Larson, Dirk R.

Abstract During the course of multiple myeloma (MM), new monoclonal proteins of an isotype distinct from the original clone, referred to as secondary monoclonal gammopathy of undetermined significance (MGUS), have been described. We report on the frequency, characteristics, and outcome of secondary MGUS. Of the 1942 patients with MM, 128 (6.6%) developed a secondary MGUS, at a median of 12 months from the diagnosis of MM. The median duration of secondary MGUS was 5.9 months. Secondary MGUS was more common in patients after stem cell transplantation than in those who had not undergone such treatment (22.7% vs 1.6%, P < .001). Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort (73 vs 38 months, respectively; P < .001). The time of onset and the duration of secondary MGUS, as well as failure to resolve spontaneously, had an effect on overall survival and require further study.

Our aim was to determine the effect of the initial pattern of fracture and the displacement of fragments on the outcome of proximal humeral fractures treated conservatively. We followed 93 consecutive patients prospectively for one year. Final movement and strength were compared with those of the contralateral side. The final American Shoulder and Elbow Society score and the Disabilities of Arm, Shoulder and Hand and Short-Form 36 questionnaires were compared with those provided by the patient on the day of the injury. Radiographs and CT scans with three-dimensional reconstruction were obtained in all patients. The pattern of the fracture and the displacement of individual fragments were analysed and correlated with the final outcome. There were two cases of nonunion and six of avascular necrosis. The majority of the fractures (84 patients; 90%) followed one of the following four patterns: posteromedial (varus) impaction in 50 patients (54%), lateral (valgus) impaction in 13 (14%), isolated greater tuberosity in 15 (16%), and anteromedial impaction fracture in six (6%). Head orientation, impaction of the surgical neck and displacement of the tuberosity correlated strongly with the outcome. In fractures with posteromedial impaction, a poor outcome was noted as the articular surface displaced inferiorly increasing its distance from the acromion. A poorer outcome was noted as a fractured greater tuberosity displaced medially overlapping with the posterior articular surface. Lateral impaction fractures had a worse outcome than other patterns of fracture.

Abstract Immunoglobulin free light chains (FLCs) are the precursors of amyloid fibrils in primary amyloidosis (AL). We studied the relationship between FLC levels and clinical features in 730 patients with newly diagnosed AL. The plasma cell clone was λ in 72% patients, and κ in 28% patients. κ-AL had more GI tract and liver involvement, where as renal involvement was more with λ-AL. While the overall survival (OS) was similar for κ and λ-AL, the median OS for those without an identifiable serum heavy chain was significantly shorter (12.6 vs 29.9 months; P = .02). The OS was shorter among those with a higher dFLC (involved FLC−uninvolved FLC; κ > 29.4 mg/dL or λ > 18.2 mg/dL using median for cutoff); 10.9 vs 37.1 months; P < .001. In multivariate analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (≥ 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.

Abstract The current definition of complete response in multiple myeloma includes a requirement for a bone marrow (BM) examination showing less than 5% plasma cells in addition to negative serum and urine immunofixation. There have been suggestions to eliminate the need for BM examinations when defining complete response. We evaluated 92 patients with multiple myeloma who achieved negative immunofixation in the serum and urine after therapy and found that 14% had BM plasma cells more than or equal to 5%. Adding a requirement for normalization of the serum-free light chain ratio to negative immunofixation studies did not negate the need for BM studies; 10% with a normal serum-free light chain ratio had BM plasma cells more than or equal to 5%. We also found that, on achieving immunofixation-negative status, patients with less than 5% plasma cells in the BM had improved overall survival compared with those with 5% or more BM plasma cells (6.2 years vs 2.3 years, respectively; P = .01).

Abstract Background: The repertoire of serologic tests for identifying a monoclonal gammopathy includes serum and urine protein electrophoresis (PEL), serum and urine immunofixation electrophoresis (IFE), and quantitative serum free light chain (FLC). Although there are several reports on the relative diagnostic contribution of these assays, none has looked at the tests singly and in combination for the various plasma cell proliferative disorders (PCPDs). Methods: Patients with a PCPD and all 5 assays performed within 30 days of diagnosis were included (n = 1877). The diagnoses were multiple myeloma (MM) (n = 467), smoldering multiple myeloma (SMM) (n = 191), monoclonal gammopathy of undetermined significance (MGUS) (n = 524), plasmacytoma (n = 29), extramedullary plasmacytoma (n = 10), Waldenström macroglobulinemia (WM) (n = 26), primary amyloidosis (AL) (n = 581), light chain deposition disease (LCDD) (n = 18), and POEMS syndrome (n = 31). Results: Of the 1877 patients, 26 were negative in all assays. Omitting urine from the panel lost an additional 23 patients (15 MGUS, 6 AL, 1 plasmacytoma, 1 LCDD), whereas the omission of FLC lost 30 patients (6 MM, 23 AL, and 1 LCDD). The omission of serum IFE as well as urine lost an additional 58 patients (44 MGUS, 7 POEMS, 5 AL, 1 SMM, and 1 plasmacytoma). Conclusions: The major impact of using a simplified screening panel of serum PEL plus FLC rather than PEL, IFE, and FLC is an 8% reduction in sensitivity for MGUS, 23% for POEMS (7 patients), 4% for plasmacytoma (1 patient), 1% for AL, and 0.5% for SMM. There is no diminution in sensitivity for detecting MM, macroglobulinemia, and LCDD.

Objective To investigate 35‐year epidemiological trends in tonsillectomy and adenotonsillectomy. Study Design/Subjects Cross‐sectional survey. Subjects included all patients from birth to age 29 years who had tonsillectomy or adenotonsillectomy from 1970 to 2005. Results Study included 8106 patients (median age 8.0 years; range, 6 months to 29 years; male 3646 patients [45%]). Overall tonsillectomy incidence increased from 126 (95% confidence interval [CI], 111‐140) per 100,000 person‐years in 1970 through 1974 to 153 (95% CI, 139‐166) in 2000 through 2005. A dominant factor, adenotonsillectomy incidence rose sharply from 243 (95% CI, 223‐261) per 100,000 person‐years in 1970 through 1974 to 485 (95% CI, 462‐509) in 2000 through 2005. The indication of upper airway obstruction increased from 12 percent of patients in 1970 to 77 percent in 2005. Conclusions Epidemiological trends in tonsillectomy and adenotonsillectomy have shifted substantially. Overall numbers have increased, and surgical indications have shifted from infection to upper airway obstruction.

Abstract We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, ≥ 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.