The differentiating effect of COVID-19-associated stress on the morbidity of blood donors with symptoms of hidradenitis suppurativa, hyperhidrosis, or psoriasis.

PURPOSE: The burden of different skin diseases may vary leading individuals to have different sensitivity to stress. Therefore, we compared the health-related quality of life (HRQoL) and stress before and during the universal stress from the severe acute respiratory syndrome coronavirus-2-pandemic in individuals with and without hyperhidrosis, hidradenitis suppurativa, or psoriasis. METHODS: The study cohort was the Danish Blood Donor Study. Overall, 12,798 participants completed a baseline questionnaire before the pandemic, in 2018-2019, and a follow-up questionnaire during the pandemic, in 2020. Regression determined the association between the skin diseases and outcomes. Outcomes were the physical and mental component summary (MCS, PCS, respectively), which assess the mental and physical HRQoL, and the perceived stress scale, which assesses stress in the past four weeks. RESULTS: Overall, 1168 (9.1%) participants had hyperhidrosis, 363 (2.8%) had hidradenitis suppurativa, and 402 (3.1%) had psoriasis. At follow-up, the participants with hyperhidrosis had worse MCS (coefficient -0.59 [95% confidence interval (CI) -1.05, -0.13]) and higher odds of moderate-to-severe stress (odds ratio 1.37 [95% CI 1.13, 1.65]) and the participants with hidradenitis suppurativa worse PCS (coefficient -0.74 [95% CI -1.21, -0.27]) than the control groups. The associations were independent of baseline HRQoL, stress, the Connor-Davidson Resilience scale, and other covariables. Psoriasis was not associated with the outcomes. CONCLUSION: Individuals with hyperhidrosis or hidradenitis suppurativa experienced worse mental or physical well-being and individuals with hyperhidrosis also had higher stress during the pandemic compared to healthy individuals. This suggests that individuals with these skin diseases are particularly susceptible to external stress.

Human leukocyte antigen system associations in Malassezia-related skin diseases.

BACKGROUND: The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD. MATERIALS AND METHODS: Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests. RESULTS: A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94). CONCLUSION: Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles.

Patients' perspectives on point-of-care diagnostics and treatment by emergency medical technicians in acute COPD exacerbations: A qualitative study.

BACKGROUND: In Denmark emergency medical technicians transport patients with acute COPD exacerbations to the nearest emergency department. From a clinical and economic perspective, this transport and assessment at the hospital may be inconvenient if the patient is immediately discharged from the emergency department. We established an emergency technical technicians point-of-care diagnostics and treatment program of patients with COPD with use of ultrasound and blood analysis. Patients' perspectives on treatment at home and sense of security are important to qualify clinical practice at home with patients with acute exacerbation. AIM AND OBJECTIVES: To explore patient's and relatives' experience of treatment at home during emergency calls due to COPD in exacerbation and to investigate their attitude to avoid hospitalization as well as experience of stress during point-of-care diagnostics in their own home. METHOD: A qualitative study comprising semi-structured interviews with 16 patients carried out from April 1st, 2019 to March 31st, 2020 in Denmark. Data was analysed inspired by Malteruds' text condensation and informed by Critical Psychology with first person perspective focusing on the patient's views on point-of-care diagnostics and treatment of their COPD in acute exacerbation. RESULTS: The interviews revealed that in order to ensure an experience of quality in the assessment and treatment of patients in their own homes, it was important that the ambulance staff showed great safety and experience in the use of the technical equipment and treatment of dyspnea. It was also of importance that the patients felt confident that their general practitioner followed up on the home treatment initiated. CONCLUSION: Patients' perspectives showed that point-of-care diagnostics and treatment of acute COPD in exacerbation was considered a qualitative offer by the patients and their relatives. At the same time, it was crucial that the emergency medical technicians showed experience and safety in handling shortness of breath as well as the technical equipment. TRIAL REGISTRATION: Approved by the Danish Data Protection Agency Project-ID: 20/24845.

Hoof conformation in Icelandic competition horses and its interrelationship with hoof pathologies and tölt performance.

In order to improve the four-beat-rhythm and forelimb action of the tölt in Icelandic horses (ICE), special shoeing techniques are applied particularly in the front hooves by increasing hoof length and height, or by adding weight to the distal limbs. Although regulations limit dorsal hoof wall length (LDHW) in competition ICE, their shoeing often deviates from a biomechanically optimal distal limb conformation. This study aimed to qualitatively and quantitatively describe current shoeing practices of ICE in competition. Moreover, the influence of LDHW on the occurrence of deviations from a standard hoof conformation, as well as on tölt performance was investigated. At four European competition sites, hoof dimensions of 133 randomly selected ICE were measured manually, and limb conformation and hoof balance were described. Dorsopalmar/-plantar and lateromedial radiographs of the left front and hind hooves were taken of each horse. Various parameters related to hoof dimensions and balance were measured on radiographs using the Metron-Hoof-Pro software. Flares of the dorsal hoof wall had the highest prevalence of all investigated hoof deformities. Multiple logistic regression analysis revealed that longer LDHW was associated with the occurrence of toe flares (P = 0.045), a broken hoof pastern axis (P = 0.003), and asymmetry of the quarter wall heights (P = 0.015). However, horses with a longer LDHW achieved higher scores in competition. In spite of its positive effect on tölt performance, a long LDHW is not recommendable as it may be associated with a higher prevalence of certain hoof deformities.

Pre-hospital advanced airway management by anaesthetist and nurse anaesthetist critical care teams: a prospective observational study of 2028 pre-hospital tracheal intubations.

BACKGROUND: Pre-hospital tracheal intubation success and complication rates vary considerably among provider categories. The purpose of this study was to estimate the success and complication rates of pre-hospital tracheal intubation performed by physician anaesthetist or nurse anaesthetist pre-hospital critical care teams. METHODS: Data were prospectively collected from critical care teams staffed with a physician anaesthetist or a nurse anaesthetist according to the Utstein template for pre-hospital advanced airway management. The patients served by six ambulance helicopters and six rapid response vehicles in Denmark, Finland, Norway, and Sweden from May 2015 to November 2016 were included. RESULTS: The critical care teams attended to 32 007 patients; 2028 (6.3%) required pre-hospital tracheal intubation. The overall success rate of pre-hospital tracheal intubation was 98.7% with a median intubation time of 25 s and an on-scene time of 25 min. The majority (67.0%) of the patients' tracheas were intubated by providers who had performed >2500 tracheal intubations. The success rate of tracheal intubation on the first attempt was 84.5%, and 95.9% of intubations were completed after two attempts. Complications related to pre-hospital tracheal intubation were recorded in 10.9% of the patients. Intubations after rapid sequence induction had a higher success rate compared with intubations without rapid sequence induction (99.4% vs 98.1%; P=0.02). Physicians had a higher tracheal intubation success rate than nurses (99.0% vs 97.6%; P=0.03). CONCLUSIONS: When performed by experienced physician anaesthetists and nurse anaesthetists, pre-hospital tracheal intubation was completed rapidly with high success rates and a low incidence of complications. CLINICAL TRIAL NUMBER: NCT 02450071.

The continuous reaction time test for minimal hepatic encephalopathy validated by a randomized controlled multi-modal intervention-A pilot study.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. AIM: To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). METHODS: Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines. RESULTS: The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 ± 1.83, p = 0.03). There was no such effect in any of the other study groups. CONCLUSION: In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment.

Termination of pre-hospital resuscitation by anaesthesiologists - causes and consequences. A retrospective study.

AIM: Differentiating between a newly deceased patient and the lifeless patient in whom immediate resuscitation is required may be facilitated by a pre-hospital anaesthesiologist. The purpose of our study was to investigate to what extent and why the pre-hospital anaesthesiologist pronounced life extinct in situations where an emergency medical technician (EMT) would have been required to resuscitate. METHODS: All lifeless patients seen pre-hospitally by the anaesthesiologist-manned Mobile Emergency Care Unit in Odense, Denmark, from 2010 to 2014 were retrospectively studied. RESULTS: Of 17 035 contacts, 1275 patients were lifeless without reliable signs of death. In 642 of these patients (3.8%) resuscitation was initiated (median age 68 years). The remaining 633 patients (3.7%) were declared dead at the scene without any resuscitation attempt (median age 77 years). These latter patients would have been attempted resuscitated, had the anaesthesiologist not been present. In 54.5% of cases where documentation was available in the patient records, reasons for not resuscitating these patients included time elapsed from incident to contact with physician, 'overall assessment', chronic disease, or do-not-resuscitate order. CONCLUSION: In one patient in 30, the MECU refrained from futile resuscitation in cases where legislation required an EMT to initiate resuscitation. This practice reduced unethical attempts of resuscitation, reduced unnecessary emergency ambulance transports, and reduced the work load of the hospital resuscitation teams for one unnecessary alarm every third day. Differentiating between lifeless patients and dead patients not exhibiting reliable signs of death, however, is a complex task which is only sparsely documented.

Digital questionnaire platform in the Danish Blood Donor Study.

OBJECTIVES: The Danish Blood Donor Study (DBDS) is a prospective, population-based study and biobank. Since 2010, 100,000 Danish blood donors have been included in the study. Prior to July 2015 all participating donors had to complete a paper-based questionnaire. Here we describe the establishment of a digital tablet-based questionnaire platform implemented in blood bank sites across Denmark. METHODS: The digital questionnaire was developed using the open source survey software tool LimeSurvey. The participants accesses the questionnaire online with a standard SSL encrypted HTTP connection using their personal civil registration numbers. The questionnaire is placed at a front-end web server and a collection server retrieves the completed questionnaires. Data from blood samples, register data, genetic data and verification of signed informed consent are then transferred to and merged with the questionnaire data in the DBDS database. RESULTS: The digital platform enables personalized questionnaires, presenting only questions relevant to the specific donor by hiding unneeded follow-up questions on screening question results. New versions of questionnaires are immediately available at all blood collection facilities when new projects are initiated. CONCLUSION: The digital platform is a faster, cost-effective and more flexible solution to collect valid data from participating donors compared to paper-based questionnaires. The overall system can be used around the world by the use of Internet connection, but the level of security depends on the sensitivity of the data to be collected.

A novel multiplex RT-qPCR method based on dual-labelled probes suitable for typing all known genotypes of viral haemorrhagic septicaemia virus.

Viral haemorrhagic septicaemia (VHS) is a notifiable fish disease, whose causative agent is a rhabdovirus isolated from a wide range of fish species, not only in fresh but also in marine and brackish waters. Phylogenetic studies have identified four major genotypes, with a strong geographical relationship. In this study, we have designed and validated a new procedure--named binary multiplex RT-qPCR (bmRT-qPCR)--for simultaneous detection and typing of all four genotypes of VHSV by real-time RT-PCR based on dual-labelled probes and composed by two multiplex systems designed for European and American/Asiatic isolates, respectively, using a combination of three different fluorophores. The specificity of the procedure was assessed by including a panel of 81 VHSV isolates covering all known genotypes and subtypes of the virus, and tissue material from experimentally infected rainbow trout, resulting in a correct detection and typing of all strains. The analytical sensitivity was evaluated in a comparative assay with titration in cell culture, observing that both methods provided similar limits of detection. The proposed method can be a powerful tool for epidemiological analysis of VHSV by genotyping unknown samples within a few hours.

Fishpathogens.eu/noda: a free and handy online platform for Betanodavirus targeted research and data sharing.

Viral nervous necrosis (VNN) is a severe neuropathological disease affecting a broad variety of finfish species worldwide. The causative agents of VNN are small viruses with a bi-segmented RNA genome known as betanodaviruses. At least four species with distinct but yet insufficiently characterized epidemiological features are recognized. The spread of VNN to an increasing number of host species, its wide geographic extent and its economical and ecological impacts justify the importance of collating as much molecular data as possible for tracing the origin of viral isolates and highlight the need for a freely accessible tool for epidemiological and molecular data sharing and consultation. For this purpose, we established a web-based specific database using the www.fishpathogens.eu platform, with the aim of collecting molecular and epidemiological information on VNN viruses, with relevance to their control, management and research studies.

Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact.

Murine gammaherpesvirus-68 (MHV-68), a natural pathogen of mice, is being evaluated as a model of Epstein Barr Virus (EBV) infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogenesis in humans. Immunosuppressive agents are used for treatment of a variety of autoimmune diseases as well as for prevention of tissue rejection after organ transplantation and can result in recrudescence of latent herpesvirus infections. Prior to examination of MHV-68 as a suitable model for EBV, better characterization of the MHV-68 model was desirable. Characterization of the MHV-68 model involved development of assays for detecting virus and for demonstration of safety when present in murine colonies. Limited information is available in the literature regarding MHV-68 transmission, although recent reports indicate the virus is not horizontally spread in research facilities. To further determine transmission potential, immunocompetent and immunodeficient mice were infected with MHV-68 and co-habitated with naïve animals. Molecular pathology assays were developed to characterize the MHV-68 model and to determine viral transmission. Horizontal transmission of virus was not observed from infected animals to naïve cagemates after fluorescence microscopy assays and quantitative PCR (qPCR). Serologic analysis complemented these studies and was used as a method of monitoring infection amongst murine colonies. Overall, these findings demonstrate that MHV-68 infection can be controlled and monitored in murine research facilities, and the potential for unintentional infection is low.

Individual and work-unit measures of psychological demands and decision latitude and the use of antihypertensive medication.

PURPOSE: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication. METHODS: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish National Prescription Registry. Odds ratios (OR) comparing the highest and lowest third of the population at individual and work-unit level, respectively, were estimated by multilevel logistic regression adjusted for confounders. Psychological demands and decision latitude were tested for interaction. Supplementary analyses of 21 months follow-up were conducted. RESULTS: Among women, increasing psychological demands at individual (adjusted OR 1.54; 95 % CI 1.02-2.33) and work-unit level (adjusted OR 1.41; 95 % CI 1.04-1.90) was significantly associated with purchase of antihypertensive medication. No significant association was found for decision latitude. Follow-up results supported an association with psychological demands but they were not significant. All results for men showed no association. Psychological demands and decision latitude did not interact. CONCLUSION: High psychological work demands were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job strain model.

Effect of early supervised progressive resistance training compared to unsupervised home-based exercise after fast-track total hip replacement applied to patients with preoperative functional limitations. A single-blinded randomised controlled trial.

OBJECTIVE: To examine if 2 weekly sessions of supervised progressive resistance training (PRT) in combination with 5 weekly sessions of unsupervised home-based exercise is more effective than 7 weekly sessions of unsupervised home-based exercise in improving leg-extension power of the operated leg 10 weeks after total hip replacement (THR) in patients with lower pre-operative function. METHOD: A total of 73 patients scheduled for THR were randomised (1:1) to intervention group (IG, home based exercise 5 days/week and PRT 2 days/week) or control group (CG, home based exercise 7 days/week). The primary endpoint was change in leg extension power at 10 week follow up. Secondary outcomes were isometric hip muscle strength, sit-to-stand test, stair climb test, 20 m walking speed and patient-reported outcome (HOOS). RESULTS: Sixty-two completed the trial (85%). Leg extension power increased from baseline to the 10 week follow up in both groups; mean [95% CI] IG: 0.29 [0.13; 0.45] and CG: 0.26 [0.10; 0.42] W/kg, with no between-group difference (primary outcome) (P = 0.79). Maximal walking speed (P = 0.008) and stair climb performance (P = 0.04) improved more in the IG compared to CG, no other between-group differences existed. CONCLUSIONS: In this trial, supervised PRT twice a week in addition to 5 weekly sessions of unsupervised exercise for 10 weeks was not superior to 7 weekly sessions of unsupervised home-based exercise for 10 weeks in improving the primary outcome, leg-extension power of the operated leg, at the primary endpoint 10 weeks after surgery in THR patients with lower pre-operative function. TRIAL REGISTRATION: NCT01214954.

Emergency patients receiving anaesthesiologist-based pre-hospital treatment and subsequently released at the scene.

BACKGROUND: The Mobile Emergency Care Unit in Odense, Denmark consists of a rapid response car, manned with an anaesthesiologist and an emergency medical technician. Eleven per cent of the patients are released at the scene following treatment. The aim of the study was to investigate which diagnoses were assigned to patients released at the scene following treatment, to investigate the need for secondary contact with the hospital and to assess mortality in patients released at the scene. METHODS: All records regarding patients released at the scene from 1 January 2008 to 31 December 2010 were investigated. In each patient, diagnosis as well as any renewed contact with the Mobile Emergency Care Unit or the hospital within 24 h was registered. RESULTS: One thousand six hundred nine: patients were released at the scene. Diagnoses within the category 'examination and investigation' [International Classification of Diseases 10th revision (ICD-10) chapter XXI] represented the largest group of patients (28%). Diseases not elsewhere classified (ICD-10 chapter XVIII) including 'syncope and collapse' represented the second largest group of patients (24%). One hundred thirteen (7%) had a renewed contact with the Mobile Emergency Care Unit within 24 h. Of the 143 victims of traffic accidents, 19 (13%) required renewed contact with the emergency department and one required admission to hospital (0.7%). Of all 1609 patients, four died within 24 h of contact (0.2%). CONCLUSION: Patients treated and released at the scene presented poorly defined conditions. Ninety-three per cent of all cases required no secondary contacts with the health care system. However, caution should be exercised when releasing patients at the scene following traffic accidents.

Does reduced movement restrictions and use of assistive devices affect rehabilitation outcome after total hip replacement? A non-randomized, controlled study.

BACKGROUND: Improvements in surgical techniques and increase of femoral head size might have changed the rationale for movement restrictions after total hip replacement (THR). AIM: To evaluate the influence of movement restrictions and assistive devices on rehabilitation after fast track THR. DESIGN: Non-randomized, controlled study. SETTING: Inpatient. POPULATION: 365 consecutively included THR patients. METHODS: Patients included the 3 initial month of the study underwent rehabilitation with restrictions in hip movement and a standard package of assistive devices (restricted group). This group was compared to patients included the following 3 months with less restricted hip movement and use of assistive devices according to individual needs (unrestricted group). Questionnaires on function, pain, quality of life (HOOS), anxiety (HADS), working status and patient satisfaction were completed before THR, 3 and 6 weeks after. RESULTS: The HOOS function score at the 3 measurement times was (mean ± SD); unrestricted group: 46 ± 17 - 76 ± 9 - 83 ± 14 compared to restricted group: 43 ± 16 - 81 ± 14 - 83 ± 13. Changes over time was significantly higher in the restricted group (P=0.004). Return to work 6 weeks after THR for the unrestricted group compared to restricted group was: 53% versus 32% (P=0.045). No significant differences between groups in pain, symptoms, quality of life, anxiety/depression, hip dislocations and patient satisfaction. CONCLUSION: This study showed slightly slower recovery in patient-reported function after reduction in movement restrictions and use of assistive devices, but the difference was eliminated after 6 weeks. Reduced movement restrictions did not affect the other patient-reported outcomes and led to earlier return to work. CLINICAL REHABILITATION IMPACT: It is possible to reduce movement restrictions and use of assistive devices considerably. More research on safety issues is needed to elucidate the effect of unrestricted rehabilitation on hip dislocation.

Pre-hospital critical care by anaesthesiologist-staffed pre-hospital services in Scandinavia: a prospective population-based study.

BACKGROUND: All Scandinavian countries provide anaesthesiologist-staffed pre-hospital services. Little is known of the incidence of critical illness or injury attended by these services. We aimed to investigate anaesthesiologist-staffed pre-hospital services in Scandinavia with special emphasis on incidence and severity. METHODS: This population-based, prospective study recorded activity in 16 anaesthesiologist-staffed pre-hospital services in Denmark, Finland, Norway and Sweden serving half of the Scandinavian population. We calculated population incidence of medical conditions, and the proportion of patients with severely deranged vital signs and/or receiving advanced therapy. RESULTS: Four thousand two hundred thirty-six alarm calls were recorded during 4 weeks. Two thousand two hundred fity-six alarms resulted in a patient encounter. The population incidence varied from 74.9 missions per 10,000 person-years (Denmark), followed by Finland with 14.6, Norway with 11, and Sweden with 5. Medical aetiology was most frequent (14.9 missions per 10,000 person-years, 95% CI: 14.2-15.8). Trauma was second (5.6 missions per 10,000 person-years, 95%CI: 5.12-6.09). Twenty-three per cent of patients had severely deranged vital functions, and advanced emergency medical procedures were performed in every four to twelve encounters (Denmark 8%, Sweden 15%, Norway 23%, and Finland 25%). The probability that the patient was physiologically deranged, received advanced medication, or procedure was 35%. Critical illness or injury occured at a rate of 25-30 per 10,000 person-years. CONCLUSIONS: The incidence of pre-hospital anaesthesiologist patient encounters in Scandinavia varies. Medical aetiology is most frequent. Almost one-quarter of patients presents with deranged vital functions requiring emergency measures. The Scandinavian pre-hospital population incidence of critical illness and injury is 25-30 per 10,000 person-years.

Case report: binding of a clinically relevant human leukocyte antigen-DQα-specific antibody in a kidney graft recipient is inhibited by donor-type human leukocyte antigen-DQß chain.

In this case report, we have found what may be an immunization with donor-specific human leukocyte antigen (HLA)-DQα in combination with recipient-specific HLA-DQß. A renal allograft recipient who did not comply with immunosuppressive therapy during pregnancy had graft failure 23 months posttransplantation with biopsy-proven humoral and cellular rejection. Sera were tested in a Luminex-based single-antigen bead assay. We compared Luminex reactivity with the degree of eplet mismatching between the recipient's own HLA-DQ chains and the HLA-DQ chains bound to the Luminex beads. Eplet calculations were done with the HLAMatchmaker. HLA-DQ similarities were compared further by dissimilarity scoring in HistoCheck. We observed that Luminex beads with donor-type HLA-DQα and HLA-DQß bound less antibody than beads with donor-type HLA-DQα combined with recipient HLA-DQß. In HLAMatchmaker, we identified all eplet mismatches between donor and recipient HLA-DQ. Next, we counted how many of these eplets were represented on the various Luminex beads. We found that antibody binding to the bead increased with the number of such mismatches for HLA-DQα. Surprisingly, antibody binding decreased as the number of eplet mismatches for HLA-DQß increased, from a mean fluorescence intensity (MFI) value of 18,800 for no mismatched eplets to approximately 10,000 for 12 mismatched eplets. These findings were confirmed by comparing antibody binding with the structural dissimilarity score between the recipient HLA-DQ type and the HLA-DQ bound to the Luminex beads. In this patient, clinically relevant antibodies bound strongly to donor-like HLA-DQα chains when combined with recipient-like HLA-DQß. HLA-DQß chains more similar to those of the donor reduced the binding of donor- specific HLA-DQα antibody.

MicroCT with energy-resolved photon-counting detectors.

The goal of this paper was to investigate the benefits that could be realistically achieved on a microCT imaging system with an energy-resolved photon-counting x-ray detector. To this end, we built and evaluated a prototype microCT system based on such a detector. The detector is based on cadmium telluride (CdTe) radiation sensors and application-specific integrated circuit (ASIC) readouts. Each detector pixel can simultaneously count x-ray photons above six energy thresholds, providing the capability for energy-selective x-ray imaging. We tested the spectroscopic performance of the system using polychromatic x-ray radiation and various filtering materials with K-absorption edges. Tomographic images were then acquired of a cylindrical PMMA phantom containing holes filled with various materials. Results were also compared with those acquired using an intensity-integrating x-ray detector and single-energy (i.e. non-energy-selective) CT. This paper describes the functionality and performance of the system, and presents preliminary spectroscopic and tomographic results. The spectroscopic experiments showed that the energy-resolved photon-counting detector was capable of measuring energy spectra from polychromatic sources like a standard x-ray tube, and resolving absorption edges present in the energy range used for imaging. However, the spectral quality was degraded by spectral distortions resulting from degrading factors, including finite energy resolution and charge sharing. We developed a simple charge-sharing model to reproduce these distortions. The tomographic experiments showed that the availability of multiple energy thresholds in the photon-counting detector allowed us to simultaneously measure target-to-background contrasts in different energy ranges. Compared with single-energy CT with an integrating detector, this feature was especially useful to improve differentiation of materials with different attenuation coefficient energy dependences.