Poststroke hip fracture: Prevalence, clinical characteristics, mineral-bone metabolism, outcomes, and gaps in prevention

Objective. To assess the prevalence, clinical and laboratory characteristics, and short-term outcomes of poststroke hip fracture (HF). Methods. A cross-sectional study of 761 consecutive patients aged ≥60 years (82.3±8.8 years; 75% females) with osteo

Directional migration of recirculating lymphocytes through lymph nodes via random walks.

Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator (LASSO) or regularised S-LASSO to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node insilico. On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times) of discrete one dimensional and continuous (Brownian) three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean) fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen presenting cells carrying cognate antigen

Generation of cardio-protective antibodies after pneumococcal polysaccharide vaccine: Early results from a randomised controlled trial.

BACKGROUND AND AIMS: Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years. METHODS: A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH). RESULTS: Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up. CONCLUSIONS: PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events

Lower serum PINP/beta CTX ratio and hypoalbuminemia are independently associated with osteoporotic nonvertebral fractures in older adults

PURPOSE: To estimate the discriminative value of serum P1NP/βCTX ratio and albumin levels in hospitalized orthogeriatric patients with and without nonvertebral fractures. METHODS: In 1,239 orthogeriatric patients (mean age 78.1±9.52 years, 69.1% women) including 854 (68.9%) with osteoporotic nonvertebral fractures (455 [36.7%] with hip fracture [HF]) and 385 (31.1%) without fractures, markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], and bone resorption (beta-C-terminal cross-linking telopeptide of type 1 collagen [βCTX]), indices of mineral metabolism, and parameters of liver and renal functions were assessed; data on clinical and laboratory characteristics were collected prospectively. RESULTS: Both lower serum P1NP/βCTX ratio and albumin concentration (as continuous or categorical variables) were independently associated with fracture presence in multivariate logistic regressions. Compared with the highest P1NP/βCTX tertile, the prevalence of HF, after adjustment for multiple covariates, was 3-fold higher in the lowest tertile and 1.5 times higher in the middle tertile; presence of any fracture was 2.3- and 1.6-fold higher, respectively; patients with albumin levels in the lowest tertile had multivariate odds ratio (OR) of 4.6 for HF and 2.8 for any fracture, in the middle tertile the ORs were 2.2 and 1.3, respectively. The P1NP/βCTX <100.0 (median) and hypoalbuminemia (<33 g/L) demonstrated area under the curve values for HF of 0.802 and 0.806, respectively, and for any fractures of 0.711 and 0.706, respectively. When both characteristics were combined, the ORs for HF or any fracture, compared with the nonfractured group, were 7.8 and 3.2, respectively, with an accuracy of 79.6% and 71.6%, respectively. CONCLUSIONS: In orthogeriatric patients, both serum P1NP/βCTX ratio and albumin levels demonstrated an inverse dose-effect relationship with the prevalence of nonvertebral fractures and independently indicated fracture presence with acceptable discriminatory power. Lower P1NP/βCTX (<100) and hypoalbuminemia could be useful simple additive prognostic tools for fracture risk stratification in the elderly

The Neutrophil to Lymphocyte Ratio on Admission and Short-Term Outcomes in Orthogeriatric Patients

AIM: To investigate the association of the neutrophil to lymphocyte ratio (NLR) at admission with presence of fracture, comorbid conditions, and its prognostic value for short-term outcomes in orthogeriatric patients. METHODS: On 415 consecutive patients (mean age 78.8 ±8.7[SD] years, 281 women, 255 with a non-vertebral bone fracture, including 167 with a hip fracture, HF) admitted to the Department of Orthopaedic Surgery at the Canberra hospital (2010 - 2011) data on clinical and laboratory characteristics were collected prospectively. The validation dataset included 294 consecutive patients (mean age 82.1 ± 8.0 years, 72.1% women) with HF. RESULTS: Multivariate regression revealed four variables, presence of HF, hypoalbuminaemia (6.8 pmol/L), as independent determinants of admission NLR≥5.1. There was a dose-graded relationship between presence of fracture, especially HF, postoperative complications and levels of NLR categorized as tertiles. Compared to patients with NLR100mg/L after the 3rd postoperative day), respectively, while in subjects with NLR>8.5 (third tertile) these risks were 2.6-, 4.9-, 5.9- and 4.5-times higher, respectively; subjects with NLR>8.5 had a 9.7 times higher chance of dying in the hospital compared to patients with NLR 5.1-8.5; the NLR retained its significance on multivariate analyses. The NLR ≥5.1 predicted postoperative myocardial injury with an area under the curve (AUC) of 0.626, CRP>100mg/L with AUC of 0.631 and the NLR >8.5 predicted in-hospital mortality with an AUC of 0.793, showing moderately high sensitivity (86.7%, 80% and 90%, respectively) and negative predictive value (92.9%, 71.2%, 99.6%, respectively), but low specificity. Admission NLR was superior to other, except hypoalbuminaemia, prognostic markers; combined use of both NLR≥5.1 and albumin<33g/L only moderately increased the accuracy of prediction. The validation study confirmed the prognostic value of the admission NLR. CONCLUSIONS: In orthogeriatric patients, high NLR on admission is an independent indicator of fracture presence, a significant risk factor and moderate predictor of postoperative myocardial injury, high inflammatory response/infection and in-hospital death

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

A Fisher,1,3 W Srikusalanukul,1 M Davis,1,3 P Smith2,31Departments of Geriatric Medicine, 2Orthopaedic Surgery, The Canberra Hospital, 3Australian National University Medical School, Canberra, ACT, AustraliaBackground: Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures.Aims and methods: To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured.Results: CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P &lt; 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH &gt; 6.8 pmol/L, 43.0% vs 23.3%, P &lt; 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] &gt; 7.5 nmol/&micro;mol, 87.9% vs 74.8%, P &lt; 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P &lt; 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death.Conclusion: SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets.Keywords: cardiovascular disease, hip fracture, PTH, 25(OH)D, secondary hyperparathyroidism, bone turnover, mineral metabolis

Does heart rate predict mortality in older, low-level care residents?

To determine whether abnormalities in heart rate (HR) were associated with long-term mortality in older, low-level care residents, 179 randomly selected persons aged 65 and older (mean, 83.2+/-7.0 [SD] years; 80% women) were prospectively assessed. At baseline, duplicate measurements of HR and blood pressure were recorded in the supine position and after standing. During the 5-year follow-up period, 97 (54%) participants died. Cox survival analysis revealed no association with total mortality when resting HR was analyzed as a continuous or categoric variable ( 90 bpm). However, HR > or = 90 bpm was associated with increased risk of dying in residents who used a walking aid (relative risk, 3.48; 95% confidence interval, 1.07-11.30; p=0.038). Postural HR change was not associated with mortality risk. The authors concluded that resting HR and postural change in HR are not significant predictors of 5-year mortality in older, low-level care residents, except in persons using a walking aid

Elevated Serum PTH Is Independently Associated with Poor Outcomes in Older Patients with Hip Fracture and Vitamin D Inadequacy

To determine whether serum 25(OH)D and/or PTH levels in older patients with hip fracture (HF) could predict short-term clinical outcomes, we conducted a prospective observational study of 287 consecutive HF patients (mean age 81.9 ± 7.5 [SD] years, 72%

Bone Turnover Status: Classification Model and Clinical Implications

Aim: To develop a practical model for classification bone turnover status and evaluate its clinical usefulness. Methods: Our classification of bone turnover status is based on internationally recommended biomarkers of both bone formation (N-terminal propeptide of type1 procollagen, P1NP) and bone resorption (beta C-terminal cross-linked telopeptide of type I collagen, bCTX), using the cutoffs proposed as therapeutic targets. The relationships between turnover subtypes and clinical characteristic were assessed in1223 hospitalised orthogeriatric patients (846 women, 377 men; mean age 78.1±9.50 years): 451(36.9%) subjects with hip fracture (HF), 396(32.4%) with other non-vertebral (non-HF) fractures (HF) and 376 (30.7%) patients without fractures. Resalts: Six subtypes of bone turnover status were identified: 1 - normal turnover (P1NP>32 μg/L, bCTX≤0.250 μg/L and P1NP/bCTX>100.0[(median value]); 2- low bone formation (P1NP ≤32 μg/L), normal bone resorption (bCTX≤0.250 μg/L) and P1NP/bCTX>100.0 (subtype2A) or P1NP/bCTX0.250 μg/L) and P1NP/bCTX100.0 (subtype 4A) or P1NP/bCTX75 years and hyperparathyroidism. Hypoalbuminaemia and not using osteoporotic therapy were two independent indicators common for subtypes 3, 4A and 4B; these three subtypes were associated with in-hospital mortality. Subtype 3 was associated with fractures (OR 1.7, for HF OR 2.4), age>75 years, chronic heart failure (CHF), anaemia, and history of malignancy, and predicted post-operative myocardial injury, high inflammatory response and length of hospital stay (LOS) above10 days. Subtype 4A was associated with chronic kidney disease (CKD), anaemia, history of malignancy and walking aids use and predicted LOS>20 days, but was not discriminative for fractures. Subtype 4B was associated with fractures (OR 2.1, for HF OR 2.5), age>75 years, CKD and indicated risks of myocardial injury, high inflammatory response and LOS>10 days. Conclusions: We proposed a classification model of bone turnover status and demonstrated that in orthogeriatric patients altered subtypes are closely related to presence of nonvertebral fractures, comorbidities and poorer in-hospital outcomes. However, further research is needed to establish optimal cut points of various biomarkers and improve the classification model