Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients.

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

[Video-Assisted Psychotherapy For Refugees: A Pilot Study]. / Videogestützte Psychotherapie für Geflüchtete: Eine Pilotstudie.

OBJECTIVE: Global conflicts and humanitarian crises led to an increase in forced migration to Germany in recent years. To improve the mental health care system for refugees and asylum seekers in Germany perspectively, we aim to examine the feasibility of implementing the culturally sensitive group psychotherapy Empowerment for refugees with affective disorders in a video-assisted setting. METHODS: Empowerment is a culturally sensitive, interpreter-assisted intervention for the treatment of depressive and stress-related symptoms in refugees. Four male refugees from Afghanistan participated in a pilot study. The intervention included 16 modules delivered via video over a 12-week period. RESULTS: The internet connection was frequently unstable and led to organizational challenges. The therapy was feasible in terms of linguistic and interactional aspects. DISCUSSION: The stability of the internet connection represents the major criterion for a successful implementation of the therapy. Implications for future studies are discussed. CONCLUSION: Regarding the potential opportunities to improve the mental health care provision to refugees and asylum seekers in the future, the video-assisted therapy concept could be investigated in a randomized controlled trial.

Nirmatrelvir/ritonavir treatment in SARS-CoV-2 positive kidney transplant recipients - a case series with four patients.

BACKGROUND: Despite vaccination coronavirus disease 2019 (COVID-19)-associated mortality caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains high in kidney transplant recipients. Nirmatrelvir is a protease inhibitor with activity against SARS-CoV-2. Nirmatrelvir reduces the risk for mortality and hospitalization, which is approved for treating adults at risk for severe disease. Nirmatrelvir is metabolized by the cytochrome P-450 (CYP) 3A4 isozyme CYP3A4 and is therefore co-administered with the irreversible CYP3A4 inhibitor ritonavir, which results in a drug interaction with tacrolimus. A limited number of patients with nirmatrelvir/ritonavir and tacrolimus therapy after kidney transplantation have been reported to date. It has been reported that tacrolimus was paused during the five-day nirmatrelvir/ritonavir therapy and subtherapeutic tacrolimus levels were observed after finishing nirmatrelvir/ritonavir in two patients. Therefore, optimization of tacrolimus dosing is urgently needed in transplant recipients receiving nirmatrelvir/ritonavir treatment. CASE PRESENTATION: Here, we present our first-hand experience with four patients receiving tacrolimus therapy following kidney transplantation and nirmatrelvir/ritonavir therapy due to COVID-19. Tacrolimus was paused during nirmatrelvir/ritonavir therapy in all patients, which resulted in stable therapeutic tacrolimus levels. Tacrolimus was continued directly after finishing nirmatrelvir/ritonavir to avoid subtherapeutic levels in the first patient treated. This patient received his usual tacrolimus maintenance dose, which resulted in toxic levels. Based on this observation, tacrolimus therapy was continued 24 h after finishing nirmatrelvir/ritonavir treatment at a reduced dose in the subsequent patients. In these patients, therapeutic to supratherapeutic tacrolimus levels were observed despite the therapeutic break and dose reduction. DISCUSSION AND CONCLUSIONS: Based on altered CYP3A4 metabolism, tacrolimus levels have to be closely monitored after treatment with nirmatrelvir/ritonavir. Our study suggests that tacrolimus treatment should be paused during nirmatrelvir/ritonavir medication and be continued 24 h after completing nirmatrelvir/ritonavir therapy at a reduced dose and under close monitoring. Based on the limited number of patients in this study, results must be interpreted with caution.

Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations.

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022. Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1-4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models' predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models' forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models' past predictive performance. Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models' forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models' forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models' forecasts of deaths (N=763 predictions from 20 models). Across a 1-4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models. Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks. Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z).

Interventional Management of Vascular Complications after Renal Transplantation. / Interventionelle Therapieoptionen vaskulärer Komplikationen nach Nierentransplantation.

BACKGROUND: Kidney transplantations are increasing due to demographic changes and are the treatment of choice for end-stage renal disease. Non-vascular and vascular complications may occur in the early phase after transplantation and at later stages. Overall postoperative complications after renal transplantations occur in approximately 12 % to 25 % of renal transplant patients. In these cases, minimally invasive therapeutic interventions are essential to ensure long-term graft function. This review article focuses on the most critical vascular complications after renal transplantation and highlights current recommendations for interventional treatment. METHOD: A literature search was performed in PubMed using the search terms "kidney transplantation", "complications", and "interventional treatment". Furthermore, the 2022 annual report of the German Foundation for Organ Donation and the EAU guidelines for kidney transplantation (European Association of Urology) were considered. RESULTS AND CONCLUSION: Image-guided interventional techniques are favorable compared with surgical revision and should be used primarily for the treatment of vascular complications. The most common vascular complications after renal transplantation are arterial stenoses (3 %-12.5 %), followed by arterial and venous thromboses (0.1 %-8.2 %) and dissection (0.1 %). Less frequently, arteriovenous fistulas or pseudoaneurysms occur. In these cases, minimally invasive interventions show a low complication rate and good technical and clinical results. Diagnosis, treatment, and follow-up should be performed in an interdisciplinary approach at highly specialized centers to ensure the preservation of graft function. Surgical revision should be considered only after exhausting minimally invasive therapeutic strategies. KEY POINTS: · Vascular complications after renal transplantation occur in 3 % to 15 % of patients.. · Image-guided interventional procedures should be performed primarily to treat vascular complications of renal transplantation.. · Minimally invasive interventions have a low complication rate with good technical and clinical outcomes.. CITATION FORMAT: · Verloh N, Doppler M, Hagar MT et al. Interventional Management of Vascular Complications after Renal Transplantation. Fortschr Röntgenstr 2023; 195: 495 - 504.

[Renal manifestations in vasculitides of small and medium-sized vessels]. / Nierenmanifestationen bei Vaskulitiden kleiner und mittelgroßer Gefäße.

Small-vessel vasculitides, in particular, are frequently manifested in the kidneys. A distinction is made between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immune complex vasculitides. Even within the AAVs there are differences with respect to renal involvement, which manifest as necrotizing glomerulonephritis (GN) but renal involvement is much rarer in eosinophilic granulomatosis with polyangiitis than in microscopic polyangiitis and granulomatosis with polyangiitis. Disease progression, organ manifestation and prognosis vary according to the ANCA status. In immune complex vasculitides (cryoglobulinemic vasculitis, IgA vasculitis, hypocomplementemic urticarial vasculitis and antiglomerular basement membrane, GBM, disease), endothelial-adjacent activation of neutrophilic granulocytes leads to local vessel wall damage with subsequent ischemic tissue damage, similar to AAV. The sparse evidence of immune complexes is different in pauci-immune AAV. Polyarteritis nodosa is a disease with variable clinical presentations with necrotizing vasculitis of small and medium-sized arteries. Intrarenal aneurysms and hemorrhages but not GN lead to renal damage. Diagnostically, the detection of specific autoantibodies (e.g. anti-GBM), cryoglobulins or increased complement turnover can be decisive. Renal biopsy with qualified immunohistopathology is particularly important in cases of initial manifestation and unclear constellation of findings. The treatment of renal vasculitis is adapted to the severity, stage of disease, extrarenal organ manifestation and pathogenesis. It ranges from glucocorticoid monotherapy to moderate immunosuppression, up to targeted biologic therapy, chemotherapy and plasmapheresis.

Evaluation of Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program in Comparison to Standard Allocation.

BACKGROUND The organ shortage and long waiting times have dramatically increased the age of potential kidney transplant recipients. The Eurotransplant Senior Program (ESP) was initiated to allocate kidneys from deceased donors aged ≥65 years to recipients with a comparable age independent of pre-transplant human leucocyte antigen (HLA) matching; however, parameters affecting the long-term benefits of this strategy remain poorly defined. MATERIAL AND METHODS We retrospectively evaluated outcome and risk factors for mortality in kidney recipients aged ≥65 years that were transplanted according to the ESP protocol relative to patients aged >50 years transplanted according to the Eurotransplant kidney allocation system (ETKAS) criteria at the University Freiburg Medical Center, Germany, between 2008 and 2018. RESULTS Graft survival, graft function, the maintenance immunosuppressive therapy, and the incidence of rejections and infections did not differ between groups. Infectious diseases were the main cause of death in both groups; however, infection-associated mortality was more than double in the ESP group, and 5-year patient survival was 61.4% in the ESP group compared to 83.2% in the ETKAS group. Multivariate analysis identified age, the number of HLA mismatches, and the CMV serostatus with a seropositive donor and negative recipient as the main risk factors for mortality. CONCLUSIONS A comparable immunosuppressive regimen used in ESP and ETKAS patients was associated with similar rejection rates and infectious disease complications, and infections were the most common cause of death in both groups. CMV-negative patients receiving an organ from a CMV-positive donor and patients with a high number of HLA mismatches require close follow-up to reduce mortality.

Dynamics of vascular refilling in extended nocturnal hemodialysis.

INTRODUCTION: Long dialysis treatments are generally assumed to mitigate the ultrafiltration (UF) induced volume perturbation and to improve vascular refilling because of reduced UF rates and sufficient time for volume re-equilibration. The time course of vascular refilling was therefore examined during extended nocturnal dialysis. METHODS: For each hour of dialysis, vascular refilling volume was calculated from the absolute blood volume changes and UF volume removed. Absolute blood volume was estimated by indicator dilution at the beginning of dialysis and then tracked with a relative blood volume monitor. The refilling fraction was defined as the ratio of refilling volume to UF volume. FINDINGS: Ten stable chronic hemodialysis (HD) patients were studied during extended (7 h) nocturnal treatment sessions. Specific UF rate was 4.8 ± 1.8 ml/kg/h. In the 1 h, refilling volume amounted to only 23% of UF volume. Thereafter, refilling fraction steeply increased and reached maximum values in the 2, 3 and 4 h at about mean 90% (91.5%, 88.7%, and 91.1% respectively). From the 5 h on, refilling volume decreased (5 h 81.3%, 6 h 72.5%, 7 h 70.0% of UF volume). Cumulative refilling reached 73.6% of UF volume after 4 h of treatment time. This did not change during the further course of HD. Cumulative refilling volume showed a strong correlation (r = 0.94; p < 0.001) with UF volume. The ratio of blood volume to extracellular volume (Rbex ) was 0.306 ± 0.029 before and slightly but significantly increased to 0.326 ± 0.030 after UF. DISCUSSION: In spite of low-UF rates and extended treatment times, overall refilling fraction reached only 74% and was not different from the refilling fraction observed in regular HD. This value seems to represent a point where UF-induced volume perturbation is adequately compensated by physiologic control mechanisms.

Effect of Cyclophosphamide and Glucocorticoid Therapy in IgA Nephropathy: A Single-Center Retrospective Analysis.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in adults, which causes ESKD in ≤45% of patients in the long term. The optimal therapeutic approach remains undetermined. In this study, we report the results of a single-center retrospective analysis of patients with IgAN. Methods: We retrospectively evaluated the therapeutic approach and outcome of all patients at our center with biopsy-proven IgAN between 2000 and 2020, focusing on the effect of intravenous cyclophosphamide therapy combined with glucocorticoids ("immunosuppressive therapy group"). The control group received standard supportive care. Results: Patients in the immunosuppressive therapy group had worse kidney function before the initiation of therapy, as indicated by higher serum creatinine, more proteinuria, and a higher degree of hematuria than the control group; they also displayed a higher body mass index. The Oxford classification of IgA nephropathy (MEST-C score) suggested more inflammatory activity in the immunosuppressive therapy group, including more crescents and endocapillary hypercellularity. During the follow-up, proteinuria and hematuria decreased in both groups, and to a significantly greater extent in the immunosuppressive therapy group. Cyclophosphamide treatment significantly improved kidney function as determined by the fold-change of eGFR during the observation period. The number of infections and hospitalizations did not differ, but the incidence of diabetes was increased in the immunosuppressive therapy group. Conclusions: This study suggests immunosuppressive therapy with cyclophosphamide combined with glucocorticoids improves kidney function, proteinuria, and hematuria. The therapy was safe for infectious complications, but was associated with an increased incidence of diabetes, which might be attributable in part to the use of steroids in patients with a higher body mass index at baseline. Although immunosuppressive therapy in IgAN remains controversial, our findings suggest that at least some patients benefit from more aggressive therapy.

Decision-support systems for ambulatory care, including pandemic requirements: using mathematically optimized solutions.

BACKGROUND: The healthcare sector poses many strategic, tactic and operational planning questions. Due to the historically grown structures, planning is often locally confined and much optimization potential is foregone. METHODS: We implemented optimized decision-support systems for ambulatory care for four different real-world case studies that cover a variety of aspects in terms of planning scope and decision support tools. All are based on interactive cartographic representations and are being developed in cooperation with domain experts. The planning problems that we present are the problem of positioning centers for vaccination against Covid-19 (strategical) and emergency doctors (strategical/tactical), the out-of-hours pharmacy planning problem (tactical), and the route planning of patient transport services (operational). For each problem, we describe the planning question, give an overview of the mathematical model and present the implemented decision support application. RESULTS: Mathematical optimization can be used to model and solve these planning problems. However, in order to convince decision-makers of an alternative solution structure, mathematical solutions must be comprehensible and tangible. Appealing and interactive decision-support tools can be used in practice to convince public health experts of the benefits of an alternative solution. The more strategic the problem and the less sensitive the data, the easier it is to put a tool into practice. CONCLUSIONS: Exploring solutions interactively is rarely supported in existing planning tools. However, in order to bring new innovative tools into productive use, many hurdles must be overcome.

Quantifying Covid19-vaccine location strategies for Germany.

BACKGROUND: Vaccines are an important tool to limit the health and economic damage of the Covid-19 pandemic. Several vaccine candidates already provided promising effectiveness data, but it is crucial for an effective vaccination campaign that people are willing and able to get vaccinated as soon as possible. Taking Germany as an example, we provide insights of using a mathematical approach for the planning and location of vaccination sites to optimally administer vaccines against Covid-19. METHODS: We used mathematical programming for computing an optimal selection of vaccination sites out of a given set (i.e., university hospitals, health department related locations and general practices). Different patient-to-facility assignments and doctor-to-facility assignments and different constraints on the number of vaccinees per site or maximum travel time are used. RESULTS: In order to minimize the barriers for people to get vaccinated, i.e., limit the one-way travel journey (airline distance) by around 35 km for 75% of the population (with a maximum of 70 km), around 80 well-positioned facilities can be enough. If only the 38 university hospitals are being used, the 75% distance increases to around 50 km (with a maximum of 145 km). Using all 400 health departments or all 56 000 general practices can decrease the journey length significantly, but comes at the price of more required staff and possibly wastage of only partially used vaccine containers. CONCLUSIONS: In the case of free assignments, the number of required physicians can in most scenarios be limited to 2 000, which is also the minimum with our assumptions. However, when travel distances for the patients are to be minimized, capacities of the facilities must be respected, or administrative assignments are prespecified, an increased number of physicians is unavoidable.

Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25-29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known. METHODS: We retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients. RESULTS: In non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597). CONCLUSION: Triple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.

Risk Factors and Management of Leukopenia After Kidney Transplantation: A Single-Center Experience.

BACKGROUND: Leukopenia is a common complication after kidney transplantation. The etiology is multifactorial, with medication adverse effects and cytomegalovirus infection as main causes. Optimal strategies to prevent or treat posttransplant leukopenia remain unknown. We aimed to identify risk factors for leukopenia and to investigate the benefit of switching the immunosuppressive therapy to hydrocortisone as a continuous infusion. METHODS: We retrospectively evaluated all patients with leukopenia after kidney transplantation between 2007 and 2017 at our center relative to age- and sex-matched controls. RESULTS: Leukopenia was associated with the degree of rejection therapy before leukopenia, the immunosuppressive therapy before transplantation, and an induction therapy with rabbit antithymocyte globulin. Patients with leukopenia exhibited increased mortality, an increased incidence of bacterial and viral infections, and more acute rejections. Switching to hydrocortisone as a continuous infusion in patients with severe leukopenia decreased the duration of leukopenia and the incidence of subsequent viral infections, especially with cytomegalovirus. CONCLUSION: Leukopenia is a risk factor for infectious complications and mortality, and it is associated with acute rejection. Switching immunosuppressive therapy to hydrocortisone as a continuous infusion is a safe approach to reduce the duration of leukopenia and the incidence of viral infections.

Case Report: Blurred Vision and Eruptive Nevi - Bilateral Diffuse Uveal Melanocytic Proliferation With Mucocutaneous Involvement in a Lung Cancer Patient.

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ. What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases. What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma in situ and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a "Cultured melanocyte elongation and proliferation (CMEP)" factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma in situ should be considered making a thorough diagnostic workup mandatory.

Toward Understanding COVID-19 Recovery: National Institutes of Health Workshop on Postacute COVID-19.

Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in an enormous worldwide burden of infection and mortality. However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection, representing in the broadest sense a failure to return to a baseline state of health after acute SARS-CoV-2 infection. On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps regarding this condition.

Experiences and Short-Term Outcomes of Kidney Transplantation During the Coronavirus Disease 2019 Pandemic From a Medium-Volume Transplantation and Superregional Coronavirus Disease 2019 Treatment Center.

INTRODUCTION: The coronavirus, which first appeared in 2019, developed into a pandemic during 2020. It remains unclear to what extent the pandemic endangers the safety of kidney transplantation programs. In this study, we evaluated the short-term outcomes of our patients receiving a kidney transplant during the first phase and compared them with patients who received a kidney transplant immediately before the coronavirus pandemic. MATERIALS AND METHODS: Our retrospective study includes 34 kidney transplant recipients between October 1, 2019, and April 30, 2020. Nineteen patients from the phase immediately prior to the first coronavirus wave (pre-corona group), and 15 patients from the phase of the first coronavirus wave (corona group) were studied. We retrospectively evaluated demographic data, postoperative short-term outcomes and complications, immunosuppression regime, coronavirus infection status, and behavior during the first phase of the pandemic. RESULTS: There were no differences between the 2 groups regarding short-term outcomes and postoperative complications or in immunosuppressive medication. After the introduction of intensified hygienic conditions and routine swabs prior to transplantation, no nosocomial SARS-CoV-2 infections occurred. In the outpatient setting, none of the patients developed a SARS-CoV-2 infection. The majority of patients performed voluntary quarantine. CONCLUSIONS: The short-term outcomes after kidney transplantation during the first phase of the coronavirus pandemic were comparable to pre-pandemic patients, and no SARS-CoV-2-associated death or transplant failure occurred in our small cohort. We considered patient compliance with hygiene and self-isolation measures very high. Nevertheless, in further phases of the pandemic, the continuation of the living kidney donation program must be critically evaluated.

[Hypertensive Disorders in Pregnancy]. / Hypertensive Erkrankungen in der Schwangerschaft.

Hypertensive disorders occur in up to 10 % of pregnancies and increase both maternal and fetal morbidity and mortality. The most important differential diagnoses comprise pre-existing chronic hypertension, pregnancy-associated hypertension, and preeclampsia with simultaneous proteinuria. Antihypertensive therapy during pregnancy should be initiated when blood pressure is 150-160/100-110 mmHg. With regard to an earlier initiation of therapy, the data situation is not clear. Pre-eclampsia is defined as new or pre-existing elevated blood pressure ≥ 140/90 mmHg in pregnancy with at least one new organ manifestation, usually proteinuria ≥ 300 mg/day or ≥ 30 mg/mmol in the protein-creatinine ratio. Thrombotic microangiopathies TTP and aHUS are altogether rare but potentially life-threatening diseases that should be clarified in case of severe or atypical courses.

Two cases of carfilzomib-induced thrombotic microangiopathy successfully treated with Eculizumab in multiple myeloma.

BACKGROUND: Treatment with proteasome inhibitors like carfilzomib in patients with multiple myeloma (MM) can induce thrombotic microangiopathy (TMA) characterized by neurological symptoms, acute kidney injury, hemolysis and thrombocytopenia. Successful treatment with the monoclonal antibody eculizumab was described for these patients, but reports of ideal management and definitive treatment protocols are lacking. CASE PRESENTATION: The first case describes a 43-years-old IgG-kappa-MM patient that developed TMA during the first course of carfilzomib-lenalidomide-dexamethasone (KRd) consolidation after autologous stem cell transplantation (ASCT). In the second case, a 59-years-old IgG-kappa-MM patient showed late-onset TMA during the fourth and last cycle of elotuzumab-KRd consolidation within the DSMM XVII study of the German study group MM (DSMM; clinicalTrials.gov Identifier: NCT03948035). Concurrently, he suffered from influenza A/B infection. Both patients had a high TMA-index for a poor prognosis of TMA. Therapeutically, in both patients plasma exchange (TPE) was initiated as soon as TMA was diagnosed. In patient #1, dialysis became necessary. For both patients, only when the complement inhibitor eculizumab was administered, kidney function and blood values impressively improved. CONCLUSION: In this small case series, two patients with MM developed TMA due to carfilzomib treatment (CFZ-TMA), the second patient as a late-onset form. Even though TMA could have been elicited by influenza in the second patient and occurred after ASCT in both patients, with cases of TMA post-transplantation in MM being described, a relation of TMA and carfilzomib treatment was most likely. In both patients, treatment with eculizumab over two months efficiently treated TMA without recurrence and with both patients remaining responsive months after TMA onset. Taken together, we describe two cases of TMA in MM patients on carfilzomib-combination treatment, showing similar courses of this severe adverse reaction, with good responses to two months of eculizumab treatment.

Psychosocial emergency care in times of COVID-19: the Essen University Hospital concept for corona-infected patients, their relatives, and medical staff.

Due to the SARS CoV-2-virus (COVID-19), anxiety, distress, and insecurity occur more frequently. In particular, infected individuals, their relatives, and medical staff face an increased risk of high psychological distress as a result of the ongoing pandemic. Thus, structured psychosocial emergency concepts are needed. The University hospital of Essen has taken up this challenge by creating the PEC concept to reduce psychosocial long-term consequences for infected patients, relatives, and medical staff at the university hospital. The concept includes professional medical as well as psychological support to convey constructive coping strategies and the provision of adequate tools such as the low-threshold online training program (CoPE It), which is accessible via the webpage www.cope-corona.de .