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Introduction: Zoledronic acid infusion is used to treat osteoporosis but patients, especially Japanese patients, often experience acute-phase reactions (APRs). In this multicenter, randomized, open-label, parallel-group study, we examined the efficacy of the most commonly used non-steroidal anti-inflammatory drug loxoprofen in Japan in reducing the incidence rate of zoledronic acid-induced APRs and body temperature, and investigated risk/protective factors for APRs in this population., Materials and Methods: Patients aged ≥ 60 years with primary osteoporosis (n = 368) were allocated randomly to zoledronic acid plus loxoprofen (ZOL + LOX) or zoledronic acid alone (ZOL). All patients received 5-mg zoledronic acid infusion on day 1, and patients in the ZOL + LOX group also received 120 mg and 180 mg of oral loxoprofen on days 1 and 2, respectively. Adverse events and body temperature were recorded during the 7-day observation period., Results: The incidence rates of APRs were 34.4% (64/186 patients) and 47.8% (87/182 patients) in the ZOL + LOX and ZOL groups, respectively (P = 0.0109). The proportions of patients with increased body temperature (≥ 1 °C and ≥ 37.5 °C) were similar in both groups (P = 0.1186). Past bisphosphonate users had a significantly lower incidence rate of APRs than treatment-naïve patients (odds ratio 0.444, 95% confidence interval 0.285-0.692, P = 0.0003)., Conclusions: Zoledronic acid-induced APRs appeared to be suppressed by loxoprofen. Known risk/protective factors, including prior osteoporosis treatment, were applicable to Japanese patients.

Context: Intravenous aminobisphosphonates (N-BPs) can induce an acute phase reaction (APR) in up to 40% to 70% of first infusions, causing discomfort and often requiring intervention with analgesics or antipyretics., Objective: Our aim was to explore the risk factors of APR in a large sample of patients with Paget's disease of bone (PDB) and to assess the possible preventive effects of vitamin D administration., Methods: An observational analysis was performed in 330 patients with PDB at the time of N-BP infusion. Then, an interventional study was performed in 66 patients with active, untreated PDB to evaluate if vitamin D administration (oral cholecalciferol 50 000 IU/weekly for 8 weeks before infusion) may prevent APR., Results: In a retrospective study, APR occurred in 47.6% and 18.3% of naive or previously treated patients, respectively. Its prevalence progressively increased in relation to the severity of vitamin D deficiency, reaching 80.0% in patients with 25-hydroxyvitamin D (25OHD) levels below 10 ng/mL (relative risk (RR) = 3.7; 95% confidence interval (CI) 2.8-4.7, P < .0001), even in cases previously treated with N-BPs. Moreover, APR occurred more frequently in patients who experienced a previous APR (RR = 2.8; 95% CI 1.5-5.2; P < .001) or in carriers of SQSTM1 mutation (RR = 2.3; 95% CI 1.3-4.2; P = .005). In the interventional study, vitamin D supplementation prevented APR in most cases, equivalent to a RR of 0.31 (95% CI 0.14-0.67; P < .005) with respect to prevalence rates of the observational cohort. A similar trend was observed concerning the occurrence of hypocalcemia., Conclusions: The achievement of adequate 25OHD levels is recommended before N-BP infusion in order to minimize the risk of APR or hypocalcemia in PDB., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The most common adverse reaction to zoledronic acid (ZOL) infusion is the acute phase reaction (APR), characterized by transient, usually mild, flu-like symptoms. Previous treatment with oral amino-bisphosphonates (BPs) was reported as an independent protective factor for APR, and an association between APR and 25-hydroxyvitamin D (25(OH)D) levels in BP-naïve patients treated with ZOL was identified. The aims of our study were to confirm this association and to see if it was different in patients previously treated with oral BPs compared with BP-naïve patients and to investigate the role of 25(OH)D for the time of APR onset., Methods: We included 153 consecutive patients with postmenopausal osteoporosis undergoing their first ZOL infusion. Sixty-eight had been previously treated with oral BPs. Clinical, demographic, and serologic data were recorded., Results: 25(OH)D levels were significantly lower in patients experiencing APR compared to patients without APR (26.3 ± 12.7 vs. 37.0 ± 13.5 ng/mL, respectively; P<.0001). Patients with 25(OH)D <30 ng/mL had a significantly higher risk of APR (odds ratio [OR] 4.2 [95% confidence interval [CI] 2.1-8.2]) occurring in 65%. APR was significantly less frequent in patients previously treated with oral BPs than in BP-naïve subjects (33.8% [23/68] vs 52.9% [45/85], P = .018), but only a weak association remained after correction for 25(OH)D (OR 0.5, 95% CI 0.3-1.1, P = .08)., Conclusion: Higher baseline 25(OH)D levels appear to be protective for APR post-ZOL infusion. The role of previous treatment with oral BPs as an independent protective factor for APR should be evaluated in a larger cohort., Abbreviations: APR = acute phase reaction; BPs = amino-bisphosphonates; CI = confidence interval; 25(OH)D = 25-hydroxyvitamin D; OP = osteoporosis; OR = odds ratio; PTH = parathyroid hormone; ROC = receiver operating characteristic; ZOL = zoledronic acid.

Objective: It has been reported that acute-phase reactions (APR) after infusion of 5 mg zoledronic acid for the first time is common. This study surveyed the incidence and characteristics of APR in Chinese postmenopausal women receiving 5 mg zoledronic acid intravenously for osteoporosis and to evaluate the efficacy of non-steroidal anti-inflammatory drugs (NSAID) in preventing or alleviating APR following the first 5 mg zoledronic acid infusion., Methods: A total of 2601 patients with an average age of 68.14 ± 9.89 years and a mean body mass index of 22.90 ± 3.24 kg/m 2 from 62 centers in China were treated with 5 mg zoledronic acid intravenously for the first time. The incidence of fever and pain were observed in these patients, and the time of fever or pain onset and duration, and the intensity of fever and grade of pain were also recorded. The dosage, duration, and efficacy of NSAID and safety outcomes were also documented., Results: At the end of the study, 18 patients are eliminated due to incomplete records of temperature. The incidence of fever was 28.65% (740/2583) within 7 days following zoledronic acid infusion; 98.34% (727/740) occurred at 1.03 ± 0.66 days after infusion and lasted 1.72 ± 0.93 days. A total of 456 (17.53%) patients had newly onset pain (312 of 1187, 26.28%) or experienced pain aggravation (144 of 1414, 10.18%), which mostly occurred within 3 days after zoledronic acid infusion. A total of 1246 (47.6%) patients had received NSAID for a median time of 2.63 ± 2.45 days. Using NSAID for at least 2 days could decrease body temperature by 0.54 ± 0.86°C, increase the percentage of pain-free patients by 6.17%, and reduce the percentage of patients with moderate to severe pain by 8.7%., Conclusions: Compared with Western populations, Chinese patients had a higher rate of fever and pain after their first zoledronic acid infusion. These symptoms were often mild to moderate in intensity and transient in duration. NSAID could effectively reduce the incidence and severity of such APR., (© 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2·3 mg/l, while only 25% had serum ferritin levels 2·3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 μg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy.

Background: Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis., Methods: In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire., Results: The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p < 0.001). Except for occurrence of fever (more common after zoledronic acid infusion), other influenza-like symptoms (myalgia, arthralgia, headache) appeared in a similar proportion of patients after IV treatment (within 24-36 h). Symptoms lasted for >3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing., Conclusion: Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.

We determined in a prospective cohort of patients treated with vitamin K antagonists for venous thrombosis, the course of factor VIII (FVIII:C), C-reactive protein (CRP) and fibrinogen levels, to assess the influence of the acute phase reaction on FVIII:C levels. Second, we hypothesized that patients with preceding infectious symptoms might have higher levels of FVIII:C at baseline than patients without those. We included 75 patients. Blood was sampled at baseline, once during treatment (t=1) and at the end of treatment (t=2). Mean levels of FVIII:C were 207, 186 and 175IU/dL (p for trend 0.003) at baseline, t=1 and t=2 respectively. Eight-eight percent of patients had an elevated FVIII:C at baseline, 75% at t=1 and 72% at t=2 (p for trend 0.045). Mean levels of FVIII:C were not different in patients with or without preceding infectious symptoms (206 versus 205IU/dL respectively). A baseline CRP level below 62mg/L could best distinguish between patients who will keep an elevated FVIII:C and those who will drop below 150IU/dL. We conclude that FVIII:C levels are partially influenced by the acute phase reaction, especially in patients who keep a persistent elevated FVIII:C during treatment. Preceding infectious symptoms did not influence baseline FVIII:C levels., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The transplantation of allogeneic or autologous haematopoietic stem cells is an established treatment for many malignant and non-malignant diseases of the bone marrow. Intensive cytoreductive regimens administered before transplantation induce prolonged and severe cytopenia of all haematopoietic lineages. Thrombocytopenia leads to an increased risk of bleeding, which may be further aggravated by consumption of plasmatic factors as a result of tumour lysis or after antibody administration. At the same time, patients after transplantation are also at increased risk of thrombotic complications. Endothelial damage induced by radio- and chemotherapy, indwelling catheters, prolonged immobilization and a high incidence of systemic infection all contribute to the frequent occurrence of thromboembolic events in this population. This review discusses the incidence and risk factors for haemorrhagic and thrombotic complications after stem cell transplantation. Special emphasis is given to complications occurring specifically in the context of transplantation such as diffuse alveolar haemorrhage, haemorrhagic cystitis, veno-occlusive disease, and transplant associated microangiopathy.

Allogeneic and autologous hematopoietic stem cell transplantations are important therapeutic options for patients with hematologic disorders. Hemostatic complications are frequent after hematopoietic stem cell transplantation with a considerable morbidity and mortality. The incidence of bleedings and thrombosis is highest in the first few weeks after transplantation, but may also occur later. However, beyond the first year of transplantation only limited data are available. In long-term survivors the risk for premature atherosclerosis increases over time after allogeneic hematopoietic stem cell transplantation and it is higher than in the age-adjusted general population and in recipients of autologous transplantation.

There were analyzed the results of surgical treatment of 60 patients, suffering extended peritonitis (EP), in whom the content changes in the blood serum, concerning the acute phase of inflammation proteins (C-reactive protein, lactoferrin and ferritin) were studied. To all the patients a conventional basic intensi therapy was conducted postoperatively. The EP course severity was estimated using Manheim's peritoneal index (MPI): in 17 patients a I degree MPI was established, in 23 - MPI of II degree, in 20 - MPI of III degree. According to the investigation results obtained, there was established, that severity of changes of the studied indices depends on the disease course severity. The adduced indices detection makes it possible to estimate a severity of inflammatory process and efficacy of treatment conducted.

Controlled, experimental studies on the effects of acute sleep loss in humans have shown that mediators of inflammation are altered by sleep loss. Elevations in these mediators have been found to occur in healthy, rigorously screened individuals undergoing experimental vigils of more than 24h, and have also been seen in response to various durations of sleep restricted to between 25 and 50% of a normal 8h sleep amount. While these altered profiles represent small changes, such sub-clinical shifts in basal inflammatory cytokines are known to be associated with the future development of metabolic syndrome disease in healthy, asymptomatic individuals. Although the mechanism of this altered inflammatory status in humans undergoing experimental sleep loss is unknown, it is likely that autonomic activation and metabolic changes play key roles., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Context: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied., Objective: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development., Design: The study was an analysis of adverse events from a large randomized trial., Setting: This was a multicenter international trial., Patients: Patients included 7765 postmenopausal women with osteoporosis., Intervention: Zoledronic acid 5 mg annually or placebo was the intervention., Main Outcome Measure: Adverse events occurring within 3 d of zoledronic acid infusion were measured., Results: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all)., Conclusion: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study.

Background & Aims: The hypothesis of reverse epidemiology holds that some cardiovascular risk factors, such as obesity, hypercholesterolemia and hypertension, in the elderly or in some chronic diseases are not harmful but permit better survival. However, this phenomenon is controversial and the underlying reasons are poorly understood., Objective: To search for factors simultaneously linked to reverse epidemiology and to short or long term survival., Methods: We included 400 patients, older than 60 years, hospitalized in a general internal medicine unit; 61 died in hospital and 338 were followed up by telephone., Results: Obesity, higher blood pressure and serum cholesterol, besides being related to lower mortality both in hospital and after discharge, were associated with better nutrition and functional capacity, less intense acute phase reaction and organ dysfunction, and lower incidence of high-mortality diseases such as dementia, pneumonia, sepsis or cancer. These associations may explain why obesity and other reverse epidemiology data are inversely related to mortality. Weight loss was related to mortality independently of BMI. Patients with BMI under 30 kg/m(2) who died in hospital showed more weight loss than those who survived; the lower the BMI, the greater the weight loss. In contrast, patients with BMI over 30 kg/m(2) who died in hospital gained more weight than those who survived; the higher the BMI, the greater the weight gain., Conclusion: In patients over 60 years of age admitted to an internal medicine ward, obesity did not show independent survival value, being displaced by other nutritional parameters, functional capacity, acute phase reaction, organ dysfunction and diseases with poor prognosis., (Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Mastitis is one of the most prevalent diseases in cattle and remains among the most costly diseases to the dairy industry. Various surveys have indicated a greater prevalence of and risk for mastitis in Holstein cows than in Jersey cows. The innate immune system comprises the immediate host defense mechanisms that respond to infection, and differences in the magnitude and rapidity of this response are known to influence susceptibility to and clearance of infectious pathogens. The reported differences in the prevalence of mastitis between Holstein and Jersey cows may suggest the occurrence of breed-dependent differences in the innate immune response to intramammary infection. The objective of the current study was to compare the acute phase and cytokine responses of Holstein and Jersey cows following intramammary infection by the bacterial pathogen Escherichia coli, a leading cause of clinical mastitis. All cows in the study were in similar stages of lactation, of the same parity, subjected to the same housing and management conditions, and experimentally infected on the same day with the same inoculum preparation. Before and after infection, the following innate immune parameters were monitored: bacterial clearance; febrile response; induction of the acute phase proteins serum amyloid A and lipopolysaccharide-binding protein; alterations in total and differential white blood cell counts; changes in milk somatic cell counts and mammary vascular permeability; and induction of the cytokines IFN-gamma, IL-1beta, IL-8, IL-12, and tumor necrosis factor-alpha. Overall innate immune responses were similar between the 2 breeds; however, temporal differences in the onset, cessation, and duration of several responses were detected. Despite these differences, intramammary clearance of E. coli was comparable between the breeds. Together, these data demonstrate a highly conserved innate immune response of Holstein and Jersey cows to E. coli intramammary infection.

Rationale: Physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD). COPD has a systemic component that includes significant extrapulmonary effects that may contribute to its severity in individual patients., Objectives: To investigate the association of extrapulmonary effects of the disease and its comorbidities with reduced physical activity in patients with COPD., Methods: In a cross-sectional study, 170 outpatients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages I-IV; BODE [body mass index, airway obstruction, dyspnea, and exercise capacity] score 0-10) underwent a series of tests. Physical activity was assessed over 5 to 6 consecutive days by using a multisensor accelerometer armband that records steps per day and the physical activity level (total daily energy expenditure divided by whole-night sleeping energy expenditure). Cardiovascular status was assessed by echocardiography, vascular Doppler sonography, and levels of N-terminal pro-B-type natriuretic peptide. Mental status, metabolic/muscular status, systemic inflammation, and anemia were assessed by Beck Depression Inventory, bioelectrical impedance analysis, handgrip strength, high-sensitivity C-reactive protein/fibrinogen, and hemoglobin, respectively., Measurements and Main Results: In a multivariate linear regression analysis using either steps per day or physical activity level as a dependent variable, the extrapulmonary parameters that were associated with reduced physical activity in patients with COPD independently of GOLD stages or BODE score were N-terminal pro-B-type natriuretic peptide levels, echocardiographically measured left ventricular diastolic function, and systemic inflammation., Conclusions: Higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with COPD.

This study examined the ethnic difference in the association between increased serum ferritin (SF) (>300 microg/l) and acute inflammation (AI) (C-reactive protein > or = 1.0 mg/dl) between black and white males aged > or = 20 years. Using data from the third National Health and Nutrition Examination Survey (NHANES III), we determined the risk for having elevated SF in black males (n=164) and white males (n=325) with AI present as well as black males (n=1731) and white males (n=2877) with AI absent. Black subjects with AI present were 1.71 times (95% CI 1.18-2.49), and 1.87 times (95% CI 1.46-2.40) more likely to have increased SF than AI absent blacks and AI present whites, respectively. Furthermore, with AI present, every increment of C-reactive protein, white blood cell count, serum albumin, lymphocyte count and platelet count was associated with higher odds of having elevations in SF in blacks than whites. Regardless of AI status, blacks were more likely to have elevations in SF than whites, and the prevalence of elevated SF was significantly higher in blacks than whites. This finding suggested that black males may respond to inflammation with a more aggressive rise in SF compared to white males. Future research is needed to investigate the underlying mechanisms.

Background: Bisphosphonates are synthetic analogs of inorganic pyrophosphates with high avidity for bone, where they bind to hydroxyapatite crystals. Bisphosphonates are effective in decreasing bone resorption, the incidence of skeletal-related events, and pain from bone metastases. These agents have recently become incorporated into the treatment regimen of patients with osteolytic and osteoblastic metastatic bone disease. Although relatively well tolerated, the initial dose(s) of intravenous aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia., Objective: The purpose of this article is to provide an updated review of the literature in this field., Data Source: A search of PubMed was performed using the key terms bisphosphonate, acute phase response, and cancer, and limited to publications in English. The published literature on acute phase response with bisphosphonate therapy was reviewed., Results and Conclusions: Approximately 40% of patients receiving aminobisphosphonates experience an acute phase response, which generally occurs only on first exposure to the drug and typically last <72 h. Not all bisphosphonates induce acute phase responses to the same extent. This article reviews acute phase response in patients with metastatic bone disease treated with aminobisphosphonates.

The objectives of the present study were to determine whether induction of parturition in mares at term with low doses of oxytocin (2.5 i.u. i.v. every 20 min) affected the incidence of peri-partum complications or inflammatory responses in the neonatal foal. Parturition was induced in 11 of 26 mares and the remainder foaled spontaneously. Serum concentrations of amyloid A (AA; an acute phase protein) were measured (with a commercial ELISA) from 0 to 72 h postpartum in 18 of the neonatal foals. The incidence of dystocia and premature placental separation was higher in induced mares (2 of 11 and 1 of 11 versus 0 of 15 and 0 of 15, respectively), whereas retained fetal membranes were more common in spontaneous foalings (2 of 15 versus 0 of 11). When abnormal foals were excluded (to decrease the influence of endogenous serum AA elevations), serum concentrations of AA increased to the same extent over time in foals with induced versus spontaneous parturition; foals with spontaneous parturition had a mean serum AA concentration of 7.8 microg/mL at birth that increased to a maximum of 58.9 microg/mL at 36 h; foals with induced parturition had a mean serum AA concentration of 5.4 microg/mL at birth that increased to a maximum of 41.4 microg/mL at 48 h. Baseline serum AA concentrations were lower in induced foals. We concluded that inducing parturition with low doses of oxytocin in mares at term did not affect (relative to spontaneous parturition) the temporal dynamics of serum AA concentrations in the normal foal in the first 72 h of life. However, the induction procedure may lead to complications during parturition that, if not detected early, could result in the development of an inflammatory response in the neonate.

Background: Moderately elevated serum C-reactive protein (CRP) concentration is a systemic marker of inflammation and a documented risk factor for cardiovascular disease in otherwise healthy persons. Unrecognized infections, such as periodontal disease, may induce an acute-phase response, elevating CRP levels. We evaluated the association between periodontal disease and CRP levels in adults in the Atherosclerosis Risk in Communities study., Methods: Oral examinations were conducted between January 1, 1996, and December 31, 1998, on 5552 ARIC participants (aged 52-74 years) from 4 US communities. Periodontal disease was quantified as the percentage of periodontal sites with pocket depth of 4 mm or more. Serum CRP concentration was quantified in milligrams per liter using an enzyme-linked immunosorbent assay., Results: Mean (SE) CRP level was 7.6 (0.6) mg/L among people with extensive periodontal pockets (>30% of sites with pocket depth > or =4 mm), approximately one-third greater than that for people with less extensive periodontal pockets (5.7 [0.1] mg/L). In a multivariable linear regression model that controlled for age, sex, diabetes mellitus, cigarette use, and nonsteroidal anti-inflammatory drug use, the association of extensive periodontal pockets with CRP concentration was modified by body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters). For people with a BMI of 20, the model predicted a 2-fold difference in mean CRP concentration between periodontal pocket groups (7.5 vs 3.6 mg/L), but the difference decreased with increasing BMI and was negligible when BMI equaled 35., Conclusions: Extensive periodontal disease and BMI are jointly associated with increased CRP levels in otherwise healthy, middle-aged adults, suggesting the need for medical and dental diagnoses when evaluating sources of acute-phase response in some patients.

Objectives: To determine the incidence of neurogenic fever (NF) in a population of patients in the acute phase following severe traumatic brain injury (TBI); to identify factors associated with the development of NF following severe TBI in adults., Methods: Charts of patients admitted from 1996 to 1999 with severe TBI at a large, urban mid-Atlantic teaching hospital were retrospectively evaluated based on diagnostic criteria for each episode of hyperthermia to determine the diagnosis of NF. Data were collected regarding mechanism and area of injury, severity of injury, and demographic factors to determine potential predictors of NF., Results: Diffuse axonal injury (DAI) (OR 9.06, 95% CI 0.99 to 82.7) and frontal lobe injury of any type (OR 6.68, 95% CI 1.1 to 39.3) are independently predictive of an increased risk of development of NF following severe TBI. The presence of a skull fracture and lower initial Glasgow Coma Score (GCS) were individual predictors of development of NF, but did not contribute to the final model., Conclusions: These findings examine known and novel risk factors for this phenomenon in comparison to previously published literature on NF. A set of predictor variables was identified to help clinicians target patients at high risk for development of NF following severe TBI. It is hoped that earlier diagnosis and appropriate intervention for fever in the TBI patient will lead to improved outcomes.

Rheumatoid arthritis (RA) patients experience a markedly increased frequency of cardiovascular disease. We evaluated cardiovascular risk profiles in 79 RA patients and in 39 age-matched and sex-matched osteoarthritis (OA) patients. Laboratory tests comprised ultrasensitive C-reactive protein (CRP) and fasting lipids. Insulin sensitivity (IS) was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) in all OA patients and in 39 of the RA patients. Ten RA patients were on glucocorticoids. RA patients exercised more frequently than OA patients (chi2 = 3.9, P < 0.05). Nine RA patients and one OA patient had diabetes (chi2 = 4.5, P < 0.05). The median CRP, the mean QUICKI and the mean high-density lipoprotein (HDL) cholesterol were 9 mg/l (range, 0.5-395 mg/l), 0.344 (95% confidence interval [CI], 0.332-0.355) and 1.40 mmol/l (95% CI, 1.30-1.49 mmol/l) in RA patients, respectively, as compared with 2.7 mg/l (range, 0.3-15.9 mg/l), 0.369 (95% CI, 0.356-0.383) and 1.68 mmol/l (95% CI, 1.50-1.85 mmol/l) in OA patients. Each of these differences was significant (P < 0.05). After controlling for the CRP, the QUICKI was similar in RA and OA patients (P = 0.07), while the differences in HDL cholesterol were attenuated but still significant (P = 0.03). The CRP correlated with IS, while IS was associated with high HDL cholesterol and low triglycerides in RA patients and not in OA patients. A high CRP (>/= 8 mg/l) was associated with hypertension (chi2 = 7.4, P < 0.05) in RA patients. RA glucocorticoid and nonglucocorticoid users did not differ in IS and lipids (P > 0.05). Excess cardiovascular risk in RA patients as compared with OA patients includes the presence of decreased IS and HDL cholesterol in RA patients. The latter is only partially attributable to the acute phase response. The CRP, IS, HDL cholesterol, triglycerides and hypertension are inter-related in RA patients, whereas none of these relationships were found in OA patients.

Background: Several epidemiological studies have documented the presence of a 'J' or 'U' association between total cholesterol levels and total mortality. Not only the mechanism underlying the association between increased mortality and low total cholesterol values is not completely clear, but the relationship itself also appears to be complex in the elderly., Objective: The aim of the study was to evaluate the possible association between some biohumoral markers of the acute phase, comorbidity, disability, and reduced levels of some lipoprotein parameters in a sample of hospitalized elderly subjects., Methods: 341 patients over 65 years of age (185 males, 156 females; mean age 76.2 years), consecutively admitted to our department from 1994 to 1995, were studied. Acute phase was defined as the simultaneous presence of: (1) increased alpha2-plasma protein on electrophoresis (>12%); (2) high fibrinogen concentration (>450 mg/dl), and (3) increased blood sedimentation rate (>15 and >20 mm 1 h in males and females, respectively)., Results: The prevalence of signs of acute phase was higher in males and in the youngest patients, but did not change with the level of comorbidity. Patients with signs of acute phase were characterized by lower total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol levels compared to subjects without signs of acute phase; this difference was significant even after adjustment for indicators of comorbidity, disability, and nutritional status. Multivariate logistic regression analysis evidenced that the simultaneous presence of these three markers of acute phase was independently associated with low levels of total cholesterol [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1 - 3.9], and HDL-cholesterol (OR 2.3, 95% CI 1.2 - 4.2), considered as the sex-specific first quintile., Conclusion: The findings of this study demonstrate an independent association between acute phase markers and low levels of total and HDL-cholesterol, suggesting that recognized or subclinical diseases in elderly patients may determine a reduction in these plasma lipids. Low level of total and HDL-cholesterol should be considered as possible clinical markers of an underlying state of acute phase rather than a sign of malnutrition. Given the high prevalence of chronic diseases in the elderly, epidemiological studies addressing the lipid profile in this age group should take into account the possible confounding effect of the presence of signs of acute phase.

Moderate elevation of serum C-reactive protein (CRP) is a risk factor for cardiovascular disease among apparently healthy individuals, although factors that create this inflammatory response in the absence of systemic illness have not been clarified. This study aimed to: (1) evaluate associations among periodontal disease, established risk factors for elevated CRP, and CRP levels within the US population; and (2) determine whether total tooth loss is associated with reduced CRP. Data were obtained from the third National Health and Nutrition Examination Survey. A random sample of the US population was interviewed in their homes and examined at mobile examination centers. CRP was quantified from peripheral blood samples and analyzed as a continuous variable and as the prevalence of elevated CRP (> or = 10 mg/L). Some 12,949 people aged 18+ years who had periodontal examinations and an additional 1,817 edentulous people aged 18+ years were included in the analysis. Dentate people with extensive periodontal disease (> 10% of sites with periodontal pockets 4+ mm) had an increase of approximately one-third in mean CRP and a doubling in prevalence of elevated CRP compared with periodontally healthy people. Raised CRP levels among people with extensive periodontal disease persisted in multivariate analyses (P < 0.01), with established risk factors for elevated CRP (diabetes, arthritis, emphysema, smoking, and anti-inflammatory medications) and sociodemographic factors controlled for. However, CRP levels were similarly raised in edentulous people. Furthermore, the established risk factors for elevated CRP modified relationships between oral status and CRP levels. Periodontal disease and edentulism were associated with systemic inflammatory response in the US population, most notably among people who had no established risk factors for elevated CRP.

Objective: To investigate the incidence of a preoperative acute phase response and its association with low albumin concentrations., Design: Prospective open study., Setting: Teaching hospital, Germany., Subjects: 225 patients who were to undergo major abdominal operations, and who had no acute infections., Interventions: Measurements of serum concentrations of albumin, C-reactive protein (CRP), alpha-1 antitrypsin, and interleukin-6 (IL-6)., Results: Abnormal concentrations of acute phase proteins (indicating an acute phase response) were detected in 43 of 225 patients (19%). The mean (SD) albumin concentration in these patients (35[5]g/L) was lower than that of patients who did not mount an acute phase response preoperatively (40[5]g/L). High concentrations of CRP (> or =60mg/L) were associated with low albumin concentrations (33[5]g/L); high alpha-1 antitrypsin concentrations (> or =4.0g/L) were associated with low albumin concentrations (34[6]g/L); and high IL-6 concentrations (> or =4pg/ml) were associated with low albumin concentrations (37[6]g/L) compared with a mean(SD) albumin concentration of 40(5)g/L in patients who had no evidence of an acute phase response., Conclusion: A metabolic response to disease referred to as an acute phase response may explain low preoperative albumin concentrations. This association interferes with the association of low preoperative albumin concentrations and malnutrition. It is a new aspect of preoperative risk evaluation and may indicate a potential for prevention.

Study Objectives: This study was conducted to evaluate to what extent the cardiopulmonary bypass (CPB) procedure in patients undergoing coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response. Therefore, we measured bactericidal permeability increasing protein (BPI) as an indicator of neutrophil activation, interleukin 6 as inducer of the acute phase response, and lipopolysaccharide binding protein and C-reactive protein as parameters of the acute phase response in patients undergoing CABG either with or without the use of CPB., Design: Prospective study., Setting: Cardiopulmonary surgery department in a university hospital., Patients: Sixteen patients undergoing elective CABG were included. Eight patients underwent surgery with CPB, and eight patients underwent surgery without CPB (non-CPB)., Interventions: In the CPB group, blood samples were taken upon induction of anesthesia, at the start of aortic cross-clamping, at aortic unclamping, and 0.5, 4, 8, and 18 h thereafter. In the non-CPB group, blood samples were taken upon induction of anesthesia, and 0.5, 4, 8, and 18 h after completion of the bypass graft anastomoses., Measurements and Results: BPI release from neutrophil granules markedly increased during surgery in CPB patients but not in non-CPB patients. The increase in acute phase reactants, however, was the same in both patient groups., Conclusions: These data indicate that the acute phase response in CABG patients, which has historically been ascribed to the CPB procedure, is predominantly caused by the surgical procedure per se. Early neutrophil activation, however, is seen only when extracorporeal circulation is used.

Two hundred twenty-one consecutive adult cardiac surgical patients were examined prospectively for nutritional protein state, acute phase protein response, and delayed hypersensitivity reaction in an attempt to identify patients at high risk for the development of sternal wound infection, which occurred in 6 patients (2.7%). There was no significant correlation between preoperative nutritional protein concentrations (retinol-binding protein, prealbumin, and transferrin) and acute phase protein levels (C-reactive protein, alpha 1-acid glycoprotein, and complements B and C3), nor a statistically significant relationship between nutritional state or acute phase protein response and the development of sternal infection. Preoperative complement C3 levels were elevated, however, in 80.0% of those in whom sternal infections developed compared with 30.6% of those with well-healed wounds. Similarly, postoperative concentrations of alpha 1-acid glycoprotein were elevated in 80.0% of those in whom sternal infections developed compared with 28.6% of those with well-healed wounds. There was no correlation between delayed hypersensitivity and the risk of sternal infection, nor between preoperative nutritional protein and acute phase protein values. Seventy-three percent of patients were anergic on postoperative day 2. Stepwise logistic regression showed that age, body weight, preoperative intensive care unit stay, repeat median sternotomy, internal mammary artery grafting, postoperative hemorrhage, and postoperative cardiac arrest correlated with the development of sternal infection, whereas transfusion requirement, reexploration for bleeding, and the operation performed did not. We conclude that routine delayed hypersensitivity testing is of no value in predicting high-risk cardiac surgical patients when the anergy battery is placed on the preoperative day. Although statistically insignificant, possibly due to the small number of patients in whom sternal infection developed in this study (type II error), a larger study might find preoperative complement C3 and post-operative alpha 1-acid glycoprotein levels to be predictive of patients at risk for the development of sternal wound infection. The final logistic model for the predicted risk 2%) of sternal wound infection is: PREDSWC = exp(EQ)/1 + exp(EQ) where EQ = (0.38 x age) + (0.24 x weight) + (5.42 x preop ICU) + (4.39 x redo) + (7.14 x IMA) + (4.49 x hemorrhage) + (8.81 x arrest) - 62.72, and where preop ICU, redo, hemorrhage, and arrest are defined as yes (1) or no (0), IMA-is defined as 0, 1, or 2, age is in years, and weight is in kilograms.