[Clinical acute and emergency medicine curriculum-focus on internal medicine : Recommendations for advanced training in internal medicine in the emergency department]. / Curriculum Klinische Akut- und Notfallmedizin ­ Schwerpunkt Innere Medizin : Empfehlung zu Weiterbildungsinhalten der Inneren Medizin in der Notaufnahme.

In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients. These include general aspects (structure and process quality, primary diagnostics and therapy as well as indication for subsequent treatment; resuscitation room management; diagnostics and monitoring; general therapeutic measures; hygiene measures; and pharmacotherapy) and also specific aspects concerning angiology, endocrinology, diabetology and metabolism, gastroenterology, geriatric medicine, hematology and oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology and toxicology. Publications focussing on contents of advanced training are quoted in order to support this concept. The curriculum has primarily been written for internists for their advanced emergency training, but it may generally show practising emergency physicians the broad spectrum of internal medicine diseases or comorbidities presented by patients attending the emergency department.

Relevance of histopathological findings for predictive scoring of short-term treatment response to plasma exchange in severe ANCA-associated renal vasculitides.

Introduction: Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of kidney function, affecting both renal and overall patient survival. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems including the kidney, and among most frequent causes of RPGN. We here aimed to validate a recently described scoring system for short-term treatment response to therapeutic plasma exchange (PLEX) in a well-characterized and independent cohort of severe renal AAV presenting with RPGN. Furthermore, we compared this scoring with established classification systems in renal AAV including histopathological findings. Methods: We here directly compare the scoring system with retrospective data about PLEX treatment in our own clinical practice and according to current recommendations in a cohort of 53 patients with severe AAV presenting with RPGN confirmed by kidney biopsy. Results: We here confirm that PLEX scoring is capable to identify patients at risk for short-term poor outcome in severe AAV presenting with RPGN (p<0.0001). Furthermore, multiple stepwise regression analysis revealed that the PLEX score with renal biopsy performed best to predict poor outcome in this patient population (p<0.0001). Conclusion: Our observations underscore the relevance of performing a kidney biopsy in this patient population that is often challenged in the setting of intensive care treatment, requirement of KRT with need for anticoagulation and bleeding risk. Therefore, validation of our observations and this recent scoring system for treatment response to PLEX in independent cohorts would be of great clinical relevance in the treatment of patients with severe AAV presenting with RPGN.

Serum Uric Acid Associates with Systemic Complement C3 Activation in Severe ANCA-Associated Renal Vasculitides.

Involvement of the complement system is key to the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, but immunometabolic implications, especially on serum uric acid (UA) levels, still need to be elucidated. A total of 34 patients with biopsy-proven ANCA-associated renal vasculitis between 2015 and 2020 were retrospectively enrolled. Serum UA levels were correlated with clinical and histopathological characteristics, separated for critically ill (CI, n = 19), myeloperoxidase (MPO)-ANCA (n = 21) and proteinase 3 (PR3)-ANCA (n = 13) subgroups. We here identified inverse correlations of serum UA levels and complement C3 levels in the total cohort (p = 0.005) and the CI subgroup (p < 0.001). Intrarenal complement C4d deposition in venules correlated with serum UA levels in the total cohort (p = 0.007) and in the CI subgroup (p = 0.016). Significant associations of serum UA levels and tubulitis in areas of scarred cortex (t-IFTA) were identified in the total cohort (p = 0.008), and both subgroups of CI (p = 0.034) and MPO-ANCA (p = 0.029). In PR3-ANCA, interstitial fibrosis (ci) was observed as the strongest association with serum UA levels (p = 0.022). Our observations broaden our current understanding of contributory metabolic factors that influence the initial disease course in ANCA-associated renal vasculitis.

A Transcriptome Array-Based Approach Links Proteinuria and Distinct Molecular Signatures to Intrarenal Expression of Type I Interferon IFNA5 in Lupus Nephritis.

In systemic lupus erythematosus (SLE), the relevance of non-hematopoietic sources of type I interferon in human autoimmunity has recently been recognized. Particularly, type I interferon production precedes autoimmunity in early skin lesions related to SLE. However, the relevance of intrarenal type I interferon expression has not been shown in lupus nephritis. From transcriptome array datasets, median-centered log2 mRNA expression levels of IFNα (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, and IFNA21), IFNω (IFNW1), and IFNß (IFNB1) in lupus nephritis were extracted specifically from microdissected tubulointerstitial (n = 32) and glomerular compartments (n = 32). We found an association between proteinuria and tubulointerstitial expression of type I interferon IFNA5 (p = 0.0142), while all others were not significantly associated. By contrast, no such correlation was observed between proteinuria and any type I interferon expression in the glomerular compartment in lupus nephritis. Interestingly, there was no difference between female and male patients (p = 0.8237) and no association between type I interferon IFNA5 expression and kidney function or lupus nephritis progression. Finally, we identified distinct molecular signatures involved in transcriptional regulation (GLI protein-regulated transcription, IRF7 activation, and HSF1-dependent transactivation) and receptor signaling (BMP signaling and GPCR ligand binding) in association with tubulointerstitial expression of type I interferon IFNA5 in the kidney. In summary, this transcriptome array-based approach links proteinuria to the tubulointerstitial expression of type I interferon IFNA5 in lupus nephritis. Because type I interferon receptor subunit I antagonism has recently been investigated in active SLE, the current study further emphasizes the role of type I interferons in lupus nephritis and might also be of relevance for mechanistic studies.

Study protocol: a prospective single-center study for non-invasive biomonitoring of renal complications in cancer patients treated with immune checkpoint inhibitors.

Background: The advent of immune checkpoint inhibitors (ICIs) has powerfully broadened the scope of treatment options for malignancies with an ongoing increase of indications, but immune-related adverse events (irAEs) represent a serious threat to treatment success. Agents directed against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) are known to cause renal complications with an incidence of 3%. In contrast, subclinical renal involvement is estimated to be much higher, up to 29%. We recently reported about urinary flow cytometry-based detection of urinary PD-L1-positive (PD-L1+) kidney cells correlating with tubular PD-L1-positivity that reflected susceptibility to develop ICI-related nephrotoxicity as an irAE attending ICI treatment. Therefore, we designed a study protocol to evaluate urinary detection of PD-L1+ kidney cells as a tool for non-invasive biomonitoring of renal complications in cancer patients treated with ICIs. Methods: A prospective, controlled, non-interventional, longitudinal, single-center observational study will be conducted at the Department of Nephrology and Rheumatology of the University Medical Center Göttingen, Germany. We intend to enroll approximately 200 patients treated with immunotherapy from the Departments of Urology, Dermatology, and Hematology and Medical Oncology of the University Medical Center Göttingen, Germany. First, we will assess clinical, laboratory, histopathological, and urinary parameters in addition to urinary cell collection. Then, we will perform a correlative analysis between urinary flow cytometry of different PD-L1+ cell of renal origin with the onset of ICI-related nephrotoxicity. Discussion: Because of growing ICI-treatment applicability with an expectable incidence of renal complications, providing cost-efficient and easily performable diagnostic tools for treatment-attendant and non-invasive biomonitoring becomes vital to improve both renal and overall survival rates in cancer patients receiving immunotherapy. Trial registration: https://www.drks.de, DRKS-ID DRKS00030999.

C-Reactive Protein Levels Are Associated with Complement C4 Deposits and Interstitial Arteritis in ANCA-Associated Renal Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis in case of kidney involvement, representing a major denominator of AAV mortality. Innate immunity with complement system activation is increasingly recognized in the pathogenesis of AAV and as an attractive therapeutic target. Although C-reactive protein (CRP) was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self-determinants. Elevated baseline CRP at disease onset of AAV has already been described as a determinant of poor long-term outcomes. However, its clinical implications at disease onset of AAV, with respect to vasculitis manifestations and complement system activation that might also affect long-term outcomes, remain elusive. CRP levels were retrospectively analyzed in 53 kidney-biopsy-confirmed cases of ANCA-associated renal vasculitis; a total of 138 disease controls were also evaluated. Univariate and multivariate regression analysis was performed on clinicopathological parameters associated with CRP levels in ANCA-associated renal vasculitis. Results: Compared to disease controls, CRP elevation was common in ANCA-associated renal vasculitis and associated with de novo disease (p = 0.0169), critical illness (p = 0.0346), and severe deterioration of kidney function (p = 0.0167), independent of extrarenal disease manifestations. As confirmed by multiple regression analysis, CRP levels were correlated with active lesions predominated by interstitial arteritis in renal vasculitis, specifically with MPO-ANCA seropositivity (p = 0.0017). Based on analysis of systemic complement system activation and intrarenal complement deposits, CRP elevation was correlated specifically with complement C4 deposits in interstitial arteries in the subgroup with myeloperoxidase (MPO)-ANCA seropositivity (p = 0.039). Finally, this association was independent of systemic complement system activation, as reflected by the consumption of respective complement components. Here, we expand our current understanding of CRP in ANCA-associated renal vasculitis not only as an inflammatory marker, but potentially also as being involved in the pathogenesis of kidney injury by interaction with the complement system.

Renal disease in sarcoidosis patients in a German multicentric retrospective cohort study.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease potentially affecting every organ system. Renal involvement is reportedly rare, and the evidence consists of case reports and cohort studies. Systematic investigations are scarce and show a varying prevalence ranging from <1% to 30-50%. METHODS: We retrospectively analyzed data from patients with a recent diagnosis of sarcoidosis from five tertiary care centers focusing on renal sarcoidosis. RESULTS: We analyzed data from 327 patients with sarcoidosis between 2001 and 2021. Of 327 patients, 109 (33.3%) had probable or definite renal sarcoidosis. 90 (27.5%) had histopathologic confirmation. 57 (64%) had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The most prominent associated finding was an elevated soluble interleukin-2 receptor. Patients with renal sarcoidosis more frequently received glucocorticoids than other non-renal sarcoidosis patients (92% vs. 78%, p < 0.01). Also, azathioprine (38% vs. 16%, p < 0.001) and mycophenolate mofetil (5% vs. 1%, p < 0.05) were more frequently used in renal sarcoidosis compared to non-renal sarcoidosis, whereas methotrexate was used less frequently (7% vs. 17%, p < 0.05). CONCLUSIONS: Our data of the largest cohort with biopsy-confirmed renal sarcoidosis demonstrate a higher prevalence (27.5% of all patients) than previously published with a relevant disease burden. The urinary findings in most cases were only mildly abnormal, and some patients did not have renal biopsy despite abnormal urinary results. A renal workup should be performed in all patients with a new diagnosis of sarcoidosis.

[Myositis]. / Myositis.

The S2e guidelines on myositis were completely updated and revised under the leadership of the German Society for Neurology and the participation of many other specialist societies. Immune-mediated necrotizing myopathy and antisynthetase syndrome are now regarded as independent entities in the classification of myositis. With respect to the diagnostics, the guidelines provide concrete recommendations on dysphagia screening, especially for inclusion body myositis and for cancer diagnostics in certain forms of myositis. Following the positive ProDERM study, the use of intravenous immunoglobulins (Octagam®) is available for treatment as an approved substance. Based on the INBUILD study, antifibrotic treatment with nintedanib is available for progressive fibrosing pulmonary involvement. For rheumatologists, the updated guidelines represent a document relevant for daily practice with many recommendations for the treatment of patients with myositis.

Fulminant Lyme myocarditis without any other signs of Lyme disease in a 37-year-old male patient with microscopic polyangiitis-a case report.

Background: Lyme disease is a tick-borne multisystem infection. The most common cardiac manifestation is an acute presentation of Lyme carditis, which often manifests as conduction disorder and rarely as myocarditis. Case summary: We report the case of a 37-year-old male with a history of microscopic polyangiitis receiving immunosuppressive therapy. He was admitted for severe dyspnoea secondary to acute heart failure. Echocardiography and cardiac magnetic resonance imaging indicated a severely reduced left ventricular ejection fraction (LVEF) with global hypokinesia. Coronary heart disease was excluded, and endomyocardial biopsies (EMB) were performed. The left ventricular EMB revealed a rare case of fulminant Lyme carditis with evidence of typical lymphocytic myocarditis. Borrelia afzelii-DNA was detected without any relevant atrioventricular blockage or systemic signs of Lyme disease. The patient had no clinically apparent tick-borne infection or self-reported history of a tick bite. Immunological testing revealed a positive ELISA and Immunoblot for anti-Borrelia immunoglobulin G antibodies. After specific intravenous antibiotic therapy and optimized medical therapy for heart failure, the LVEF recovered, and the patient could be discharged in an improved condition. Repeat EMB a few months later revealed a dramatic regression of the cardiac inflammation and absence of Borrelia DNA in the myocardium. Discussion: A severely reduced LVEF can be the primary manifestation of Lyme disease even without typical systemic findings and can have a favourable prognosis with antibiotic treatment. A thorough workup for Lyme carditis is required in patients with unexplained heart failure, particularly with EMB, especially in immunosuppressed patients.

Treatment and outcomes in anti-HMG-CoA reductase-associated immune-mediated necrotising myopathy. Comparative analysis of a single-centre cohort and published data.

OBJECTIVES: Anti-hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) antibody-associated myopathy was recognised as a new form of immune-mediated necrotising myopathy (IMNM) a decade ago. Due to the rarity of the disease, only limited data on clinical manifestations and therapeutic outcomes are available. METHODS: We retrospectively analysed a monocentric cohort of HMGCR-associated IMNM patients treated at the University Medical Centre Göttingen. Clinical, laboratory, and biopsy data, as well as treatment outcomes, were analysed. In addition, a literature search was performed on published HMGCR IMNM cohorts in Medline and Web of Science. RESULTS: We identified nine patients; five were female. The median age was 68 years (47-77). Six were statin-exposed and older than statin-naive patients (71 years [65-77] vs. 51 years [47-67]). All had muscle weakness, seven myalgias. Strength (MRC sum score) was 53/65 (46-61) at baseline and increased to 63/65 (50-65) with therapy. Creatine kinase (CK) levels decreased from a median level of 12837 U/L (range 6346-25011) to 624 U/L (35-1564 U/L). All received glucocorticoids (GC) and at least one immunosuppressive therapy. The literature review identified 26 studies comprising 691 patients. 57.9% were female, 61.3% statin exposed. 95.2% had weakness, 39.1% myalgia. Dysphagia affected 28.8%. 84.9% received GC and a median of 1.5 additional immunosuppressants. Compared to published data, our patients had higher baseline CK values (12837 [6346-25011] vs. 6951 [2539-10500], p<0.001), and we used azathioprine and intravenous immunoglobulins (p<0.001) more frequently but methotrexate and rituximab less frequently (p<0.001). CONCLUSIONS: HMGCR-associated IMNM is a rare subset of myositis. With systemic treatment, patients usually achieve partial or complete remission. Optimal treatment has not been established, but glucocorticoids, azathioprine, and methotrexate are generally effective with or without intravenous immunoglobulins.

Comparative Histological Subtyping of Immune Cell Infiltrates in MPO-ANCA and PR3-ANCA Glomerulonephritis.

Background: Acute kidney injury (AKI) is a common and severe complication of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), potentially leading to chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response with intrarenal immune cell infiltration resulting in a pauci-immune necrotizing and crescentic glomerulonephritis (GN). However, a systematic analysis of intrarenal immune cell subtypes concerning neutrophils, eosinophils, plasma cells, and mononuclear cell infiltrates (macrophages, lymphocytes) in ANCA GN remains elusive. Therefore, we aimed to compare distinct immune cell infiltrates in association with clinicopathological findings in ANCA GN. Methods: A total of 53 kidney biopsies with ANCA GN at the University Medical Center Göttingen were retrospectively analyzed. Histological infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the total area of inflammation. Results: Neutrophilic infiltrates were associated with glomerular necrosis and severe kidney injury in ANCA GN. Among tubulointerstitial lesions, intrarenal neutrophils correlated with interstitial inflammation, tubulitis, and inflammation in areas of interstitial fibrosis/tubular atrophy (IFTA), representing active inflammatory lesions. Concerning eosinophils, infiltrates were associated with severe kidney injury, interstitial inflammation, and cellular casts independent of glomerular lesions, implicating a distinct role in inflammation and damage in ANCA GN. Plasma cell infiltrates correlated with tubulitis and interstitial fibrosis and were associated with renal replacement therapy during the short-term disease course. Finally, mononuclear cell infiltrates correlated with severe kidney injury and active histopathological lesions (glomerular crescents, interstitial inflammation, tubulitis, inflammation, and tubulitis in areas of IFTA) besides chronic lesions (interstitial fibrosis and tubular atrophy) in ANCA GN. Interestingly, intrarenal subtypes of immune cell infiltrates differed in MPO-ANCA versus PR3-ANCA GN and were associated with distinct glomerular and tubulointerstitial lesions, implicating different pathogenic mechanisms of kidney injury in ANCA subtypes. Conclusion: Our observations imply distinct pathomechanisms contributing to inflammation and renal injury in MPO vs. PR3-associated ANCA GN and potentially contribute to new therapeutic targets in specific ANCA subtypes.

Comprehensive Analysis of Sex Differences at Disease Manifestation in ANCA-Associated Glomerulonephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Besides investigations focusing on renal outcomes, sex differences associated with distinct clinical and histopathological findings in ANCA glomerulonephritis (GN) have not been systematically investigated. Therefore, we here aimed to systematically analyze sex differences in patients with AAV and biopsy-proven ANCA GN. We provide a comprehensive analysis of 53 kidney biopsies with ANCA GN retrospectively included between 2015 and 2020 and identified specific sex differences in ANCA GN concerning laboratory parameters and systematic scoring of renal histopathology glomerular and tubulointerstitial lesions, and extrarenal manifestations of AAV. We did not observe any correlation between sex and short-term clinical AAV course or disease severity by comparing general AAV parameters. AAV manifestations in females occurred at an older age with more joint involvement. Regarding histopathological findings, we, again, observed no sex difference among ANCA GN classification, but a significant correlation between females and distinct histopathological findings with less tubulointerstitial inflammation and vasculitis of peritubular capillaries. Finally, we here identified fewer associations between clusters of clinical, laboratory parameters, and histopathological findings in females as compared to males. These findings are of great relevance and further improve our understanding of sex differences in the pathogenesis of ANCA GN. While future studies about specific sex differences and conclusions in these clusters are crucial, our observations further support that sex differences are relevant, affect distinct parameters, and influence clinical, laboratory parameters, and histopathological findings in AAV, particularly ANCA GN.

Sarcoidosis Following Hematopoietic Stem Cell Transplantation: Clinical Characteristics and HLA Associations.

Purpose: Extrinsic factors and genetic predisposition contribute to the etiology of sarcoidosis, converging in a phenotype of altered immune response associated with multisystemic inflammatory granulomatous tissue infiltration. Immunological reconstitution after hematopoietic stem cell transplantation (HSCT) may represent a unique window for the pathogenesis of the disease. We describe the incidence, clinicopathological features, and HLA associations of sarcoidosis after HSCT in a single-center cohort of patients, together with data from previously published cases. Methods: We retrospectively analyzed clinical characteristics and HLA haplotypes from allogeneic (allo) or autologous (auto) HSCT patients from January 2001 through May 2021 at the University Medicine Goettingen (UMG), and data from previously published cases. Results: A total number of 19 patients was identified. These included 4 patients from our center (3 allo HSCT and 1 auto HSCT) and 15 patients from the literature review. Thirteen patients had received an allo HSCT, and six patients had received an auto HSCT. Sarcoidosis occurred after a median interval of 20 (after allo HSCT) and 7 (after auto HSCT) months, respectively. The predominant HLA allele associated with sarcoidosis was HLA DRB1*03:01. Sarcoidosis involved the respiratory tract in 15 patients (three unknown, one without pulmonary involvement), and it was associated with graft-versus-host disease in 7 of 13 patients receiving allo HSCT. None of the donors or patients had a history of sarcoidosis before transplantation. Disease manifestations resolved with standard glucocorticoid treatment without long-term sequelae. Conclusion: Sarcoidosis may occur at low frequency during reconstitution of the immune system after HSCT. HLA allele associations reflect the associations observed in the general population, particularly with DRB1*03:01. Further insights into the interplay between Tcell reconstitution and the development of sarcoidosis could also provide novel approaches to an improved understanding of the pathogenesis in sarcoidosis.

Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. METHODS: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Göttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. RESULTS: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. CONCLUSIONS: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments.

Consideration of Therapeutic Plasma Exchange in Association With Inflammatory Lesions in ANCA-Associated Glomerulonephritis: A Real-World Retrospective Study From a Single Center.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Pathogenic ANCAs trigger a deleterious immune response resulting in pauci-immune necrotizing and crescentic glomerulonephritis (GN). Standard therapeutical regimens include aggressive immunosuppressive therapy. Since some patients require renal replacement therapy (RRT) despite intensive immunosuppressive therapy, additional therapeutic plasma exchange (PEX) to deplete pathogenic ANCAs has been recommended but its value has recently been questioned. Because therapeutic decision making is crucial in these critically ill patients, we here aimed to identify inflammatory lesions in association with PEX consideration in a retrospective study from a single center tertiary hospital in a real-world population of 46 patients with severe AAV requiring intensive care treatment. The decision to consider PEX was more likely in patients with need for intensive care treatment and severe renal dysfunction. In contrast, short-term outcomes did not depend on clinical, or laboratory characteristics assessed at admission. Histopathological analysis confirmed active disease reflected by increased glomerular necrosis and crescents, but these histopathological findings did not associate with short-term outcome either. Interestingly, only increased global glomerular sclerosis in renal biopsies associated with a detrimental short-term outcome. In conclusion, our study investigated determinants for the consideration of therapeutic PEX in patients with severe AAV requiring intensive care treatment. This aspect underscores the need for renal biopsy and requires further investigation in a prospective controlled setting for therapeutic decision making especially in patients with severe AAV requiring intensive care treatment, especially important for treating intensivists.

Impact of the COVID-19 Pandemic on Kidney Diseases Requiring Renal Biopsy: A Single Center Observational Study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic impacted healthcare services for kidney disease patients. Lockdown and social distancing were mandated worldwide, resulting in closure of medical services. The diagnosis of various kidney diseases may have been delayed during the COVID-19 pandemic because non-urgent tests and visits were postponed due to closure of medical services during the lockdown. METHODS: We here report the impact of the COVID-19 pandemic on a total number of 209 native kidney diseases requiring renal biopsy for diagnosis in a retrospective observational study from a tertiary hospital in Germany. RESULTS: The lockdown period in March and April 2020 primarily affected patients admitted to the normal medical ward with a compensatory increased rate of renal biopsies in the postlockdown phase. In addition, there was a shift toward more patients admitted with hemoglobinuria during the COVID-19 pandemic. This phenomenon of an increased number of patients with hemoglobinuria during the COVID-19 pandemic was specifically observed in a subgroup with hypertensive nephropathy requiring renal biopsy and associated with increased proteinuria, not attributed to the COVID-19 lockdown period itself. CONCLUSION: To our knowledge, this is the first report of identifying a subpopulation susceptible to closure of medical services during the COVID-19 pandemic and diagnostic delay of specific kidney diseases. Therefore, the COVID-19 pandemic should be regarded as a risk factor especially in patients with diseases other than COVID-19 primarily admitted to the normal medical ward.

COVID-19 and Sarcoidosis, Readiness for Vaccination: Challenges and Opportunities.

Sarcoidosis is an immune mediated chronic inflammatory disorder that is best characterized by non-caseating granulomas found in one or more affected organs. The COVID-19 pandemic poses a challenge for clinicians caring for sarcoidosis patients who may be at increased risk of infection compared to the general population. With the recent availability of COVID-19 vaccines, it is expected that clinicians raise questions regarding efficacy and safety in sarcoidosis. However, studies examining safety and efficacy of vaccines in sarcoidosis are lacking. In this review, we examine the current literature regarding vaccination in immunocompromised populations and apply them to sarcoidosis patients. The available literature suggests that vaccines are safe and effective in patients with autoimmune disorders and in those taking immunosuppressive medications. We strongly recommend the administration of COVID-19 vaccines in patients with sarcoidosis. We also present a clinical decision algorithm to provide guidance on vaccination of sarcoidosis patients against COVID-19.