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Objective: To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based risk classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C‐reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88–0.94) with a sensitivity of 87.0% (95% CI 82.0–91.0%) and specificity of 94.8% (95% CI 91.0–97.4%). Conclusion: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate new classification criteria for Takayasu arteritis (TAK). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate criteria items, 2) collection of candidate items present at diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large‐vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1), and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% confidence interval [95% CI] 0.94–0.99) with a sensitivity of 93.8% (95% CI 88.6–97.1%) and specificity of 99.2% (95% CI 96.7–100.0%). Conclusion: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research. [ABSTRACT FROM AUTHOR]

The aim of this systematic review and network meta‐analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non‐medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS‐CoV, MERS‐CoV and SARS‐CoV‐2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask‐wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23–0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20–0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID‐19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings. [ABSTRACT FROM AUTHOR]

Sexual health among male cancer survivors is becoming an increasingly important aspect of health care as the number of survivors increases. Here the authors analyse the impact of cancer treatment and cancer types on the prevalence of erectile dysfunction among these men. [ABSTRACT FROM AUTHOR]

The aim of this study is to provide a more accurate representation of COVID‐19's case fatality rate (CFR) by performing meta‐analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID‐19 for every country reporting COVID‐19 cases. On the basis of data, we performed random and fixed meta‐analyses for CFR of COVID‐19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed‐ and random‐model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random‐model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random‐model results showed an increase near 5.0%. In high‐income countries, pooled estimates and fixed‐model showed gradually increasing trends with a final pooled estimates and random‐model reached about 8.0% and 4.0%, respectively. In middle‐income, the pooled estimates and fixed‐model have gradually increased reaching up to 4.5%. in low‐income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID‐19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries. Highlights: Europe showed the highest COVID‐19 case fatality rate (CFR) until mid‐October 2020, and North America and South America follows.Asia showed the highest CFR since the first confirmed case of COVID‐19 emerged, however, it had shown a declining tendency since March 2020.CFRs in high‐income countries showed an explosive increase compared with those in low‐income countries, which can be interpreted as due to the under‐reporting of mortality cases from COVID‐19. [ABSTRACT FROM AUTHOR]

Two messenger RNA (mRNA) vaccines developed by Pfizer‐BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID‐19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID‐19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID‐19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID‐19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID‐19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47–65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62–24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain‐Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real‐world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting, or sino‐nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (+5); pulmonary nodules, mass, or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci‐immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (−1); and eosinophil count ≥1 × 109/liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% confidence interval [95% CI] 87–96%) and the specificity was 94% (95% CI 89–97%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate classification criteria for microscopic polyangiitis (MPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti–myeloperoxidase‐ANCA positivity (+6), pauci‐immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino‐nasal symptoms or signs (−3), cytoplasmic ANCA or anti–proteinase 3 ANCA positivity (−1), and eosinophil count ≥1 × 109/liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% confidence interval [95% CI] 85–95%) and the specificity was 94% (95% CI 92–96%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109/liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77–91%) and the specificity was 99% (95% CI 98–100%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research. [ABSTRACT FROM AUTHOR]

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID‐19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV‐ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC‐CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug‐induced CV‐ADRs from COVID‐19 effects, we restricted analyses to patients with COVID‐19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC‐CMs in time‐ and dose‐dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin. [ABSTRACT FROM AUTHOR]

Anti‐glomerular basement membrane (GBM) disease (Goodpasture disease) often presents with severe kidney failure and pulmonary hemorrhage. Anti‐GBM antibodies are pathogenic, and other autoantibodies such as laminin‐521 have been identified recently, potentially indicating a subset with a more severe disease phenotype and poor prognosis. Around 30%–40% of patients are also anti‐neutrophil cytoplasmatic antibody (ANCA)‐positive and this subset combines features of anti‐GBM disease and ANCA‐associated vasculitis, with particular impact on long‐term treatment. A combination of therapeutic plasma exchange (or immunoadsorption), cyclophosphamide, and glucocorticoids is considered standard of care management, but despite early initiation, patients with poor prognostic factors often remain dialysis dependent. Imlifidase (IdeS), capable to cleave IgG within hours, has been tested in a phase II trial. Among 15 patients, 10 with poor prognosis at baseline (eGFR <15 ml/min/1.73 m2) were dialysis independent at 6 months. Further developments are needed to refine treatment approaches in anti‐GBM disease. [ABSTRACT FROM AUTHOR]

We report the case of a 63‐year‐old Caucasian woman with multiple relapsed IgM multiple myeloma (MM) and elevated free kappa light chains (fκLC). Due to hyperviscosity syndrome with visual impairment, regular plasma exchanges were performed. As part of her 11th line of therapy, an experimental protocol consisting of pembrolizumab, pomalidomide, and dexamethasone was initiated. To reduce fκLC and immunoglobulin (Ig) M, we performed immunoadsorption (IA) using columns containing recombinant single domain camelid antibody fragments as ligands. We measured pembrolizumab (humanized IgG4 kappa anti‐PD1 antibody) levels before and after each IA session and found a 98.1% reduction from baseline with five sessions of IA. Comparable elimination kinetics were observed for serum IgG, whereas fκLC and IgM were eliminated to a substantially lesser extent. These findings highlight that in hyperviscosity syndrome due to IgM MM, broad spectrum IA columns might be only moderately effective compared to total plasma exchange or double filtration plasmapheresis. Monoclonal antibodies are efficiently reduced by extracorporeal therapies and re‐dosing is necessary to provide sufficient efficacy. In the case of serious adverse events such as immune‐related adverse events, IA might be used to eliminate the monoclonal antibody. Measuring IgG levels might be a reasonable strategy for monitoring drug levels of monoclonal antibodies during IA. [ABSTRACT FROM AUTHOR]

Background: Cancer risk has been associated with certain gene variations in microRNA (miRNA), but conflicting evidence warrants re‐assessing of significant results in meta‐analyses. We summarized published meta‐analyses that assess the associations between miRNA polymorphism and cancers to show the validity of the findings. Method: We searched PubMed and investigated the results of meta‐analyses published through November 2018. We re‐assessed the results based on false‐positive report probability (FPRP) to test the noteworthiness of the associations. Results: Sixty‐eight miRNA polymorphisms in 45 meta‐analyses associated with cancer were included. Four (7.4%) and sixteen (25.0%) single nucleotide polymorphisms (SNPs) were noteworthy (FPRP < 0.2) at a prior probability of 0.001 for interesting candidate genes and a statistical power to detect an odds ratio (OR) of 1.1 and 1.5, respectively. The four miRNA SNPs noteworthy at an OR of 1.1 were as follows: miR‐146a/rs2910164 Cvs.G; miR‐27a/rs895819 Cvs.T; miR‐423/rs6505162 Cvs.A; and miR‐605/rs2043556 Cvs.T. The 16 SNPs noteworthy at an OR of 1.5 include the four genotype comparisons at an OR of 1.1, and the additional 12 genotype comparisons were as follows: miR‐196a2/rs11614913 Tvs.C; miR‐27a/rs895819 GGvs.AA + AG; miR‐196a2/rs11614913 C vs.T; miR‐146a/rs2910164 Gvs.C; miR‐196a2/rs11614913 Tvs.C; miR‐146a/rs2910164 Cvs.G; miR‐499/rs3746444 homozygous model; miR‐146a/rs2910164 CCvs.GG + GC; miR‐499/rs3746444 TCvs.TT; miR‐499/rs3746444 GAvs.AA; miR‐146a/rs2910164 CCvs.GG; and miR‐499/rs3746444 Gvs.A. No association was noteworthy at a prior probability of 0.000001. Conclusion: Out of 68 published associations of miRNA polymorphisms with cancer, sixteen have shown noteworthiness in our re‐assessing meta‐analysis. Our findings summarize the results of meta‐analyses on the association of cancer with SNPs and underline the importance of interpreting results with caution. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is the most common glomerular childhood disease. A body of literature has described the long-term renal prognosis of childhood-onset idiopathic NS. However, the nonrenal outcomes have not been studied as much.Aim: We aimed to discuss the long-term non-renal outcomes of childhood NS, highlighting studies with a follow-up period of more than 10 years.Results: We reviewed the literature and found that a number of immunosuppressive agents have stopped inflammation, stabilised the podocyte cytoskeleton and reduce proteinuria. However, prolonged treatment has frequently been associated with a high risk of renal and non-renal complications in patients with a complicated disease course, defined as frequent relapses or steroid dependency. Non-renal complications may include impaired longitudinal growth and pubertal development, undesirable fertility outcomes, ocular complications, bone mineral diseases and potential malignancies.Conclusion: This review discusses and summarises the non-renal outcomes of idiopathic childhood NS. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods: VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA‐associated vasculitis (AAV). Results: VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0–2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247–134.842]; P = 0.006), positive proteinase 3 (PR3)–ANCA (HR 7.731 [95% CI 1.021–58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448–10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491–69.854]; P < 0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95% CI 2.566–185.805]; P = 0.005), PR3‐ANCA (HR 9.12 [95% CI 1.158–71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95% CI 1.453–10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95% CI 3.607–75.075]; P < 0.001) remained. Conclusion: Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3‐ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background Primary focal segmental glomerulosclerosis ( FSGS) is a common cause of nephrotic syndrome. Aims The pathogenic steps leading to primary FSGS are still obscure, although evidence suggests that circulatory factor(s) are involved in the onset of disease. Results Recent technical advances allow the analysis of mi RNA expression in tissues and body fluids, leading to reports of mi RNAs involved in the molecular mechanisms of FSGS-aetiopathogenesis. Moreover, investigations have also highlighted mi RNAs that might serve as biomarkers for primary FSGS. Discussion/Conclusions The aim of this review was to summarize reports showing a direct relation between mi RNAs and primary FSGS. In addition, the impact of identified mi RNAs on treatment response, prediction of the disease onset as well as the regulation in different disease activities is summarized. [ABSTRACT FROM AUTHOR]

Background Micro RNAs (mi RNAs) contribute to chronic kidney disease (CKD) progression via regulating mRNAs involved in renal homeostasis. However, their association with clinical outcome remains poorly understood. Materials and methods We performed mi RNA and mRNA expression profiling on renal biopsy sections by qPCR (mi RNA) and microarrays ( mRNA) in a discovery ( n = 43) and in a validation ( n = 29) cohort. mi RNAs differentiating stable and progressive cases were inversely correlated with putative target mRNAs, which were further characterized by pathway analysis using KEGG pathways. Results miR-30d, miR-140-3p, miR-532-3p, miR-194, miR-190, miR-204 and miR-206 were downregulated in progressive cases. These seven mi RNAs correlated with upregulated 29 target mRNAs involved in inflammatory response, cell-cell interaction, apoptosis and intra-cellular signalling. In particular, miR-206 and miR-532-3p were associated with distinct biological processes via the expression of their target mRNAs: Reduced expression of miR-206 in progressive disease correlated with the upregulation of target mRNAs participating in inflammatory pathways ( CCL19, CXCL1, IFNAR2, NCK2, PTK2B, PTPRC, RASGRP1 and TNFRSF25). Progressive cases also showed a lower expression of miR-532-3p and an increased expression of target transcripts involved in apoptosis pathways ( MAP3K14, TNFRSF10B/ TRAIL-R2, TRADD and TRAF2). In the validation cohort, we confirmed the decreased expression of miR-206 and miR-532-3p, and the inverse correlation of these mi RNAs with the expression of nine of the 12 target genes. The levels of the identified mi RNAs and the target mRNAs correlated with clinical parameters and histological damage indices. Conclusions These results suggest the involvement of specific mi RNAs and mRNAs in biological pathways associated with the progression of CKD. [ABSTRACT FROM AUTHOR]

Background Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are potentially life-threatening disorders. Materials and methods Even though immunosuppressive therapy improves the prognosis, adverse events, either attributable to persistent disease activity or side effects of treatment remain a challenge. Infectious complications are the leading cause of death in the first year after diagnosis and a major cause of morbidity and mortality thereafter. Results Their incidence in clinical trials varies considerably but opportunistic and life-threatening infections, such as Pneumocystis jirovecii pneumonia or systemic cytomegalovirus infections, are frequent and thus predisposing/risk factors need to be defined. Pneumocystis jirovecii pneumonia has been associated with a lymphocyte count below 300/mm3. Additionally, besides the aggressiveness of the immunosuppressive regimen administered (especially the cumulative dose of steroids and cyclophosphamide), an elevated serum creatinine or dialysis dependency, older age and pulmonary involvement increase the rate of infectious complications. Conclusions We suggest to routinely prescribe trimethoprim-sulfamethoxazole or antimicrobial agents such as pentamidine in case of intolerance or contraindication in the early phase of induction therapy irrespective of the immunosuppressive strategy used and to continue therapy, together with other targeted measures (antiviral, antimycotic or antibiotic) in the presence of risk factors for a prolonged period of time. Finally, there is an urgent need to standardize the reporting of infectious complications in clinical trials to enable comparing the adverse event spectrum of distinct treatment approaches more appropriately. [ABSTRACT FROM AUTHOR]