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Background: Kidney failure is an established risk factor for tuberculosis (TB), but little is known about TB risk in people with chronic kidney disease (CKD) who have not initiated kidney replacement therapy (CKD without kidney failure). Our primary objective was to estimate the pooled relative risk of TB disease in people with CKD stages 3-5 without kidney failure compared with people without CKD. Our secondary objectives were to estimate the pooled relative risk of TB disease for all stages of CKD without kidney failure (stages 1-5) and by each CKD stage., Methods: This review was prospectively registered (PROSPERO CRD42022342499). We systematically searched MEDLINE, Embase, and Cochrane databases for studies published between 1970 and 2022. We included original observational research estimating TB risk among people with CKD without kidney failure. Random-effects meta-analysis was performed to obtain the pooled relative risk., Results: Of the 6915 unique articles identified, data from 5 studies were included. The estimated pooled risk of TB was 57% higher in people with CKD stages 3-5 than in people without CKD (adjusted hazard ratio: 1.57; 95% CI: 1.22-2.03; I2 = 88%). When stratified by CKD stage, the pooled rate of TB was highest in stages 4-5 (incidence rate ratio: 3.63; 95% CI: 2.25-5.86; I2 = 89%)., Conclusions: People with CKD without kidney failure have an increased relative risk of TB. Further research and modeling are required to understand the risks, benefits, and CKD cutoffs for screening people for TB with CKD prior to kidney replacement therapy., Competing Interests: Potential conflicts of interest . V. J. C. reports participation on a Data and Safety Monitoring Board (DSMB) (unrelated to this manuscript) and a role as co-chair of the British Columbia Provincial TB Committee. J. C. J. reports research grants from the US Department of Health and Human Services, Canadian Institutes of Health Research, TB Vets, and the BC Lung Foundation (paid to institution) and a contract with the Michael Smith Foundation for health research (personal salary). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue disease (CTD) with substantial variability in prevalence and outcomes reported across CTD subtypes. This systematic review summarises the prevalence, risk factors and ILD patterns on chest computed tomography of CTD-ILD., Methods: A comprehensive search was performed in Medline and Embase to identify eligible studies. Meta-analyses were completed using a random effects model to determine the pooled prevalence of CTD-ILD and ILD patterns., Results: 11 582 unique citations were identified with 237 articles included. Pooled prevalence of ILD was 11% in rheumatoid arthritis (95% CI 7-15%), 47% in systemic sclerosis (44-50%), 41% in idiopathic inflammatory myositis (33-50%), 17% in primary Sjögren's syndrome (12-21%), 56% in mixed connective tissue disease (39-72%) and 6% in systemic lupus erythematosus (3-10%). Usual interstitial pneumonia was the most prevalent ILD pattern in rheumatoid arthritis (pooled prevalence of 46%), while nonspecific interstitial pneumonia was the most common ILD pattern in all other CTD subtypes (pooled prevalence range 27-76%). Across all CTDs with available data, positive serology and higher inflammatory markers were risk factors for development of ILD., Discussion: We identified substantial variability in ILD across CTD subtypes suggesting that CTD-ILD is too heterogenous to be considered a single entity., Competing Interests: Conflict of interest: G.M. Joy has nothing to disclose. Conflict of interest: O.A. Arbiv has nothing to disclose. Conflict of interest: C.K. Wong has nothing to disclose. Conflict of interest: S.D. Lok has received fees, honoraria, or contracts from University of Saskatchewan CoM, Boehringer Ingelheim, Roche, and AstraZeneca unrelated to this work. Conflict of interest: N.A. Adderley has nothing to disclose. Conflict of interest: K.M. Dobosz has nothing to disclose. Conflict of interest: K.A. Johannson has received fees, honoraria, or contracts from Three Lakes Foundation, Chest Foundation, University of Calgary CSM, University Hospital Foundation, Boehringer Ingelheim, Hoffman-La Roche Ltd, Pliant Therapeutics, Thyron SAB, and PFOX trial all unrelated to this work. Conflict of interest: C.J. Ryerson has received fees, honoraria, or contracts from Boehringer Ingelheim, Hoffman-La Roche Ltd, Pliant Therapeutics, AstraZeneca, Veracyte, Ensho, Cipla Ltd, all unrelated to this work., (Copyright ©The authors 2023.)

Background: There is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens., Methods: We searched MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews and clinicaltrials.gov for prospective studies comparing daily therapy with HDRs to SDRs. Rifamycins included rifampicin, rifapentine and rifabutin. Our primary outcome was the rate of severe adverse events (SAEs), with secondary outcomes of death, all adverse events, SAE by organ and efficacy outcomes of 2-month culture conversion and relapse. This study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020142519)., Results: We identified 9057 articles and included 13 studies with 6168 participants contributing 7930 person-years (PY) of follow-up (HDR: 3535 participants, 4387 PY; SDR: 2633 participants, 3543 PY). We found no significant difference in the pooled incidence rate ratio (IRR) of SAE between HDR and SDR (IRR 1.00, 95% CI 0.82 to 1.23, I 2 =41%). There was no significant difference when analysis was limited to SAE possibly, probably or likely medication-related (IRR 1.07, 95% CI 0.82 to 1.41, I 2 =0%); studies with low risk of bias (IRR 0.98, 95% CI 0.79 to 1.20, I 2 =44%); or studies using rifampicin (IRR 1.00, 95% CI 0. 0.75-1.32, I 2 =38%). No significant differences were noted in pooled outcomes of death, 2-month culture conversion and relapse., Conclusions: HDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Classification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment of treatment. Unfortunately, 30% of patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified with a specific syndromic diagnosis. We analyzed the outcome of hematopoietic stem cell transplantation (HSCT) in unclassified IBMFSs (uIBMFSs) and the factors associated with outcome. Twenty-two patients with uIBMFSs and 70 patients with classified IBMFSs underwent HSCT. Five-year overall survival of uIBMFS patients after HSCT was inferior to that of patients with classified IBMFSs (56% vs 76.5%). The outcome of patients with uIBMFS who received cord blood was significantly lower than that of patients who received other stem cell sources (14.8% vs 90.9%). Engraftment failure was higher among patients with uIBMFS who received cord blood than those who received bone marrow. None of the following factors were significantly associated with poor survival: transfusion load, transplant indication, the intensity of conditioning regimen, human leukocyte antigen-identical sibling/alternative donor. We suggest that identifying the genetic diagnosis is essential to modulate the transplant procedure including conditioning agents and stem cell sources for better outcome and the standard cord blood transplantation (CBT) should be avoided in uIBMFS., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diamond-Blackfan anemia (DBA) features hypoplastic anemia and congenital malformations, largely caused by mutations in various ribosomal proteins. The aim of this study was to characterize the spectrum of genetic lesions causing DBA and identify genotypes that correlate with phenotypes of clinical significance. Seventy-four patients with DBA from across Canada were included. Nucleotide-level mutations or large deletions were identified in 10 ribosomal genes in 45 cases. The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups. Patients with RPS19 mutations, however, were more likely to maintain long-term corticosteroid response without requirement for further chronic transfusions. Conversely, patients with RPL11 mutations were less likely to need chronic treatment. Birth defects, including cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations, also varied among the various genetic groups. Patients with RPS19 mutations had the fewest number of defects, while patients with RPL5 had the greatest number of birth defects. This is the first study to show differences between DBA genetic groups with regards to treatment. Previously unreported differences in the rate and types of birth defects were also identified. These data allow better patient counseling, a more personalized monitoring plan, and may also suggest differential functions of DBA genes on ribosome and extra-ribosomal functions., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)