Dirk Larson - Academia.edu (original) (raw)

Papers by Dirk Larson

The Annals of Thoracic Surgery, 2006

Background. Little information is available regarding long-term survival after pulmonary metastas... more Background. Little information is available regarding long-term survival after pulmonary metastasectomy for gynecologic malignancies.

Global Spine Journal, 2015

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 1998

In this population-based descriptive study covering the 65-year period, 1928-92, there was a 5-fo... more In this population-based descriptive study covering the 65-year period, 1928-92, there was a 5-fold increase in hip fracture prevalence among Rochester, Minnesota residents between 1928-42 and 1973-82, from 135.8 to 675.8 per 100,000. This change was dictated almost entirely by an increase in the incidence of first hip fractures due to moderate trauma (n = 2058) that was observed among Rochester women through 1950, and among men through 1980, that affected all age groups. Declining incidence rates thereafter led to a 9% fall in hip fracture prevalence from 1973-82 to 1983-92 to a rate of 612.7 per 100,000. A 13.7-year increase in age at first hip fracture over the study period was accounted for by aging of the underlying population, and a comparable 13.9-year increase in the age at death following hip fracture appeared to result from improved survival in the population generally. Thus, trends in hip fracture prevalence were mainly determined by changes in incidence rather than relat...

European journal of haematology, Jan 10, 2014

To determine the prognosis of patients with non-secretory myeloma. Methods: We studied 124 patien... more To determine the prognosis of patients with non-secretory myeloma. Methods: We studied 124 patients diagnosed with multiple myeloma who had no monoclonal protein detected on serum and urine immunofixation at diagnosis and on all subsequent follow up testing (non-secretory myeloma). The overall survival (OS) of patients with non-secretory myeloma was compared with 7075 patients with typical myeloma seen during the same time period in whom a monoclonal protein was detected at the time of diagnosis. One hundred and twenty four patients met criteria for non-secretory multiple myeloma. The median follow-up was 102 months (range, 1-204 months). The median progression free survival with initial therapy was 28.6 months, and the median OS was 49.3 months. There was a significant improvement in OS since 2001; median survival 99.2 versus 43.8 months (prior to 2001) versus 99.2 months (2001-2012), P<0.001. OS was superior in patients with a normal baseline FLC ratio (n=10) compared to patien...

The Lancet Haematology, 2014

Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain ... more Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain protein. About 15-20% of patients with multiple myeloma secrete monoclonal light chains only, without expression of the normal immunoglobulin heavy chain, which constitutes light-chain multiple myeloma. The definition, prevalence, and progression of these premalignant phases of light-chain multiple myeloma have not been fully characterised. We aimed to identify a subset of patients with idiopathic Bence Jones proteinuria who had a high risk of progression to light-chain multiple myeloma analogous to that seen in patients with smouldering multiple myeloma. In this retrospective cohort study, we studied all patients seen at the Mayo Clinic (Rochester, MN, USA) within 30 days of diagnosis of idiopathic Bence Jones proteinuria between Jan 1, 1960, and June 30, 2004. Inclusion criteria were monoclonal light chain in the urine (≥0·2 g/24 h), absence of intact monoclonal immunoglobulin (M protein) in the serum, and no evidence of multiple myeloma, light-chain amyloidosis, or other related plasma-cell proliferative disorders. The primary endpoint was progression to symptomatic multiple myeloma or light-chain amyloidosis. We examined the cumulative probability of progression and the association of potential risk factors on progression rates to identify patients with a high risk of progression to multiple myeloma or light-chain amyloidosis. We identified 101 patients with idiopathic Bence Jones proteinuria. During 901 total person-years of follow-up, 27 (27%) patients developed multiple myeloma and seven (7%) developed light-chain amyloidosis. The major risk factors for progression were amount of urinary excretion of M protein per 24 h, proportion of bone marrow plasma cells, presence of a markedly abnormal free-light-chain ratio (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·01 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;100), and reduction of all three uninvolved immunoglobulins. Based on the risk of progression, monoclonal light-chain excretion of 0·5 g/24 h or greater or at least 10% bone marrow plasma cells, or both, in the absence of end-organ damage was used to define light-chain smouldering multiple myeloma. The cumulative probability of progression to active multiple myeloma or light-chain amyloidosis in patients with light-chain smouldering multiple myeloma was 27·8% (95% CI 14·2-39·2) at 5 years, 44·6% (27·9-57·4) at 10 years, and 56·5% (36·3-70·2) at 15 years. Light-chain smouldering multiple myeloma as defined in this study is associated with a high risk of progression to symptomatic light-chain multiple myeloma, and this subset of patients needs careful observation and could benefit from clinical trials of early intervention. Jabbs Foundation (Birmingham, UK), US National Cancer Institute, and Henry J Predolin Foundation (Madison, WI, USA).

The Journal of rheumatology, Jan 15, 2015

Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arth... more Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arthritis (RA) and are associated with all-cause mortality in the general population. Our objective was to evaluate the relationships of serum FLC to preclinical disease, RA characteristics, and mortality in RA compared to non-RA subjects. A population-based study in Olmsted County, Minnesota, USA, was performed by crosslinking a large cohort in the general population having available serum FLC measurements with established RA incidence and prevalence cohorts. Serum κ, λ, and total FLC and their trends relative to RA incidence were compared between RA and non-RA subjects. Regression models were used to determine the associations between FLC, disease characteristics, and mortality, testing for differential effects of FLC on mortality in RA. Among 16,609 subjects, 270 fulfilled the criteria for RA at the time of FLC measurement. Mean total FLC were significantly higher in RA compared to non-RA...

Surgical Endoscopy, 2007

The aim of this analysis was to determine the impact of complicated and uncomplicated diverticuli... more The aim of this analysis was to determine the impact of complicated and uncomplicated diverticulitis on conversion rates and complications in patients undergoing laparoscopic surgery (LS) for diverticular disease. Between 1993 and 2004, 125 patients underwent LS [91 laparoscopic-assisted (LA) and 34 hand-assisted (HA) colectomy for diverticular disease, 79 uncomplicated and 46 complicated]. Cases not completed laparoscopically were considered converted. Complicated diverticulitis was defined as diverticular disease associated with abscess, fistula, bleeding or stricture. The mean age was 59 years with 67 (54%) men with a mean follow-up of 23 months. The conversion rate was 26% (33 patients). The only factor independently associated with conversion was a history of previous abdominal surgery (37% vs. 14%, p = 0.004). Among the subset of patients undergoing surgery for uncomplicated diverticulitis, the number of diverticulitis episodes (DE), the time between the first and last DE, and the time between the last DE and surgery, were not significantly associated with conversion. Early complications (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 days from surgery) occurred in 30 (25%) patients. Twenty-one long-term complications (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30 days from surgery) occurred in 20 patients and the one and two-year cumulative probabilities of these complications were 14% and 22%, respectively. Early complications were significantly higher among patients requiring conversion (44% vs. 24%, p = 0.04) but were not significantly higher among patients with complicated diverticulitis (39% vs. 24%, p = 0.11). The rates of long-term complications were not significantly higher among patients that required conversion or had complicated diverticulitis (one-year rate 23% vs. 11%, p = 0.47; 18% vs. 13%, p = 0.70). A previous history of abdominal surgery was associated with a higher conversion rate in patients undergoing laparoscopic surgery for diverticular disease. Long-term patient outcomes are not adversely impacted by laparoscopic surgery for complicated diverticulitis or laparoscopic surgery requiring conversion to an open procedure.

Spine, 2008

Experimental dog model of acute spinal cord injury. To compare the relative value of methylpredni... more Experimental dog model of acute spinal cord injury. To compare the relative value of methylprednisolone, surgical decompression, or both for the treatment of traumatic spinal cord injury. Acute spinal cord injury results from both primary damage to the spinal cord at the time of the initial injury as well as a deleterious secondary cascade of events, which leads to further damage. Surgical decompression is known to improve clinical outcomes, but the timing of surgical decompression remains controversial. A nylon tie was used to constrict the spinal cord in 18 adult male beagle dogs. The animals were then prospectively randomized to 3 groups: 1) surgical decompression at 6 hours and intravenous methylprednisolone; 2) surgical decompression at 6 hours and intravenous saline; and 3) intravenous methylprednisolone without surgical decompression. Each animal was evaluated by somatosensory-evoked potentials, daily neurologic assessment, and histologic examination at 2 weeks following injury. Immediately following spinal cord constriction, all animals were paraplegic, incontinent, and the somatosensory-evoked potentials were abolished. Surgical decompression 6 hours after injury, with or without methylprednisolone, led to significantly better neurologic function at 2 weeks than methylprednisolone alone. In the setting of acute and persistent spinal cord compression in beagle dogs, surgical decompression 6 hours after injury, with or without methylprednisolone, is more effective for improving neurologic recovery than methylprednisolone alone.

New England Journal of Medicine, 2002

Background A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent ... more Background A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent of persons 50 years of age or older. Reliable predictors of progression have not been identified, and information on prognosis is limited.

New England Journal of Medicine, 2007

Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder ... more Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis. Prognostic factors for the progression and outcome of this disease are unclear.

Mayo Clinic Proceedings, 2006

To determine the relative diagnostic contribution of urine assays as part of the screening algori... more To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain kappa/lambda ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal gammopathy. Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.

Mayo Clinic Proceedings, 2009

Objective: To systematically study the association of monoclonal gammopathy of undetermined signi... more Objective: 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.

Mayo Clinic Proceedings, 1997

Mayo Clinic Proceedings, 2003

Objective: To determine the clinical and laboratory features of newly diagnosed multiple myeloma.... more Objective: To determine the clinical and laboratory features of newly diagnosed multiple myeloma. • Patients and Methods: Records of all patients in whom multiple myeloma was initially diagnosed at the Mayo Clinic in Rochester, Minn, from January 1, 1985, to December 31, 1998, were reviewed.

Mayo Clinic Proceedings, 2004

OBJECTIVE: To study the clinical course of patients with multiple myeloma (MM) that relapses afte... more OBJECTIVE: To study the clinical course of patients with multiple myeloma (MM) that relapses after initial therapy.

Mayo Clinic Proceedings, 2004

To determine the long-term outcome of patients with monoclonal gammopathy of undetermined signifi... more To determine the long-term outcome of patients with monoclonal gammopathy of undetermined significance (MGUS).

Mayo Clinic Proceedings, 2007

To assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a large ... more To assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a large Japanese population. From October 1, 1988, to March 31, 2004, a total of 52,802 (of 71,675) Japanese survivors of the atomic bomb explosion in Nagasaki City, Japan, were screened for M protein. The youngest participant was 42.3 years as of October 1, 1988. A 2-step screening was performed with a serum protein electrophoresis followed by immunoelectrophoresis and a quantitative determination of serum concentration of immunoglobulins. Twenty-one patients who were diagnosed for the first time at the time of screening as having multiple myeloma and Waldenström macroglobulinemia were excluded from analyses. Age- and sex-specific prevalence rates of MGUS were calculated. Monoclonal gammopathy of undetermined significance was identified in 1088 of the 52,781 study participants. The overall prevalence of MGUS was 2.1% (95% confidence interval [CI], 1.9%-2.2%) in the total population screened and 2.4% (95% CI, 2.0%-2.6%) in those 50 years or older. The prevalence was significantly higher in men than in women (2.8% vs 1.6%; age-adjusted odds ratio, 2.0; 95% CI, 1.8-2.3; P less than .001). In both sexes, the prevalence rose with increasing age from 1.0% in participants aged 42 to 49 years, 1.9% in those 50 to 59 years, 2.6% in those 60 to 69 years, and 3.0% in those 70 to 79 years, to 4.4% in those 80 years and older. The heavy chain isotypes of immunoglobulin were IgG in 73.6% of patients, IgA in 17.7%, IgM in 7.5%, and oligoclonal gammopathies in 1.1%. The prevalence of MGUS is lower in this Japanese population than that reported in Western countries among people older than 60 years, especially among women.

Leukemia, 2008

To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symp... more To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symptomatic multiple myeloma (MM), baseline serum samples from a well-characterized cohort of 790 newly diagnosed MM patients were tested with the FLC assay. FLC ratio was calculated as κ/λ (reference range 0.26-1.65). On the basis of the distribution of values, a cutpoint κ/λ FLC ratio of <0.03 or >32 was chosen for further analysis. Overall survival was significantly inferior in patients with an abnormal FLC ratio of <0.03 or >32 (n=479) compared with those with an FLC ratio between 0.03 and 32 (n=311), with median survival of 30 versus 39 months, respectively. We incorporated abnormal FLC ratio with the International Staging System (ISS) risk factors (that is, albumin <3.5 g/dl and serum β 2 -microglobulin ≥3.5 g/l), to create a risk stratification model with improved prognostic capabilities. Patients with 0, 1, 2 or 3 adverse risk factors had significantly different overall survival, with median survival times of 51, 39, 30 and 22 months, respectively (P<0.001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification.

The Lancet, 2010

Background Monoclonal gammopathy of undetermined signifi cance (MGUS) is defi ned by expression o... more Background Monoclonal gammopathy of undetermined signifi cance (MGUS) is defi ned 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, lightchain MGUS.

The Annals of Thoracic Surgery, 2006

Background. Little information is available regarding long-term survival after pulmonary metastas... more Background. Little information is available regarding long-term survival after pulmonary metastasectomy for gynecologic malignancies.

Global Spine Journal, 2015

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 1998

In this population-based descriptive study covering the 65-year period, 1928-92, there was a 5-fo... more In this population-based descriptive study covering the 65-year period, 1928-92, there was a 5-fold increase in hip fracture prevalence among Rochester, Minnesota residents between 1928-42 and 1973-82, from 135.8 to 675.8 per 100,000. This change was dictated almost entirely by an increase in the incidence of first hip fractures due to moderate trauma (n = 2058) that was observed among Rochester women through 1950, and among men through 1980, that affected all age groups. Declining incidence rates thereafter led to a 9% fall in hip fracture prevalence from 1973-82 to 1983-92 to a rate of 612.7 per 100,000. A 13.7-year increase in age at first hip fracture over the study period was accounted for by aging of the underlying population, and a comparable 13.9-year increase in the age at death following hip fracture appeared to result from improved survival in the population generally. Thus, trends in hip fracture prevalence were mainly determined by changes in incidence rather than relat...

European journal of haematology, Jan 10, 2014

To determine the prognosis of patients with non-secretory myeloma. Methods: We studied 124 patien... more To determine the prognosis of patients with non-secretory myeloma. Methods: We studied 124 patients diagnosed with multiple myeloma who had no monoclonal protein detected on serum and urine immunofixation at diagnosis and on all subsequent follow up testing (non-secretory myeloma). The overall survival (OS) of patients with non-secretory myeloma was compared with 7075 patients with typical myeloma seen during the same time period in whom a monoclonal protein was detected at the time of diagnosis. One hundred and twenty four patients met criteria for non-secretory multiple myeloma. The median follow-up was 102 months (range, 1-204 months). The median progression free survival with initial therapy was 28.6 months, and the median OS was 49.3 months. There was a significant improvement in OS since 2001; median survival 99.2 versus 43.8 months (prior to 2001) versus 99.2 months (2001-2012), P<0.001. OS was superior in patients with a normal baseline FLC ratio (n=10) compared to patien...

The Lancet Haematology, 2014

Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain ... more Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain protein. About 15-20% of patients with multiple myeloma secrete monoclonal light chains only, without expression of the normal immunoglobulin heavy chain, which constitutes light-chain multiple myeloma. The definition, prevalence, and progression of these premalignant phases of light-chain multiple myeloma have not been fully characterised. We aimed to identify a subset of patients with idiopathic Bence Jones proteinuria who had a high risk of progression to light-chain multiple myeloma analogous to that seen in patients with smouldering multiple myeloma. In this retrospective cohort study, we studied all patients seen at the Mayo Clinic (Rochester, MN, USA) within 30 days of diagnosis of idiopathic Bence Jones proteinuria between Jan 1, 1960, and June 30, 2004. Inclusion criteria were monoclonal light chain in the urine (≥0·2 g/24 h), absence of intact monoclonal immunoglobulin (M protein) in the serum, and no evidence of multiple myeloma, light-chain amyloidosis, or other related plasma-cell proliferative disorders. The primary endpoint was progression to symptomatic multiple myeloma or light-chain amyloidosis. We examined the cumulative probability of progression and the association of potential risk factors on progression rates to identify patients with a high risk of progression to multiple myeloma or light-chain amyloidosis. We identified 101 patients with idiopathic Bence Jones proteinuria. During 901 total person-years of follow-up, 27 (27%) patients developed multiple myeloma and seven (7%) developed light-chain amyloidosis. The major risk factors for progression were amount of urinary excretion of M protein per 24 h, proportion of bone marrow plasma cells, presence of a markedly abnormal free-light-chain ratio (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·01 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;100), and reduction of all three uninvolved immunoglobulins. Based on the risk of progression, monoclonal light-chain excretion of 0·5 g/24 h or greater or at least 10% bone marrow plasma cells, or both, in the absence of end-organ damage was used to define light-chain smouldering multiple myeloma. The cumulative probability of progression to active multiple myeloma or light-chain amyloidosis in patients with light-chain smouldering multiple myeloma was 27·8% (95% CI 14·2-39·2) at 5 years, 44·6% (27·9-57·4) at 10 years, and 56·5% (36·3-70·2) at 15 years. Light-chain smouldering multiple myeloma as defined in this study is associated with a high risk of progression to symptomatic light-chain multiple myeloma, and this subset of patients needs careful observation and could benefit from clinical trials of early intervention. Jabbs Foundation (Birmingham, UK), US National Cancer Institute, and Henry J Predolin Foundation (Madison, WI, USA).

The Journal of rheumatology, Jan 15, 2015

Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arth... more Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arthritis (RA) and are associated with all-cause mortality in the general population. Our objective was to evaluate the relationships of serum FLC to preclinical disease, RA characteristics, and mortality in RA compared to non-RA subjects. A population-based study in Olmsted County, Minnesota, USA, was performed by crosslinking a large cohort in the general population having available serum FLC measurements with established RA incidence and prevalence cohorts. Serum κ, λ, and total FLC and their trends relative to RA incidence were compared between RA and non-RA subjects. Regression models were used to determine the associations between FLC, disease characteristics, and mortality, testing for differential effects of FLC on mortality in RA. Among 16,609 subjects, 270 fulfilled the criteria for RA at the time of FLC measurement. Mean total FLC were significantly higher in RA compared to non-RA...

Surgical Endoscopy, 2007

The aim of this analysis was to determine the impact of complicated and uncomplicated diverticuli... more The aim of this analysis was to determine the impact of complicated and uncomplicated diverticulitis on conversion rates and complications in patients undergoing laparoscopic surgery (LS) for diverticular disease. Between 1993 and 2004, 125 patients underwent LS [91 laparoscopic-assisted (LA) and 34 hand-assisted (HA) colectomy for diverticular disease, 79 uncomplicated and 46 complicated]. Cases not completed laparoscopically were considered converted. Complicated diverticulitis was defined as diverticular disease associated with abscess, fistula, bleeding or stricture. The mean age was 59 years with 67 (54%) men with a mean follow-up of 23 months. The conversion rate was 26% (33 patients). The only factor independently associated with conversion was a history of previous abdominal surgery (37% vs. 14%, p = 0.004). Among the subset of patients undergoing surgery for uncomplicated diverticulitis, the number of diverticulitis episodes (DE), the time between the first and last DE, and the time between the last DE and surgery, were not significantly associated with conversion. Early complications (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 days from surgery) occurred in 30 (25%) patients. Twenty-one long-term complications (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30 days from surgery) occurred in 20 patients and the one and two-year cumulative probabilities of these complications were 14% and 22%, respectively. Early complications were significantly higher among patients requiring conversion (44% vs. 24%, p = 0.04) but were not significantly higher among patients with complicated diverticulitis (39% vs. 24%, p = 0.11). The rates of long-term complications were not significantly higher among patients that required conversion or had complicated diverticulitis (one-year rate 23% vs. 11%, p = 0.47; 18% vs. 13%, p = 0.70). A previous history of abdominal surgery was associated with a higher conversion rate in patients undergoing laparoscopic surgery for diverticular disease. Long-term patient outcomes are not adversely impacted by laparoscopic surgery for complicated diverticulitis or laparoscopic surgery requiring conversion to an open procedure.

Spine, 2008

Experimental dog model of acute spinal cord injury. To compare the relative value of methylpredni... more Experimental dog model of acute spinal cord injury. To compare the relative value of methylprednisolone, surgical decompression, or both for the treatment of traumatic spinal cord injury. Acute spinal cord injury results from both primary damage to the spinal cord at the time of the initial injury as well as a deleterious secondary cascade of events, which leads to further damage. Surgical decompression is known to improve clinical outcomes, but the timing of surgical decompression remains controversial. A nylon tie was used to constrict the spinal cord in 18 adult male beagle dogs. The animals were then prospectively randomized to 3 groups: 1) surgical decompression at 6 hours and intravenous methylprednisolone; 2) surgical decompression at 6 hours and intravenous saline; and 3) intravenous methylprednisolone without surgical decompression. Each animal was evaluated by somatosensory-evoked potentials, daily neurologic assessment, and histologic examination at 2 weeks following injury. Immediately following spinal cord constriction, all animals were paraplegic, incontinent, and the somatosensory-evoked potentials were abolished. Surgical decompression 6 hours after injury, with or without methylprednisolone, led to significantly better neurologic function at 2 weeks than methylprednisolone alone. In the setting of acute and persistent spinal cord compression in beagle dogs, surgical decompression 6 hours after injury, with or without methylprednisolone, is more effective for improving neurologic recovery than methylprednisolone alone.

New England Journal of Medicine, 2002

Background A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent ... more Background A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent of persons 50 years of age or older. Reliable predictors of progression have not been identified, and information on prognosis is limited.

New England Journal of Medicine, 2007

Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder ... more Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis. Prognostic factors for the progression and outcome of this disease are unclear.

Mayo Clinic Proceedings, 2006

To determine the relative diagnostic contribution of urine assays as part of the screening algori... more To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain kappa/lambda ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal gammopathy. Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.

Mayo Clinic Proceedings, 2009

Objective: To systematically study the association of monoclonal gammopathy of undetermined signi... more Objective: 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.

Mayo Clinic Proceedings, 1997

Mayo Clinic Proceedings, 2003

Objective: To determine the clinical and laboratory features of newly diagnosed multiple myeloma.... more Objective: To determine the clinical and laboratory features of newly diagnosed multiple myeloma. • Patients and Methods: Records of all patients in whom multiple myeloma was initially diagnosed at the Mayo Clinic in Rochester, Minn, from January 1, 1985, to December 31, 1998, were reviewed.

Mayo Clinic Proceedings, 2004

OBJECTIVE: To study the clinical course of patients with multiple myeloma (MM) that relapses afte... more OBJECTIVE: To study the clinical course of patients with multiple myeloma (MM) that relapses after initial therapy.

Mayo Clinic Proceedings, 2004

To determine the long-term outcome of patients with monoclonal gammopathy of undetermined signifi... more To determine the long-term outcome of patients with monoclonal gammopathy of undetermined significance (MGUS).

Mayo Clinic Proceedings, 2007

To assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a large ... more To assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a large Japanese population. From October 1, 1988, to March 31, 2004, a total of 52,802 (of 71,675) Japanese survivors of the atomic bomb explosion in Nagasaki City, Japan, were screened for M protein. The youngest participant was 42.3 years as of October 1, 1988. A 2-step screening was performed with a serum protein electrophoresis followed by immunoelectrophoresis and a quantitative determination of serum concentration of immunoglobulins. Twenty-one patients who were diagnosed for the first time at the time of screening as having multiple myeloma and Waldenström macroglobulinemia were excluded from analyses. Age- and sex-specific prevalence rates of MGUS were calculated. Monoclonal gammopathy of undetermined significance was identified in 1088 of the 52,781 study participants. The overall prevalence of MGUS was 2.1% (95% confidence interval [CI], 1.9%-2.2%) in the total population screened and 2.4% (95% CI, 2.0%-2.6%) in those 50 years or older. The prevalence was significantly higher in men than in women (2.8% vs 1.6%; age-adjusted odds ratio, 2.0; 95% CI, 1.8-2.3; P less than .001). In both sexes, the prevalence rose with increasing age from 1.0% in participants aged 42 to 49 years, 1.9% in those 50 to 59 years, 2.6% in those 60 to 69 years, and 3.0% in those 70 to 79 years, to 4.4% in those 80 years and older. The heavy chain isotypes of immunoglobulin were IgG in 73.6% of patients, IgA in 17.7%, IgM in 7.5%, and oligoclonal gammopathies in 1.1%. The prevalence of MGUS is lower in this Japanese population than that reported in Western countries among people older than 60 years, especially among women.

Leukemia, 2008

To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symp... more To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symptomatic multiple myeloma (MM), baseline serum samples from a well-characterized cohort of 790 newly diagnosed MM patients were tested with the FLC assay. FLC ratio was calculated as κ/λ (reference range 0.26-1.65). On the basis of the distribution of values, a cutpoint κ/λ FLC ratio of <0.03 or >32 was chosen for further analysis. Overall survival was significantly inferior in patients with an abnormal FLC ratio of <0.03 or >32 (n=479) compared with those with an FLC ratio between 0.03 and 32 (n=311), with median survival of 30 versus 39 months, respectively. We incorporated abnormal FLC ratio with the International Staging System (ISS) risk factors (that is, albumin <3.5 g/dl and serum β 2 -microglobulin ≥3.5 g/l), to create a risk stratification model with improved prognostic capabilities. Patients with 0, 1, 2 or 3 adverse risk factors had significantly different overall survival, with median survival times of 51, 39, 30 and 22 months, respectively (P<0.001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification.

The Lancet, 2010

Background Monoclonal gammopathy of undetermined signifi cance (MGUS) is defi ned by expression o... more Background Monoclonal gammopathy of undetermined signifi cance (MGUS) is defi ned 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, lightchain MGUS.