per 1000 person-weeks; control: 11.69 per 1000 person-weeks). Group was not a significant factor for any of the injuries assessed in either the unadjusted or adjusted analysis, despite widespread reports of pain (58.6%), perceived injury attribution (15.7%), perceived deleterious effect on performance (25.3%), general dissatisfaction (46.3%) and intended discontinuance of use following graduation (87.7%). CONCLUSION: MSKI continues to be a major source of morbidity in the recruit training population. The policy that allowed USCG recruits to self-select athletic footwear did not decrease or increase the risk of MSKI. While regulations pertaining to footwear choice did not influence injury outcomes, there was general dissatisfaction with the prescribed uniform athletic footwear conveyed by the recruits and widespread reports of discomfort, perceived deleterious effects from wear and intended discontinued use following training completion.

Indeterminate pediatric acute liver failure: Clinical characteristics of a temporal cluster of five children in the Netherlands in the spring of 2022.

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS-CoV-2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children.

Does agreement mean accuracy? Evaluating glance annotation in naturalistic driving data.

Naturalistic driving studies often make use of cameras to monitor driver behavior. To analyze the resulting video images, human annotation is often adopted. These annotations then serve as the 'gold standard' to train and evaluate automated computer vision algorithms, even though it is uncertain how accurate human annotation is. In this study, we provide a first evaluation of glance direction annotation by comparing instructed, actual glance direction of truck drivers with annotated direction. Findings indicate that while for some locations high annotation accuracy is achieved, for most locations accuracy is well below 50%. Higher accuracy can be obtained by clustering these locations, but this also leads to reduced detail of the annotation, suggesting that decisions to use clustering should take into account the purpose of the annotation. The data also show that high agreement between annotators does not guarantee high accuracy. We argue that the accuracy of annotation needs to be verified experimentally more often.

In Vitro Evaluation of Pro- and Anticoagulant Drugs in Children with End-Stage Liver Disease Undergoing Liver Transplantation.

BACKGROUND: Pro- and anticoagulant drugs are commonly used in pediatric liver transplantation to prevent and treat thrombotic and bleeding complications. However, the combination of baseline hemostatic changes in children with liver disease and additional changes induced by transplantation makes this very challenging. This study aimed to analyze the efficacy of clinically available pro- and anticoagulant drugs in plasma from children undergoing liver transplantation. METHODS: In vitro effects of pro- and anticoagulant drugs on thrombin generation capacity were tested in plasma samples of 20 children (≤ 16 years) with end-stage liver disease undergoing liver transplantation, and compared with 30 age-matched healthy controls. RESULTS: Addition of pooled normal plasma had no effect in patients or controls, while 4-factor prothrombin complex concentrate increased thrombin generation in both patients and controls, with enhanced activity in patients. At start of transplantation, dabigatran and unfractionated heparin had a higher anticoagulant potency in patients, whereas 30 days after transplantation low molecular weight heparin was slightly less effective in patients. Effects of rivaroxaban were comparable between patients and controls. CONCLUSION: This study revealed important differences in efficacy of commonly used pro- and anticoagulant drugs in children with end-stage liver disease undergoing liver transplantation. Therefore, dose adjustments of these drugs may be required. The results of this study may be helpful in the development of urgently needed protocols for strategies to prevent and treat bleeding and thrombotic complications in pediatric liver transplantation.

Total Luminal Volume Predicts Risk after Endovascular Aneurysm Repair.

OBJECTIVE: Large aneurysm diameter represents a well known predictor of late complications after endovascular aneurysm repair (EVAR). However, the role of the thrombus free lumen inside the abdominal aortic aneurysm (AAA) sac is not clear. It was hypothesised that greater luminal volume represents a relevant risk factor for late complications after EVAR. METHODS: A retrospective cohort analysis was performed including all patients undergoing EVAR from 2005 to 2016 at a tertiary referral institution. Pre-operative AAA lumen volume was measured in centre lumen line reconstructions and patients were stratified into quartiles according to luminal volume. The primary endpoint was freedom from AAA related complications. Secondary endpoints were freedom from neck events (type 1A endoleak, migration >5 mm or any pre-emptive neck related intervention), iliac related events (type 1B endoleak or pre-emptive iliac related intervention), and overall survival. RESULTS: Four hundred and four patients were included: 101 in the first quartile (Q1; <61 cm3). Patients with higher luminal volumes had wider, shorter, and more angulated proximal necks. There were more ruptured AAAs, more aorto-uni-iliac implanted devices and patients outside neck instructions for use in the 4th quartile. Five year freedom from AAA related complications was 79%, 66%, 58% and 56%, respectively (p = .007). At five years, freedom from neck related events was 86%, 84%, 73%, and 71%, respectively, for the four groups (p = .009), and freedom from iliac related events was 96%, 91%, 88%, and 88%, respectively (p = .335). On multivariable analysis, luminal volume was an independent predictor of late complications (Q4 vs. Q1 - hazard ratio: 1.91, 95% confidence interval 1.01-3.6, p = .046). Overall survival at five years was not affected by lumen volume (p = .75). CONCLUSION: AAA luminal volume represents an important risk factor for AAA related complications. This information may be considered when deciding tailoring surveillance protocols after EVAR. However, larger studies are needed to validate this hypothesis.

Routine Postoperative Antithrombotic Therapy in Pediatric Liver Transplantation: Impact on Bleeding and Thrombotic Complications.

BACKGROUND: Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) are serious causes of morbidity and mortality after pediatric liver transplantation. To reduce thrombotic complications, routine antithrombotic therapy consisting of 1 week heparin followed by 3 months acetylsalicylic acid, was implemented in our pediatric liver transplant program in 2003. This study aimed to evaluate incidences of bleeding and thrombotic complications since the implementation of routine antithrombotic therapy and to identify risk factors for these complications. METHODS: This retrospective cohort study includes 200 consecutive pediatric primary liver transplantations performed between 2003 and 2016. Uni- and multivariate logistic regression analysis, Kaplan-Meier method, and Cox regression analysis were used to evaluate recipient outcome. RESULTS: HAT occurred in 15 (7.5%), PVT in 4 (2.0%), and venous outflow tract thrombosis in 2 (1.0%) recipients. Intraoperative vascular interventions (odds ratio [OR] 14.45 [95% confidence interval [CI] 3.75-55.67]), low recipient age (OR 0.81 [0.69-0.95]), and donor age (OR 0.96 [0.93-0.99]) were associated with posttransplant thrombosis. Clinically relevant bleeding occurred in 37%. Risk factors were high recipient age (OR 1.08 [1.02-1.15]), high Child-Pugh scores (OR 1.14 [1.02-1.28]), and intraoperative blood loss in mL/kg (OR 1.003 [1.001-1.006]). Both posttransplant thrombotic (hazard ratio [HR] 3.38 [1.36-8.45]; p = 0.009) and bleeding complications (HR 2.50 [1.19-5.24]; p = 0.015) significantly increased mortality. CONCLUSION: In 200 consecutive pediatric liver transplant recipients receiving routine postoperative antithrombotic therapy, we report low incidences of posttransplant vascular complications. Posttransplant antithrombotic therapy seems to be a valuable strategy in pediatric liver transplantation. Identified risk factors for bleeding and thrombotic complications might facilitate a more personalized approach in antithrombotic therapy.

Evidence for a rebalanced hemostatic system in pediatric liver transplantation: A prospective cohort study.

In adults with end-stage liver disease concurrent changes in pro- and antihemostatic pathways result in a rebalanced hemostasis. Children though, have a developing hemostatic system, different disease etiologies, and increased risk of thrombosis. This study aimed to assess the hemostatic state of children during and after liver transplantation. Serial blood samples were obtained from 20 children (≤16 years) undergoing primary liver transplantation (September 2017-October 2018). Routine hemostasis tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic proteins were measured. Reference values were established using an age-matched control group of 30 children. Thrombocytopenia was present in study patients. Von Willebrand factors were doubled and ADAMTS13 levels decreased during and after transplantation up until day 30, when platelet count had normalized. Whereas prothrombin time and activated partial thromboplastin time were prolonged during transplantation, thrombin generation was within normal ranges, except during perioperative heparin administration. Fibrinogen, factor VIII levels, and clot lysis time were elevated up until day 30. In conclusion, children with end-stage liver disease are in tight hemostatic balance. During transplantation a temporary heparin-dependent hypocoagulable state is present, which rapidly converts to a hemostatic balance with distinct hypercoagulable features that persist until at least day 30. This hypercoagulable state may contribute to the risk of posttransplant thrombosis.

The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis.

Extracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarkers or drug delivery vehicles. EVs contain membrane and intraluminal proteins, affecting their structure and thereby likely their functioning. Here, we use atomic force microscopy for mechanical characterization of erythrocyte, or red blood cell (RBC), EVs from healthy individuals and from patients with hereditary spherocytosis (HS) due to ankyrin deficiency. While these EVs are packed with proteins, their response to indentation resembles that of fluid liposomes lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15 kbT, similar to the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, patient EVs have a significantly (~40%) lower bending modulus than donor EVs. These results shed light on the mechanism and effects of EV budding and might explain the reported increase in vesiculation of RBCs in HS patients.

A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405).

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (±SD) of +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

Source geometry factors for HDR ¹9²Ir brachytherapy secondary standard well-type ionization chamber calibrations.

Well-type ionization chambers are used for measuring the source strength of radioactive brachytherapy sources before clinical use. Initially, the well chambers are calibrated against a suitable national standard. For high dose rate (HDR) (192)Ir, this calibration is usually a two-step process. Firstly, the calibration source is traceably calibrated against an air kerma primary standard in terms of either reference air kerma rate or air kerma strength. The calibrated (192)Ir source is then used to calibrate the secondary standard well-type ionization chamber. Calibration laboratories are usually only equipped with one type of HDR (192)Ir source. If the clinical source type is different from that used for the calibration of the well chamber at the standards laboratory, a source geometry factor, k(sg), is required to correct the calibration coefficient for any change of the well chamber response due to geometric differences between the sources. In this work we present source geometry factors for six different HDR (192)Ir brachytherapy sources which have been determined using Monte Carlo techniques for a specific ionization chamber, the Standard Imaging HDR 1000 Plus well chamber with a type 70010 HDR iridium source holder. The calculated correction factors were normalized to the old and new type of calibration source used at the National Physical Laboratory. With the old Nucletron microSelectron-v1 (classic) HDR (192)Ir calibration source, ksg was found to be in the range 0.983 to 0.999 and with the new Isodose Control HDR (192)Ir Flexisource k(sg) was found to be in the range 0.987 to 1.004 with a relative uncertainty of 0.4% (k = 2). Source geometry factors for different combinations of calibration sources, clinical sources, well chambers and associated source holders, can be calculated with the formalism discussed in this paper.

Mortality due to a retained circle hook in a longfin mako shark Isurus paucus (Guitart-Manday).

A female longfin mako shark Isurus paucus (Guitart-Manday, 1966) was found moribund on the Atlantic Ocean beach near Canaveral National Seashore, Florida; the shark died shortly after stranding. Macroscopic lesions included a partially healed bite mark on the left pectoral fin, a clefted snout, pericardial effusion and a pericardial mass surrounding a 12/0 circle fishing hook. The heart, pericardial mass, gills, ovary, oviduct, shell gland, epigonal organ, liver, kidney and intrarenal and interrenal glands were processed for histopathology and examined by brightfield microscopy. Microscopic examination revealed chronic proliferative and pyogranulomatous pericarditis and myocarditis with rhabdomyolysis, fibrosis and thrombosis; scant bacteria and multifocal granular deposits of iron were found intralesionally. In addition, acute, multifocal infarcts within the epigonal organ and gill filaments were found in association with emboli formed by necrocellular material. The ovary had high numbers of atretic follicles, and the liver had diffuse, severe hepatocellular degeneration, multifocal spongiosis and moderate numbers of melanomacrophage cells. This report provides evidence of direct mortality due to systemic lesions associated with retained fishing gear in a prohibited shark species. Due to the large numbers of sharks released from both recreational and commercial fisheries worldwide, impact of delayed post-release mortality on shark populations is an important consideration.

Air kerma and absorbed dose standards for reference dosimetry in brachytherapy.

This article reviews recent developments in primary standards for the calibration of brachytherapy sources, with an emphasis on the currently most common photon-emitting radionuclides. The introduction discusses the need for reference dosimetry in brachytherapy in general. The following section focuses on the three main quantities, i.e. reference air kerma rate, air kerma strength and absorbed dose rate to water, which are currently used for the specification of brachytherapy photon sources and which can be realized with primary standards from first principles. An overview of different air kerma and absorbed dose standards, which have been independently developed by various national metrology institutes over the past two decades, is given in the next two sections. Other dosimetry techniques for brachytherapy will also be discussed. The review closes with an outlook on a possible transition from air kerma to absorbed dose to water-based calibrations for brachytherapy sources in the future.

Intestinal malrotation and volvulus in adult life.

INTRODUCTION: Midgut volvulus due to intestinal malrotation is a rare cause of intestinal obstruction when occurring in adult life. This paper documents the difficulties in reaching an early diagnosis. PRESENTATION OF CASE: We describe the case of an 85-year-old man with non-specific abdominal complaints for 20 years, who presented with sudden onset central abdominal pain. An acute median laparotomy under general anaesthesia was performed during which a 360° clockwise rotation of the small bowel around the mesenteric pedicle of the superior mesenteric artery and vein was found. DISCUSSION: Malrotation is considered any deviation of the normal rotation of the midgut in embryological development, causing intermittent episodes of gastrointestinal obstruction or acute events of midgut volvulus. Although mainly a paediatric diagnosis, some cases do present in adult life. Radiologic investigations include: upper gastrointestinal contrast studies, Doppler sonography and a contrast enhanced CT of the abdomen. If a true malrotation is diagnosed or found by coincidence, a Ladd's procedure is advised, even if the patient is asymptomatic. There is no proven surgical strategy for preventing the recurrence of small bowel volvulus in case of malfixation of the midgut. CONCLUSION: Non-specific recurrent abdominal complaints in adults of any age should raise suspicion of the possibility of a midgut malrotation or malfixation with or without intermittent volvulus. This case highlights the importance of diagnosis in an early stage.

Identification enhancement of auditory evoked potentials in EEG by epoch concatenation and temporal decorrelation.

Event-related potentials (ERP) recorded by electroencephalography (EEG) are brain responses following an external stimulus, e.g., a sound or an image. They are used in fundamental cognitive research and neurological and psychiatric clinical research. ERPs are weaker than spontaneous brain activity and therefore it is difficult or even impossible to identify an ERP in the brain activity following an individual stimulus. For this reason, a blind source separation method relying on statistical information is proposed for the isolation of ERP after auditory stimulation. In this paper it is suggested to integrate epoch concatenation into the popular temporal decorrelation algorithm SOBI/TDSEP relying on time shifted correlations. With the proposed epoch concatenation temporal decorrelation (ecTD) algorithm a component representing the auditory evoked potential (AEP) is found in electroencephalographic data from an auditory stimulation experiment lasting 3min. The ecTD result is compared with the averaged AEP and it is superior to the result from the SOBI/TDSEP algorithm. Furthermore the ecTD processing leads to significant increases in the signal-to-noise ratio (shape SNR) of the AEP and reduces the computation time by 50% if compared to the SOBI/TDSEP calculation. It can be concluded that data concatenation in combination with temporal decorrelation is useful for isolating and improving the properties of an AEP especially in a short duration stimulation experiment.