Leung, Nelson

Introduction: Tissue biopsies are needed to establish a diagnosis of systemic AL amyloidosis. Biopsy can be obtained from an involved organ with suspected amyloid deposition (target biopsy) or from sites in which amyloid commonly deposits (surrogate biopsy). The choice of biopsy site depends on institutional and physician preference. Two commonly used sites for surrogate biopsies are abdominal fat pad and bone marrow. The present systematic review and meta-analysis aims to evaluate the diagnostic test accuracy of fat pad and bone marrow biopsies as surrogate biopsy sites in the diagnosis of AL amyloidosis. Methods: As part of the ASH AL Amyloidosis Diagnostic Guideline, we performed systematic reviews for seven prioritized PICO questions related to the screening, diagnosis and organ involvement evaluation of AL amyloidosis. We conducted electronic searches on PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception until January 2024. Two reviewers independently and in duplicate performed title and abstract screening and full text article screening on LASER AI, with conflicts resolved by a third reviewer. Studies were eligible if they included patients that had a fat pad sample or bone marrow biopsy and a target organ biopsy for suspicion of AL amyloidosis allowing for the calculation of diagnostic test accuracy measures. Diagnostic test accuracy measures of interest were sensitivity, specificity, positive and negative predictive value. Statistical analysis was performed on OpenMeta[Analyst]. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Results: After deduplication, we retrieved 29,237 studies.. 20 studies with 2955 patients reporting on bone marrow biopsy, 25 with 4702 patients on fat pad sampling were included. The pooled sensitivity for bone marrow biopsy was 55.1% (95% CI 45.8-64.0, I2 = 94%) (Certainty of evidence: Low ⨁⨁◯◯), For fat pad sampling sensitivity was 76.6% (95% CI 72.1-80.8, I2 = 84.2%) (Certainty of evidence: Moderate ⨁⨁⨁◯). Among the included studies, 1 evaluated the sensitivity of fat pad sampling and bone marrow biopsy combined and found it to be 89%. No included studies evaluated specificity for bone marrow biopsy or fat pad sample. Conclusion: Combination of fat pad and bone marrow biopsy together significantly improve sensitivity for amyloid detection compared to either fat pad sampling or bone marrow biopsy alone.

Background: Two-stage exchange arthroplasty with a high-dose antibiotic-loaded bone cement (ALBC) spacer and intravenous or oral antibiotics is the most common method of managing a periprosthetic joint infection (PJI) after a total knee arthroplasty (TKA). However, little is known about the contemporary incidence, the risk factors, and the outcomes of acute kidney injuries (AKIs) in this cohort. Methods: We identified 424 patients who had been treated with 455 ALBC spacers after resection of a PJI following a primary TKA from 2000 to 2017. The mean age at resection was 67 years, the mean body mass index (BMI) was 33 kg/m 2 , 47% of the patients were women, and 15% had preexisting chronic kidney disease (CKD). The spacers (87% nonarticulating) contained a mean of 8 g of vancomycin and 9 g of an aminoglycoside per construct (in situ for a mean of 11 weeks). Eighty-six spacers also had amphotericin B (mean, 412 mg). All of the patients were concomitantly treated with systemic antibiotics for a mean of 6 weeks. An AKI was defined as a creatinine level of ≥1.5 times the baseline or an increase of ≥0.3 mg/dL within any 48-hour period. The mean follow-up was 6 years (range, 2 to 17 years). Results: Fifty-four AKIs occurred in 52 (14%) of the 359 patients without preexisting CKD versus 32 AKIs in 29 (45%) of the 65 patients with CKD (odds ratio [OR], 5; p = 0.0001); none required acute dialysis. Overall, when the vancomycin concentration or aminoglycoside concentration was >3.6 g/batch of cement, the risk of AKI increased (OR, 1.9 and 1.8, respectively; p = 0.02 for both). Hypertension (β = 0.17; p = 0.002), perioperative hypovolemia (β = 0.28; p = 0.0001), and acute atrial fibrillation (β = 0.13; p = 0.009) were independent predictors for AKI in patients without preexisting CKD. At the last follow-up, 8 patients who had sustained an AKI had progressed to CKD, 4 of whom received dialysis. Conclusions: In our study, the largest series to date that we are aware of regarding this issue, AKI occurred in 14% of patients with normal renal function at baseline, and 2% developed CKD after undergoing a 2-stage exchange arthroplasty for a PJI after TKA. However, the risk of AKI was fivefold greater in those with preexisting CKD. The causes of acute renal blood flow impairment were independent predictors for AKI. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder requiring immediate chemotherapy. More frequently, it results from a small and/or quiescent secreting B-cell clone, is completely asymptomatic, and requires regular monitoring only, defining a monoclonal gammopathy of unknown significance (MGUS). Sometimes, although quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin or to other mechanisms. The latter situation is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. To improve early recognition and management of these small B-cell clone–related disorders, we propose to introduce the concept of monoclonal gammopathy of clinical significance (MGCS). This report identifies the spectrum of MGCSs that are classified according to mechanisms of tissue injury. It highlights the diversity of these disorders for which diagnosis and treatment are often challenging in clinical practice and require a multidisciplinary approach. Principles of management, including main diagnostic and therapeutic procedures, are also described. Importantly, efficient control of the underlying B-cell clone usually results in organ improvement. Currently, it relies mainly on chemotherapy and other anti–B-cell/plasma cell agents, which should aim at rapidly producing the best hematological response.