Publications by authors named "J L Stone"

3,685 Publications

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Validation of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis as the Cause of End-Stage Renal Disease in the US Renal Data System.

ACR Open Rheumatol 2021 Oct 12. Epub 2021 Oct 12.

Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: The objective of this study was to validate the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS).

Methods: We identified patients with ESRD in the Mass General Brigham (MGB) health care system who were enrolled in the USRDS. The health records of those with AAV listed as the primary cause of ESRD in the USRDS were reviewed to confirm the diagnosis and estimate positive predictive value (PPV). Sensitivity was estimated by evaluating the primary cause of ESRD listed in the USRDS for patients with ESRD due to AAV in the MGB AAV cohort.

Results: We identified 89 MGB patients with ESRD due to AAV in the USRDS. Of these, 85 cases were confirmed to be true cases of AAV (PPV = 94%). Among the patients classified as having AAV, 84 (99%) had an ANCA test, which was predominantly myeloperoxidase/P-ANCA (47 [55%]); 36 (42%) had a renal biopsy, and all biopsies were supportive of the diagnosis. The majority (81 [90%]) was identified as AAV by International Classification of Diseases Ninth Revision or International Classification of Diseases 10th Revision codes for granulomatosis with polyangiitis (446.4 or M313.1). Of the 77 MGB AAV cohort patients with ESRD who were linked to the USRDS, 41 (53%) had AAV listed as the cause of ESRD; in the remainder, ESRD was attributed to nonspecific nephritis.

Conclusion: The diagnosis of AAV as the cause of ESRD in the USRDS has a high PPV; sensitivity was moderate. These findings support the continued use of the USRDS to study ESRD due to AAV.
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http://dx.doi.org/10.1002/acr2.11359DOI Listing
October 2021

Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis.

JCI Insight 2021 Oct 7. Epub 2021 Oct 7.

Laboratory of Immunology, University of Brest, Brest, France.

Background: Little is known about the autoreactive B cells in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3 (PR3+) B cells.

Methods: Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of peripheral blood mononuclear cells from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase (MPO)-AAV, and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3+ B cells (total and subsets).

Results: The frequency of PR3+ B cells among circulating B cells was higher in PR3-AAV (4.77% [3.98%-6.01%]), than in MPO-AAV (3.16% [2.51%-5.22%]), and in AAV compared to HCs (1.67% [1.27%-2.16%], p<0.001 for all comparisons), implying a defective central tolerance checkpoint in patients. Only PBMC from PR3-AAV contained PR3+ B cells capable of secreting PR3-ANCA IgG in vitro, proving to be functionally distinct from those of MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3+ memory B cells accumulating through the maturation process in PR3-AAV patients. PR3+ B cells were enriched in the memory B cell compartment of PR3-AAV, and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3+ B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, p<0.05) and complete remission (p<0.001).

Conclusions: This study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients in PR3-AAV, elucidating the selection process of autoreactive B cells.
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http://dx.doi.org/10.1172/jci.insight.150999DOI Listing
October 2021

Prevalence of Gastroduodenal Polyps in Children With Familial Adenomatous Polyposis.

J Can Assoc Gastroenterol 2021 Oct 24;4(5):e101-e109. Epub 2020 Dec 24.

Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.

Objective: To assess the prevalence of upper gastrointestinal adenomatous polyps in a cohort of pediatric familial adenomatous polyposis (FAP) patients to determine if early screening is warranted.

Study Design: All 11 pediatric FAP patients diagnosed in Manitoba between January 2012 and December 2019 were recruited. Patient records were examined and data on age of diagnosis, gene mutation, age of first screening endoscopy, number of endoscopies, number of gastric and colonic polyps, associated pathology, medications, symptoms and FAP-related surgeries were extracted and descriptive statistics reported.

Results: A total of 11 children were diagnosed with FAP over the study period with a mean age at diagnosis of 6.3 ± 3.2 years with 72.3% males and median follow-up of 4.8 years. The mean age at first gastroscopy was 10.9 ± 2.9 years and 10.8 ± 3.0 years at colonoscopy. Eight patients (72%) had upper gastrointestinal polyps, with adenomatous changes seen in seven of them on pathology. No patients had invasive carcinoma or high-grade dysplasia. All patients developed tubular adenomas on colorectal polyp pathology. Four (36%) patients underwent surgical colectomy.

Conclusions: Early-onset upper gastrointestinal adenomatous polyps in a pediatric FAP are common. Our study provides further data to support consideration of further, large-scale research into the benefit of early endoscopic screening for upper gastrointestinal malignancy in FAP patients.
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http://dx.doi.org/10.1093/jcag/gwaa040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489522PMC
October 2021

Allograft Anterior Cruciate Ligament Reconstruction in Patients aged 40 and Older: Patient Reported Outcomes and a Patient Acceptable Symptom State.

Arthroscopy 2021 Sep 30. Epub 2021 Sep 30.

Tufts Medical Center, Boston, MA.

Purpose: To evaluate patient satisfaction, re-tear rates, and patient reported outcomes (PROs) in patients aged 40 and older undergoing allograft anterior cruciate ligament reconstruction (ACLR). The secondary goal was to compare these parameters between groups of patients with intact versus failed grafts, and to evaluate these in relation to a historically reported International Knee Documentation Committee (IKDC) patient acceptable symptoms state (PASS) score.

Methods: Records of patients aged 40 and older who underwent ACLR between 2005-2016 at a single institution with a minimum 2-year follow-up were retrospectively reviewed. Patient reported satisfaction, outcome scores, and failure rates were analyzed. The rate of achieving a previously defined IKDC PASS score based on younger cohorts was reported, and an updated PASS threshold for older patients was calculated.

Results: 201 patients were included with a mean age of 48.6 years (range, 40-68) and mean follow-up of 6.2 years (range, 2.8-11.2). 182 (90.5%) patients reported satisfaction following surgery. 16 (8.0%) patients went on to fail their ACLR, 10 of which underwent revision ACLR. The median IKDC score in the intact ACLR group was 86.2, compared to 66.7 in the failure group (p<0.001). In total, 134 (72.4%) patients in the intact group achieved the historical PASS score of 75.9 on IKDC compared to only 4 (25%) in the failure group (χ2=15.396, p<0.001). An updated IKDC PASS threshold for older cohorts was calculated to be 66.7.

Conclusion: Patients aged 40 and older who underwent allograft ACLR had an 8.0% failure rate at a mean follow-up of 6 years. Graft failure in patients aged 40 and older was associated with worse PROs. The majority of patients achieved the historically reported IKDC PASS threshold. Additionally, an updated age appropriate IKDC PASS score of 66.7 was calculated to aid in future ACLR studies assessing older patients.
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http://dx.doi.org/10.1016/j.arthro.2021.09.024DOI Listing
September 2021

Association of renal transplantation with reduced risk of myocardial infarction and ischemic stroke in ANCA-associated vasculitis: An observational cohort study.

Semin Arthritis Rheum 2021 Sep 26;51(6):1180-1185. Epub 2021 Sep 26.

Clinical Epidemiology Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Mongan Institute, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Objective: Myocardial infarction and ischemic stroke are leading causes of cardiovascular (CV) morbidity and mortality in ANCA-associated vasculitis (AAV), especially for the 20% with end-stage renal disease (ESRD). We assessed the impact of renal transplantation on the risk of myocardial infarction and stroke among patients with ESRD due to AAV.

Methods: We identified patients from the United States Renal Data System with ESRD due to AAV between 2000 and 2016. We examined the association between renal transplantation and the risk of non-fatal and fatal myocardial infarction or ischemic stroke among waitlisted patients using Medicare claims and death data through 2017. We used time-varying Cox proportional hazards models with age as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for myocardial infarction and ischemic stroke events among patients who received a renal transplant compared to those who remained on the waitlist.

Results: Of 1029 waitlisted patients, 593 (58%) were transplanted over a mean of 5.7 years. There were 17 events (4.6/1,000 person-years) in the transplanted group and 40 events (13.7/1,000 person-years) in the group that remained waitlisted. A renal transplant was associated with a 78% lower risk of myocardial infarction or ischemic stroke (HR=0.22, 95% CI 0.11 to 0.47). These findings persisted across sex and age groups and when censoring patients after living donor transplantation.

Conclusions: Among AAV patients with ESRD, renal transplantation can substantially reduce the risk of myocardial infarction and ischemic stroke. Improving access to transplantation for this population may further improve outcomes.
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http://dx.doi.org/10.1016/j.semarthrit.2021.09.007DOI Listing
September 2021
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