Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells (PCs) in the bone marrow (BM). MM is viewed as a clonal disorder due to lack of verified intraclonal sequence diversity in the immunoglobulin heavy chain variable region gene (IGHV). However, this conclusion is based on analysis of a very limited number of IGHV subclones and the methodology employed did not permit simultaneous analysis of the IGHV repertoire of non-malignant PCs in the same samples. Here we generated genomic DNA and cDNA libraries from purified MM BMPCs and performed massively parallel pyrosequencing to determine the frequency of cells expressing identical IGHV sequences. This method provided an unprecedented opportunity to interrogate the presence of clonally related MM cells and evaluate the IGHV repertoire of non-MM PCs. Within the MM sample, 37 IGHV genes were expressed, with 98.9% of all immunoglobulin sequences using the same IGHV gene as the MM clone and 83.0% exhibiting exact nucleotide sequence identity in the IGHV and heavy chain complementarity determining region 3 (HCDR3). Of interest, we observed in both genomic DNA and cDNA libraries 48 sets of identical sequences with single point mutations in the MM clonal IGHV or HCDR3 regions. These nucleotide changes were suggestive of putative subclones and therefore were subjected to detailed analysis to interpret: 1) their legitimacy as true subclones; and 2) their significance in the context of MM. Finally, we report for the first time the IGHV repertoire of normal human BMPCs and our data demonstrate the extent of IGHV repertoire diversity as well as the frequency of clonally-related normal BMPCs. This study demonstrates the power and potential weaknesses of in-depth sequencing as a tool to thoroughly investigate the phylogeny of malignant PCs in MM and the IGHV repertoire of normal BMPCs.

Objectives

Obesity is protective for the development of hip fractures yet a risk factor for cardiac disease. Whether obesity impacts cardiac complications following hip fracture repair is unknown.

Design

A population-based, historical study using the Rochester Epidemiology Project

Setting

Olmsted County, Minnesota

Participants

All urgent hip fracture repairs between 1988–2002.

Measurements

Body mass index (BMI) was categorized as underweight (<18.5kg/m2), normal (18.5–24.9kg/m2), overweight (25.0–29.9kg/m2) and obese (≥30kg/m2). Post-operative cardiac complications were defined as myocardial infarction, angina, congestive heart failure, or new-onset arrhythmias within one-year of surgery. Incidence rates were estimated for each outcome and overall cardiac complications were assessed using Cox proportional hazard models, adjusted for age, sex, year of surgery, use of beta-blockers and the Revised Cardiac Risk Index.

Results

There were 184 (15.6%) underweight, 640 (54.2%) normal, 251 (21.3%) overweight, and 105 (8.9%) obese hip fracture repairs (mean age, 84.2±7.5 years; 80% female). Baseline American Society of Anesthesia status was similar among all groups (ASA I/II vs. III–V, p=0.14). Underweight patients had a significantly higher risk of developing myocardial infarction (odds ratio [OR] 1.44; 95%CI 1.0–2.1; p=0.05) and arrhythmias (OR 1.59; 95%CI:1.0–2.4;p=0.04) than normal BMI patients. Multivariate analysis demonstrated underweight patients had a higher risk of developing an adverse cardiac event of any type (OR 1.56; 95%CI:1.22–1.98; p<0.001). Overweight and obese hip fracture patients had no excess risk of any cardiac complication.

Conclusion

The obesity paradox and low functional reserve in underweight patients may influence the development of post-operative cardiac events in this elderly hip fracture population.

BACKGROUND

Hip operation (total hip arthroplasty [THA] or fracture repair) is the most common noncardiac surgical procedure performed in patients age 65 years and older.

OBJECTIVE

To determine the predictors of ischemic stroke in patients who have undergone hip operation.

DESIGN

Population-based historical cohort study, in which postoperative ischemic strokes were identified from medical record review for stroke diagnostic codes and brain imaging results and were confirmed by physician review.

SETTING

Tertiary care center in Olmsted County, Minnesota.

PATIENTS

Residents of Olmsted County who underwent hip surgical procedure.

MEASUREMENTS

Incidence of ischemic stroke within 1 year of hip operation.

RESULTS

In total, 1606 patients underwent 1886 hip procedures from 1988 through 2002 and were observed for ischemic stroke for 1 year after their procedure. Sixty-seven ischemic strokes were identified. The rate of stroke at 1 year after hip operation was 3.9%. In univariate analysis, history of atrial fibrillation (hazard ratio [HR], 2.16; P = 0.005), hip fracture repair vs. total hip arthroplasty (HR, 3.80; P < 0.001), age 75 years or older (HR, 2.20; P = 0.02), aspirin use (HR, 1.8; P = 0.01), and history of previous stroke (HR, 4.18; P < 0.001) were significantly associated with increased risk of stroke. In multivariable analysis, history of stroke (HR, 3.27; P < 0.001) and hip fracture repair (HR, 2.74; P = 0.004) were strong predictors of postoperative stroke.

CONCLUSIONS

This population-based historical cohort of patients with hip operation had a 3.9% cumulative probability of ischemic stroke over the first postoperative year. Hip fracture repair and history of stroke were the strongest predictors of this complication.

Background

Obese patients are thought to be at higher risk of post-operative medical complications. We sought to determine whether body mass index (BMI) is associated with post-operative in-hospital non-cardiac complications following urgent hip fracture repair.

Methods

We conducted a population-based study of Olmsted County, Minnesota residents operated for hip fracture in 1988–2002. BMI was categorized as underweight (<18.5kg/m2), normal (18.5–24.9kg/m2), overweight (25.0–29.9kg/m2) and obese (≥30kg/m2). Post-operative inpatient non-cardiac medical complications were assessed. Complication rates were estimated for each BMI category and overall complication rates were assessed using logistic regression models adjusted for age, sex, calendar year, and American Society of Anesthesia (ASA) class.

Results

There were 184 (15.6%) underweight, 640 (54.2%) normal, 251 (21.3%) overweight, and 105 (8.9%) obese hip fracture repairs (mean age, 84.2±7.5 years; 80% female). No significant difference was found among the BMI categories for baseline ASA status (ASA III–IV vs. I–II; p=0.14). After adjustment, the risk of developing an inpatient non-cardiac complication for each BMI category, compared to normal BMI, was: underweight (OR 1.33; 95%CI: 0.95–1.88; p=0.10), overweight (OR 1.01;95%CI: 0.74–1.38; p=0.95), and obese (OR 1.28;95%CI: 0.82–1.98; p=0.27). Multivariate analysis using stepwise selection demonstrated that an ASA status of III–V vs. I–II(OR 1.84, 95%CI: 1.25–2.71; p=0.002), a history of chronic obstructive pulmonary disease or asthma (OR 1.58; 95%CI: 1.18–2.12; p=0.002), male sex (OR 1.49, 95%CI:1.10–2.02; p=0.01) and older age (OR 1.05;95%CI: 1.03–1.06; p<0.001), significantly contributed to an increased risk of developing a post-operative non-cardiac inpatient complication. Underweight patients had higher in-hospital mortality rates than normal BMI patients (9.3 vs. 4.4%; p=0.01).

Conclusions

BMI has no significant influence on post-operative non-cardiac medical complications in hip fracture patients. These results attenuate concerns that obese or frail underweight hip fracture patients may be at higher risk post-operatively for inpatient complications.

Background

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been shown to be useful for diagnosis of prosthetic hip and knee infection. Little information is available on CRP and ESR in patients undergoing revision or resection of shoulder arthroplasties or spine implants.

Methods/Results

We analyzed preoperative CRP and ESR in 636 subjects who underwent knee (n = 297), hip (n = 221) or shoulder (n = 64) arthroplasty, or spine implant (n = 54) removal. A standardized definition of orthopedic implant-associated infection was applied. Receiver operating curve analysis was used to determine ideal cutoff values for differentiating infected from non-infected cases. ESR was significantly different in subjects with aseptic failure infection of knee (median 11 and 53.5 mm/h, respectively, p = <0.0001) and hip (median 11 and 30 mm/h, respectively, p = <0.0001) arthroplasties and spine implants (median 10 and 48.5 mm/h, respectively, p = 0.0033), but not shoulder arthroplasties (median 10 and 9 mm/h, respectively, p = 0.9883). Optimized ESR cutoffs for knee, hip and shoulder arthroplasties and spine implants were 19, 13, 26, and 45 mm/h, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 89 and 74% for knee, 82 and 60% for hip, and 32 and 93% for shoulder arthroplasties, and 57 and 90% for spine implants. CRP was significantly different in subjects with aseptic failure and infection of knee (median 4 and 51 mg/l, respectively, p<0.0001), hip (median 3 and 18 mg/l, respectively, p<0.0001), and shoulder (median 3 and 10 mg/l, respectively, p = 0.01) arthroplasties, and spine implants (median 3 and 20 mg/l, respectively, p = 0.0011). Optimized CRP cutoffs for knee, hip, and shoulder arthroplasties, and spine implants were 14.5, 10.3, 7, and 4.6 mg/l, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 79 and 88% for knee, 74 and 79% for hip, and 63 and 73% for shoulder arthroplasties, and 79 and 68% for spine implants.

Conclusion

CRP and ESR have poor sensitivity for the diagnosis of shoulder implant infection. A CRP of 4.6 mg/l had a sensitivity of 79 and a specificity of 68% to detect infection of spine implants.