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Summary The decline in hip fracture incidence is now accompanied by a further reduction in the likelihood of a recurrent hip fracture among survivors of the first fracture. Introduction Hip fracture incidence is declining in North America, but trends in hip fracture recurrence have not been described. Methods All hip fracture events among Olmsted County, Minnesota residents in 1980-2006 were identified. Secular trends were assessed using Poisson regression, and predictors of recurrence were evaluated with Andersen-Gill time-to-fracture regression models. Results Altogether, 2,752 hip fractures (median age, 83 years; 76% female) were observed, including 311 recurrences. Between 1980 and 2006, the incidence of a first-ever hip fracture declined by 1.37%/year for women (p < 0.001) and 0.06%/year for men (p = 0.917). Among 2,434 residents with a first-ever hip fracture, the cumulative incidence of a second hip fracture after 10 years was 11% in women and 6% in men with death treated as a competing risk. Age and calendar year of fracture were independently associated with hip fracture recurrence. Accounting for the reduction in first-ever hip fracture rates over time, hip fracture recurrence appeared to decline after 1997. Conclusion A recent reduction in hip fracture recurrence is somewhat greater than expected from the declining incidence of hip fractures generally. Additional research is needed to determine the extent to which this can be attributed to improved patient management.

Multiple myeloma (MM) consists of several distinct cytogenetic subtypes, and we hypothesized that each subtype may have a unique mode of initial presentation and end-organ damage. We studied 484 patients with newly diagnosed MM to determine the relationship between specific myeloma-defining event (MDE) and the cytogenetic subtype. Patients were divided into four non-overlapping groups based on the MDE at diagnosis: isolated renal failure, isolated anemia, isolated lytic bone disease or a combination (mixed). MM with translocations without trisomies accounted for 30% of all patients, but accounted for 50% of patients with renal failure. Specifically, the t(14;16) translocation accounted for only 5% of all MM patients, but was present in 13.5% of patients with renal failure as MDE. Among patients with t(14;16), 25% presented with renal failure only as MDE. Patients with isolated renal failure as MDE had significantly poorer survival compared with all other groups, whereas patients with bone disease as MDE had the best outcome ( P <0.001). Our findings support the hypothesis that in addition to prognostic differences, there is significant heterogeneity in clinical presentation associated with the cytogenetic subtype, suggesting that MM encompasses a group of cytogenetically and phenotypically distinct disorders rather than a single entity.

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.

We hypothesized that the suppression of uninvolved immunoglobulin in monoclonal gammopathy of undetermined significance (MGUS) as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression) increases the risk of progression to malignancy. This approach required quantitation of individual heavy/light chains (for example, IgGλ in IgGκ MGUS patients). Of 1384 MGUS patients from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 999 persons. We identified HLC-pair suppression in 27% of MGUS patient samples compared with 11% of patients with suppression of uninvolved IgG, IgA or IgM. HLC-pair suppression was a significant risk factor for progression (hazard ratio (HR), 2.3; 95% confidence interval (CI) 1.5–3.7; P <0.001). On multivariate analysis, HLC-pair suppression was an independent risk factor for progression to malignancy in combination with serum M-spike size, heavy chain isotype and free light chain ratio (HR, 1.8; 95% CI, 1.1–3.00; P =0.018). The finding that HLC-pair suppression predicts progression in MGUS and occurs several years before malignant transformation has implications for myeloma biology.

Primary systemic amyloidosis is an uncommon disease characterized by deposits of fibrillar aggregates of monoclonal immunoglobulin light chains in vital organs. These amyloid deposits cause cardiac or renal dysfunction and, ultimately, death. The Mayo Clinic reported a median duration of survival of 15 months for 132 patients in 1975 and of 12 months for 229 patients in 1983. 1 , 2 In a recent series of 474 patients seen at the Mayo Clinic within 1 month of diagnosis, the median duration of survival was 13 months. 3 Because amyloid fibrils consist of monoclonal immunoglobulin light chains, treatment with alkylating agents that are effective . . .

Multiple myeloma (MM) incidence is markedly higher in blacks compared with whites, which may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS). Our objective was to define the prevalence and risk factors of MGUS in a large cohort representative of the US population. Stored serum samples from the National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999–2004 were available for 12 482 individuals of age ⩾50 years (2331 ‘blacks’, 2475 Hispanics, 7051 ‘whites’ and 625 ‘others’) on which agarose-gel electrophoresis, serum protein immunofixation, serum-free light-chain assay and M-protein typing were performed. MGUS was identified in 365 participants (2.4%). Adjusted prevalence of MGUS was significantly higher ( P <0.001) in blacks (3.7%) compared with whites (2.3%) ( P =0.001) or Hispanics (1.8%), as were characteristics that posed a greater risk of progression to MM. The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus South/West regions of the United States, respectively ( P =0.052). MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. A strong geographic disparity in the prevalence of MGUS between the North/Midwest versus the South/West regions of the United States was found, which has etiologic implications.

Summary Adjusting for age, sex, and precipitating cause, the relative risk of death was increased following fractures at most skeletal sites. Introduction This study aims to determine long-term survival following fractures due to any cause at each skeletal site. Methods In a historical cohort study, 2,901 Olmsted County, MN, USA, residents ≥35 years old who experienced any fracture in 1989–1991 were followed passively for up to 22 years for death from any cause. Standardized mortality ratios (SMRs) compared observed to expected deaths. Results During 38,818 person-years of follow-up, 1,420 deaths were observed when 1,191 were expected (SMR, 1.2; 95 % CI, 1.1–1.3). The overall SMR was greatest soon after fracture, especially among the men, but remained elevated for over a decade thereafter. Adjusting for age and sex, relative death rates were greater for pathological fractures and less for severe trauma fractures compared to the fractures due to no more than moderate trauma. In the latter group, long-term mortality was increased following fractures at many skeletal sites. After further adjustment for precipitating cause, overall SMRs were elevated not only following fractures at the traditional major osteoporotic sites (i.e., distal forearm, proximal humerus, thoracic/lumbar vertebrae, and proximal femur) combined (SMR, 1.2; 95 % CI, 1.1–1.3) but also following all other fracture types combined (SMR 1.2; 95 % CI, 1.1–1.4), excluding the hand and foot fractures not associated with any increased mortality. Conclusions The persistence of increased mortality long after the occurrence of a fracture has generally been attributed to underlying comorbidity, but this needs to be defined in much greater detail if specific opportunities are to be identified for reducing the excess deaths observed.

To describe a natural history model for primary sclerosing cholangitis (PSC) that is based on routine clinical findings and test results and eliminates the need for liver biopsy. Using the Cox proportional hazards analysis, we created a survival model based on 405 patients with PSC from 5 clinical centers. Independent validation of the model was undertaken by applying it to 124 patients who were not included in the model creation. Based on the multivariate analysis of 405 patients, a risk score was defined by the following formula: R = 0.03 (age [y]) + 0.54 loge (bilirubin [mg/dL]) + 0.54 loge (aspartate aminotransferase [U/L]) + 1.24 (variceal bleeding [0/1]) - 0.84 (albumin [g/dL]). The risk score was used to obtain survival estimates up to 4 years of follow-up. Application of this model to an independent group of 124 patients showed good correlation between estimated and actual survival. A new model to estimate patient survival in PSC includes more reproducible variables (age, bilirubin, albumin, aspartate aminotransferase, and history of variceal bleeding), has accuracy comparable to previous models, and obviates the need for a liver biopsy.

Serum from almost 80 percent of the residents of Olmsted County, Minnesota, was screened for the presence of a monoclonal gammopathy of undetermined significance. Small amounts of monoclonal immunoglobulin were found in 3.2 percent of persons 50 years of age or older and in 5.3 percent of persons 70 years of age or older. Small amounts of monoclonal immunoglobulin were found in 3.2 percent of persons 50 years of age or older and in 5.3 percent of persons 70 years of age or older. Although multiple myeloma is the prototypical monoclonal gammopathy, the most common plasma-cell disorder is the premalignant precursor of myeloma, monoclonal gammopathy of undetermined significance (MGUS). MGUS is defined by a monoclonal immunoglobulin concentration in serum of 3 g per deciliter or less; the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the proliferation of monoclonal plasma cells; and a proportion of plasma cells in the bone marrow of 10 percent or less. 1 – 3 In large referral centers, half the patients with a monoclonal gammopathy have MGUS, whereas only 15 to 20 percent have multiple myeloma. MGUS . . .

Study Design: Retrospective chart review. Objectives: To identify factors predictive of survival after spinal cord injury (SCI). Setting: Tertiary care institution. Methods: Multiple-variable Cox proportional hazards regression analysis for 759 patients with SCI (535 nontraumatic and 221 traumatic) included age, sex, completeness of injury, level of injury, functional independence measure (FIM) scores, rehabilitation length of stay and SCI cause. Estimated years of life lost in the decade after injury was calculated for patients vs uninjured controls. Results: Median follow-up was 11.4 years. Population characteristics included paraplegia, 58%; complete injury, 11%; male sex, 64%; and median rehabilitation length of stay, 16 days. Factors independently predictive of decreased survival were increased age (+10 years; hazard ratio (HR (95% CI)), 1.6 (1.4–1.7)), male sex (1.3 (1.0–1.6)), lower dismissal FIM score (−10 points; 1.3 (1.2–1.3)) and all nontraumatic causes. Metastatic cancer had the largest decrease in survival (HR (95% CI), 13.3 (8.7–20.2)). Primary tumors (HR (95% CI), 2.5 (1.7–3.8)), vascular (2.5 (1.6–3.8)), musculoskeletal/stenosis (1.7 (1.2–2.5)) and other nontraumatic SCI (2.3 (1.5–3.6)) were associated with decreased survival. Ten-year survival was decreased in nontraumatic SCI (mean (s.d.), 1.8 (0.3) years lost), with largest decreases in survival for metastatic cancer and spinal cord ischemia. Conclusions: Age, male sex and lower dismissal FIM score were associated with decreased survival, but neither injury severity nor level was associated with it. Survival after SCI varies depending on SCI cause, with survival better after traumatic SCI than after nontraumatic SCI. Metastatic cancer and vascular ischemia were associated with the greatest survival reduction.