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92 result(s) for "Larson, Dirk R."
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Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance
MGUS affects more than 5% of persons older than 70 years and shortens survival, as compared with age-matched controls. In a long-term study involving more than 1000 patients, those with IgM MGUS had a higher rate of progression to B-cell cancer than those with IgG MGUS.
Use of Nonclonal Serum Immunoglobulin Free Light Chains to Predict Overall Survival in the General Population
To determine whether the free light chain (FLC) assay provides prognostic information relevant to the general population. After excluding persons with a known plasma cell disorder, we studied 15,859 Olmsted County, Minnesota, residents 50 years or older in whom unmasked data and samples for FLC testing were available. Baseline information was obtained between March 13, 1995, and November 21, 2003, and follow-up status and cause of death were identified through June 30, 2009. The κ and λ FLC sum (Σ FLC) was evaluated for its ability to predict overall survival. Specific causes of death were also investigated. In 158,003 person-years of follow-up, 4348 individuals died. A high Σ FLC was significantly predictive of worse overall survival; the risk ratio for death for those with the highest decile of Σ FLC (ie, ≥4.72 mg/dL) was 4.4 (95% confidence interval, 4.1-4.7) relative to the remaining study participants. Multivariate analyses demonstrated that this excess risk of death was independent of age, sex, and renal insufficiency, with a corrected risk ratio of 2.1 (95% confidence interval, 1.9-2.2). The increased mortality was not restricted to any particular cause of death because the observed-to-expected risk of death from most causes was significantly higher among those individuals with an antecedent Σ FLC of 4.72 mg/dL or higher, which is near the upper limit of normal for the test. A nonclonal elevation of Σ FLC is a significant predictor of worse overall survival in the general population of persons without plasma cell disorders.
Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple Myeloma
In this study, the risk of progression of asymptomatic smoldering multiple myeloma to active multiple myeloma was found to be related to the level of serum monoclonal immunoglobulin and the proportion of plasma cells in the bone marrow at the time of diagnosis. The risk of progression of smoldering multiple myeloma to active multiple myeloma was found to be related to the level of serum monoclonal immunoglobulin and the proportion of plasma cells in the bone marrow at the time of diagnosis. Smoldering multiple myeloma is an asymptomatic proliferative disorder of plasma cells with a high risk of progression to symptomatic, or active, multiple myeloma. Previous studies have used various definitions of the disease, and this variability has resulted in important differences in the reported clinical course of the disease. 1 – 7 International consensus criteria for smoldering multiple myeloma were adopted recently to rectify this problem. 8 We report here on the prognosis and risk factors for progression of smoldering multiple myeloma in a large cohort of patients for whom long-term follow-up data were available and in whom the disease was defined with the . . .
Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study
Monoclonal gammopathy of undetermined significance (MGUS) is defined by expression of heavy-chain immunoglobulin (IgH) and is the precursor lesion for 80% of cases of multiple myeloma. The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS. We used a population-based cohort, previously assembled to estimate MGUS prevalence, of 21 463 residents of Olmsted County, MN, USA, aged 50 years and older. We did a serum free light-chain assay on all samples with sufficient serum remaining, and immunofixation electrophoresis was done for all samples with an abnormal free light-chain ratio or abnormal protein electrophoresis results from the original study. Light-chain MGUS was defined as an abnormal free light-chain ratio with no IgH expression, plus increased concentration of the involved light chain. We calculated age-specific and sex-specific prevalence and rates of progression to lymphoproliferative disorders for light-chain and conventional MGUS and assessed incidence of renal disorders in patients with light-chain MGUS. 610 (3·3%) of 18 357 people tested had an abnormal free light-chain ratio, of whom 213 had IgH expression that was diagnostic of conventional MGUS. 146 of the remaining 397 individuals had an increase of at least one free light chain and met criteria for light-chain MGUS. Prevalence of light-chain MGUS was 0·8% (95% CI 0·7–0·9), contributing to an overall MGUS prevalence of 4·2% (3·9–4·5). Risk of progression to multiple myeloma in patients with light-chain MGUS was 0·3 (0·1–0·8) per 100 person-years. 30 (23%) of 129 patients with light-chain MGUS were diagnosed with renal disease. We define a clinical entity representing the light-chain equivalent of conventional MGUS and posing a risk of progression to light-chain multiple myeloma and related disorders. US National Cancer Institute, National Institute of Health.
The Chitranjan Ranawat Award: Running Subcuticular Closure Enables the Most Robust Perfusion After TKA: A Randomized Clinical Trial
Background Maintaining robust perfusion is an important physiologic parameter in wound healing. The effect of different closure techniques on wound perfusion after total knee arthroplasty (TKA) has not been established previously and may have implications for wound healing. Questions/purposes We asked whether a running subcuticular, vertical mattress, or skin staple closure technique enables the most robust wound perfusion after TKA as measured by laser-assisted indocyanine green angiography (LA-ICGA) in patients without specific risk factors for wound healing complications. Methods Forty-five patients undergoing primary TKA without comorbidities known to impact wound healing and perfusion were prospectively randomized to receive superficial skin closure with one of the following techniques: (1) running subcuticular (3-0 monofilament); (2) vertical mattress (2-0 nylon); or (3) skin staples. Twenty procedures were performed by RTT, 15 by RJS, and 10 by FHS. All surgeons used an anterior skin incision over the medial third of the patella in combination with a median parapatellar arthrotomy. Perfusion was assessed with a LA-ICGA device and software system immediately after closure to quantify fluorescence. Twenty-seven points were assessed immediately after closure in the operating room in each patient (nine along the incision and nine pairs medial and lateral to the incision). Mean incision perfusion was determined from the nine points along the incision with higher values indicating greater blood flow. Mean perfusion impairment was determined by calculating the difference between the nine pairs of surrounding skin and the nine points along the incision with smaller values indicating less perfusion impairment. These parameters were compared with analysis of variance (ANOVA) and subsequent pairwise comparisons with an unadjusted analysis as well as a multivariate analysis that adjusted for age, sex, and body mass index. Patients were followed for a mean of 7 months after surgery (range, 3–12 months) for possible incision-related complications. No patents were lost to followup. Results Running subcuticular closure demonstrated the best overall perfusion. Mean incision perfusion in fluorescent units with SD was as follows: running subcuticular, 64 (16); vertical mattress, 32 (18); and staples, 19 (7) (ANOVA p < 0.001). The running subcuticular closure demonstrated the least impairment of perfusion among the closures compared. Mean perfusion impairment was as follows: running subcuticular, 21 (12); vertical mattress, 37 (24); and staples, 69 (27) (ANOVA p < 0.001). All Tukey-adjusted pairwise comparisons from both metrics likewise favored the subcuticular closure (p < 0.001) both before and after adjusting for age, sex, and body mass index. One patient in the vertical mattress cohort experienced a surgical site infection; no other wound-related complications were observed in this study. Conclusions The method of closure can influence skin and soft tissue perfusion after TKA. Running subcuticular closure enables the most physiologic robust blood flow, which may improve wound healing. However, the clinical importance of these findings remains uncertain, because patients in this study were selected because they lacked risk factors for wound healing complications. Studies with this modality in specific patient populations at higher risk for wound complications will be necessary to quantify the clinical advantage of using running subcuticular closure. Level of Evidence Level I, therapeutic study.
Disease Associations With Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study of 17,398 Patients
To systematically study the association of monoclonal gammopathy of undetermined significance (MGUS) with all diseases in a population-based cohort of 17,398 patients, all of whom were uniformly tested for the presence or absence of MGUS. Serum samples were obtained from 77% (21,463) of the 28,038 enumerated residents in Olmsted County, Minnesota. Informed consent was obtained from patients to study 17,398 samples. Among 17,398 samples tested, 605 cases of MGUS and 16,793 negative controls were identified. The computerized Mayo Medical Index was used to obtain information on all diagnoses entered between January 1, 1975, and May 31, 2006, for a total of 422,663 person-years of observations. To identify and confirm previously reported associations, these diagnostic codes were analyzed using stratified Poisson regression, adjusting for age, sex, and total person-years of observation. We confirmed a significant association in 14 (19%) of 75 previously reported disease associations with MGUS, including vertebral and hip fractures and osteoporosis. Systematic analysis of all 16,062 diagnostic disease codes found additional previously unreported associations, including mycobacterium infection and superficial thrombophlebitis. These results have major implications both for confirmed associations and for 61 diseases in which the association with MGUS is likely coincidental.
Essential Thrombocythemia Beyond the First Decade: Life Expectancy, Long-term Complication Rates, and Prognostic Factors
To describe the long-term natural history of essential thrombocythemia (ET) in terms of life expectancy, risk of disease transformation into a more aggressive myeloid disorder, and prognostic factors for both survival and disease complications. The study population consisted of a consecutive cohort of patients seen at the Mayo Clinic in Rochester, Minn, in whom a diagnosis of ET was established before 1992, thus allowing a minimum of 10 years of potential follow-up. The conventional criteria-based diagnosis was confirmed by bone marrow biopsy in all instances. A total of 322 patients were studied (median age, 54 years; median follow-up, 13.6 years). With a median survival time of 18.9 years, survival in the first decade of disease was similar to that of the control population (risk ratio, 0.72; 95% confidence interval, 0.50-0.99) but became significantly worse thereafter (risk ratio, 2.21; 95% confidence interval, 1.74-2.76). Multivariable analysis identified age at diagnosis of 60 years or older, leukocytosis, tobacco use, and diabetes mellitus as independent predictors of poor survival. A 2-variable model based on an age cutoff of 60 years and leukocyte count of 15 × 10 9/L resulted in 3 risk groups with significant difference in survival. In addition, age at diagnosis of 60 years or older, leukocytosis, and history of thrombosis were independent predictors of major thrombotic events. The risk of leukemic or any myeloid disease transformation was low in the first 10 years (1.4% and 9.1%, respectively) but increased substantially in the second (8.1% and 28.3%, respectively) and third (24.0% and 58.5%, respectively) decades of the disease. Life expectancy in patients with ET is significantly worse than that of the control population. Leukocytosis is identified as a novel independent risk factor for both inferior survival and thrombotic events.
Balance disorder and increased risk of falls in osteoporosis and kyphosis: significance of kyphotic posture and muscle strength
This controlled trial was designed to investigate the influence of osteoporosis-related kyphosis (O-K) on falls. Twelve community-dwelling women with O-K (Cobb angle, 50-65 degrees measured from spine radiographs) and 13 healthy women serving as controls were enrolled. Mean age of the O-K group was 76 years (+/-5.1), height 158 cm (+/-5), and weight 61 kg (+/-7.9), and mean age of the control group was 71 years (+/-4.6), height 161 cm (+/-3.8), and weight 66 kg (+/-11.7). Quantitative isometric strength data were collected. Gait was monitored during unobstructed level walking and during stepping over an obstacle of four different heights randomly assigned (2.5%, 5%, 10%, and 15% of the subject's height). Balance was objectively assessed with computerized dynamic posturography consisting of the sensory organization test. Back extensor strength, grip strength, and all lower extremity muscle groups were significantly weaker in the O-K group than the control group (P <0.05), except right ankle plantar flexors (P =0.09). There was a significant difference in the anteroposterior and mediolateral displacements and velocities. The O-K subjects had less anteroposterior displacement, greater mediolateral displacement, reduced anteroposterior velocity, and increased mediolateral velocity compared with controls for all conditions of unobstructed and obstructed level walking. Obstacle height had a significant effect on all center-of-mass variables. The O-K subjects had significantly greater balance abnormalities on computerized dynamic posturography than the control group (P =0.002). Data show that thoracic hyperkyphosis on a background of reduced muscle strength plays an important role in increasing body sway, gait unsteadiness, and risk of falls in osteoporosis.
Body mass index associated with monoclonal gammopathy of undetermined significance (MGUS) progression in Olmsted County, Minnesota
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder that progresses to multiple myeloma (MM), or other plasma-cell or lymphoid disorders at a rate of 1%/year. We evaluate the contribution of body mass index (BMI) to MGUS progression beyond established clinical factors in a population-based study. We identified 594 MGUS through a population-based screening study in Olmsted County, Minnesota, between 1995 and 2003. Follow-up time was calculated from the date of MGUS to last follow-up, death, or progression to MM/another plasma-cell/lymphoid disorder. BMI (kg/m2 < 25/≥25) was measured close to screening date. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of BMI ≥ 25 versus BMI < 25 with MGUS progression and also evaluated the corresponding c-statistic and 95% CI to describe discrimination of the model for MGUS progression. Median follow-up was 10.5 years (range:0–25), while 465 patients died and 57 progressed and developed MM (N = 39), AL amyloidosis (N = 8), lymphoma (N = 5), or Waldenstrom-macroglobulinemia (N = 5). In univariate analyses, BMI ≥ 25 (HR = 2.14,CI:1.05–4.36, P = 0.04), non-IgG (HR = 2.84, CI:1.68–4.80, P = 0.0001), high monoclonal (M) protein (HR = 2.57, CI:1.50–4.42, P = 0.001), and abnormal free light chain ratio (FLCr) (HR = 3.39, CI:1.98–5.82, P < 0.0001) were associated with increased risk of MGUS progression, and were independently associated in a multivariable model (c-statistic = 0.75, CI:0.68–0.82). The BMI association was stronger among females (HR = 3.55, CI:1.06–11.9, P = 0.04) vs. males (HR = 1.39, CI:0.57–3.36, P = 0.47), although the interaction between BMI and sex was not significant (P = 0.15). In conclusion, high BMI is a prognostic factor for MGUS progression, independent of isotype, M protein, and FLCr. This association may be stronger among females.
Osteosarcoma of the Pelvis: Outcome Analysis of Surgical Treatment
Risk factors to explain the poor survival of patients with osteosarcoma of the pelvis are poorly understood. Therefore, we attempted to identify factors affecting survival and development of local recurrence and metastasis. We retrospectively reviewed 43 patients who had high-grade pelvic tumors and were treated surgically. Twenty lesions were chondroblastic, 10 fibroblastic, 11 osteoblastic, and one each was giant cell-rich and small cell osteosarcomas. At a median of 3.5 years (range, 0.3–21 years) postoperatively, 13 patients were alive with no evidence of disease. The overall and disease-free 5-year survival rates were 38% and 29%, respectively, at 5 years. Anatomic location, tumor size, and margin predicted survival. Fifteen patients (35%) had local recurrence. The 5-year cumulative incidence of recurrence with death as a competing risk factor was 34%. Location in the ilium and size of the tumor predicted local recurrence. Twenty-one (49%) of 43 patients had metastases develop. The cumulative incidence of metastasis with death as a competing risk factor was 48% at 5 years. Six patients who presented with metastasis had a worse survival than patients who had no evidence of metastasis at presentation (2-year survival, 33% versus 76%). If distant metastasis is diagnosed subsequent to primary treatment, aggressive therapy may be justified. Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.