Modeling of culture conditions by culture system, glucose and propionic acid and their impact on metabolic profile in IPEC-J2.

The microbiological environment and their corresponding secreted metabolite spectrum are an essential modulator of the enterocyte function, effecting the whole organism. Intestinal porcine jejunal epithelial cell line (IPEC-J2) is an established in vitro model for differentiation of enterocytes in different cell culture models. An improved oxygen supply seems to be the main reason for differentiation in an air-liquid-interface culture, but this has not yet been conclusively clarified. In this context, the nutrition of the cell and its influence on the metabolism is also of crucial importance. The interest in short-chain fatty acids (SCFAs) has grown steadily in recent years due to their clinical relevance in certain diseases such as multiple sclerosis and other inflammatory diseases, but not much is known of FFAR2 and FFAR3 (free fatty acid receptor 2 and 3) in pigs. We want to address the questions: 1. about the distribution of FFAR2 and FFAR3 in vivo and in vitro in sus scrofa 2. whether there is an influence of propionic acid, glucose content and cultivation on metabolism of enterocytes? The morphological analysis of FFAR2 and FFAR3 in vivo was investigated through immunostaining of frozen sections of the porcine gut segments jejunum, ileum and colon. Both receptors are expressed along the gut and were found in the smooth muscle cells of the tunica muscularis and lamina muscularis mucosae. Furthermore, a high expression of FFAR2 and a low expression of FFAR3 in the enteric nerve system was also observed in jejunum, ileum and colon of sus scrofa. In addition, FFAR2 and FFAR3 within the vessels was investigated. FFAR3 showed a strong expression on endothelial cells of veins and lymphatic vessels but was not detectable on arteries. Furthermore, we demonstrate for the first time, FFAR2 and FFAR3 in IPEC-J2 cells on RNA- and protein level, as well as with confocal microscopy. In addition, ENO1 and NDUFA4 were investigated on RNA-level in IPEC-J2 cells as 2 important genes, which play an essential role in metabolism. Here, NDUFA4 is detected in the model animal sus scrofa as well as in the porcine cell line IPEC-J2. A potential impact of propionic acid and/or glucose and/or cultivation method on the metabolism of the cells was tested with the Seahorse analyzer. Here, a significant higher ECAR was observed in the SMC than in the OCR. In summary, we were able to show that the cultivation system appears to have a greater influence than the medium composition or nutrition of the cells. However, this can be modulated by incubation time or combination of different SCFAs.

Riverbed depth-specific microplastics distribution and potential use as process marker.

Riverbed sediments have been identified as temporary and long-term accumulation sites for microplastic particles (MPs), but the relocation and retention mechanisms in riverbeds still need to be better understood. In this study, we investigated the depth-specific occurrence and distribution (abundance, type, and size) of MPs in river sediments down to a depth of 100 cm, which had not been previously investigated in riverbeds. In four sediment freeze cores taken for the Main River (Germany), MPs (≥ 100 µm) were detected using two complementary analytical approaches (spectroscopy and thermoanalytical) over the entire depth with an average of 21.7 ± 21.4 MP/kg or 31.5 ± 28.0 mg/kg. Three vertical trends for MP abundance could be derived, fairly constant in top layers (0-|30 cm), a decrease in middle layers (30-60 cm), and a strong increase in deep layers (60-100 cm). The dominant polymer types were polyethylene (PE), polypropylene (PP), and polystyrene (PS). Polyethylene terephthalate (PET) and PP were also found in deep layers, albeit with the youngest age of earliest possible occurrence (EPO age of 1973 and 1954). The fraction of smaller-sized MPs (100-500 µm) increased with depth in shallow layers, but the largest MPs (> 1 mm) were detected in deep layers. Based on these findings, we elucidate the relationship between the depth-specific MP distribution and the prevailing processes of MP retention and sediment dynamics in the riverbed. We propose some implications and offer an initial conceptual approach, suggesting the use of microplastics as a potential environmental process tracer for driving riverbed sediment dynamics.

Institutional Surgical Setting and Volume Effects of Certified Arthroplasty Centers in Germany: Evaluation of the Quality of Care in a 5-Year Comparison.

To improve arthroplasty care quality, the EndoCert initiative focuses on structural, processual, and surgeon-related quality assurance. The aim of this study was to assess the impact of a surgeon's case load in certified centers on quality of care, distinguished by different types of surgeons. Data from the annual reports of EndoCert certified centers for the years 2017 to 2021 were analyzed. The study revealed reduced numbers of cases, while the number of surgeons remained constant. Since 2020, the decrease in the average case load per surgeons has become more pronounced. There were also differences between senior (sECrs) and EndoCert-registered surgeons (ECrs). Before the 2020 pandemic, over half of surgeons exceeded minimum annual case requirements, while, afterwards, this number declined, especially for the ECrs. Affiliated surgeons, who are also sECrs or ECrs, performed predominantly lower numbers of arthroplasties. However, a higher percentage of affiliated surgeons in a center correlated with faster surgeries and lower mortality rates. High numbers of arthroplasties per center or surgeon were not necessarily associated with better quality indicators, especially in the knee. While the comprehensive quality standards may offset volume effects, EndoCert should reconsider minimum volume regulations based on surgeon, but also on each joint.

Assessing the responses of ecosystem patterns, structures and functions to drought under climate change in the Yellow River Basin, China.

Understanding how ecosystems respond and adapt to drought has become an urgent issue as drought stress intensifies under climate change, yet this topic is not fully understood. Currently, conclusions on the response of ecosystems in different regions to drought disturbance are inconsistent. Based on long MODIS data and observed data, this study systematically explored the relationships between ecosystem patterns, structures and functions and drought, taking a typical climate change-sensitive area and an ecologically fragile area-the Yellow River Basin-as a case study. Drought assessment results revealed that the Yellow River Basin has experienced meteorological and hydrological drought during most of the last two decades, predominantly characterized by medium and slight droughts. The ecosystem patterns and structures changed dramatically as the grassland decreased and the landscape fragmentation index (F) increased with increasing wetness. The annual gross primary productivity (GPP) increased, the water use efficiency (WUE) declined and ecosystem service value (ESV) exhibited a W-shaped increase at the watershed scale, but there were significant regional differences. There were positive correlations between F, GPP, ESV and drought indices, while there was a negative correlation between WUE and drought indices at the watershed scale. Under drought stress, the ecosystem structure in the basin was disrupted, the GPP and ESV decreased, but the WUE increased. Notably, approximately 106 %, 20 %, and 1 % of the maximum reductions in F, GPP, and ESV, respectively, were caused by drought, while the maximum 4 % of WUE increased. Responses of some functions in the wetland and grassland to drought vary from those in other ecosystems. The mechanisms underlying ecosystem responses to drought were further investigated. This study enhances the understanding of these responses and will help stakeholders formulate drought mitigation policies and protect ecosystem health.

Histopathology of congestive nephropathy: a case description and literature review.

Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right-sided heart failure or intra-abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion-driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low-grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation.

Use of human predictive patch test (HPPT) data for the classification of skin sensitization hazard and potency.

Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. https://doi.org/10.1787/b92879a4-en ). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825-2837, 2023. https://doi.org/10.1007/s00204-023-03530-3 ). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA.

Correlation of CT-based bone mineralization with drilling-force measurements in anatomical specimens is suitable to investigate planning of trans-pedicular spine interventions.

This interdisciplinary study examined the relationship between bone density and drilling forces required during trans-pedicular access to the vertebra using fresh-frozen thoraco-lumbar vertebrae from two female body donors (A, B). Before and after biomechanical examination, samples underwent high-resolution CT-quantification of total bone density followed by software-based evaluation and processing. CT density measurements (n = 4818) were calculated as gray values (GV), which were highest in T12 for both subjects (GVmaxA = 3483.24, GVmaxB = 3160.33). Trans-pedicular drilling forces F (Newton N) were highest in L3 (FmaxB = 5.67 N) and L4 (FmaxA = 5.65 N). In 12 out of 13 specimens, GVs significantly (p < 0.001) correlated with force measurements. Among these, Spearman correlations r were poor in two lumbar vertebrae, fair in five specimens, and moderately strong in another five specimens, and highest for T11 (rA = 0.721) and L5 (rB = 0.690). Our results indicate that CT-based analysis of vertebral bone density acquired in anatomical specimens is a promising approach to predict the drilling force appearance as surrogate parameter of its biomechanical properties by e.g., linear regression analysis. The study may be of value as basis for biomechanical investigations to improve planning of the optimal trajectory and to define safety margins for drilling forces during robotic-assisted trans-pedicular interventions on the spine in the future.

Mild but effective skin cleansing-Evaluation of laureth-23 as a primary surfactant.

OBJECTIVE: Skin cleansing products are among the main reasons for the development of hand eczema. Therefore, a mild but effective skin cleansing product is of particular interest, especially in the work place, where various contaminations frequently have to be removed from hands. METHODS: In this study, the potential of laureth-23 as a primary surfactant was evaluated and compared to other fatty alcohol ethoxylates (FAEO). Also, different laureth-23 surfactant combinations were compared to each other. Therefore, transepidermal water loss, erythema and visual scoring were measured after occlusive patch testing in 24 healthy subjects (aged 18-55). Afterwards, the results were ranked from low to high irritant potential and an irritation score was calculated. Furthermore, the cleaning performance was tested using an automated cleansing device in 10 healthy subjects (aged 18-55). RESULTS: The results confirmed the low irritant potential of laureth-23 and blends thereof. Within the different laureth-23 surfactant combinations, the combination of laureth-23 with a mild amphoteric and a mild anionic surfactant was superior to other laureth-23 surfactant combinations like laureth-23/anionic/anionic regarding skin compatibility as well as cleaning performance. CONCLUSION: In conclusion, laureth-23 showed very good performance as a primary surfactant. Especially, the combination of laureth-23, cocamidopropyl betaine and disodium laureth sulfosuccinate was mild to the skin while also showing good cleansing performance.

OBJECTIF: Les produits de nettoyage de la peau sont l'une des principales causes du développement de l'eczéma des mains. Un produit de nettoyage de la peau doux mais efficace présente un réel intérêt, en particulier sur le lieu de travail, où diverses contaminations doivent fréquemment être éliminées des mains. MÉTHODES: Dans cette étude, le potentiel du laureth­23 en tant que surfactant primaire a été évalué et comparé à d'autres éthoxylates d'alcool gras (FAEO). Plusieurs associations de surfactant laureth­23 ont également été comparées entre elles, ce qui a permis de mesurer la perte d'eau trans­épidermique, l'érythème et le score visuel après un test épicutané occlusif chez vingt­quatre sujets en bonne santé (âgés de 18 à 55 ans). Par la suite, les résultats ont été classés selon leur potentiel irritant, du plus faible au plus fort, et un score d'irritation a été calculé. En outre, la performance de nettoyage a été testée à l'aide d'un dispositif de nettoyage automatisé chez dix sujets en bonne santé (âgés de 18 à 55 ans). RÉSULTATS: Les résultats ont confirmé le faible potentiel irritant du laureth­23 et de ses mélanges. Parmi les différentes associations de surfactant laureth­23, l'association de laureth­23 avec un léger surfactant amphotérique et un léger surfactant anionique était supérieure aux autres associations de surfactant laureth­23 comme laureth­23/anionique/anionique en ce qui concerne la compatibilité cutanée et les performances de nettoyage. CONCLUSION: En conclusion, laureth­23 a montré de très bonnes performances en tant que surfactant primaire. L'association de laureth­23, de cocamidopropyl bêtaine et de laureth sulfosuccinate disodique s'est notamment avérée avoir peu d'impact sur la peau tout en montrant de bonnes performances de nettoyage.

Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.

Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.

Inhibition of the glucocorticoid receptor attenuates proteinuric kidney diseases in multiple species.

BACKGROUND AND HYPOTHESIS: Glucocorticoids are the treatment of choice for proteinuric patients with minimal-change disease (MCD) and primary focal and segmental glomerulosclerosis (FSGS). Immunosuppressive as well as direct effects on podocytes are believed to mediate their actions. In this study, we analyzed the anti-proteinuric effects of inhibition of the glucocorticoid receptor (GR) in glomerular epithelial cells, including podocytes. METHODS: We employed genetic and pharmacological approaches to inhibit the GR. Genetically, we used Pax8-Cre/GRfl/fl mice to specifically inactivate the GR in kidney epithelial cells. Pharmacologically, we utilized a glucocorticoid antagonist called mifepristone. RESULTS: Genetic inactivation of GR, specifically in kidney epithelial cells, using Pax8-Cre/GRfl/fl mice, ameliorated proteinuria following protein overload. We further tested the effects of pharmacological GR inhibition in three models and species: the puromycin-aminonucleoside-induced nephrosis model in rats, the protein overload model in mice and the inducible transgenic NTR/MTZ zebrafish larvae with specific and reversible podocyte injury. In all three models, both pharmacological GR activation and inhibition consistently and significantly ameliorated proteinuria. Additionally, we translated our findings to humans, where three nephrotic adult patients with MCD or primary FSGS with contraindications or insufficient responses to corticosteroids, were treated with mifepristone. This treatment resulted in a clinically relevant reduction of proteinuria. CONCLUSIONS: Thus, across multiple species and proteinuria models, both genetic and pharmacological GR inhibition was at least as effective as pronounced GR activation. While, the mechanism remains perplexing, GR inhibition may be a novel and targeted therapeutic approach to treat glomerular proteinuria potentially bypassing adverse actions of steroids.

General prognostic models may neglect vulnerable subgroups in ANCA-associated vasculitis.

BACKGROUND: ANCA-associated vasculitis is an organ and life-threatening disease with the highest incidence in elderly patients. However, few studies have focussed on characteristics and treatment outcomes in a direct comparison of elderly and younger patients. METHODS: In a retrospective, single-centre, renal biopsy-cohort, patients were dichotomized by age ≥ 65 years to analyse baseline clinical, histological, laboratory and immunological characteristics and outcome differences in elderly and younger patients as regard to mortality, renal recovery from dialysis and eGFR after two years. RESULTS: In the biopsy registry, n = 774 patients were identified, of whom 268 were ≥ 65 years old. Among them, ANCA-associated vasculitis was the most prevalent kidney disease (n = 54 ≈ 20%). After a follow-up of 2 years, overall mortality was 13.4%, with 19% and 4% in patients ≥ and < 65 years of age, respectively. While 41% of elderly and 25% of younger patients were dialysis-dependent at the time of biopsy, renal recovery was achieved in 41% and 57% of patients, respectively. The accuracy of prediction differed significantly between the whole cohort and elderly patients as regard to mortality (sensitivity 46% vs. 90%, respectively) and between younger and elderly patients as regard to eGFR (r2 = 0.7 vs. 0.46, respectively). Age-group-wise analysis revealed patients above 80 years of age to have particularly dismal renal outcome and survival. CONCLUSION: In our cohort, ANCA-associated vasculitis is the single most frequent histopathological diagnosis among the elderly patients in our cohort. Elderly and younger patients have comparable chances of recovering from dialysis-dependent renal failure, with comparable residual independent kidney function after two years. This study suggests (1) relevant predictors differ between age groups and hence (2) models involving all patients with ANCA-associated vasculitis neglect important features of vulnerable subgroups, i.e., patients above 80 years old.

Risk Factors and Clinical Outcomes after Antegrade Intramedullary Nailing in Proximal Humeral Fractures: Insights and Implications for Patient Satisfaction.

BACKGROUND: Proximal humeral fractures (PHFs) are common injuries that can lead to significant functional impairment. This retrospective cohort study aimed to evaluate the clinical outcomes and complications associated with the use of the Targon PH+ (Fa. Aesculap, Germany) intramedullary nail for the treatment of PHFs. METHODS: A subgroup consisting of 70 patients with a mean follow-up of 4.91 years out of 479 patients who underwent treatment with the Targon PH+ intramedullary nail for PHFs at a single center between 2014 and 2021 were included. Patient-reported outcome measures (PROMs) and health-related quality of life (HRQoL) were assessed using validated German versions of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, American Shoulder and Elbow Surgeons (ASES) score, Oxford Shoulder Score (OSS), and EuroQol 5-Dimension 5-Level (EQ-5D-5L). Radiographic assessment was performed using pre- and postoperative imaging. RESULTS: Among the 70 patients of the subgroup who completed follow-up, 21.4% experienced complications, including major complications in 15.7% of cases, all of which were revised (revision rate of 15.7%). Anatomical reduction was achieved in 48,5% of cases. The mean DASH, ASES, and OSS scores were 25.4 ± 22.0, 76.2 ± 21.1, and 38.8 ± 10.3, respectively. Significant correlations were observed among the PROMs, indicating their convergent validity. Additionally, a significant correlation of all used PROMs and patient well-being (HRQoL) was observed. Severe complications and revisions were associated with significantly lower ASES scores (-11.1%, p = 0.013). There was a tendency for PROM scores to slightly decline with increasing fracture complexity, although this trend did not reach statistical significance. Our findings indicate that patients over the age of 65 years tend to exhibit lower scores in PROMs and HRQoL measures. CONCLUSION: The use of the Targon PH+ intramedullary nail for the treatment of PHFs resulted in satisfactory clinical outcomes and acceptable complication and revision rates. The PROMs and HRQoL measures indicated varying levels of disability and symptoms, with major complications, revision surgery, and age negatively impacting shoulder function after midterm follow-up.

A database of human predictive patch test data for skin sensitization.

Critical to the evaluation of non-animal tests are reference data with which to assess their relevance. Animal data are typically used because they are generally standardized and available. However, when regulatory agencies aim to protect human health, human reference data provide the benefit of not having to account for possible interspecies variability. To support the evaluation of non-animal approaches for skin sensitization assessment, we collected data from 2277 human predictive patch tests (HPPTs), i.e., human repeat insult patch tests and human maximization tests, for skin sensitization from 1555 publications. We recorded protocol elements and positive or negative outcomes, developed a scoring system to evaluate each test for reliability, and calculated traditional and non-traditional dose metrics. We also traced each test result back to its original report to remove duplicates. The resulting database, which contains information for 1366 unique substances, was characterized for physicochemical properties, chemical structure categories, and protein binding mechanisms. This database is publicly available on the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods website and in the Integrated Chemical Environment to serve as a resource for additional evaluation of alternative methods and development of new approach methodologies for skin sensitization assessments.

Mid- to Long-Term Survival of Geriatric Patients with Primary Septic Arthritis of the Shoulder: A Retrospective Study over a Period of 20 Years.

Septic arthritis of the shoulder is an urgent medical emergency that often occurs in elderly patients and is associated with high morbidity and mortality. Retrospectively, 56 patients aged ≥60 years, treated for primary septic monoarthritis of the shoulder at a maximum care hospital between 1 July 2001, and 30 July 2022, were included in this study. The primary aim of the study was analyzing survival rates and different bacteria in these patients. For statistical analysis, Kaplan-Meier curves were used for survival probability and the log-rank test was used to compare a survival probability of 5 years. The mean patient age was 78.7 years and a mean follow-up time of 3011.8 days. The mean survival of the entire study population was 920.3 days or 2.5 years. Significantly impaired 5-year survival was found only with increasing age and higher American Society of Anesthesiologists (ASA) physical status (PS) classification scores. Eight different types of bacteria were detected in the synovial fluid cultures. A total of 42 of 48 overall pathogens was Gram-positive and 6 were Gram-negative bacteria. Staphylococcus aureus was identified as the most frequent variant. We conclude that the mean survival is significantly shortened within the first 5 years with increasing age and ASA PS classification.

Augmentative Plating versus Exchange Intramedullary Nailing for the Treatment of Aseptic Non-Unions of the Femoral Shaft-A Biomechanical Study in a SawboneTM Model.

BACKGROUND: Non-unions after intramedullary nailing of femoral shaft fractures are a significant problem. Treatment options such as augmenting with plates or exchange nailing have been proposed. The ideal treatment remains controversial. METHODS: Augmentative plating using a 4.5 mm LCP or a 3.2 mm LCP leaving the nail in situ was tested biomechanically and compared to exchange intramedullary nailing in a SawboneTM model of a femoral shaft non-union. RESULTS: The difference of fracture gap motion in axial testing was small. In rotational testing, the exchange nail allowed for the largest amount of motion. The 4.5 mm augmentative plate was the most stable construct in all loading conditions. CONCLUSIONS: Augmentative plating using a 4.5 mm LCP plate while leaving the nail in situ is biomechanically superior to exchange intramedullary nailing. A small fragment 3.2 mm LCP is undersized and does not reduce fracture motion sufficiently in a femoral shaft non-union.

MRI Characteristics and Alterations in Patellar Height in Patients with Patellar Tendinopathy-A Retrospective Study.

(1) Background: Patellar tendinopathy (PT) is an overuse condition of the knee extensor mechanism characterized by ventral knee pain at the lower pole of the patella and limited functionality. (2) Methods: In this retrospective study, a group of patients with PT (n = 41) was compared with a control group (n = 50) in terms of patient-related data and magnetic resonance imaging (MRI) characteristics. (3) Results: Patellar height was higher in the PT patient group and there was a significant difference in Caton-Deschamps index (CD) compared to the control group (p = 0.021). Patients with PT showed a lower patella-patellar tendon angle (PPTA) (p = 0.011). The patellar tendon thickness (PTT) in the proximal (PTTprox), middle (PTTmid) and distal (PTTdistal) part of the tendon was significantly thickened (p < 0.001). Increased signal intensity in MRI was detected in symptomatic tendons over 6 months compared to a duration of less than 6 months (p = 0.025). A significant relationship between the PTTprox and an increased signal intensity was observed (p < 0.001). (4) Conclusions: Patients with PT showed a significant difference in the patellar height and PPTA. With persistence of symptoms over 6 months, MRI seems suitable to detect the morphologic tendon changes and further identify patients suitable for surgical procedures.

Efficacy of Double Membrane Filtration Immunoadsorption in Severe C1q-Binding Donor-Specific Antibody-Positive Acute Humoral Kidney Allograft Rejection: A Case Series.

INTRODUCTION: Acute antibody-mediated rejection (ABMR) is an important threat to renal allograft survival in the early transplant period and the major single cause of graft loss in the first postoperative year. Semi-selective immunoadsorption (IA) remains one of the commonly applied treatments in ABMR, reducing allo-reactive antibody load. Adding double filtration plasmapheresis (DFPP) to IA might enhance therapeutic efficacy by also addressing innate humoral effectors like complement factors. METHODS: Four patients with ABMR were treated with DFPP + IA. Clinical, histological, and immunological data and adverse events were retrospectively collected. RESULTS: Here we present four high-risk treatment-refractory ABMR cases with C1q-binding donor-specific antibodies and histology of humoral rejection under treatment with DFPP + IA. While the earlier cases (within the first year after transplantation) showed marked reduction in ABMR severity and improvement of kidney function, the later cases did not respond accordingly. Late ABMR patient 1 stabilized, whereas late ABMR patient 2 did not respond to treatment. CONCLUSIONS: Our data support the consideration of DFPP + IA as a rescue treatment option in early, severe, high-risk ABMR cases in which other treatments failed.