Investigation Into the Effects of Intra-Articular Steroid on Post-Traumatic Osteoarthritis in Distal Radius Fractures: A Randomized Controlled Pilot Study.

PURPOSE: The aim of this prospective, randomized, controlled, double-blinded pilot study was to determine the rates of post-traumatic osteoarthritis and assess joint space width in the presence or absence of a single intra-articular injection of corticosteroid after an acute, intra-articular distal radius fracture (DRF). METHODS: Forty patients received a single, intra-articular, radiocarpal joint injection of 4 mg of dexamethasone (DEX) (n = 19) or normal saline placebo (n = 21) within 2 weeks of a surgically or nonsurgically treated intra-articular DRF. The primary outcome measure was minimum radiocarpal joint space width (mJSW) on noncontrast computed tomography scans at 2 years postinjection. Secondary outcomes were obtained at 3 months, 6 months, 1 year, and 2 years postinjection and included Disabilities of the Arm, Shoulder, and Hand; Michigan Hand Questionnaire; Patient-Rated Wrist Evaluation; wrist range of motion; and grip strength. RESULTS: At 2-year follow-up, there was no difference in mean mJSW between the DEX group (2.2 mm; standard deviation, 0.6; range, 1.4-3.2) and the placebo group (2.3 mm; standard deviation, 0.7; range, 0.9-3.9). Further, there were no differences in any secondary outcome measures at any postinjection follow-up interval. CONCLUSIONS: Radiocarpal joint injection of corticosteroid within 2 weeks of an intra-articular DRF does not appear to affect the development of post-traumatic osteoarthritis within 2 years follow-up in a small pilot cohort. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Porous Tantalum Tibial Metaphyseal Cones in Revision Total Knee Arthroplasty: Excellent 10-Year Survivorship.

BACKGROUND: Highly porous metal tibial metaphyseal cones (TMCs) are commonly utilized in revision total knee arthroplasty (TKA) to address bone loss and obtain biologic fixation. Mid-term (5 to 10 year) studies have previously demonstrated excellent survivorship and high rates of osseointegration, but longer-term studies are lacking. We aimed to assess long-term (≥ 10 year) implant survivorship, complications, and clinical and radiographic outcomes after revision TKA with TMCs. METHODS: Between 2004 and 2011, 228 revision TKAs utilizing porous tantalum TMCs with stemmed tibial components were performed at a single institution and were retrospectively reviewed. The mean age at revision was 65 years, the mean body mass index was 33, and 52% were women. Implant survivorship, complications, and clinical and radiographic outcomes were assessed. The mean follow-up was 6.3 years. RESULTS: The 10-year survivorship free of aseptic loosening leading to TMC removal was 97%, free of any TMC removal was 88%, free of any re-revision was 66%, and free of any reoperation was 58%. The most common indications for re-revision were periprosthetic joint infection, instability, and aseptic femoral component loosening. The 10-year nonoperative complication rate was 24%. The mean Knee Society scores increased from 38 preoperatively to 69 at 10 years. There were 8 knees that had evidence of partial, progressive tibial radiolucencies at 10 years. CONCLUSIONS: Porous tantalum TMCs demonstrated persistently durable longer-term survivorship with a low rate of implant removal. The rare implant removals for component loosening or instability were offset by those required for periprosthetic joint infection, which accounted for 80% of cone removals. Porous tantalum TMCs provide an extremely reliable tool to address tibial bone loss and achieve durable long-term fixation in revision TKA. LEVEL OF EVIDENCE: IV.

Surgical Approach and Body Mass Index Impact Risk of Wound Complications Following Total Hip Arthroplasty.

BACKGROUND: Previous studies have suggested that wound complications may differ by surgical approach after total hip arthroplasty (THA), with particular attention toward the direct anterior approach (DAA). However, there is a paucity of data documenting wound complication rates by surgical approach and the impact of concomitant patient factors, namely body mass index (BMI). This investigation sought to determine the rates of wound complications by surgical approach and identify BMI thresholds that portend differential risk. METHODS: This multicenter study retrospectively evaluated all primary THA patients from 2010 to 2023. Patients were classified by skin incision as having a laterally based approach (posterior or lateral approach) or DAA (longitudinal incision). We identified 17,111 patients who had 11,585 laterally based (68%) and 5,526 (32%) DAA THAs. The mean age was 65 years (range, 18 to 100), 8,945 patients (52%) were women, and the mean BMI was 30 (range, 14 to 79). Logistic regression and cut-point analyses were performed to identify an optimal BMI cutoff, overall and by approach, with respect to the risk of wound complications at 90 days. RESULTS: The 90-day risk of wound complications was higher in the DAA group versus the laterally based group, with an absolute risk of 3.6% versus 2.6% and a multivariable adjusted odds ratio of 1.5 (P < .001). Cut-point analyses demonstrated that the risk of wound complications increased steadily for both approaches, but most markedly above a BMI of 33. CONCLUSIONS: Wound complications were higher after longitudinal incision DAA THA compared to laterally based approaches, with a 1% higher absolute risk and an adjusted odds ratio of 1.5. Furthermore, BMI was an independent risk factor for wound complications regardless of surgical approach, with an optimal cut-point BMI of 33 for both approaches. These data can be used by surgeons to help consider the risks and benefits of approach selection. LEVEL OF EVIDENCE: Level III.

The Chitranjan S. Ranawat Award: Manipulation Under Anesthesia to Treat Postoperative Stiffness After Total Knee Arthroplasty: A Multicenter Randomized Clinical Trial.

BACKGROUND: Manipulation under anesthesia (MUA) occurs in 4% of patients after total knee arthroplasty (TKA). Anti-inflammatory medications may target arthrofibrosis pathogenesis, but the data are limited. This multicenter randomized clinical trial investigated the effect of adjuvant anti-inflammatory medications with MUA and physical therapy on range of motion (ROM) and outcomes. METHODS: There were 124 patients (124 TKAs) who developed stiffness after primary TKA for osteoarthritis enrolled across 15 institutions. All received MUA when ROM was < 90° at 4 to 12 weeks postoperatively. Randomization proceeded via a permuted block design. Controls received MUA and physical therapy, while the treatment group also received one dose of pre-MUA intravenous dexamethasone (8 mg) and 14 days of oral celecoxib (200 mg). The ROM and clinical outcomes were assessed at 6 weeks and 1 year. This trial was registered with ClinicalTrials.gov. RESULTS: The ROM significantly improved a mean of 46° from a pre-MUA ROM of 72 to 118° immediately after MUA (P < .001). The ROM was similar between the treatment and control groups at 6 weeks following MUA (101 versus 99°, respectively; P = .35) and at one year following MUA (108 versus 108°, respectively; P = .98). Clinical outcomes were similar at both end points. CONCLUSIONS: In this multicenter randomized clinical trial, the addition of intravenous dexamethasone and a short course of oral celecoxib after MUA did not improve ROM or outcomes. However, MUA provided a mean ROM improvement of 46° immediately, 28° at 6 weeks, and 37° at 1 year. Further investigation in regards to dosing, duration, and route of administration of anti-inflammatory medications remains warranted. LEVEL OF EVIDENCE: Level 1, RCT.

Propensity Scores: Confounder Adjustment When Comparing Nonrandomized Groups in Orthopaedic Surgery.

Many studies in arthroplasty research are based on nonrandomized, retrospective, registry-based cohorts. In these types of studies, patients belonging to different treatment or exposure groups often differ with respect to patient characteristics, medical histories, surgical indications, or other factors. Consequently, comparisons of nonrandomized groups are often subject to treatment selection bias and confounding. Propensity scores can be used to balance cohort characteristics, thus helping to minimize potential bias and confounding. This article explains how propensity scores are created and describes multiple ways in which they can be applied in the analysis of nonrandomized studies. Please visit the following (https://www.youtube.com/watch?v=sqgxl_nZWS4&t=3s) for a video that explains the highlights of the paper in practical terms.

How to Distinguish Correlation From Causation in Orthopaedic Research.

Correlations in observational studies are commonly misinterpreted as causation. Although correlation is necessary to establish a causal relationship between two variables, correlations may also arise due to chance, reverse causality, or confounding. There are several methods available to orthopaedic researchers to determine whether the observed correlations are causal. These methods depend on the key components of the study including, but not limited to, study design and data availability on confounders. In this article, we illustrate the main concepts surrounding correlation and causation using intuitive real-world examples from the orthopaedic literature. Please visit the following https://www.youtube.com/watch?v=WW7pFudZbHA&t=52s for a video that explains the highlights of the paper in practical terms.

Nuts and Bolts of Patient-Reported Outcomes in Orthopaedics.

Patient-reported outcomes (PROs) are commonly used in orthopaedic clinical practice, comparative effectiveness research (CER), and label claims. In this paper, we provide an overview of PROs, their development, validation, and use in orthopaedic research with examples and conclude with practical guidelines for researchers and reviewers. We discuss considerations for conceptual framework, validity, reliability, factor analysis, and measurement of change with Knee Injury and Osteoarthritis Outcome score (KOOS), as an example. We also describe advantages of instruments developed based on item response theory and statistical analyses for data collected using PRO measures. Please visit the following (https://www.youtube.com/watch?v=4p-DtZgUHOA&t=354s) for a video that explains the highlights of the paper in practical terms.

How to Develop and Validate Prediction Models for Orthopedic Outcomes.

Prediction models are common in medicine for predicting outcomes such as mortality, complications, or response to treatment. Despite the growing interest in these models in arthroplasty (and orthopaedics in general), few have been adopted in clinical practice. If robustly built and validated, prediction models can be excellent tools to support surgical decision making. In this paper, we provide an overview of the statistical concepts surrounding prediction models and outline practical steps for prediction model development and validation in arthroplasty research. Please visit the followinghttps://www.youtube.com/watch?v=9Yrit23Rkicfor a video that explains the highlights of the paper in practical terms.

Primary Total Hip Arthroplasty in Dialysis-Dependent Patients: 35% Mortality at 5 years.

BACKGROUND: Limited knowledge exists on contemporary results of primary total hip arthroplasty (THA) in dialysis-dependent patients. We sought to analyze the mortality rates and cumulative incidences of any revision or reoperation in dialysis-dependent patients undergoing primary THAs. METHODS: We identified 24 dialysis-dependent patients who underwent 28 primary THAs between 2000 and 2019 using our institutional total joint registry. Mean age was 57 years (range, 32 to 86), with 43% being women and mean body mass index was 31 (range, 20 to 50). The leading cause for dialysis was diabetic nephropathy (18%). The mean preoperative creatinine and glomerular filtration rate were 6 mg/dL and 13 mL/min, respectively. Kaplan-Meier survivorship methods and a competing risk analysis using death as the competing risk were performed. The mean follow-up was 7 years (range, 2 to 15). RESULTS: The 5-year survivorship free from death was 65%. The 5-year cumulative incidence of any revision was 8%. There were a total of 3 revisions as follows: 2 for aseptic loosening of the femoral component and one for a Vancouver B2 fracture. The 5-year cumulative incidence of any reoperation was 19%. There were 3 additional reoperations, and all were irrigation and debridement. Postoperative creatinine and glomerular filtration rate were 6 mg/dL and 15 mL/min, respectively. At a mean of 2 years after THA, 25% successfully received a renal transplant. CONCLUSIONS: Dialysis-dependent patients undergoing primary THAs had high 5-year mortality (35%) but an acceptably low cumulative incidence of any revision. While renal metrics remained consistent after THA, only one in 4 patients underwent successful renal transplant. LEVEL OF EVIDENCE: IV.

John N. Insall Award: Randomized Clinical Trial of Cementless Versus Cemented Tibial Components: Durable and Reliable at a Mean 10-Years Follow-Up.

BACKGROUND: Cementless fixation is gaining popularity for primary total knee arthroplasties (TKAs). The prior 5-year results of our randomized clinical trial that included 3 different tibial designs found minimal differences. The purpose of the current study was to investigate the 10-year results in the same cohort. METHODS: Between 2003 and 2006, 389 primary TKAs were randomized: traditional modular cemented tibia (135); hybrid (cemented baseplate with uncemented pegs) monoblock tibia (128); and cementless monoblock tibia (126). Implant survivorships, radiographs, and clinical outcomes were analyzed. Mean age at TKA was 68 years (range, 41 to 85), 46% were male, and mean body mass index was 32 (range, 21 to 59). The mean follow-up was 10 years. RESULTS: The 10-year survivorship free of any revision was similar between the hybrid monoblock and cementless monoblock groups at 96%, but lower (89%) for the traditional modular cemented tibia (P = .05). The traditional modular cemented tibia group had significantly more revisions for aseptic tibial loosening than the other 2 groups (7 versus 0%) at 10 years (P = .003). The traditional modular cemented tibia group had significantly more nonprogressive radiolucent lines than the hybrid and cementless monoblock groups (24, 12, and 9%, respectively). Clinical outcomes were similar and excellent between all 3 groups. CONCLUSION: Cementless and hybrid monoblock tibial components have excellent implant survivorship (96%) with no cases of aseptic tibial loosening to date. The traditional cemented modular tibial group had a 7% cumulative incidence of aseptic loosening at 10 years. LEVEL OF EVIDENCE: Level I, Prospective Randomized Control Trial.

Extensively Porous-Coated Stems Demonstrate Excellent Long-Term Survivorship in Revision Total Hip Arthroplasty.

BACKGROUND: Extensively porous-coated cylindrical stems have demonstrated excellent results in revision total hip arthroplasties (THAs). However, most studies are midterm follow-ups and of modest cohort size. This study aimed to evaluate long-term outcomes of a large series of extensively porous-coated stems. METHODS: From 1992 to 2003, 925 extensively porous-coated stems were utilized in revision THAs at a single institution. The mean age was 65 years, and 57% of patients were males. Harris hip scores were calculated, and clinical outcomes were assessed. Radiographic assessment for stem fixation was categorized as either in-grown, fibrous stable, or loose according to Engh criteria. Risk analysis used Cox proportional hazard method. The mean follow-up was 13 years. RESULTS: Mean Harris hip scores improved from 56 to 80 at the last follow-up (P < .001). Fifty-three femoral stems (5%) were rerevised: 26 for aseptic loosening, 11 for stem fractures, 8 for infection, 5 for periprosthetic femoral fractures, and 3 for dislocation. Cumulative incidence of aseptic femoral loosening and femoral rerevision for any reason were 3% and 6.4% at 20 years, respectively. Nine of eleven stem fractures occurred with 10.5-13.5 mm diameters (mean 6 years). Radiographic review of unrevized stems demonstrated 94% bone-ingrown. Demographics, femoral bone loss, stem diameter, and length were not predictors of femoral rerevision. CONCLUSION: In this large series of revision THAs using a single extensively porous-coated stem design, the cumulative incidence of rerevision for aseptic femoral loosening was 3% at 20 years. These data confirm the durability of this stem in femoral revision, providing a long-term benchmark for newer uncemented revision stems. LEVEL OF EVIDENCE: Level IV, retrospective study.

Spinal Versus General Anesthesia in Contemporary Revision Total Knee Arthroplasties.

BACKGROUND: Interest in spinal anesthesia utilization in revision total knee arthroplasties (TKAs) is rising. This study investigated the pain control, length of stay (LOS), and complications associated with spinal versus general anesthesia in a single institution series of revision TKAs. METHODS: We identified 3,711 revision TKAs (3,495 patients) from 2001 to 2016 using our institutional total joint registry. There were 66% who had general anesthesia and 34% who had spinal anesthesia. Mean age, sex, and BMI were similar between groups at 67 years, 53% women, and 32, respectively. Data were analyzed using inverse probability of treatment weighted models based on propensity scores that accounted for patient and operative factors. Mean follow-up was 6 years (range, 2 to 17). RESULTS: Patients treated with spinal anesthesia required fewer postoperative oral morphine equivalents (OMEs) (P < .0001) and had lower numeric pain rating scale scores (P < .001). Spinal anesthesia was associated with shorter LOS (4.0 versus 4.6 days; P < .0001), less cases of altered mental status (AMS; Odds Ratio (OR) 2.0, P = .004), less intensive care unit (ICU) admissions (OR 1.6, P = .02), fewer re-revisions (OR 1.7, P < .001), and less reoperations (OR 1.4, P < .001). There was no difference in the incidence of VTE (P = .82), 30-day readmissions (P = .06), or 90-day readmissions (P = .18) between anesthetic techniques. CONCLUSION: We found that spinal anesthesia for revision TKAs was associated with significantly lower pain scores, reduced OME requirements, and decreased LOS. Furthermore, spinal anesthesia was associated with fewer cases of AMS, ICU admissions, and re-revisions even after accounting for numerous patient and operative factors. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Study.

Frank Stinchfield Award: Creation of a Patient-Specific Total Hip Arthroplasty Periprosthetic Fracture Risk Calculator.

BACKGROUND: Many risk factors have been described for periprosthetic femur fracture (PPFFx) following total hip arthroplasty (THA), yet a patient-specific risk assessment tool remains elusive. The purpose of this study was to develop a high-dimensional, patient-specific risk-stratification nomogram that allows dynamic risk modification based on operative decisions. METHODS: We evaluated 16,696 primary nononcologic THAs performed between 1998 and 2018. During a mean 6-year follow-up, 558 patients (3.3%) sustained a PPFFx. Patients were characterized by individual natural language processing-assisted chart review on nonmodifiable factors (demographics, THA indication, and comorbidities), and modifiable operative decisions (femoral fixation [cemented/uncemented], surgical approach [direct anterior, lateral, and posterior], and implant type [collared/collarless]). Multivariable Cox regression models and nomograms were developed with PPFFx as a binary outcome at 90 days, 1 year, and 5 years, postoperatively. RESULTS: Patient-specific PPFFx risk based on comorbid profile was wide-ranging from 0.4-18% at 90 days, 0.4%-20% at 1 year, and 0.5%-25% at 5 years. Among 18 evaluated patient factors, 7 were retained in multivariable analyses. The 4 significant nonmodifiable factors included the following: women (hazard ratio (HR) = 1.6), older age (HR = 1.2 per 10 years), diagnosis of osteoporosis or use of osteoporosis medications (HR = 1.7), and indication for surgery other than osteoarthritis (HR = 2.2 for fracture, HR = 1.8 for inflammatory arthritis, HR = 1.7 for osteonecrosis). The 3 modifiable surgical factors were included as follows: uncemented femoral fixation (HR = 2.5), collarless femoral implants (HR = 1.3), and surgical approach other than direct anterior (lateral HR = 2.9, posterior HR = 1.9). CONCLUSION: This patient-specific PPFFx risk calculator demonstrated a wide-ranging risk based on comorbid profile and enables surgeons to quantify risk mitigation based on operative decisions. LEVEL OF EVIDENCE: Level III, Prognostic.

P-Values and Power in Orthopedic Research: Myths and Reality.

The results of statistical tests in orthopedic studies are typically reported using P-values. If a P-value is smaller than the pre-determined level of significance (eg, < .05), the null hypothesis is rejected in support of the alternative. This automaticity in interpreting statistical results without consideration of the power of the study has been denounced over the years by statisticians, since it can potentially lead to misinterpretation of the study conclusions. In this paper, we review fundamental misconceptions and misinterpretations of P-values and power, along with their connection with confidence intervals, and we provide guidelines to orthopedic researchers for evaluating and reporting study results. We provide real-world orthopedic examples to illustrate the main concepts. Please visit the followinghttps://youtu.be/bdPU4luYmF0for videos that explain the highlights of the paper in practical terms.

Study Types in Orthopaedics Research: Is My Study Design Appropriate for the Research Question?

When performing orthopaedic clinical research, alternative study designs can be more appropriate depending on the research question, availability of data, and feasibility. The most common observational study designs in total joint arthroplasty research are cohort and cross-sectional studies. This article describes methodological considerations for different study designs with examples from the total joint arthroplasty literature. We highlight the advantages and feasibility of experimental and observational study designs using real-world examples. We illustrate how to avoid common mistakes, such as incorrect labeling of matched cohort studies as case-control studies. We further guide investigators through a step-by-step design of a case-control study. We conclude with considerations when choosing between alternative study designs. Please visit the followinghttps://youtu.be/Zvce61cMYi8for videos that explain the highlights of the article in practical terms.

Avoiding Systematic Bias in Orthopedics Research Through Informed Variable Selection: A Discussion of Confounders, Mediators, and Colliders.

There are 3 common variable types in orthopedic research-confounders, colliders, and mediators. All 3 types of variables are associated with both the exposure (eg, surgery type, implant type, body mass index) and outcome (eg, complications, revision surgery) but differ in their temporal ordering. To reduce systematic bias, the decision to include or exclude a variable in an analysis should be based on the variable's relationship with the exposure and outcome for each research question. In this article, we define 3 types of variables with case examples from orthopedic research. Please visit the followinghttps://youtu.be/V-grpgB1ShQfor videos that explain the highlights of the article in practical terms.

Measurement Error and Misclassification in Orthopedics: When Study Subjects are Categorized in the Wrong Exposure or Outcome Groups.

Datasets available for orthopedic research often contain measurement and misclassification errors due to errors in data collection or missing data. These errors can have different effects on the study results. Measurement error refers to inaccurate measurement of continuous variables (eg, body mass index), whereas misclassification refers to assigning subjects in the wrong exposure and/or outcome groups (eg, obesity categories). Misclassification of any type can result in underestimation or overestimation of the association between exposures and outcomes. In this article, we offer practical guidelines to avoid, identify, and account for measurement and misclassification errors. We also provide an illustrative example on how to perform a validation study to address misclassification based on real-world orthopedic data. Please visit the followinghttps://youtu.be/9-ekW2NnWrsor videos that explain the highlights of the article in practical terms.

Changing Surgical Approach From Primary to Revision Total Hip Arthroplasty Is Not Associated With Increased Risk of Dislocation or Re-Revisions.

BACKGROUND: No prior studies have examined outcomes based on approach concordance between primary and revision total hip arthroplasty (THA). There is theoretical concern that performing surgery through multiple planes could potentiate dislocation risk. This study aimed to assess the impact of utilizing concordant vs discordant surgical approaches between primary and revision THA on incidence of dislocation, re-revision, reoperation, and nonoperative complications. METHODS: Between 2000 and 2018, 705 revision THAs were retrospectively identified in patients who underwent primary THA at the same academic center. Surgical approach was determined for primary and revision THA from operative notes with dislocations, re-revisions, reoperations, and complications determined from our total joint registry. Complication rates were compared between those with concordant and discordant surgical approaches. Mean age was 65 years, 50% were female, mean body mass index was 31 kg/m2, and mean follow-up was 4 years. RESULTS: Surgical approach discordance occurred in 97 cases (14%), which was more frequent when the direct anterior approach was used for primary THA (72%, P < .001) compared to lateral (12%) or posterior (10%) approaches. There were no statistically significant differences in the incidence of dislocations, re-revisions, reoperations, and nonoperative complications among those with concordant and discordant approaches for the overall cohort and when analyzed by primary approach (P > .05 for all). CONCLUSION: Comparable dislocation and complication rates were observed among revision THAs with concordant and discordant approaches between primary and revision THA. These data provide reassurance that changing vs maintaining the surgical approach from primary to revision THA does not significantly increase dislocation or re-revision risk. LEVEL OF EVIDENCE: IV.

Analysis of patient characteristics and outcomes related to distance traveled to a tertiary center for primary reverse shoulder arthroplasty.

INTRODUCTION: The reasons for referral and travel patterns are lacking for patients undergoing reverse shoulder arthroplasty (RSA). The purpose of this study was to compare comorbidities, surgical time, cost and complications between local and distant primary RSA patients. METHODS: Between 2007 and 2015, 1,666 primary RSAs were performed at our institution. Patients were divided into two cohorts, local patients (from within Olmstead county and surrounding counties, 492 RSAs) and those from a distance (1,174 RSAs). RESULTS: Local patients were older (74 vs 71 years, p < .001), more likely to have RSA for fracture, had a higher Charlson comorbidity score (3.8 vs 3.2, p < .001) and longer hospital stays (2.0 vs 1.8 days, p < 0.001) compared to referred patients. Referral patients required longer operative times (95 vs 88 min, p = .002), had higher hospitalization costs ($19,101 vs $18,735, p < .001), and had a higher rate of prior surgery (32% vs 24%, p < .001). There were no differences between cohorts regarding complications or need for reoperation. CONCLUSIONS: Patients traveling from a distance to undergo primary RSA had longer operative times and were more likely to have had prior surgery than local patients. This may demonstrate the referral bias seen at large academic centers and should be considered when reviewing RSA outcomes, hospital performance, and calculating insurance reimbursement. LEVEL OF EVIDENCE: Level IV.

Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. METHODS: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as high as the rate in the control population. The risk of progression without accounting for death due to competing causes was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) - was associated with a risk of progression at 20 years of 55%, as compared with 41% among patients who had one adverse risk factor and 19% among patients who had neither risk factor. Among patients with non-IgM MGUS, the risk of progression at 20 years was 30% among those who had the two risk factors, 20% among those who had one risk factor, and 7% among those who had neither risk factor. Patients with MGUS had shorter survival than was expected in the control population of Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001). CONCLUSIONS: Significant differences were noted in the risk of progression between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was shorter among patients with MGUS than was expected in a matched control population. (Funded by the National Cancer Institute.).