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1.
Medicine (Baltimore) ; 103(18): e38063, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701306

ABSTRACT

In this research, we aimed to investigate the predictive value of the systemic immune inflammation index and prognostic nutritional index on mortality among patients with an endoprosthesis after a hip fracture. In this retrospective, cross-sectional study, a total of 915 patient files applied to our hospital between 2020 and 2023 with an endoprosthesis after a hip fracture were subjected to the study. The patients were divided into 2 groups: alive (n = 396; 43.3%) and deceased (n = 519; 56.7%). The eosinophil-to-lymphocyte ratio, hemoglobin-to-red cell distribution width ratio (HRR), mean platelet volume-to-platelet ratio (MPVPR), neutrophil-to-lymphocyte ratio, monocyte/lymphocyte ratio, platelet-to-lymphocyte ratio, MPV-to-lymphocyte ratio, monocyte-to-eosinophil ratio (MER), neutrophile-to-monocyte ratio, systemic inflammation index (SII), and prognostic nutritional index (PNI) parameters of the patients were evaluated. The mortality rate was higher among male patients, with a statistically significant difference (P < .05). The follow-up duration, albumin, HGB, eosinophil, lymphocyte, eosinophil %, eosinophil-to-lymphocyte ratio, HRR, and PNI means were significantly higher in the living group (P < .05). Age, MPV, MPVPR, neutrophil-to-lymphocyte ratio, monocyte/lymphocyte ratio, platelet-to-lymphocyte ratio, MPV-to-lymphocyte ratio, MER, and systemic inflammation index were significantly higher in the deceased group (P < .05). The predictive value of gender (B = -0.362; P < .01), age (B = 0.036; P < .01), HRR (B = -1.100; P < .01), MPVPR (B = 8.209; P < .01), MER (B = 0.006; P < .01), and PNI (B = -0.078; P < .01) were statistically significant at the multivariate level. The time of death was significantly predicted by gender (B = 0.10; P < .05), age (B = -0.02; P < 0 = 1), HRR (B = 0.61; P < .01), MPVPR (r = -4.16; P < .01), MER (B = -0.01; P < .05), and PNI (B = 0.03; P < .01). The predictive value of PNI for the 30-day mortality rate was statistically significant (AUC: 0.643; P < .01). For a PNI cutoff value of 34.475, sensitivity was 69.7%, and specificity was 51.1%. The PNI has predictive value both in estimating overall mortality and in predicting the 30-day mortality rates among patients undergoing endoprosthesis after a hip fracture.


Subject(s)
Hip Fractures , Inflammation , Nutrition Assessment , Predictive Value of Tests , Humans , Male , Female , Hip Fractures/mortality , Hip Fractures/immunology , Hip Fractures/surgery , Hip Fractures/blood , Retrospective Studies , Aged , Cross-Sectional Studies , Prognosis , Aged, 80 and over , Middle Aged
2.
J Orthop Surg Res ; 16(1): 681, 2021 Nov 18.
Article in English | MEDLINE | ID: mdl-34794459

ABSTRACT

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is a crucial prognosis predictor following several major operations. However, the association between NLR and the outcome after hip fracture surgery is unclear. In this meta-analysis, we investigated the correlation between NLR and postoperative mortality in geriatric patients following hip surgery. METHOD: PubMed, Embase, Cochrane library, and Google Scholar were searched for studies up to June 2021 reporting the correlation between NLR and postoperative mortality in elderly patients undergoing surgery for hip fracture. Data from studies reporting the mean of NLR and its 95% confidence interval (CI) were pooled. Both long-term (≥ 1 year) and short-term (≤ 30 days) mortality rates were included for analysis. RESULT: Eight retrospective studies comprising a total of 1563 patients were included. Both preoperative and postoperative NLRs (mean difference [MD]: 2.75, 95% CI: 0.23-5.27; P = 0.03 and MD: 2.36, 95% CI: 0.51-4.21; P = 0.01, respectively) were significantly higher in the long-term mortality group than in the long-term survival group. However, no significant differences in NLR were noted between the short-term mortality and survival groups (MD: - 1.02, 95% CI: - 3.98 to 1.93; P = 0.5). CONCLUSION: Higher preoperative and postoperative NLRs were correlated with a higher risk of long-term mortality following surgery for hip fracture in the geriatric population, suggesting the prognostic value of NLR for long-term survival. Further studies with well-controlled confounders are warranted to clarify the predictive value of NLR in clinical practice in geriatric patients with hip fracture.


Subject(s)
Hip Fractures , Lymphocytes , Neutrophils , Orthopedic Procedures/mortality , Aged , Aged, 80 and over , Biomarkers/blood , Hip Fractures/blood , Hip Fractures/immunology , Hip Fractures/mortality , Hip Fractures/surgery , Humans , Leukocyte Count , Orthopedic Procedures/adverse effects , Postoperative Period , Predictive Value of Tests , Prognosis , Retrospective Studies
3.
Front Immunol ; 11: 571759, 2020.
Article in English | MEDLINE | ID: mdl-33072114

ABSTRACT

Background: Hip fracture (HF) is common in the geriatric population and is associated with a poor vital and functional prognosis which could be impacted by immunological changes. The objective here is to decipher immune changes occurring in the 1st days following HF and determine how phenotype, function, and regulation of innate and adaptive compartments adapt during acute stress event. Methods: We included HF patients, aged over 75 years. For each patient, blood samples were taken at five different timepoints: four in the perioperative period (day 0 to hospital discharge) and one at long term (6-12 months). Phenotypical and functional analysis were performed longitudinally on fresh blood or cryopreserved PBMCs. Clinical data were prospectively collected. Results: One-hundred HF patients and 60 age-matched controls were included. Innate compartment exhibits pro-inflammatory phenotypes (hyperleukocytosis, increase of CD14+ CD16+ proportion and CCR2 expression), maintaining its ability to produce pro-inflammatory cytokines. Adaptive compartment extends toward a transitory immunosuppressive profile (leucopenia) associated with an active T-cell proliferation. Furthermore, increases of LAG-3 and PD-1 and a decrease of 2-B4 expression are observed on T-cells, reinforcing their transitory suppressive status. Of note, these immune changes are transitory and sequential but may participate to a regulation loop necessary for homeostatic immune control at long term. Conclusion: HF is associated with several transitory immunological changes including pro-inflammatory phenotype in innate compartment and immunosuppressive profile in adaptive compartment. A comprehensive assessment of immune mechanisms implicated in the patient's prognosis after HF could pave the way to develop new immune therapeutics strategies.


Subject(s)
Hip Fractures/immunology , Inflammation/immunology , T-Lymphocytes/immunology , Adaptive Immunity , Aged , Aged, 80 and over , Cells, Cultured , Female , Homeostasis , Humans , Immunity, Innate , Immunosuppression Therapy , Leukocytosis , Lymphocyte Activation , Male , Perioperative Period , Programmed Cell Death 1 Receptor/metabolism
4.
Osteoporos Int ; 30(5): 1025-1031, 2019 May.
Article in English | MEDLINE | ID: mdl-30701344

ABSTRACT

Mortality and remaining bedridden following the hip fracture surgery are not rare. We tried to measure the levels of inflammatory markers tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) following the hip fracture surgery and compare their levels with controls. We aimed to show a relationship between the levels of these markers and post-operative mortality and walking capability. INTRODUCTION: Osteoporosis is a condition, causing the hip fractures in the elderly. Hip fractures have a high rate of overall mortality up to 30% following the incident. Cytokines such as IL-6 and TNF-α are suggested to play a role in bone resorption and, thus, in the etiology of osteoporosis. METHODS: Plasma levels of IL-6 and TNF-α were measured pre-operatively and on the first and second days after the surgery in 40 Turkish hip fracture patients. The levels of these cytokines were compared with 40 Turkish age-matched healthy controls. The levels of these cytokines were compared between the deceased and surviving patients, as well as the existence of walking capability following the surgery. RESULTS: Significantly higher IL-6 levels were shown on the first and second days after the surgery (p = 0.005; p = 0.01, respectively). The overall death rate of our study group within the 2-year follow-up time was found to be 35%. No statistical significance was found in the means of 2-year follow-up mortality between the patients. Presence of walking capability did not differ between the patients, as well. CONCLUSION: We demonstrated an association between IL-6 levels and hip fracture in our study group following the surgery. We also suggest that TNF-α and IL-6 levels are not related to the occurrence of death and walking capability after the surgery. However, these findings need further functional and clinical confirmation.


Subject(s)
Hip Fractures/immunology , Inflammation Mediators/metabolism , Interleukin-6/blood , Osteoporotic Fractures/immunology , Tumor Necrosis Factor-alpha/blood , Aged , Biomarkers/blood , Case-Control Studies , Female , Follow-Up Studies , Hip Fractures/mortality , Hip Fractures/surgery , Humans , Male , Middle Aged , Osteoporotic Fractures/mortality , Osteoporotic Fractures/surgery , Postoperative Period , Preoperative Period , Prognosis , Turkey/epidemiology , Walking
5.
J Orthop Surg Res ; 13(1): 17, 2018 Jan 22.
Article in English | MEDLINE | ID: mdl-29357879

ABSTRACT

BACKGROUND: Hip fracture is commonly associated with an overwhelming inflammatory response, which may lead to high rates of morbidity and mortality in the elderly. MicroRNAs (miRNAs) play important roles in the functions of immune system. However, the association between miRNA dysregulation and immune disturbance (IMD) related to elderly hip fracture is largely unknown. METHODS: In this study, microarray profiling was carried out to evaluate the differential expression patterns of miRNAs in plasma of the aged hip fracture rats with IMD, those without IMD, and normal aged rats, followed by validation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Genes and signaling pathways of the dysregulated miRNAs related to elderly hip fracture-induced IMD were investigated in silico using Gene Ontology and analysis of Kyoto Encyclopedia of Genes or Genomes. RESULTS: Dead or moribund rats with hip fracture exhibited significantly reduced TNF-α/IL-10 ratio compared with healthy controls and other hip fracture rats, which were therefore named as hip fracture rats with IMD. Seven serum miRNAs in hip fracture rats with IMD were significantly downregulated. qRT-PCR and in silico analysis revealed that miR-130a-3p likely participated in regulating the hip fracture-induced IMD. Furthermore, Western blot experiment demonstrated that in lung tissue, the reduction of miR-130a-3p was accompanied with the increase of the protein expression of interferon regulatory factor-1 (IRF1) and sphingosine-1-phosphate receptor 1 (SIPR1). CONCLUSIONS: miR-130a-3p desregulation may be associated with elderly hip fracture-induced IMD, which might act as a new potential biomarker for the diagnosis and prognosis of elderly hip fracture-induced IMD and a potential therapeutic target as well.


Subject(s)
Hip Fractures/genetics , Hip Fractures/immunology , MicroRNAs/immunology , Animals , Down-Regulation/immunology , Gene Expression Profiling/methods , Gene Expression Regulation/immunology , Gene Regulatory Networks/immunology , Interferon Regulatory Factor-1/biosynthesis , Interleukin-10/blood , Lung/metabolism , Male , MicroRNAs/genetics , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Receptors, Lysosphingolipid/biosynthesis , Sphingosine-1-Phosphate Receptors , Tumor Necrosis Factor-alpha/blood , Up-Regulation/immunology
6.
Injury ; 48(2): 454-459, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28073488

ABSTRACT

INTRODUCTION: Hip fracture in the elderly can induce systemic inflammatory response (SIRS) and lung injury which increases the risk of lung infection and death. Mitochondrial DNA (mtDNA) plays a role in SIRS and lung injury in patients with multi-trauma, and also in patients with hip fractures. This study evaluated the potential value of plasma mtDNA in the early prognosis of lung injury in elderly fracture patients. METHODS: This study enrolled 156 elderly patients with intertrochanteric fracture. Plasma mtDNA, IL-6, IL-10, prostaglandin E2 (PGE2) levels were measured at admission. Sixty-one and 31 patients were diagnosed with systemic inflammatory response syndrome (SIRS) and lung injury, respectively. RESULTS: Plasma mtDNA levels were higher in hip fracture patients compared to healthy controls (P<0.001) and significantly higher in the lung injury subgroup compared to the lung injury absent subgroup (P<0.001). MtDNA levels were correlated with the SIRS score (r=0.446, P<0.001), IL-6 (r=0.506, P<0.001), IL-10 (r=0.523, P<0.001), and PGE2 (r=0.360, P<0.001). Logistic regression analysis revealed that plasma mtDNA, IL-6, PGE2 and SIRS score were independent predictors of the risk of lung injury. CONCLUSION: Plasma mtDNA release induced by hip fracture in elderly patients, might be an early predictor of lung injury in these patients.


Subject(s)
DNA, Mitochondrial/blood , Hip Fractures/blood , Hip Fractures/complications , Lung Injury/blood , Lung Injury/complications , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/complications , Aged , China/epidemiology , Dinoprostone/blood , Dinoprostone/immunology , Female , Hip Fractures/immunology , Humans , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-6/blood , Interleukin-6/immunology , Lung Injury/immunology , Lung Injury/physiopathology , Male , Predictive Value of Tests , Prospective Studies , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/physiopathology
7.
Biogerontology ; 17(1): 229-39, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26112234

ABSTRACT

Hip fracture is a common physical trauma in older adults that is also associated with a high incidence of new onset depression. The immune system declines with age and is also compromised by physical and psychological stress. This study examined whether hip fracture and depressive symptoms had additive effects upon the aged immune system that might contribute to poor health outcomes after hip fracture. We assessed the frequency of regulatory T cells, Tregs (CD4(+) CD25(+) Foxp3(+)) and IL10 production by CD4 T cells, and the frequency and IL10 production by regulatory B cells, Bregs (CD19(+) CD24(hi) CD38(hi)) in 101 hip fracture patients (81 female) 6 weeks after injury and 43 healthy age-matched controls (28 female). 38 hip fracture patients (37%) developed depressive symptoms. Hip fracture did not have an effect on circulating Tregs frequency but a significant reduction in the frequency of Bregs was observed in patients who developed depression compared with non-depressed patients (p = 0.001) or healthy controls (p < 0.001). Bregs also showed a significant decline in IL10 production in depressed hip fracture patients compared with controls (p = 0.04) and non-depressed patients (p = 0.01). In contrast, there was an increase in IL10 production by CD4 T cells in hip fracture patients with new onset depression compared to hip fracture patients without depression (p = .04) and healthy controls (p = .02). We conclude that the reduced immunity associated with new onset depression post hip fracture could include a contribution by heightened Tregs function.


Subject(s)
B-Lymphocytes/immunology , Depression/immunology , Hip Fractures/immunology , Immune Tolerance/immunology , Immunosenescence/immunology , T-Lymphocytes, Regulatory/immunology , Adaptive Immunity/immunology , Aged , Aged, 80 and over , Aging/immunology , Cytokines/immunology , Depression/etiology , Female , Hip Fractures/complications , Humans , Male , Middle Aged
8.
Mediators Inflamm ; 2015: 587378, 2015.
Article in English | MEDLINE | ID: mdl-26273137

ABSTRACT

Conventional concept suggests that immediate surgery is the optimal choice for elderly hip fracture patients; however, few studies focus on the adverse effect of immediate surgery. This study aims to examine the adverse effect of immediate surgery, as well as to explore the meaning of mtDNA release after trauma. In the experiment, elderly rats, respectively, received hip fracture operations or hip fracture plus intramedullary nail surgery. After fracture operations, the serum mtDNA levels as well as the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. After immediate surgery, the above variables were further increased. The serum mtDNA levels were significantly related with the serum cytokine (TNF-α and IL-10) levels and pulmonary histological score. In order to identify the meaning of mtDNA release following hip fracture, the elderly rats received injections with mtDNA. After treatment, the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. These results demonstrated that the immediate surgery increased the mtDNA release that could aggravate systemic inflammatory response and lung injury induced by elderly hip fracture; serum mtDNA might serve as a potential biomarker of systemic inflammatory response and lung injury following elderly hip fracture.


Subject(s)
DNA, Mitochondrial/metabolism , Fracture Fixation, Intramedullary/adverse effects , Hip Fractures/immunology , Hip Fractures/surgery , Inflammation/immunology , Lung Injury/immunology , Animals , DNA, Mitochondrial/blood , Inflammation/etiology , Interleukin-10/blood , Lung Injury/etiology , Male , Rats , Rats, Sprague-Dawley , Time Factors , Tumor Necrosis Factor-alpha/blood
9.
Age (Dordr) ; 37(1): 9748, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25663421

ABSTRACT

NK cell cytotoxicity (NKCC) reduces with age and this has been associated previously with increased mortality. The immune response is also modulated by stress, and here, we assessed the effect of the physical stress of hip fracture and the psychological stress of depression on NKCC in an aged immune system. NKCC was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and in 50 healthy age-matched controls (28 female). Thirty-eight patients were depressed at 6 weeks post-injury, and NKCC was reduced in patients who developed depression compared with non-depressed hip fracture patients (p = 0.004) or controls (p < 0.02). NKCC remained lower in the depressed patients compared to those without depression 6 months post-fracture (p = 0.017). We found reduced expression of perforin in NK cells of depressed hip fracture patients compared with controls at 6 weeks (p = 0.001) post-fracture. Serum cortisol levels were also elevated in patients with depression compared to non-depressed patients at 6 weeks (p = 0.01) and 6 months (p = 0.05). NK cells treated with dexamethasone showed a concentration-dependent reduction in NKCC and perforin expression. We propose that depression is the major factor affecting NK cell immunity after hip fracture.


Subject(s)
Depressive Disorder/immunology , Hip Fractures/immunology , Hydrocortisone/blood , Killer Cells, Natural/physiology , Perforin/blood , Stress, Psychological/immunology , Age Factors , Aged , Case-Control Studies , Depressive Disorder/blood , Depressive Disorder/complications , Female , Hip Fractures/blood , Hip Fractures/psychology , Humans , Male , Stress, Psychological/blood , Stress, Psychological/complications
10.
J Orthop Res ; 32(1): 24-30, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24115247

ABSTRACT

The aim of this investigation was to examine the influence of hip fracture on systemic inflammation and lung injury in aged chronic cigarette smoke exposed rats. Male Sprague Dawley (SD) aged rats (22-25 months old, 460-570 g) were used. Animals were subjected to either chronic cigarette smoke (CS) or air exposure for 12 weeks. These animals then underwent a sham procedure or hip fracture. Endpoint was 24 h. Systemic inflammation was assessed by TNF-α, IL-6, and IL-10 levels. Pulmonary function, inflammatory cell counts and protein concentrations in BAL, pulmonary pathological changes and scores were obtained to assess lung injury. And TLR4 mRNA expression in lung tissue was determined. The indices mentioned above were unchanged in air-exposed rats after hip fracture. However, CS-exposed animals were found to have increased serum levels of TNF-α, IL-6, and IL-10, impaired pulmonary function, increased inflammatory cell counts and protein concentrations in BAL, and intensified pathologic changes and scores. In addition, lung tissue harvested following CS-exposure demonstrated increased TLR4 mRNA expression. Our results indicate that systemic inflammation and lung injury in aged CS-exposed animals were further aggravated by hip fracture. The overexpression of TLR4 mRNA induced by CS exposure may, at least in part, involve in this process.


Subject(s)
Femoral Fractures/immunology , Hip Fractures/immunology , Lung Injury/immunology , Tobacco Smoke Pollution/adverse effects , Aging/immunology , Animals , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Chronic Disease , Cytokines/blood , Disease Models, Animal , Femoral Fractures/diagnostic imaging , Hip Fractures/diagnostic imaging , Lung Injury/diagnosis , Male , Radiography , Rats , Rats, Sprague-Dawley , Respiratory Function Tests , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/immunology
11.
Mediators Inflamm ; 2013: 536435, 2013.
Article in English | MEDLINE | ID: mdl-24163505

ABSTRACT

Pulmonary infections frequently occur following hip fracture surgery in aged patients. However, the underlying reasons are not fully understood. The present study investigates the systemic inflammatory response and pulmonary conditions following hip fracture surgery as a means of identifying risk factors for lung infections using an aged rodent model. Aged, male Sprague-Dawley rats (8 animals per group) underwent a sham procedure or hip fracture plus femoral intramedullary pinning. Animals were sacrificed 1, 3, and 7 days after the injury. Markers of systemic inflammation and pulmonary injury were analyzed. Both sham-operated and injured/surgical group animals underwent intratracheal inoculation with Pseudomonas aeruginosa 1, 3, and 7 days after surgery. P. aeruginosa counts in blood and bronchoalveolar lavage (BAL) fluid and survival rates were recorded. Serum TNF- α , IL-6, IL-1 ß , and IL-10 levels and markers of pulmonary injury were significantly increased at 1 and 3 days following hip fracture and surgery. Animals challenged with P. aeruginosa at 1 and 3 days after injury had a significantly decreased survival rate and more P. aeruginosa recovered from blood and BAL fluid. This study shows that hip fracture and surgery in aged rats induced a systemic inflammatory response and lung injury associated with increased susceptibility to infection during the acute phase after injury and surgery.


Subject(s)
Hip Fractures/surgery , Inflammation/pathology , Lung Injury/pathology , Aging , Animals , Bronchoalveolar Lavage Fluid , Caspase 3/metabolism , Cytokines/metabolism , Hip Fractures/immunology , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lung/enzymology , Lung/immunology , Male , Models, Animal , Pneumonia/microbiology , Postoperative Complications , Pseudomonas aeruginosa , Rats , Rats, Sprague-Dawley , Time Factors , Tumor Necrosis Factor-alpha/metabolism
12.
Brain Behav Immun ; 33: 173-82, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23876747

ABSTRACT

Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p=.001) or controls (p=.004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.


Subject(s)
Depression/diagnosis , Depression/pathology , Down-Regulation/immunology , Hip Fractures/immunology , Hip Fractures/pathology , Neutrophils/pathology , Aged , Aged, 80 and over , Aging/immunology , Aging/pathology , Case-Control Studies , Depression/etiology , Escherichia coli/immunology , Female , Hip Fractures/complications , Humans , Male , Middle Aged , Neutrophils/immunology , Neutrophils/microbiology , Phagocytosis/immunology , Prospective Studies
13.
Tissue Antigens ; 82(4): 235-42, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24461002

ABSTRACT

Inclusion of human leukocyte antigen (HLA) matching in donor kidney allocation schemes has been based solely on its association with graft survival. Other long-term effects associated with HLA incompatibility are largely unexplored. Data from deceased donor kidney transplants reported to the Collaborative Transplant Study have been analyzed to assess the relation between HLA mismatching and clinical events to 3 years post-transplant, and an overview of these analyses is presented. A significant correlation was observed between the number of mismatches and the need for anti-rejection therapy during the first year post-transplant, which was maintained for HLA-DR and HLA-A + B mismatching separately and at years 2 and 3 post-transplant. The number of HLA-DR mismatches and the number of HLA-A + B mismatches as well as rejection treatment showed significant associations with the dose of maintenance steroids. The cumulative incidences of death with a functioning graft from infection or cardiovascular causes, but not from cancer, were also significantly associated with HLA mismatching. The number of HLA-DR mismatches showed a significant association with the incidence of non-Hodgkin lymphoma and hip fractures. These findings show that the adverse consequences of HLA mismatching on kidney transplants extend beyond an effect on graft survival, and include an increased risk of death with a functioning graft, non-Hodgkin lymphoma and hip fracture.


Subject(s)
Cardiovascular Diseases/mortality , HLA Antigens/immunology , Hip Fractures/mortality , Kidney Transplantation/mortality , Lymphoma, Non-Hodgkin/mortality , Adolescent , Cardiovascular Diseases/etiology , Cardiovascular Diseases/immunology , Graft Survival , Hip Fractures/etiology , Hip Fractures/immunology , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Kidney/drug effects , Kidney/immunology , Kidney Transplantation/adverse effects , Lymphoma, Non-Hodgkin/etiology , Lymphoma, Non-Hodgkin/immunology , Steroids/therapeutic use , Survival Analysis , Tissue Donors
14.
J Bone Miner Res ; 27(5): 1167-76, 2012 May.
Article in English | MEDLINE | ID: mdl-22392817

ABSTRACT

Cytokines play a major role in bone remodeling in vitro and in animal models, with evidence supporting the involvement of inflammatory markers in the pathogenesis of osteoporosis. However, less is known about the longitudinal association of inflammatory markers with hip fracture. We tested whether high receptor levels of proinflammatory cytokines are associated with an increased risk of hip fracture in older women. We used a nested case-control study design from the Women's Health Initiative Observational Study (WHI-OS) and selected 400 cases with physician-adjudicated incident hip fractures and 400 controls matched on age, race, and date of blood draw. Participants were chosen from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Incident hip fractures (median follow-up 7.1 years) were verified by review of radiographs and confirmed by blinded central adjudicators. Hip fractures with a pathological cause were excluded. In multivariable models, the risk of hip fracture for subjects with the highest levels of inflammatory markers (quartile 4) compared with those with lower levels (quartiles 1, 2, and 3) was 1.43 (95% confidence interval [CI], 0.98-2.07) for interleukin-6 (IL-6) soluble receptor (SR), 1.40 (95% CI, 0.97-2.03) for tumor necrosis factor (TNF) SR1, and 1.56 (95% CI, 1.09-2.22) for TNF SR2. In subjects with all three markers in the highest quartile, the risk ratio of fracture was 2.76 (95% CI, 1.22-6.25) in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.018). Elevated levels of inflammatory markers for all three cytokine-soluble receptors were associated with an increased risk of hip fractures in older women. Future clinical trials should test whether interventions to decrease inflammatory marker levels reduces hip fractures.


Subject(s)
Biomarkers/blood , Hip Fractures/blood , Women's Health , Aged , Aged, 80 and over , Case-Control Studies , Female , Hip Fractures/immunology , Humans , Longitudinal Studies , Middle Aged , Risk Factors
15.
Transplantation ; 91(1): 65-9, 2011 Jan 15.
Article in English | MEDLINE | ID: mdl-21452411

ABSTRACT

BACKGROUND: Bone fractures are a frequent complication after kidney transplantation, for which various predisposing factors have been identified. It has been suggested that human leukocyte antigen (HLA) mismatch increases the risk. METHODS: Data on hip fractures occurring in the first 5 years posttransplant were analyzed among kidney transplants from deceased donors performed between 1995 and 2008 and reported to the Collaborative Transplant Study. RESULTS: In the 20,509 patients analyzed, the cumulative rate of hip fracture by year 5 posttransplant was 0.85%. Cox regression analysis identified the following risk factors: female recipients aged 40 to 59 years (hazard ratio [HR] 2.26, P=0.029), female recipients 60 years or older (HR 5.14, P<0.001), male recipients 60 years or older (HR 2.39, P=0.028), and donor age more than or equal to 60 years (HR 1.75, P=0.009). Using the rate of fractures in recipients with zero HLA-DR mismatch as the reference, the risk of hip fracture increased for grafts with one HLA-DR mismatch to HR 1.85 (95% confidence interval [CI] 1.18-2.89, P=0.007) and with two HLA-DR mismatches to HR 2.24 (CI 1.25-4.02, P=0.007). There was a significant association between the number of HLA-DR mismatches and the diagnosis of osteoporosis 5 years after transplantation: one HLA-DR mismatch risk ratio 1.26 (CI 1.12-1.43, P<0.001) and two HLA-DR mismatches risk ratio 1.45 (CI 1.20-1.74, P<0.001). CONCLUSION: The risk of hip fracture after kidney transplantation seems to be markedly exacerbated by HLA-DR mismatching. These findings add to the growing base of evidence that HLA-DR matching influences morbidity after kidney transplantation.


Subject(s)
HLA-DR Antigens/immunology , Hip Fractures/immunology , Kidney Transplantation/adverse effects , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Azathioprine/adverse effects , Azathioprine/therapeutic use , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Diabetic Nephropathies/immunology , Female , Graft Rejection/immunology , Histocompatibility Testing , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Postoperative Complications/drug therapy , Postoperative Complications/immunology , Retrospective Studies , Tacrolimus/adverse effects , Tacrolimus/therapeutic use , Treatment Outcome
16.
Clin Appl Thromb Hemost ; 17(6): 567-71, 2011.
Article in English | MEDLINE | ID: mdl-22345625

ABSTRACT

Thromboembolic disease is a common complication of hip fracture in the elderly. Anticoagulants represent a standard of care in preventing postoperative thrombotic complications following surgical fixation. We asked whether levels of antibody to heparin-platelet factor 4 (PF4) complex were differentially present in unfractionated heparin (UFH) versus Enoxaparin, following hip fracture and whether one particular subtype of antibodies was more prevalent. Plasma samples from elderly patients sustaining a hip fracture treated with either enoxaparin or UFH were collected pre- and postoperatively and analyzed using enzyme-linked immunosorbent assay (ELISA) sandwich method for the prevalence of antiheparin-PF4 antibodies and later subtyped. The prevalence of antiheparin-PF4 antibodies was higher in the UFH group especially on postoperative day 7. Patients treated with UFH showed a greater prevalence of antiheparin-PF4 antibodies and a greater prevalence of immunoglobulin G (IgG) subtype. Heparin and enoxaparin are capable of generating heparin-induced thrombocytopenia (HIT) antibodies in elderly patients undergoing orthopedic surgery but perhaps not to the same extent. When comparing low-molecular-weight heparin (LMWH) with UFH, the incidence of new antiheparin-PF4 antibody production is higher in patients treated with UFH.


Subject(s)
Antibodies/immunology , Enoxaparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Heparin/immunology , Hip Fractures/drug therapy , Platelet Factor 4/immunology , Aged , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Enoxaparin/adverse effects , Female , Heparin/adverse effects , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/adverse effects , Hip Fractures/immunology , Hip Fractures/surgery , Humans , Male , Prospective Studies , Randomized Controlled Trials as Topic , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
18.
Ulus Travma Acil Cerrahi Derg ; 15(6): 546-52, 2009 Nov.
Article in English | MEDLINE | ID: mdl-20037871

ABSTRACT

BACKGROUND: A study was performed to determine the effects of blood albumin and total lymphocyte count on the postoperative one-year period in 74 elderly hip fracture patients. METHODS: In 2006, 74 patients (52 female, 22 male) with hip fracture who were 65 years of age or older were included in the study. Admission albumin levels and total lymphocyte counts were recorded. The outcomes examined were mortality, length of hospital stay and ambulatory ability. Ambulatory ability was assessed according to Parkland and Palmer criteria. RESULTS: There were 61 patients aged 65-84 years, and 13 patients aged 85-105 years. Forty-one patients (55.4%) had hypoalbuminemia and 23 patients (31.1%) had low total lymphocyte count. Low albumin and total lymphocyte counts were associated with higher mortality (p = 0.011). Patients with low albumin levels had longer length of hospital stay (p = 0.002). Patients with normal albumin and total lymphocyte counts had higher mobility score meaning better function (p = 0.012). Multivariate analysis yielded that low total lymphocyte count, American Society of Anesthesiologists (ASA) 3-4 and female gender remained significant independent predictors of one-year mortality. No single blood parameter was found to be effective on ambulatory status. CONCLUSION: Risk of mortality in elderly hip fracture patients increases with female gender, ASA 3-4 and low total lymphocyte counts. Hypoalbuminemia is associated with longer hospitalization. Identification of these risk factors can help in the case management for a more favorable outcome.


Subject(s)
Hip Fractures/mortality , Lymphocyte Count , Serum Albumin/pharmacology , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Enoxaparin/therapeutic use , Female , Hip Fractures/immunology , Hip Fractures/rehabilitation , Hip Fractures/surgery , Humans , Male , Multivariate Analysis , Predictive Value of Tests , Survival Analysis , Survivors
19.
J Am Geriatr Soc ; 56(9): 1704-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18691278

ABSTRACT

OBJECTIVES: To compare the time-course of cytokine levels in patients with and without delirium and investigate differences in cytokine concentrations in delirium subtypes. DESIGN: Prospective cohort study. SETTING: Academic Medical Center, Amsterdam, 2005 through 2007. PARTICIPANTS: Patients aged 65 and older admitted for surgery after hip fracture. MEASUREMENTS: Experienced geriatric physicians used the Confusion Assessment Method to assess delirium and the Delirium Symptom Interview to assess delirium subtype. Tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-8, IL-10, and IL-12 were assayed in repeated serum samples using a cytometric bead array immunoassay. RESULTS: Of 221 admitted patients, 98 (mean age 84, 50 patients with delirium) were included, resulting in a total of 324 samples. Ninety-six percent of these samples had TNF-alpha, IL-1beta, and IL-10 levels below the reliable detection level. Differences between patients with and without delirium were observed in IL-6 (median 51 vs 36 pg/mL, P=.01) and IL-8 (median 15 vs 9 pg/mL, P=.03) levels. Changes over time in IL-6 and IL-8 levels in patients with delirium differed significantly from changes in levels in patients without delirium. The highest levels of IL-6 were present during delirium, and the highest levels of IL-8 were present before the development of delirium. Patients with the hyperactive (median 71 pg/mL) or mixed (median 73 pg/mL) subtype of delirium had higher IL-6 levels than patients with hypoactive delirium (median 16 pg/mL) (P=.02). CONCLUSION: IL-6 and IL-8 may contribute to the pathogenesis of postoperative delirium in elderly people. IL-6 may play a role in the hyperactive behavior of delirium.


Subject(s)
Cytokines/blood , Delirium/immunology , Hip Fractures/immunology , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Cohort Studies , Female , Femoral Neck Fractures/immunology , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Hip Fractures/surgery , Humans , Interleukin-6/blood , Interleukin-8/blood , Male , Netherlands , Patient Admission , Postoperative Complications/immunology , Prospective Studies , Psychomotor Agitation/immunology , Statistics as Topic , Time Factors
20.
Arch Gerontol Geriatr ; 46(2): 117-24, 2008.
Article in English | MEDLINE | ID: mdl-17490758

ABSTRACT

Hip fracture is an increasing pathology in the patients with increasing age. Immunological response differences may appear between different age groups. The purpose of this study was to investigate the immune response in patients with subcapital hip fracture and the relationship with age. Prospective study of 100 patients with displaced subcapital femoral fracture between 2000 and 2004, divided into three age groups: over 90 years (13), 80-90 (56) and under 80 years (27). The chi(2)-test, analysis of variance and Student's t-test were applied. Correlation coefficient and the Spearman test were used to study linear correlation. The T helper cells decreased with age, this inverse correlation was significant. There was a direct correlation between CD16% and age. IgA, IgG and IgM levels did not show any significant relationship with age in our study. Nevertheless, the IgE levels in peripheral blood showed a significant direct correlation with age. Basophils percentage presented an inverse correlation with age. Age is associated to some immune changes in patients suffering hip fracture.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Hip Fractures/immunology , Immunity, Cellular/immunology , Killer Cells, Natural/immunology , T-Lymphocyte Subsets/immunology , Aged , Aged, 80 and over , CD3 Complex/immunology , Female , Flow Cytometry , Follow-Up Studies , Hip Fractures/blood , Hip Fractures/pathology , Humans , Immunoglobulins/blood , Lymphocyte Count , Male , Middle Aged , Nephelometry and Turbidimetry , Prospective Studies
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