Rise In C-reactive Protein Research Articles

699 Role of C-Reactive Protein as a Marker for Disease Course in Obese Patients With Inflammatory Bowel Disease

INTRODUCTION: Currently, the disease course and clinical outcomes of obese patients with inflammatory bowel disease (IBD) have been mixed. This study aims to compare biomarkers of inflammation such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in both obese and non-obese African American (AA) and Caucasian populations. METHODS: We conducted a prospective observational study of consecutive Crohn's disease (CD) and ulcerative colitis (UC) patients in the outpatient setting at a tertiary referral center between 2014-2017. Body mass index (BMI), ESR, CRP, hemoglobin (Hgb) were measured at 2 consecutive visits. Obesity was defined as a BMI ≥30. The Wilcox signed rank test was used to compare continuous variables, and the Chi square test for categorical variables. A multivariate logistic regression model was created to look at change in CRP (no change, increase by half, decrease by half) from initial to follow-up visit. The regression model analysis included ethnicity, gender, BMI, type of IBD (CD versus UC), age, alcohol use, tobacco use, hypertension, kidney disease, heart disease, and treatment as covariates. RESULTS: The study included 92 subjects, 65% had CD and 30% were AA (Table 1). The average time between visits was 136 days. In the obese group, 33% were AA and 70% were female. Also, a larger portion of CD patients were obese compared to UC patients (37% and 11% respectively with P = 0.03). There was a significant decrease in the CRP in the obese group (P = 0.029) whereas non-obese individuals had an increase in CRP (Table 2). There was no significant difference in ESR and hemoglobin (Hgb) between obese and non-obese individuals. 63 patients where included in the regression model, which showed that a decrease in CRP was significantly associated with obesity (P = 0.0081) when adjusted for the above covariates. Overall, obese individuals were more likely to experience no change in CRP or a decrease in CRP while non-obese individuals were more likely to have a rise in CRP. There was no difference in clinical disease activity indices (HBI/SCCAI) between obese and non-obese patients. CONCLUSION: In our study, the obese patients were more likely to be female, have CD, and be Caucasian. While there was no difference in Hgb or ESR in obese versus non-obese, there is a difference in CRP. CRP could have importance as a sensitive marker for disease course in patients whose BMI ≥30. A larger cohort may provide further insight into this observation.

Retrospective study to evaluate the clinical significance of a second rise in C-reactive protein level following instrumented spinal fusion surgery

BackgroundThis study aimed to identify the incidence and causes of a second rise in C-reactive protein (CRP) levels following spinal instrumentation surgery and to help determine how an abnormal CRP response should be interpreted and managed during postoperative care. MethodsThe medical records of 948 patients who underwent instrumented spine fusion surgery and met the inclusion criteria were retrospectively reviewed to assess the frequency and causes of a second rise (SR) of CRP. A SR of CRP was defined when the CRP level after postoperative day 7 increased by more than 0.5 mg/dl from that at the previous time-point. The diagnostic cut-off value of CRP elevation for detection of surgical site infection (SSI) was determined. Cut-off values were analyzed using receiver operating characteristic (ROC) curves. Bayes' theorem was used to determine blood test posterior probabilities for SSI-positive cases using cutoff values of re-evaluated CRP levels. ResultsSR of CRP occurred in 107 of the 948 patients. Of the patients with SR of CRP, 38 (35%) patients had developed SSI, 33 (31%) patients had causes other than SSI, and the remaining 36 patients had unidentified causes. Among the patients with SR, excluding those with causes other than SSI, the best diagnostic cut-off value of SR for detection of SSI was 3.04 mg/dl (area under the curve was 0.74). The posterior test probability was 84.4%. ConclusionsFor patients with SR of CRP, who had no causes other than SSI, an SR value of 3.04 mg/dl correlated with a high probability of developing SSI.

Inflammatory biomarkers in HIV-infected children hospitalized for severe malnutrition in Uganda and Zimbabwe.

A proportion of HIV-infected children with advanced disease develop severe malnutrition soon after antiretroviral therapy (ART) initiation. We tested the hypothesis that systemic inflammation underlies the pathogenesis of severe malnutrition in HIV-infected children. Cross-sectional laboratory substudy in 613 HIV-infected children initiating ART in Uganda and Zimbabwe. We measured C-reactive protein (CRP), TNFα, IL-6 and soluble CD14 by ELISA in cryopreserved plasma at baseline (pre-ART) and week-4 (children with severe malnutrition only). Independent associations between baseline biomarkers and subsequent hospitalization for severe malnutrition were identified using multivariable fractional polynomial logistic regression. Compared with children without severe malnutrition (n = 574, median age 6.3 years, median baseline weight-for-age Z-score -2.2), children hospitalized for severe malnutrition post-ART (n = 39, median age 2.3 years, median baseline weight-for-age Z-score -4.8) had higher baseline CRP [median 13.5 (interquartile range 5.5, 41.1) versus 4.1 (1.4, 14.4) mg/l; P = 0.003] and IL-6 [median 9.2 (6.7, 15.6) versus 5.9 (4.6, 9.3) pg/ml; P < 0.0001], but similar overall TNFα, soluble CD14 and HIV viral load (all P > 0.06). In a multivariable model, higher pre-ART IL-6, lower TNFα and lower weight-for-age were independently associated with subsequent hospitalization for severe malnutrition. Between weeks 0 and 4, there was a significant rise in CRP, IL-6 and soluble CD14, and fall in TNFα and HIV viral load in children hospitalized for severe malnutrition (all P < 0.02). Pre-ART IL-6 and TNFα were more strongly associated with hospitalization for severe malnutrition than CD4 cell count or viral load, highlighting the importance of inflammation at the time of ART initiation in HIV-infected children.

Serial C-Reactive Protein Measurements in Newborn Infants without Evidence of Early-Onset Infection

Background: C-reactive protein (CRP) is used to assist the diagnosis and monitoring of newborn infection. Little is known about CRP activity after birth in the absence of infection. Objective: The aim of this work was to describe postnatal CRP responses in the first days of life in asymptomatic infants with a negative blood culture. Methods: Data were collected from infants who had a blood culture taken at <72 h of age in a UK maternity hospital. All CRP values and their time from birth were recorded. Infants with signs of infection, positive blood culture, or major congenital anomalies were excluded. Infants were analysed by gestation (greater or less than 37 weeks). Normalised CRP curves were generated by linear interpolation and centile curves were derived. Comparisons of median CRP values between groups were made by Mann-Whitney U test at 24, 36, and 48 h. Results: During the study period a total of 219 babies were screened. After exclusions, 73 infants (58 term, 15 preterm) were analysed. In asymptomatic term neonates the CRP (mg/L) peaked at 9.4 after 34.6 h. In preterm babies the CRP peak was 1.75 at 43 h. The median (IQR) values were higher in the term group at 24 and 36 h: 2.5 (1–10.5) versus 0 (0–2.2; p = 0.02) and 3 (0–8.6) versus 0 (0–2.8; p = 0.031). Conclusions: A CRP rise was demonstrated in term and preterm infants without evidence of infection. This rise was greatest in term infants. CRP values must be interpreted in the context of an infant’s clinical condition and not used alone to guide clinical decision making.

C-reactive protein at ICU admission as a marker of early graft dysfunction after liver transplant. A prospective, single-center cohort study.

To explore the behavior of C-reactive protein (CRP) after orthotopic liver transplantation (OLT) during the first postoperative days, and its usefulness as a marker of severe early allograft dysfunction (EAD). A prospective, single-center cohort study was carried out. The Intensive Care Unit (ICU) of a regional hospital with a liver transplant program since 1997. The study comprised a total of 183 patients admitted to our ICU immediately after liver transplantation between 2009 and 2015. C-reactive protein levels upon ICU admission and after 24 and 48h, severe EAD and hospital mortality. The CRP levels after OLT were: upon ICU admission 57.5 (51.6-63.3)mg/L, after 24h 80.1 (72.9-87.3)mg/L and after 48h 69.9 (62.5-77.4)mg/L. Severe EAD patients (14.2%) had higher mortality (23.1 vs 2.5; OR 11.48: 2.98-44.19) and lower CRP upon ICU admission (39.3 [29.8-48.7]mg/L) than the patients without EAD (0.5 [53.9-67.0]; p<0.05] - the best cut-off point being 68mg/L (sensitivity 92.3%; specificity 40.1%; Youden index 0.33). Lower CRP upon ICU admission was correlated to higher mortality (24.5 [9.2-39.7] vs 59.4 [53.4-65.4]; p<0.01, AUC 0.79 [0.65-0.92]). Liver transplant is a strong inflammatory stimulus accompanied by high levels of C-reactive protein. A blunted rise in CRP on the first postoperative day after OLT may be a marker of poor allograft function and is related to hospital mortality.

A Prospective Randomized Controlled Trial of Single-Port and Three-Port Laparoscopic Appendectomy in Children.

Background: This study aimed to evaluate single-port laparoscopic appendectomy (SPLA) in comparison with three-port laparoscopic appendectomy (3PLA) in children about the extent of surgical trauma after SPLA and 3PLA measured by serum interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations. Materials and Methods: A total of 50 patients with a median age of 11.5 were randomized to two groups. Experts in both methods performed the surgeries. The decision on the type of planned surgery was randomly determined. Serum IL-6 and CRP levels were measured using an enzyme-linked immunosorbent assay before, and at 12 and 36 hours after surgery. Furthermore, we compared operating time, hospital stay, postoperative pain, and complication rates. Results: The operative time in the 3PLA group was shorter than that in the SPLA group (P < .05). Preoperative IL-6 levels were not different between the two groups, but the rise (pre- versus postoperative) of IL-6 in the SPLA group was remarkably higher when compared with the 3PLA group (P < .05). Similar results were obtained for CRP; basal serum CRP levels were not different between the two groups, but the rise of CRP in the 3PLA group was significantly lower compared with that in the SPLA group. During the first 12 hours postoperative, the SPLA patients reported more severe postoperative pain and longer inpatient opiate usage was noted that after 3-PLA. Only one SPLA case was converted to 3PLA. There were no conversions to open surgery. The length of hospital stay and complication rate were not different between the two groups. Conclusions: SPLA in children is associated with longer operative times, increased pain level, and more severe surgical trauma as measured by postoperative CRP and IL-6 levels in comparison with a 3PLA. The two approaches were comparable regarding the length of hospital stay and complication rate.

Rising Postoperative C-Reactive Protein in Congenital Diaphragmatic Hernia: Sepsis or Inflammation?

This study aims to determine the incidence of sepsis in neonates operated for congenital diaphragmatic hernia and ascertain if the level or pattern of C-reactive protein (CRP) could be used to differentiate neonates with sepsis from noninfective inflammation. This study suggests that CRP patterns within the first 48-hours after surgical intervention for congenital diaphragmatic hernia could be used to differentiate neonates with noninfective inflammation from sepsis. A larger, multicentric study is needed to differentiate sepsis from inflammation on the basis of CRP rise and thereby help in avoiding unnecessary use of antibiotics.

Food protein-induced enterocolitis syndrome: guidelines summary and practice recommendations.

Food protein-induced enterocolitis syndrome (FPIES) is a poorly understood non-IgE gastrointestinal-mediated food allergy that predominantly affects infants and young children. Cells of the innate immune system appear to be activated during an FPIES reaction. Acute FPIES typically presents between one and 4 hours after ingestion of the trigger food, with the principal symptom being profuse vomiting, and is often accompanied by pallor and lethargy. Additional features can include hypotension, hypothermia, diarrhoea, neutrophilia and thrombocytosis. In Australia, the most commonly reported foods responsible for FPIES are (in descending order) rice, cow's milk, egg, oats and chicken. Most children with FPIES react to only one food trigger, and thus, avoidance of multiple foods is often not indicated. FPIES is often misdiagnosed as sepsis or gastroenteritis. However, a diagnosis of FPIES is favoured if there is rapid resolution of symptoms within hours of presentation, an absence of fever, and a lack of a significant rise in C-reactive protein at presentation. Diagnosis is often hampered by the lack of awareness of FPIES, absence of reliable biomarkers, the non-specific nature of the presenting symptoms, and the delay between allergen exposure and symptoms. Although some national peak allergy bodies have attempted to improve the diagnosis and management of FPIES, up until 2017 there were no internationally agreed guidelines for its diagnosis and management.

Azathioprine Hypersensitivity Syndrome in a Cohort of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients

Azathioprine hypersensitivity syndrome is a rare complication of azathioprine therapy. Its symptoms resemble infection or relapse of inflammatory disease, hindering correct diagnosis. Current literature is limited to sporadic case reports and reviews. To estimate the incidence of azathioprine hypersensitivity syndrome and describe its characteristics in the context of an observational cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Also, to facilitate early recognition and awareness among clinicians. Within a cohort of 290 patients with ANCA-associated vasculitis receiving azathioprine maintenance therapy, frequency of azathioprine hypersensitivity was described and characteristics were compared between hypersensitive and nonhypersensitive patients. Clinical picture, laboratory abnormalities, and concurrent medication of patients with azathioprine hypersensitivity were described. Of 290 patients, 25 (9%) experienced azathioprine hypersensitivity after a median of 14 (interquartile range [IQR] 12-18) days. Frequent symptoms were fever (100%), malaise (60%), arthralgia (36%), and rash (32%). All patients used prednisolone (median 10 mg/day, IQR 9.4-16.3 mg/day) at the time of the hypersensitivity reaction. Most patients had a rise in C-reactive protein (CRP), leukocyte counts, and neutrophil counts, but no eosinophilia. Thiopurine S-methyltransferase (TPMT) activity was significantly lower in hypersensitive patients (median 74.4 [IQR 58.0-80.1] nmol/gHb/L) compared with controls (median 81.4 [71.9-90.5] nmol/gHb/L), P= .01. Hypersensitive patients had a higher risk of relapse (hazard ratio 2.2, 95% confidence interval 1.2-4.2; P= .01). Azathioprine hypersensitivity syndrome is strikingly common in ANCA-associated vasculitis, might be associated with reduced TPMT activity, is accompanied by an increase in neutrophil counts, and may occur even during concomitant prednisolone therapy. Proper recognition may prevent unnecessary hospital procedures and damage to the patient.

Behavior of C-reactive protein in association with surgery of facial fracture and the influence of dexamethasone.

To clarify pre- and postoperative C-reactive protein (CRP) levels in patients with facial fractures and to investigate the influence of perioperatively administered dexamethasone on postoperative CRP levels. Facial fracture patients were randomized to receive perioperatively a total dose of 30mg of dexamethasone (Oradexon®), whereas patients in the control group received no glucocorticoid. The analysis included patients who had CRP measured pre- and postoperatively. A total of 73 adult patients with facial fractures were included in the final analysis. Mean CRP level was elevated preoperatively and the level increased further after surgery. However, postoperative CRP rise was significantly impeded by dexamethasone (p < 0.001), regardless of gender, age, treatment delay, site of fracture, surgical approach, and duration of surgery. CRP rise halved on the 1st postoperative day when dexamethasone was used. In addition, dexamethasone resulted in a CRP decrease on the 2nd postoperative day, whereas the CRP rise continued in the control group. CRP rise is a normal body response after facial fracture and surgery that can be markedly reduced with dexamethasone. CRP changes should be considered with caution if perioperative dexamethasone is used.

Clinical study of neonatal septicemia with reference to early indicators of sepsis

Background: The use of CRP (C-reactive protein) in early diagnosis of neonatal septicemia. The usefulness of CRP in early detection of neonatal septicemia/meningitis and urinary tract infection was studied in a neonatal unit using a semi-quantitative latex-agglutination as a rapid screening method and electroimmuno assay as reference method for CRP determination.Methods: The present study was conducted among 150 patients 218 samples were taken for serum globulin determinations. Additionally, all infants born at the hospital throughout August 2016 to February 2017 with a designation of blood disease, infectious disease or tract infection (UTI) were retrospectively studied. Depending on the clinical course and therefore the results of the culture the 110 infants were divided into four groups.Results: The 110 infants in 92% of non-infected infants CRP was 16 mg/l and 80% had CRP &lt;10 mg/l up to 3 days of age. After 3 days of age 93% had CRP &lt;12 mg/l. The initial CRP level was increased in 9 out of 11 patients (82%) with bacterial septicemia. Low CRP was seen in one patient with total agranulocytosis and septicemia from Streptococcus type B and in one patient with Staphylococcus albus sepsis. A rise in CRP was also seen in very pre-term infants with septicemia. Increased initial CRP was uncommon in neonatal urinary tract infection (2 of 9) but a rise was seen in 3 additional patients.Conclusions: A comparison between CRP, total neutrophil blood cell count and hand neutrophil count as diagnostic parameters was in favor of CRP at this early stage of infection. CRP is of definite value as an aid in early diagnosis of neonatal septicemia and bacterial meningitis.

Luminal Clinical

<b>Luminal Clinical</b>

Can dynamic changes in prognostic markers predict survival in patients receiving VEGF-targeted therapy in clear cell renal cell carcinoma?

e16061 Background: Markers of the systemic inflammatory response have prognostic value in ccRCC prior to starting treatment. Dynamic changes during therapy and their role in predicting prognosis are not well characterised. Methods: A retrospective analysis was conducted of a randomised, double-blind phase II study evaluating cediranib vs cediranib and saracatinib in patients with relapsed metastatic ccRCC (COSAK). Haemoglobin (Hb), neutrophil count (N0) platelet count (Plt), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were recorded at randomisation, 8-weeks and progression (PD). Change in mean values at each time point were compared. Baseline prognostic values for overall survival (OS) were assessed using Cox regression. Absolute changes in parameters were calculated at 8 weeks and PD, patients were grouped around the upper or lower quartile. Prognostic value of dynamic changes was assessed at 8 weeks and PD using the Kaplan-Meier method. Results: 138 patients were assessed; median OS was 12.0 months (IQR 8.1-15.6 months). Outcomes in the combination arm were similar to single agent arm (HR 1.28 (1.00–1.63)). On multivariate analysis at baseline, MSKCC score (0/1-2/≥3) (HR 2.52 (1.60 -3.96)), CRP ( &lt; 10/≥10mg/L) (HR 1.72 (1.04 – 2.86)) and N0 ( &lt; 7.5/≥7.5x109) (HR 2.38 (1.43 – 3.96)) were independent predictors of OS. Mean CRP was significantly different at baseline, 8 weeks and PD (64.9, 42.3 and 85.7 mg/L respectively, p &lt; 0.001). Mean N0 count at baseline was 5.3 x109/L and was significantly higher 6.3x 109/L at PD (p &lt; 0.001). Mean Hb at baseline, 8 weeks and PD was 11.5, 13.0 and 12.9g/L respectively (P &lt; 0.001). A rise in CRP or N0 at 8 weeks was predictive of poor outcome ((HR 1.62 (1.10-2.56) and (HR 1.77 (1.19-2.61) respectively). A fall in Hb was predictive of poor outcome at 8 weeks (HR 1.75 (1.18-2.60)) and PD (HR 1.80 (1.20-2.76)). Conclusions: Dynamic changes occur in prognostic markers in patients receiving VEGF-targeted therapy in ccRCC and may predict OS.

Associations of number and severity of depressive episodes with C-reactive protein and Interleukin-6.

Many researchers have found that the inflammatory process in the body and the brain may result in psychiatric disorders. Meta-analyses of cross-sectional studies have reported increase in inflammatory markers in depression. However, the direction of the association remains unclear. To compare the levels of C-reactive protein (CRP) and Interleukin-6 (IL-6) in depressed and healthy controls. To study the associations of these biomarkers with severity and number of depressive episodes. A total of 72 subjects with major depression and 60 healthy controls were studied. CRP and IL-6 were measured in all subjects. No significant differences were noted between depressed patients and healthy controls with regard to CRP (p=0.29) and IL-6 (p=0.50). Those who were suffering from severe depression based on Beck's Depressive Inventory (BDI), were positively correlated with raised CRP (p=0.011) in comparison to patients with mild to moderate depression. Single and recurrent depressive disorder (RDD) were not associated with significant rise in CRP (p=0.866) and IL-6 (p=0.531). Severity of depression is correlated with elevated CRP but not with IL-6. No association found between number of depressive episodes and levels of CRP and IL-6. It is possible that immune dysregulation is not generally present in depression, but might be restricted to particular subgroups of depressed patients. Several factors that could influence the depression and inflammation relationship need further investigation.

C-reactive protein: an early predictor of sepsis in patients with thermal burns

Background: Due to the high mortality rate of established sepsis in patients with burn injuries, it would be beneficial if the onset can be predicted before it is fully established. The objective of the study was to estimate the predictive value of C-reactive protein in thermal burns patients. The secondary objective was to determine how much earlier CRP level allowed the prediction of sepsis in these patients.Methods: This was a case-control study, conducted prospectively on 60 human patients admitted with thermal burns. Cases were those who developed sepsis following burns and the controls were burns patients without sepsis. All patients underwent serial estimation of C-reactive protein values on alternative days, along with other blood parameters. From the data, the predictive value of C-reactive protein in sepsis was analysed.Results: A significant higher value of C-reactive protein was found in septic patients. Rise in serum C-reactive protein level predicted sepsis with an efficacy of 87%, while the sensitivity was found to be 93% and the specificity was 80%, with a significant odds ratio of 56. Also a pre-defined rise in C-reactive protein predicted the onset of sepsis about 2 days before the clinical onset.Conclusions: C-reactive protein is a useful indicator for sepsis in burns patients. In combination with clinical sepsis markers, C-reactive protein can be used to initiate intensive monitoring and appropriate antibiotic therapy.

Tocilizumab-Refractory Cytokine Release Syndrome (CRS) Triggered By Chimeric Antigen Receptor (CAR)-Transduced T Cells May Have Distinct Cytokine Profiles Compared to Typical CRS

Background: Cytokine release syndrome (CRS) in the setting of CAR T cell therapy manifests as a wide constellation of symptoms with multi-organ involvement. CRS can vary from a mild, self-limited course to a life-threatening systemic inflammatory response which, in severe cases, may be associated with manifestations similar to those seen in hemophagocytic lymphohistiocytosis (HLH). Tocilizumab, an anti-human IL-6 receptor antibody, has become a widely accepted pharmacologic intervention of first choice in severe CRS based on the observation of elevated levels of inflammatory cytokines, most notably interleukin (IL)-6 and interferon (IFN)-γ. Indeed, following administration of tocilizumab, most patients show rapid signs of improvement. However, in rare circumstances, CRS may be refractory to tocilizumab, and repeat administration or institution of additional immunosuppression is needed. Here we summarize cytokine profiles and CRS seen in patients treated with anti-CD22-CAR T cells and propose tocilizumab-refractory CRS as a potentially distinct pathophysiological entity from typical CRS that may merit alternative immunosuppressive interventions other than tocilizumab.Methods: Children and young adults with relapsed/refractory CD22+ ALL were treated with anti-CD22 CAR T cells. Serial samples for serum cytokine levels (IFN-γ, IL-6, IL-2, IL-10, IL-12p70, IL-1β, IL-15, IL-13, IL-4, IL-8, TNF-α, GM-CSF, MIP1-α) were obtained at pre-specified time points (0, 12, 24, 48, 72 hours, then daily on days 4 - 14 and 28 following CAR T cell infusion). Transduced CAR T cell dosage ranged from 3x10e5 cells/kg (dose level [DL] 1), 1x10e6 cells/kg (DL2), and 3x10e6 cells/kg (DL3). CRS severity was determined according to recently proposed grading system (Lee DW et al., Blood. 2014). Disease burden was assessed using standard morphology and flow cytometry analysis of bone marrow and peripheral blood samples.Results: Cytokine profiles are available on 10 patients treated: first 9 patients enrolled in our phase I trial (NCT02315612), and the tenth patient was treated off-protocol on an emergency investigational new drug protocol given lack of alternative treatment option for rapidly progressing disease. All subjects, median age 20 years (range, 6-22 years), had a diagnosis of multiply relapsed ALL. Seven of 10 subjects developed CRS. Five subjects with CRS were complete responders to CAR therapy (Table). The median time to the onset of CRS was 9 days (range, 7-12 days) post-infusion and resolved within 1 week with supportive care alone except in one patient who received pharmacologic intervention for grade 4 CRS. Rise in C-reactive protein (CRP) tended to correlate with clinical severity of CRS. Chronological changes in the level of IFN-γ, IL-6, IL-1β, IL-8, TNF-α, and MIP1-α generally mirrored the CRP trend, typically preceding CRP change by 1-2 days.In contrast to the CRS (maximum grade 2) seen in the first 9 patients, the 10th patient treated at DL3 developed grade 4 CRS with manifestations characteristic of HLH unresponsive to tocilizumab. Cytokine profile for this patient, compared to those of other CRS patients, was notable for a substantially higher serum IL-2 (35 pg/mL vs median 6.1 (range, 1.2-13.5)) and GM-CSF level (28 pg/mL vs median 1.0 (range, 0-6.1)) at 12 hours post infusion. Subsequent CRP elevation was not initially accompanied by a rise in IL-6 as in other patients, which may have explained the lack of response to tocilizumab (Figure). Evaluation for a genetic cause of HLH did not reveal any mutations (PRF1, MUNC13-4, RAB27A, STX11, STXBP2). Although this patient was a complete responder to therapy, the clinical course was complicated by pre-existing respiratory compromise and bacteremia, which may have contributed to increased CAR toxicity with variability in the cytokine profile.Conclusion: Based on our early experience, we postulate that patients with an early increase in GM-CSF and IL-2 may potentially experience more atypical and severe CRS, which without a concomitant rise in IL-6, may not respond to tocilizumab and thus early intervention with other immunosuppression may be indicated. Analysis of larger numbers of patients is required to better delineate clinical confounders and to develop rational pharmacological approach to CAR-mediated inflammatory responses. Ongoing efforts are underway to further analyze clinical samples for biomarkers. [Display omitted] [Display omitted] DisclosuresMackall:NCI: Patents & Royalties: B7H3 CAR.

Aortoenteric Fistula in Patient with Infected Aortic Endovascular Stent

A 70-years-old man was admitted at the emergency room for onset of fever, malaise and discharge of melena. At the admission, his vital signs were: blood pressure 135/70 mmHg, heart rate 92 bpm, O2 saturation 95%. Blood sample showed mild normocyitc anaemia (Hb 12.1 g/dL), leucocytosis (White blood cells count 12.300/mmc, Neutrophil 77%), rise of C-reactive protein (7.3 mg/dL, normal value < 0.5 mg/L), normal kidney function (creatinine 1.0 mg/dL). Clinical examination was remarkable for mild epigastric pain.

Physical activity and exercise capacity in patients with moderate COPD exacerbations

Little is known about changes in physical activity during moderate (out-patient managed) exacerbations.6-min walking distance (6MWD) was measured during 50 exacerbations when the patients were stable, and at 3 and 7 days post-exacerbation presentation. At similar time points, quadriceps maximum voluntary contraction (QMVC) was measured during 47 different exacerbations. Physical activity (SenseWear; Bodymedia Inc., Pittsburgh, PA, USA) was recorded over 2 consecutive-week periods post-presentation.6MWD fell from a median 422 m when stable to 373 m on day 3 (p=0.001). Similarly, QMVC fell from 32.6 versus 29.7 kg (p=0.026). Falls in 6MWD were associated with a rise in C-reactive protein (r= -0.364; p=0.041) and increased Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) (r= -0.44; p=0.013). Light physical activity was 2.18 h·day(-1) during the first week post-exacerbation and was less over week 2 (1.98 h·day(-1); p=0.009). Patients who had attended pulmonary rehabilitation had smaller changes in 6MWD than those who had not attended (-35.0 versus -114.9 m; p=0.013). Falls in physical activity were correlated with higher depression scores (rho= -0.51; p=0.006).These findings indicate that exercise capacity and muscle strength fall at exacerbation in chronic obstructive pulmonary disease patients who are treated at home and are free to maintain normal activity.

The evaluation of C-reactive protein as a screening tool for neonatal sepsis

Background: Bacterial sepsis and meningitis continues to be major causes of neonatal mortality and morbidity in low birth weight infants. C - reactive protein (CRP) is a simple investigation which has diagnostic potential but the previous studies have yielded variable results. A combination of screening tests along with the clinical signs is useful to diagnose/rule out neonatal sepsis along with gold standard blood culture. The objective was to study CRP in relation to other haematological parameters in diagnosis of sepsis and to find out whether CRP estimation helps in early treatment interventions like stopping empirical antibiotic therapy in neonatal sepsis. Methods: A prospective study of 62 neonates with suspected sepsis admitted in level 2 neonatal special care unit of TMH, Jamshedpur from 1 st January 2010 to 30 th September 2010 were evaluated after meeting inclusion criteria using clinical criteria, sepsis screen and blood culture, which was taken as gold standard for diagnosis of neonatal sepsis. Results: Total blood culture positive cases were 26 (42%) and CRP was positive in total 24 cases (39%) of total 62 cases, of which, it is increased in 19 cases (79%) of total 26 culture proven cases and in 5 cases (21%) of culture negative cases. The CRP was increased in 14 cases (35%) out of total 40 cases in early onset sepsis (EOS) group as compared to 10 cases (45.5%) out of 22 in late onset group. The sensitivity of CRP is more in late onset sepsis (LOS) (45.5%) than in early onset sepsis (35%). CRP rise was highest with 73% in proven sepsis, where as it is 23% and 8% in probable and no sepsis groups respectively. The CRP in present study is having sensitivity of test: 73%, specificity of test: 86.1%. The PPV and NPV were 79.1 and 81.6% respectively. If CRP is added to septic screen, it has improved the specificity of the test. Whereas, sepsis screen has sensitivity of 88.5%, the specificity of 83.3%, PPV 79.3% and NPV 90.9%. So, totally empirical antibiotic therapy was stopped in 23 cases of “no sepsis” group including both early as well as late onset sepsis. Conclusions: Based on the result of our study, the CRP is an effective parameter for the diagnosis of neonatal sepsis and when used in conjunction with the sepsis screen, which increases the sensitivity and specificity of the test, it can help identify septic neonates and help in appropriate management while also reducing the unnecessary use of antibiotics, thereby helping curb the growing menace of antibiotic resistance.

Study of serum C-reactive protein levels in acute exacerbations of chronic obstructive pulmonary disease patients

Background: C-reactive protein (CRP) is an acute phase protein synthesized in response to tissue damage or inflammation and reflects total systemic burden of inflammation in individuals. Objective: To assess the levels of serum CRP in acute exacerbations of chronic obstructive pulmonary disease (COPD) and wherever possible compare it with their stable state and to evaluate clinical severity of exacerbations viz a viz rise in serum CRP. Materials and Methods: It was a prospective study in which cases (76) were patients with acute exacerbation of COPD and control group (30) comprised of patients with acute exacerbation of other respiratory diseases such as pneumonia (15 patients), acute exacerbation of asthma (10 patients), and 5 patients of acute respiratory distress syndrome (ARDS). CRP measurement was done by Nephlometry. CRP levels were measured at time of exacerbation and at time of recovery of the patients, which were compared with the overall prognosis of the patients and with the duration and stage of COPD and also the prognosis of patients in each group is correlated to CRP levels. To achieve this objective, receiver operating characteristic curve analysis has been used with the help of MedCalc software and logistic regression analysis has been used to study the role of different stages of COPD and role of comorbidity in the final outcome of the patients using SPSS software version 22. Result: The serum CRP was significantly elevated in patients with COPD with acute exacerbation (mean value 14.78 mg/dL). There was significant elevation of CRP values in control group such as in asthma (mean value 2.71 mg/dL), pneumonia (mean value 20.28 mg/dL), and ARDS (mean value 27.02 mg/dL). Conclusion: CRP is a good discriminator and it predicts poor outcome and also predicts admission in intensive care unit (ICU) or in ward for the patients of acute exacerbation of COPD. CRP value higher than 17.5 mg/dL and above had the poor final outcome of treatment. Positive correlation was found between CRP value and admission in ICU.