Multi-view radiomics and dosiomics analysis with machine learning for predicting acute-phase weight loss in lung cancer patients treated with radiotherapy.

We propose a multi-view data analysis approach using radiomics and dosiomics (R&D) texture features for predicting acute-phase weight loss (WL) in lung cancer radiotherapy. Baseline weight of 388 patients who underwent intensity modulated radiation therapy (IMRT) was measured between one month prior to and one week after the start of IMRT. Weight change between one week and two months after the commencement of IMRT was analyzed, and dichotomized at 5% WL. Each patient had a planning CT and contours of gross tumor volume (GTV) and esophagus (ESO). A total of 355 features including clinical parameter (CP), GTV and ESO (GTV&ESO) dose-volume histogram (DVH), GTV radiomics, and GTV&ESO dosiomics features were extracted. R&D features were categorized as first- (L1), second- (L2), higher-order (L3) statistics, and three combined groups, L1 + L2, L2 + L3 and L1 + L2 + L3. Multi-view texture analysis was performed to identify optimal R&D input features. In the training set (194 earlier patients), feature selection was performed using Boruta algorithm followed by collinearity removal based on variance inflation factor. Machine-learning models were developed using Laplacian kernel support vector machine (lpSVM), deep neural network (DNN) and their averaged ensemble classifiers. Prediction performance was tested on an independent test set (194 more recent patients), and compared among seven different input conditions: CP-only, DVH-only, R&D-only, DVH + CP, R&D + CP, R&D + DVH and R&D + DVH + CP. Combined GTV L1 + L2 + L3 radiomics and GTV&ESO L3 dosiomics were identified as optimal input features, which achieved the best performance with an ensemble classifier (AUC = 0.710), having statistically significantly higher predictability compared with DVH and/or CP features (p < 0.05). When this performance was compared to that with full R&D-only features which reflect traditional single-view data, there was a statistically significant difference (p < 0.05). Using optimized multi-view R&D input features is beneficial for predicting early WL in lung cancer radiotherapy, leading to improved performance compared to using conventional DVH and/or CP features.

Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis.

BACKGROUND: Respiratory-related hospitalization, in particular acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), is common and associated with increasing mortality in patients with IPF. We aimed to evaluate the implications of a newly proposed framework of acute respiratory deterioration (ARD) and AE-IPF in hospitalized patients. METHODS: Using the data of an IPF cohort consisting of 225 consecutive patients, we retrospectively studied first hospitalizations from January 2008 to December 2017. We analysed the demographics and 90-day mortality of patients with AE-IPF and those with parenchymal cause of ARD other than AE. RESULTS: Among 122 patients with first hospitalization for ARD, 35 patients were diagnosed with AE-IPF, including 11 patients with triggered AE. Parenchymal cause of ARD other than AE was diagnosed in 71 patients, and extra-parenchymal cause in 16 patients. Almost all hospitalized patients (93%) underwent chest CT, and 83% of patients with AE-IPF underwent bronchoalveolar lavage. There was a significant difference in the anti-inflammatory therapy between the AE-IPF group and parenchymal cause of ARD other than AE group (p < 0.001). AE-IPF was independently associated with poor survival in multivariate Cox proportional regression analysis. CONCLUSIONS: AE-IPF accounted for about 30% of first hospitalizations for ARD, and differentiation between AE-IPF and the other categories in ARD is important from a therapeutic and a prognostic point of view.

The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer.

Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment.

Correlations between the levels of acute infection markers and serum albumin in elderly patients with hip fracture.

OBJECTIVE: The aim of this study was to explore a clinical index that could predict the decline of serum albumin (ALB) in elderly patients (over 60 years old) with hip fractures in 2014. METHODS: All the data came from the retrospective survey, and the correlations between the ALB changes and acute infection markers were then analyzed using correlation analysis. The changes of infection markers and ALB before and after surgery were compared using the t test. RESULTS: There was no correlation of the serum ALB blood with interleukin-6 (IL-6) (r = 0.072, P = 0.588), C-reactive protein (CRP) (r = -0.249, P = 0.057), or calcitonin (PCT) (r = -0.038, P = 0.775) when patients were admitted, but it was negatively correlated with the total amount of infection markers (TAIMs) (r = -0.301, P = 0.020). The postoperative levels of IL-6 (154.23 ± 177.14 pg/mL) (P < 0.001), CRP (69.52 ± 39.84 mg/L) (P < 0.001), and PCT (1.27 ± 2.4 ng/mL) (P < 0.001) were significantly increased than those before surgery [IL-6 (44.96 ± 54.58 pg/mL), CRP (31.78 ± 29.90 mg/L), and PCT (0.42 ± 1.06 ng/mL)]. The postoperative level of serum ALB (29.93 ± 3.02 g/L) was significantly reduced than that before surgery (33.95 ± 3.69 g/L) (P < 0.001). The serum ALB level was negatively correlated with IL-6 (r = -0.333, P = 0.015) before surgery, but not correlated with TAIMs (r = -0.256, P = 0.061). The serum ALB level was negatively correlated with IL-6 (r = -0.292, P = 0.034) and TAIMs (r = -0.271, P = 0.050) after surgery. CONCLUSIONS: The serum IL-6 level could predict the changes of ALB during the disease process.

Characterizing the Acute Phase Response in Healthy Patients Following Total Joint Arthroplasty: Predictable and Consistent.

BACKGROUND: During surgery, trauma to musculoskeletal tissue induces a systemic reaction known as the acute phase response (APR). When excessive or prolonged, the APR has been implicated as an underlying cause of surgical complications. The purpose of this study was to determine the typical APR following total joint arthroplasty in a healthy population defined by the Charlson Comorbidity Index (CCI). METHODS: This retrospective study identified 180 healthy patients (CCI < 2) who underwent total joint arthroplasty by a single surgeon for primary osteoarthritis from 2013 to 2015. Serial measurements of C-reactive protein (CRP) and fibrinogen were obtained preoperative, perioperative, and at 2 and 6 weeks postoperative. RESULTS: Postoperative CRP peaked during the inpatient period and returned to baseline by 2 weeks. Fibrinogen peaked after CRP and returned to baseline by 6 weeks. Elevated preoperative CRP correlated with a more robust postoperative APR for both total hip arthroplasty and total knee arthroplasty, suggesting that a patient's preoperative inflammatory state correlates with the magnitude of the postoperative APR. CONCLUSION: Measurement of preoperative acute phase reactants may provide an objective means to predict a patient's risk of postoperative dysregulation of the APR and complications.

Long-Term Impact of Postoperative Complications on Cancer Recurrence Following Lung Cancer Surgery.

BACKGROUND: Postoperative complications are associated with poor cancer-specific survival in various types of cancer surgery. Recent studies suggest that systemic inflammation induced by surgical trauma can accelerate the adhesion of circulating tumor cells to the vascular endothelium of distant organs, resulting in early cancer recurrence. We investigated the impact of postoperative cardiopulmonary complications on cancer recurrence following lung cancer surgery. METHODS: From a prospective database of 675 consecutive patients who underwent curative surgery for lung cancer between 2007 and 2012, the incidence of postoperative cardiopulmonary complications, white blood cell counts, and C-reactive protein levels were evaluated in the acute phase after surgery. Four patients had both cardiovascular and respiratory complications. The remaining 671 patients were divided into 3 groups: patients without cardiopulmonary complications; those with cardiovascular complications; and those with respiratory complications. The incidence of cancer recurrence was compared among the three groups. RESULTS: Postoperative cardiovascular or respiratory complications were identified in 94 (14%) or 25 (4%) patients, respectively. Postoperative white blood cell counts and C-reactive protein levels were significantly higher in those with postoperative respiratory complications than in those without. There was a significantly higher incidence of cancer recurrence in those with postoperative respiratory complications than in those without (48.0 vs. 16.8%; p < 0.0001). Multiple regression analysis adjusted for age, sex, and pathological staging showed that the incidence of postoperative respiratory complications was a significant predictor of cancer recurrence. CONCLUSIONS: The presence of respiratory complications following lung cancer surgery was a significant predictor of cancer recurrence.

Comparison of the acute-phase response after laparoscopic versus open aortobifemoral bypass surgery: a substudy of a randomized controlled trial.

PURPOSE: Minimally invasive surgical techniques have been shown to reduce the inflammatory response related to a surgical procedure. The main objective of our study was to measure the inflammatory response in patients undergoing a totally laparoscopic versus open aortobifemoral bypass surgery. This is the first randomized trial on subjects in this population. PATIENTS AND METHODS: This is a substudy of a larger randomized controlled multicenter trial (Norwegian Laparoscopic Aortic Surgery Trial). Thirty consecutive patients with severe aortoiliac occlusive disease eligible for aortobifemoral bypass surgery were randomized to either a totally laparoscopic (n=14) or an open surgical procedure (n=16). The inflammatory response was measured by perioperative monitoring of serum interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP) at six different time points. RESULTS: The inflammatory reaction caused by the laparoscopic procedure was reduced compared with open surgery. IL-6 was significantly lower after the laparoscopic procedure, measured by comparing area under the curve (AUC), and after adjusting for the confounding effect of coronary heart disease (P=0.010). The differences in serum levels of IL-8 and CRP did not reach statistical significance. CONCLUSION: In this substudy of a randomized controlled trial comparing laparoscopic and open aortobifemoral bypass surgeries, we found a decreased perioperative inflammatory response after the laparoscopic procedure measured by comparing AUC for serum IL-6.

Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection.

BACKGROUND: Gastric contents aspiration in humans is a risk factor for severe respiratory failure with elevated mortality. Although aspiration-induced local lung inflammation has been studied in animal models, little is known about extrapulmonary effects of aspiration. We investigated whether a single orotracheal instillation of whole gastric fluid elicits a liver acute phase response and if this response contributes to enrich the alveolar spaces with proteins having antiprotease activity. METHODS: In anesthetized Sprague-Dawley rats receiving whole gastric fluid, we studied at different times after instillation (4 h -7 days): changes in blood cytokines and acute phase proteins (fibrinogen and the antiproteases alpha1-antitrypsin and alpha2-macroglobulin) as well as liver mRNA expression of the two antiproteases. The impact of the systemic changes on lung antiprotease defense was evaluated by measuring levels and bioactivity of antiproteases in broncho-alveolar lavage fluid (BALF). Markers of alveolar-capillary barrier derangement were also studied. Non-parametric ANOVA (Kruskall-Wallis) and linear regression analysis were used. RESULTS: Severe peribronchiolar injury involving edema, intra-alveolar proteinaceous debris, hemorrhage and PMNn cell infiltration was seen in the first 24 h and later resolved. Despite a large increase in several lung cytokines, only IL-6 was found elevated in blood, preceding increased liver expression and blood concentration of both antiproteases. These changes, with an acute phase response profile, were significantly larger for alpha2-macroglobulin (40-fold increment in expression with 12-fold elevation in blood protein concentration) than for alpha1-antitrypsin (2-3 fold increment in expression with 0.5-fold elevation in blood protein concentration). Both the increment in capillary-alveolar antiprotease concentration gradient due to increased antiprotease liver synthesis and a timely-associated derangement of the alveolar-capillary barrier induced by aspiration, contributed a 58-fold and a 190-fold increase in BALF alpha1-antitrypsin and alpha2-macroglobulin levels respectively (p < 0.001). CONCLUSIONS: Gastric contents-induced acute lung injury elicits a liver acute phase response characterized by increased mRNA expression of antiproteases and elevation of blood antiprotease concentrations. Hepatic changes act in concert with derangement of the alveolar capillary barrier to enrich alveolar spaces with antiproteases. These findings may have significant implications decreasing protease burden, limiting injury in this and other models of acute lung injury and likely, in recurrent aspiration.

Study of the immunomodulatory properties of gamithromycin and dexamethasone in a lipopolysaccharide inflammation model in calves.

The aim of this study was to define the in vivo immunomodulatory properties of the macrolide antibiotic gamithromycin in calves, with respect to the acute phase response. Additionally, the corticosteroid dexamethasone was included as a positive control immunomodulatory drug. Both drugs, as well as their combination,were studied in a previously developed inflammation model,which was initiated by an intravenous lipopolysaccharide (LPS) challenge (0.5 µg/kg body weight). Twenty-four 4-week-old male Holstein Friesian calves were randomized into four groups: no pharmacological treatment (n = 6) or a pharmacological treatment with gamithromycin (n= 6), dexamethasone (n= 6) or their combination (n= 6) 1 h prior to LPS administration. Blood collection and clinical scoring were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6)) and acute phase proteins (serum amyloid A and haptoglobin) were subsequently determined. Gamithromycin did not have any beneficial effect on the LPS-induced clinical signs (dyspnea, fever, anorexia and depression), nor on the studied inflammatory mediators. In the dexamethasone and combination groups, the occurrence of dyspnea and fever was not prominently influenced, although the calves recovered significantly faster from the challenge. Moreover, dexamethasone significantly inhibited the levels of TNF-α and IL-6, suggesting a key role for these cytokines in sickness behaviour. In conclusion, unlike dexamethasone, gamithromycin did not directly reduce cytokine release in an LPS inflammation model in calves.

Teste rápido para detecção da Proteína C-Reativa (FASTest® CRP canino) como auxílio diagnóstico de piometra em cadelas / Fast test for C-reactive Protein detection (FASTest® CRP canine) as an aid for the diagnosis of pyometra in bitches

A piometra é uma enfermidade comum em cadelas, caracterizada pela inflamação do útero com acúmulo de exsudato purulento. A avaliação ultrassonográfica abdominal é um dos principais exames utilizados para o diagnóstico da doença e o tratamento de eleição é a ovário-histerectomia (OSH). A proteína C reativa (PCR) é uma proteína de fase aguda que apresenta concentração sérica aumentada na ocorrência de processos inflamatórios. O objetivo deste trabalho foi avaliar a eficácia do teste rápido para detecção da PCR sérica (FASTest® CRP canino), como auxiliar no diagnóstico de piometra em cadelas com suspeita da doença ao exame ultrassonográfico. Das 25 cadelas com imagem ultrassonográfica sugestiva de piometra incluídas no estudo, apenas 12 (48,0%) tiveram o diagnóstico confirmado por exame histopatológico uterino realizado após a OSH. Em todas as pacientes com o diagnóstico de piometra confirmado pelo exame histológico a PCR foi positiva. O FASTest® CRP apresentou valor preditivo positivo de 92,3%, valor preditivo negativo e sensibilidade de 100,0% e 92,3% de especificidade. Logo, a acurácia do FASTest® CRP canino para diagnóstico de piometra em cadelas com suspeita ao exame ultrassonográfico foi de 96,0%. Conclui-se que o teste rápido para detecção da PCR sérica pode ser utilizado como exame auxiliar para o diagnóstico de piometra em cadelas...

Pyometra is a common disease in bitches characterized by an inflamed uterus filled with pus. Abdominal ultrasonographic evaluation is one of the most requested exam used to diagnose the disease, whereas ovariohysterectomy is the most commonly chosen treatment. C-reactive protein (CRP) is an acute phase protein whose serum concentration increases in inflammatory processes. The goal of this study was to evaluate the effectiveness of the rapid test for detecting serum CRP (FASTest® canine CRP) in the diagnosis of pyometra in bitches with suspicion of the disease by ultrasonography. From 25 bitches with ultrasonographic image suggestive of pyometra included in this study, only 12 (48.0%) has the diagnosis confirmed by histopathological examination of the uterus after ovariohysterectomy. In all patients diagnosed with pyometra, confirmed by histology, the CRP was positive. The FASTest® CRP showed a positive predictive value of 92.3 %, negative predictive value and sensitivity of 100.0% and 92.3% of specificity. Therefore, the accuracy of FASTest® CRP for diagnosis of pyometra in bitches with suspicion by ultrasonography was 96.0%. It was concluded that the rapid test for detecting serum CRP can be used as an aid to diagnose pyometra in bitches...

Acute systemic response to intraperitoneal implantation of polypropylene mesh/chitosan-based film composite in pigs.

PURPOSE: To assess the systemic response of pigs to the intraperitoneal implantation of polypropylene mesh associated with chitosan-based film with a degree of deacetylation of 95%. METHODS: Blood samples were collected 24 hours before, and two and seven days after surgery. Systemic reactions were evaluated based on white blood cell count, C-reactive protein, and total serum protein, albumin and globulin levels. RESULTS: The systemic response was proportional to the composite response induced by polypropylene mesh, and the tissue inflammatory response was higher in the PP group (p=0.0033). CONCLUSION: The polypropylene mesh/chitosan-based film composite did not elicit a systemic response in pigs.

The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia.

Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (sVCAM) as well as interleukin 6 (IL6), total white blood cell (WBC) count, C-reactive protein (CRP) and D-dimer in a cohort of children with SCA and matched controls at baseline, immediately after, and 30, 60 and 120 min following exercise. Despite higher baseline levels of all biomarkers except CRP, the acute phase response from baseline to immediately after exercise was significantly greater in subjects versus controls for CRP (2·1 vs. 0·2 mg/l, P = 0·02) and D-dimer (160 vs. 10 µg/l, P < 0·01) only. Similar between-group trends were observed over time for all biomarkers, including sVCAM, IL6, total WBC, CRP and D-dimer. Lower fitness, defined by peak oxygen consumption (VO2 ), was independently associated with greater acute phase responses to exercise for sVCAM. Our results suggest maximal exercise may not be associated with any greater escalation of endothelial activation or inflammation in SCA and provide preliminary biomarker evidence for the safety of brief, high-intensity physical exertion in children with SCA.

Acute systemic response to intraperitoneal implantation of polypropylene mesh/chitosan-based film composite in pigs

PURPOSE:To assess the systemic response of pigs to the intraperitoneal implantation of polypropylene mesh associated with chitosan-based film with a degree of deacetylation of 95%.METHODS:Blood samples were collected 24 hours before, and two and seven days after surgery. Systemic reactions were evaluated based on white blood cell count, C-reactive protein, and total serum protein, albumin and globulin levels.RESULTS:The systemic response was proportional to the composite response induced by polypropylene mesh, and the tissue inflammatory response was higher in the PP group (p=0.0033).CONCLUSION:The polypropylene mesh/chitosan-based film composite did not elicit a systemic response in pigs.

Acute-phase response following full-mouth versus quadrant non-surgical periodontal treatment: A randomized clinical trial.

AIM: A moderate acute-phase response occurs 24-h following full-mouth non-surgical treatment (FM-SRP). The aim of this study was to compare acute-phase (24-h) and medium-term (3 months) inflammation after quadrant scaling (Q-SRP) versus FM-SRP. MATERIAL & METHODS: Thirty-eight periodontitis-affected subjects were randomly allocated to FM-SRP or Q-SRP after a baseline visit. Periodontal and anthropometric parameters were collected at baseline and 3 months. Serum samples were drawn at baseline, 1, 7, and 90 days after treatment. High-sensitivity assays of inflammation and endothelial assays were performed. RESULTS: FM-SRP produced a greater acute-phase response after 24 h [threefold increase in C-reactive protein (CRP), twofold increase in interleukin (IL-6), and a slight increase in tumour necrosis factor]. No differences in systemic biomarkers were noted between groups at any later follow-ups. Both periodontal treatments produced a comparable improvement in clinical periodontal parameters with no between-group differences. Treatment time was positively associated with the relative 24-h increase in CRP (R = 0.5, p < 0.001) and IL-6 (R = 0.5, p = 0.002), while the number of deeper (>6 mm) pockets predicted only the relative increase in IL-6 (R = 0.4, p < 0.05). CONCLUSIONS: FM-SRP triggers a moderate acute-phase response of 24 h duration compared to Q-SRP. Further research is needed to assess the eventual impact of such findings on the risk of vascular events is advocated. (ClinicalTrials.gov NCT01857804).

Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin.

Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Low transformation growth factor-ß1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni.

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers' fibrosis in humans. In this report, the effects of the host's nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-ß1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-ß1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories.

OBJECTIVE: To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients. BACKGROUND: Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival. METHODS: A total of 230 severely burned children with burns exceeding 30% of the total body surface, requiring at least 1 surgical procedure were enrolled in this prospective cohort study. Demographics, clinical outcomes, and inflammatory and acute-phase responses (serum cytokines, hormones, and proteins) were determined at admission and at 11 time points for up to 180 days postburn. Statistical analysis was performed using a 1-way analysis of variance, the Student t test, χ test, and Mann-Whitney test where appropriate. RESULTS: Survivors and nonsurvivors exhibited profound differences in critical markers of inflammation and metabolism at each time point. Nonsurvivors had significantly higher serum levels of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, C-reactive protein, glucose, insulin, blood urea nitrogen, creatinine, and bilirubin (P < 0.05). Furthermore, nonsurvivors exhibited a vastly increased hypermetabolic response that was associated with increases in organ dysfunction and sepsis when compared with survivors (P < 0.05). CONCLUSIONS: Nonsurvivors have different trajectories in inflammatory, metabolic, and acute phase responses allowing differentiation of nonsurvivors from survivors and now possibly allowing novel predictive models to improve and personalize burn outcomes.