Elevated Serum C-reactive Protein Levels Research Articles

C-reactive protein and insulin-like growth factor-1 in differential diagnosis of ascites.

Insulin-like growth factor-1 (IGF-1) and C-reactive protein (CRP) are produced mainly by the liver; the output of these markers in response to inflammatory processes may be affected in patients with hepatic dysfunction. This may explain the differences in IGF-1 and CRP values in patients with non-portal and portal hypertension ascites. We aimed to evaluate serum and ascitic fluid IGF-1 and CRP as diagnostic markers in the differential diagnosis of benign and malignant ascites. In this prospective study, 398 consecutive patients with ascites were included. Serum and ascitic fluid levels of IGF-1 and CRP were measured using an enzyme-linked immunosorbent assay. Patients were divided into group 1, due to benign ascites (n = 324), and group 2, due to malignant ascites (n = 74). Serum and ascitic IGF-1 were significantly increased in malignant ascites than benign ascites group [305 ± 65.7 ng/mL vs 95 ± 53.8 ng/mL; P < 0.001 and 288 ± 54.7 ng/mL vs 83.2 ± 36.7 ng/mL; P < 0.001], respectively. Serum and ascitic CRP were significantly higher in malignant ascites than benign ascites patients [12.8 ± 6.3 mg/mL vs 6.1 ± 4.9 mg/mL; P < 0.001 and 5.1 ± 2.2 mg/mL vs 1.6 ± 1.3 mg/mL; P < 0.001], respectively. At a cutoff value of 309.4 ng/mL and 7.8 mg/mL, serum IGF-1 and CRP had (95.1%, 81%) sensitivity and (88.6%, 75.5%) specificity for detecting malignant ascites [area under the curve: 0.932, 0.845], respectively. At a cutoff value of 291.6 ng/mL and 2.6 mg/mL, ascitic IGF-1 and CRP had (94.6%, 84%) sensitivity and (83.2%, 80.3%) specificity for detecting malignant ascites (area under the curve: 0.911, 0.893) correspondingly. Elevated serum and ascitic fluid IGF-1 and CRP levels were associated with malignant ascites.

The associations among vitamin D deficiency, C-reactive protein, and depressive symptoms

ObjectiveVitamin D deficiency has been reported to be associated with depression, but the underlying mechanisms aren't well understood. Our study aims to investigate the associations among serum vitamin D, C-reactive protein (CRP) level, and depressive symptoms. MethodsSerum levels of Vitamin D and CRP were measured from 52,228 participants. Depressive symptoms were assessed using a Korean version of the CES-D scale. We used logistic regression to calculate the odds ratio (ORs) of depressive symptoms according to vitamin D and CRP levels. The regressions were adjusted for covariates, and each model was adjusted mutually for vitamin D and CRP levels. ResultsA significant difference was found in vitamin D status between depressed and non-depressed participants, but CRP status was not significantly different. The OR for the presence of depressive symptoms was significantly increased in participants with vitamin D deficiency after adjusting for potentially confounding factors (Adjusted OR=1.158, 95% CI=1.003–1.336, p=0.046). The OR of depressive symptoms was not significantly increased in individuals with high (3.01-10mg/L) CRP level compared to individuals with low (≤3mg/L) CRP level (Adjusted OR=1.004, 95% CI=0.821–1.227, p=0.97). There was no significant association between vitamin D and CRP level. Additional adjustment for serum CRP level did not weaken the resulting association between vitamin D deficiency and the presence of depressive symptoms. ConclusionVitamin D deficiency was associated with depressive symptoms, but elevated serum CRP level was not. The results indicate that CRP level does not account for the association between vitamin D deficiency and the presence of depressive symptoms.

Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis.

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA.

Elevated serum C-reactive protein level predicts a poor prognosis for recurrent gastric cancer.

BackgroundsHigh serum C-reactive protein (CRP) was found to be associated with poor prognosis in kinds of solid tumors, however, its role in the recurrent gastric cancer (RGC) is unknown. The present study aimed to explore the prognostic value of serum CRP in RGC patients.MethodsA total 72 RGC patients who underwent radical surgery from January 2005 to May 2008 were enrolled. The clinical, pathological and survival information were collected. The serum CRP level was measured when the recurrence was confirmed, and the association between serum CRP and clinicopathological characters was analyzed. The prognostic value of serum CRP for RGC was investigated.ResultsThe serum CRP was elevated in 39 patients (H-CRP), while 33 patients were within the normal range (N-CRP). The elevated CRP was associated with Lymph node metastasis (p = 0.003) and tumor size (p = 0.004). The median survival time after recurrence was significantly worse in the H-CRP group than N-CRP group (6.5 months vs. 11.5 months, p = 0.012). Multivariate analyses identified that elevated CRP level (HR=2.325, p < 0.001), time to recurrence (HR = 0.466, p=0.033), and the follow-up treatment (HR = 2.650, p=0.001) were independent prognostic factors.ConclusionsHigh serum CRP level was associated with aggressive pathological features, was an independent poor prognostic factors for RGC, which might be a potential prognostic marker for RGC patients.

Prognostic Value of C-Reactive Protein in Resistant Hypertension.

C-reactive protein (CRP) is a biomarker of systemic low-grade inflammation and a cardiovascular risk predictor in several clinical conditions. However, its prognostic value has never been examined in patients with resistant hypertension. In a prospective study, 476 patients with resistant hypertension had CRP levels measured at baseline, together with other clinical laboratory variables, including ambulatory blood pressures (BPs). Primary end points were a composite of major fatal or nonfatal cardiovascular events, all-cause mortality, and cardiovascular mortality. Multiple Cox regression assessed the associations between CRP levels and end points. Median CRP was 3.8mg/l (interquartile range: 2.0-7.2mg/l). After a median follow-up of 9 years, 103 major cardiovascular events occurred, and 120 patients died, 62 from cardiovascular causes. Patients with CRP levels above the median value had a doubled excess risk of major cardiovascular events (95% confidence interval: 1.29-3.06; P = 0.002) and an 86% higher risk of cardiovascular death (95% confidence interval: 1.07-3.25; P = 0.029), after adjustments for potential confounders including traditional cardiovascular risk factors and ambulatory BP and dipping pattern. A high CRP equally predicted coronary (hazard ratio: 2.04; 95% confidence interval: 1.10-3.76; P = 0.023) and cerebrovascular events (hazard ratio: 2.72; 95% confidence interval: 1.30-5.67; P = 0.007). In interaction and sensitivity analyses, CRP levels were stronger predictors of worse cardiovascular outcomes in younger and obese patients, and in those with uncontrolled ambulatory BPs and with the nondipping pattern. In patients with resistant hypertension, elevated serum CRP levels is predictive of worse cardiovascular prognosis above and beyond other cardiovascular risk factors, including ambulatory BP levels and dipping patterns.

Multicentric Castleman Disease With Tubulointerstitial Nephritis Mimicking IgG4-related Disease

Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs.

Abstract 17077: Nocturnal Intermittent Hypoxia and Short Sleep Duration were Independently Associated With Elevated C-reactive Protein Level in Patients With Coronary Artery Disease

Introduction: There is growing evidence of a relationship between sleep disorders and cardiovascular diseases including coronary artery disease (CAD). However, the mechanism of these association is not well established. Enhanced vascular inflammation is implicated as a pathophysiologic mechanism in CAD. The aim of this study was to evaluate the relationship among sleep-disordered breathing (SDB), sleep duration, and serum C-reactive protein (CRP) level in patients with CAD. Methods and Results: Consecutive 225 patients with CAD who underwent percutaneous coronary intervention were evaluated. We used a nocturnal pulse oximetry as a non-invasive screening method for nocturnal intermittent hypoxia, a surrogate marker of SDB. Nocturnal intermittent hypoxia was evaluated using 3% oxygen desaturation index (3% ODI) which was the number of oxygen desaturation measurement ≤ 3% per hour, and we divided the patients into nocturnal intermittent hypoxia group (3% ODI≥15; n=64) and control group (3% ODI&lt;15; n=161). Sleep quality was assessed using validated questionnaires (Pittsburgh Sleep Quality Index [PSQI]; 5.3±3.4, sleep duration; 385±83 minutes). Nocturnal intermittent hypoxia group had significantly higher BMI compared with control group, but age, gender, other coronary risk factors, sleep disturbance (PSQI≥8), sleep duration, and angiographic findings did not differ between two groups. Laboratory data showed that serum CRP level was significantly higher in patients with nocturnal intermittent hypoxia (0.15 [0.09-0.33] vs 0.06 [0.02-0.21] mg/dl, p=0.003). Short sleep duration (&lt;6 hours) was also associated with increased CRP level (0.22 [0.04-0.40] vs 0.07 [0.03-0.14] mg/dl, p=0.036). In multiple regression analysis adjusted by age, gender, BMI, and acute coronary syndrome, 3% ODI (β=0.25; p=0.016; 95% CI, 0.153 to 1.475) and short sleep duration (β=0.20; p=0.04; 95% CI, 0.022 to 1.299) were independent determinants for log serum CRP level. Conclusions: Nocturnal intermittent hypoxia and short sleep duration were independently associated with elevated serum CRP level in CAD patients, suggesting that SDB and sleep duration could be important modifiable factors for the clinical management of patients with CAD.

Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease

Mucosal-associated invariant T (MAIT) cells have been reported to play an important role in mucosal immunity. However, little is known about the roles of MAIT cells in chronic obstructive pulmonary disease (COPD). The aims of this study were to examine the levels of circulating MAIT cells and their subsets in COPD patients and to investigate the potential relationship between clinical parameters and MAIT cell levels. Forty-five COPD patients and 57 healthy control subjects were enrolled in the study. Circulating MAIT cells and their subset levels in the peripheral blood were measured by flow cytometry. Disease grades were classified according to the GOLD criteria for the assessment of severity of COPD. Circulating MAIT cell levels were found to be significantly reduced in COPD patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets. Interestingly, elevated serum C-reactive protein level and reduced FEV1/FVC ratio were associated with MAIT cell deficiency in COPD patients. Furthermore, the circulating MAIT levels were found to be significantly lower in patients with moderate to severe COPD than in patients with mild COPD. Our data shows that MAIT cells are numerically deficient in the peripheral blood of patients with COPD. In addition, this MAIT cell deficiency was found to reflect inflammatory activity and disease severity. These findings provide important information for monitoring the changes in MAIT cell levels and for predicting the prognosis during the disease course.

Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.

Elevation in C-reactive protein (CRP) levels have been shown in patients with aortic valve stenosis (AS). Minor allele of the CRP gene (CRP) rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96) vs. 1.68 (0.98–2.90) mg/L, p < 0.001) and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01) compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

A case of neonatal-onset autoinflammatory syndrome with a de novo PSMB9 mutation resembling Nakajo-Nishimura syndrome

We report a case of neonatal-onset autoinflammatory syndrome that resembles Nakajo-Nishimura syndrome (NNS), a rare autoinflammatory syndrome caused by a homozygous PSMB8 mutation. The patient is a 7-year-old boy who demonstrated clinical findings that differ from those of typical NNS. Exudative erythemas on his face, trunk, and extremities developed 2 weeks after birth. At 1 month of age, the patient developed fever, elevated serum C-reactive protein levels, and elevated hepatic amino transferase levels. A febrile convulsion caused basal ganglia calcification at 4 months of age. Severe pulmonary arterial hypertension of unknown origin (NT-proBNP 33,445 pg/mL) was diagnosed at 7 months of age. These symptoms improved after administration of bozentan and ambrisentan, which are endothelin receptor antagonists. At 9 months of age, he developed heliotrope rash, edematous erythema on his extremities, and myositis with elevated serum creatine kinase levels (16,000 IU/L). Antinuclear antibodies, as well as anti-Jo-1 and anti-DNA antibodies, were negative. Skin and muscle biopsies revealed massive cellular inflammation, consisting primarily of lymphocytes and monocytic cells, located in the epidermis and between muscle fibers with fat tissue necrosis in the subcutis. Concomitant degeneration and regeneration of muscle fibers occurred and resulted in moderate variations in the fiber size. These results initially led to a diagnosis of juvenile dermatomyositis. His symptoms temporarily improved with corticosteroid treatment but recurred periodically. Administration of systemic agents such as azathioprine, methotrexate, cyclosporine, cyclophosphamide, mycophenolate mofetil, and intravenous immunoglobulins did not lead to remission. Hepatosplenomegaly and liver cirrhosis due to pulmonary arterial hypertension induced portal hypertension beginning at age 6. The serum levels of interleukin (IL)-1β (28 pg/mL), IL-6 (84.3 pg/mL), TNFα (21.6 pg/mL), IL-18 (595 pg/mL), and IFN-γ (7.0 IU/mL) were all increased during the periodic recurrences. These periodic symptoms were refractory to several immunosuppressive agents, which suggested an autoinflammatory syndrome. Although presence of fever, erythemas, basal ganglia calcification and hepatosplenomegaly suggested NNS, some of the characteristic symptoms of NNS, such as lipomuscular atrophy in the upper body and long clubbed fingers with joint contractures, did not occur in this patient. Since no significant mutations had been detected in the NLRP3, NOD2, MEFV, MVK, TNFRSF1A, and PSMB8 genes, whole exome sequencing of the patient and his parents was performed and a novel de novo heterozygous mutation has been identified in PSMB9, encoding the immunoproteasome subunit beta1i, in the patient. Our case might represent a novel proteasome-associated autoinflammatory syndrome similar to but distinct from NNS, in which a heterozygous mutation of the PSMB9 gene is responsible. Written informated consent for publication of their clinical details was obtained from the patient/parent/guardian/relative of the patient.

Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20mg/kg/day), or HCD plus atorvastatin (10mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and decreased the elevated I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover, flavocoxid effectively suppresses the release of inflammatory markers. In conclusion, these findings demonstrated that flavocoxid would be useful in preventing oxidative stress, inflammation, and vascular dysfunction induced by HCD.

Markers of iron status are associated with stage of pregnancy and acute-phase response, but not with parity among pregnant women in Guinea-Bissau.

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.

Syndesmophyte growth in ankylosing spondylitis.

Syndesmophytes are characteristic components of the spine disorder of ankylosing spondylitis. Understanding their growth may reveal insights to pathogenesis and potential treatment. We review recent studies on rates of development of syndesmophytes, patient characteristics associated with more rapid syndesmophyte growth, local vertebral abnormalities that precede syndesmophytes, systemic biomarkers of syndesmophytes, and studies of medications. New syndesmophytes develop in one-third of patients over 2 years. Consistent clinical predictors are male sex, elevated serum C-reactive protein levels, and preexisting syndesmophytes. Concomitant vertebral inflammation and fat dysplasia on MRI predict future syndesmophytes at the same vertebral location, but most syndesmophytes do not have recognized antecedents. Associations with serum levels of Wingless pathway proteins are inconsistent, as are the results of observational studies of tumor necrosis factor-alpha inhibitors. Although there is better understanding of the frequency of syndesmophyte development, the pathogenesis of syndesmophytes remains unclear.

Diffuse alveolar hemorrhage after use of a fluoropolymer-based waterproofing spray

A 30-year-old man developed chills, cough and dyspnea a few minutes after using a fluoropolymer-based waterproofing spray in a small closed room. He visited our hospital 1 h later. Examination revealed that the patient had incessant cough, tachypnea, fever and decreased peripheral arterial oxygen saturation. Blood tests revealed leukocytosis with elevated serum C-reactive protein levels. Chest radiographs and computed tomography (CT) scan showed bilateral ground glass opacities, mainly in the upper lobes. Bronchoalveolar lavage (BAL) fluid obtained from the right middle lobe showed a bloody appearance. Microscopic examination of a BAL cytospin specimen revealed the presence of numerous red blood cells associated with extreme neutrophilia. Microbiological studies of the BAL fluid were negative. The patient was observed without corticosteroid therapy, and his symptoms and abnormal shadows on the chest radiographs and CT improved. On day 7 after admission, the patient was discharged from the hospital. Accidental inhalation of waterproofing spray may cause diffuse alveolar hemorrhage, a rare manifestation of acute lung injury. Supportive treatment may be effective and sufficient.

A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome complicated by IgA nephropathy with nephrotic syndrome.

A 62-year-old man visited our hospital with a mild sore throat, high-grade fever, and clavicular pain. Seven years earlier, he had been diagnosed with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. His clavicles were tender and remarkably swollen. Also noted was marked pitting edema in the lower extremities and pustulosis on the palms and soles of the feet. Laboratory studies on admission showed an elevated white cell count (23,400/μl) and serum C-reactive protein level (24.4mg/dl). Urinalysis revealed proteinuria (2+) and occult blood (3+) with numerous dysmorphic red blood cells and hyalin casts. The patient was diagnosed with recurrence of his SAPHO syndrome and started on oral glucocorticoid therapy. By day 9 after admission, he had gained 16kg in body weight, and his proteinuria (6.4g/day) and serum creatinine level (2.3mg/dl) were elevated. Renal biopsy revealed mesangial proliferative glomerulonephritis with deposition of IgA and C3 in the mesangial area and along the capillary walls. The patient was diagnosed with IgA nephropathy accompanied by nephrotic syndrome. With oral prednisolone therapy, his fever, clavicular pain, and proteinuria were gradually relieved. The clinical course in this case suggests the onset of nephrotic syndrome with IgA nephropathy was associated with the recurrence of the patient's SAPHO. To our knowledge, this is the first reported case of SAPHO-associated IgA nephropathy.

Impact of Combined Use of Blood-based Inflammatory Markers on Patients with Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Proposal of a Cumulative Marker Score as a Novel Predictive Tool for Prognosis

BackgroundPrevious studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices. ObjectiveTo investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU). Design, setting, and participantsA total of 394 patients from multiple institutions were included. Median follow-up was 30 mo. InterventionAll patients underwent RNU without neoadjuvant chemotherapy. Outcome measurements and statistical analysisAssociated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP. Results and limitationsMultivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature. ConclusionsAlthough the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU. Patient summaryElevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two.

A rare case showing subacute thyroiditis-like symptoms with amyloid goiter after anti-tumor necrosis factor therapy.

SummaryAnti-tumor necrosis factor (TNF)-α therapy is established as a new standard for the treatment of various autoimmune inflammatory diseases. We report the first case showing subacute thyroiditis-like symptoms with an amyloid goiter after anti-TNF-α therapy. A 56-year-old man with Crohn's disease presented with fever and a diffuse, tender goiter. To control the diarrhea, anti-TNF therapy (infliximab) was administered 4 weeks before the thyroid symptoms emerged. The patient reported a swollen neck with tenderness on the right side and fever 4 days after the second infliximab injection. An elevated serum C-reactive protein (CRP) and serum thyroid hormone level with suppressed serum thyrotropin were observed. The thyroid-stimulating antibody was not elevated. An ultrasonograph of the thyroid revealed an enlarged goiter with posterior echogenicity attenuation and a low echoic region that was tender. The thyroid uptake value on technetium-99m scintigraphy was near the lower limit of the normal range. The patient was initially diagnosed with thyrotoxicosis resulting from subacute thyroiditis. Administration of oral prednisolone improved the fever, thyroid pain, and thyroid function, but his thyroid remained swollen. The patient developed diarrhea after prednisolone withdrawal; therefore, adalimumab, another TNF inhibitor, was administered. After three injections, his abdominal symptoms were alleviated, but the thyroid pain and fever recurred. Elevated serum CRP levels in the absence of thyroid dysfunction were observed. The patient's symptoms resolved after prednisolone retreatment, but an elastic, firm goiter persisted. A fine-needle biopsy revealed amyloid deposition in the thyroid.Learning points Many cases with thyroid dysfunction accompanied by amyloid goiter have been reported.There are cases that develop amyloid goiter with subacute thyroiditis-like symptoms after anti-TNF therapy.When the thyroid remains swollen after improvement of thyrotoxicosis following treatment with prednisolone, it should be assessed to differentiate between an amyloid goiter and common subacute thyroiditis.

The role of C-reactive protein in predicting post-metastatic survival of patients with metastatic bone and soft tissue sarcoma.

Although elevated preoperative serum C-reactive protein (CRP) level is an indicator of a poorer prognosis in many cancers including non-metastatic bone and soft tissue sarcoma, there have been no reports focused on sarcoma patients with advanced stage who had distant metastases. The aim of this study is to determine whether the serum CRP level after metastasis is associated with post-metastatic survival in patients with bone and soft tissue sarcoma. A total of 71 patients were studied including 38 male and 33 female. Of all patients, 22 patients had metastases at presentation. The remaining 49 patients developed initial metastasis after the treatment of primary tumor. The average age at the diagnosis of metastasis was 55 years. Blood was obtained after initial detection of metastasis. CRP levels ranged from 0.1 to 165 mg/L with an average of 16.4 mg/L in all patients. Elevated CRP levels (>3 mg/L) were seen in 31 patients (range 3.1-165). The disease-specific survival after metastasis estimates at 3 and 5 years was 17.1 and 17.1 % for those with an elevated CRP vs. 59.5 and 45.3 % for those with a normal CRP (p < 0.0001). In 49 patients who developed lung metastasis after initial primary treatment, patients with elevated CRP levels also had a poorer post-metastatic survival than patients with normal CRP levels (p < 0.0001). In conclusion, we recommend routine measurement of CRP level to identify the patients who have high risk of death after metastasis.

Usefulness of maternal serum C-reactive protein with vaginal Ureaplasma urealyticum as a marker for prediction of imminent preterm delivery and chorioamnionitis in patients with preterm labor or preterm premature rupture of membranes.

To assess whether maternal serum C-reactive protein (CRP) and genital mycoplasmas measured can help predict imminent preterm delivery or chorioamnionitis in patients with preterm labor (PL) or preterm premature rupture of membranes (PPROM). The study group consisted of 165 women with PL or PPROM. Vaginal cultures for genital mycoplasmas and maternal blood for CRP were obtained when they were admitted for the management of PL or PPROM. An elevated level of serum CRP was defined as ≥0.8 mg/dL. Histologic evaluation of the placenta was performed after delivery. The prevalence of positive vaginal fluid cultures for Ureaplasma urealyticum (UU) was 63.0%, and elevated maternal serum CRP was 32.7%. No outcome variables were associated with vaginal UU infection in patients with lower CRP levels. However, among women with elevated CRP, the mean gestational age at birth was significantly reduced, and low Apgar score, neonatal intensive care unit admission, histologic chorioamnionitis, and delivery within 7 days of admission were significantly more common in patients with vaginal UU. Although vaginal UU in PL or PPROM cannot act as the sole predictor of imminent preterm delivery or chorioamnionitis, it can provide predictive information in patients with elevated maternal serum CRP levels.

Prognostic value of C-reactive protein in esophageal cancer: a meta-analysis.

The classical inflammatory biomarker, C-reactive protein (CRP), has been identified to be related to progression of esophageal cancer. Some research showed that elevated pretreatment serum CRP indicated a poor prognosis, but results have been inconsistent. We searched the Medline, Embase and the Cochrane Central Search Library for suitable studies and a meta-analysis of eleven (1,886 patients) was conducted to examine the relationship between elevated serum CRP level and overall survival (OS) in esophageal cancer cases. Moreover, correlation analyses were conducted to assess links between pretreatment serum CRP level and tumor node metastasis (TNM) stage as well as T, N, M grade, respectively. The pooled analysis showed that elevated pretreatment serum CRP level was significantly associated with poorer overall survival (HR 2.09, 95%CI 1.52-2.87, p<0.01). Subgroup analyses were conducted by "country", "cut-off value", "treatment" and "number of patients", and no single factor could alter the result. Elevated pretreatment serum CRP was significantly correlated with more advanced TNM stage and T, N, M grade respectively. Elevated pretreatment serum CRP levels are associated with poorer prognosis in esophageal cancer patients, and could serve as a useful biomarker for outcome prediction.