Normal Erythrocyte Sedimentation Rate Research Articles

Callovian Ostracods of Central Dagestan: Biostratigraphy, Paleoecology, and Chorology

Analysis of the distribution of ostracods from the Armkhi Formation (Callovian) of the Tsudakhar section (Central Dagestan) enabled the identification of a stratigraphic sequence of six assemblages determined by paleoecological conditions and the first ostracod-based biostratigraphic zonation of the Callovian of Dagestan. Beds with Pleurocythere khapissovi and the Neurocythere cruciata intermedia Zone of the European ostracod scales were identified in the middle Callovian; this facilitated the interregional correlation for ostracods. Paleoecological analysis demonstrated the formation of the lower part of the section (beds with P. khapissovi and the N. cruciata intermedia Zone) in the coastal zone of the upper subtidal with normal marine salinity, good aeration, and low sedimentation rates. Sediments of the upper part of the section (paleoecological intervals with Schuleridea translucida–Cytherella perennis and with C. perennis) accumulated in the lower zone of the upper subtidal with a high sedimentation rate, high (and constantly increasing) eutrophication, and lowered pH values. Analysis of the paleogeographic distribution of the species studied revealed the connections of the Caucasus Sea to Western and Eastern Europe and to Central Asia.

Predictors of risk of fracture in inflammatory bowel diseases: a prospective study using FRAX score.

Despite the well-known risk of osteoporosis and bone fractures among patients with inflammatory bowel diseases, the WHO FRAX tool has been used in a limited number of studies in this specific population. The purpose of this study was to search for predictors of risk of fractures assessed by FRAX score. We prospectively calculated FRAX score for hip and major osteoporotic fractures in inflammatory bowel disease patients consecutively recruited. The mean risk of hip fractures at 10 years, for the 80 recruited patients, resulted 1.4%, while the mean risk of major osteoporotic fractures was 7.8%. The risk of hip fractures was 1.3% among the 30 Crohn's disease patients versus 1.4% (P=0.82) among 50 ulcerative colitis patients. A prolonged use of corticosteroids correlated with a tendency to a greater risk of hip fracture (r=0.38, P=0.08). Patients with normal erythrocyte sedimentation rate (ESR) values had a risk of osteoporotic hip fractures of 0.75%, while those with high ESR values had a risk of 1.86% (P=0.04). Regarding the risk of major bone fractures, patients with normal ESR values had a risk of 5.9%, versus a risk of 18% in those with elevated ESR (P=0.03). The correlation between increase of inflammatory markers and increased risk of osteoporotic fractures and the lack of difference between Crohn's disease and ulcerative colitis suggest a central role of inflammation over malabsorption in this population.

Afebrile and Leukopenic Sweet's Syndrome Following Partial Ileectomy in an Elderly Woman

Afebrile and Leukopenic Sweet's Syndrome Following Partial Ileectomy in an Elderly Woman

Giant Cell Arteritis in Association with Posterior Circulation Strokes: Report of Two Cases with Normal Erythrocyte Sedimentation Rate

Giant Cell Arteritis in Association with Posterior Circulation Strokes: Report of Two Cases with Normal Erythrocyte Sedimentation Rate

A New Method to Predict Erythrocyte Sedimentation Rate with Natural Geographical Factors and Location by Case-based Reasoning: A Case Study of China

Reference values of erythrocyte sedimentation rate (ESR) are the key to interpret ESR blood test in clinic. The common local reference ESR values are more accuracy in blood test that are established with natural geographical factors by using the multiple linear regression (MLR) model and the artificial neural network (ANN). These knowledge-based methods have limitations since the knowledge domains of ESR and natural geographical factors are limited. This paper presents a new cases-depended model to establish reference ESR values with natural geographical factors and location using case-based reasoning (CBR) since knowledge domain of ESR and geographical factors is weak. Overall 224 local normal ESR values of China that calculated from 13 623 samples were obtained, and the corresponding natural geographical factors and location that include altitude, sunshine hours, relative humidity, temperature, precipitation, annual temperature range and annual average wind speed were obtained from the National Geomatics Center of China. CBR was used to predict the unseen local reference ESR values with cases. The average absolute deviation (AAD), mean square error (MSE), prediction accuracy (PA), and Pearson correlation coefficient (r) between the observed and estimated data of proposed model is 33.07%, 9.02, 66.93% and 0.78, which are better than those of ANN and MLR model. The results show that the proposed model provides higher prediction accuracy than those of the artificial neural network and multiple linear regression models. The predicted values are very close to the observed values. Model results show significant agreement of cases data. Consequently, the model is used to predict the unseen local reference ESR with natural geographical factors and location. In spatial, the highest ESR reference areas are distributed in the southern-western district of China that includes Sichuan, Chongqing, Guangxi and Guizhou provinces, and the reference ESR values are greater than 23 mm/60 min. The higher ESR reference values are distributed in the middle part and northern-eastern of China which include Hubei, Henan, Shaanxi, Shanxi, Jilin and Heilongjiang provinces, and the reference ESR values are greater than 18 mm/60 min. The lowest ESR reference values are distributed in the northern-western of China that includes Tibet and Xinjiang, and the reference ESR values are lower than 5 mm/60 min.

Hypophosphatemic osteomalacia caused by urinary mesenchymal tumor: A case report

This case report concerns a 34-year-old woman who had been diagnosed with ankylosing spondylitis (AS), fibromyalgia syndrome (FMS), osteoarthritis (OA), lumbar disc herniation and the like in different hospitals during the past 18 months. She had progressive osteoarthrosis, significant muscle weakness, gait abnormalities in weightbearing areas, however without typical inflammatory low back pain, while the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was invalid, with normal inflammation index, negative results for rheumatic factor (RF) and human leukocyte antigen (HLA)-B27, and normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She had hyphosphatemia, normal serum calcium, 1,25-(OH)2-D3 reduction, elevated alkaline phosphatase (ALP) and normal parathyroid hormone (PTH), however with elevated urinary phosphorus. Finally, the medial thigh nodule was found in the subcutaneous of her inner leg by careful examination and imaging scans including B-ultrasound and PET/CT. The final pathology confirmed that the nodule was phosphate urinary mesenchymal tumors. After the tumor was removed, the patient was treated with anti-osteoporosis and phosphorus supplementation. The symptoms of bone pain and muscle weakness were alleviated, and hypophosphatemia was corrected. It was confirmed that the patient had low-phosphorus osteomalacia due to tumor. Tumor-induced hypophosphatemia osteomalacia (TIO) was a rare paraneoplastic syndrome which was caused by excessive phosphorus excretion induced by the tumor, and was thus categorized as an acquired hypophosphatemic osteomalacia. TIO had an occult onset and was associated with a high rate of misdiagnosis, although TIO has some typical clinical features. Early diagnosis, correctly positioning of the tumor, and surgical resection can achieve good outcomes.

Serum Uric Acid Shows Inverted "U" Type Correlation with Osteoporosis in Chinese Ankylosing Spondylitis Patients: A Retrospective Study.

BackgroundThis study was to investigate the correlation between osteoporosis and serum uric acid in ankylosing spondylitis (AS) patients, and to further identify potential factors that might be associated with osteoporosis in AS patients.Material/MethodsWe included 182 AS patients, consisted of 143 male patients and 39 female patients, who visited our hospital from January 1, 2014 to December 31, 2018. We used dual-energy x-ray absorptiometry to measure bone mineral density (BMD) of orthotopic lumbar vertebrae in patients with AS. The gender, age, disease duration, BMD, T-score, Z-score, uric acid, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood platelet (PLT), and status of treatment with biologics of the patients were collected. Then, the Spearman correlation coefficient and multivariate liner regression analysis were applied to identify the relationship between the factors and BMD, T-score, and Z-score in AS patients.ResultsMale AS patients between the ages of 16 and 30 years old had a higher risk of osteoporosis (P<0.05). AS patients with uric acid value between 300–360 μmol/L had the highest BMD, T-score, and Z-score. The BMD had a positive correlation with age and disease duration (P<0.01) while had a negative correlation with PLT (P<0.05). BMD in AS patients with elevated ESR was significantly (P<0.05) lower than in AS patients with normal ESR. There were no significant differences in BMD between AS patients with elevated CRP and the patients with normal CRP and PLT. Treatment with TNFi (tumor necrosis factor alpha inhibitor) did not improve BMD in AS patients.ConclusionsThe relationship between uric acid and BMD in AS patients was observed as inverted “U”-type. Keeping uric acid within 300–360 μmol/L might be helpful in preventing AS patients from developing osteoporosis.

Disease Activity in Takayasu’s Arteritis Affects Long-term Graft Related Outcomes

Introduction - Takayasu’s Arteritis (TA) is a rare, inflammatory large-vessel vasculitis of unknown etiology. This disease occasionally requires surgical intervention. There is a paucity of published data on the long-term outcomes of surgical intervention in these patients. There is limited data on the results of these procedures in patients with or without active disease. Methods - A retrospective review was conducted of patients with Takayasu’s arteritis who underwent open, noncardiac vascular procedures at our institution between 1994 and 2017. Basic demographics, diagnostic workup, treatment and outcomes were reviewed. Active disease was defined by the National Institute of Health or/and the Mayo Clinic criteria. Results - Between 1994 and 2017, 51 patients with Takayasu’s Arteritis underwent open noncardiac vascular surgery. Forty-four patients (86) were female with a mean age of 38 years (range 10-72 years). At the time of surgery 36 patients (77%) were on steroids, with 23 patients (49%) taking an additional immunomodulate pharmaceutical. Twenty patients (42%) had required prior vascular interventions. Six patients (13%) had an additional autoimmune disorder diagnosed previously. The most common location for disease was the aorta (86%) with the subclavian (80%), carotid (69%), innominate (41%), and the renal (33%) arterial lesions also seen. Vascular reconstruction was performed on 82 arterial lesions. The most common locations requiring reconstruction was the carotid artery (28%) followed by the subclavian (22%), aorta (15%) and renal arteries (11%). Mean follow-up was 74 months (range 1-265 months). Early complications (less than 30 days) occurred in 14 patients (31%). Late complications (greater than 31 days) occurred in 22 patients (49%). There were two perioperative mortalities (4%). Eighteen patients (40%) required endovascular and/or surgical reintervention. The primary and primary assisted patency were 72% and 89% respectively. Seventeen patients (35%) had active disease at the time of surgery and three (18%) of these patients developed graft occlusion and underwent revision. Six patients (35%) with active disease required eight additional graft related re-interventions. Thirty-one patients (65%) had quiescent disease with three (10%) of patients occluding their reconstruction follow-up. Four patients (13%) with quiescent disease required four additional graft related re-interventions. The incidence of graft related re-interventions was higher on patients with active disease (p<0.05). Erythrocyte sedimentation rate (ESR) demonstrates a sensitivity rate of 29% with a positive predictive valve of 63% in active disease. 71% of patients with active disease had a normal ESR. Conclusion - The outcome of the intervention appears to be related to the presence of active disease. Patients with active disease had worse graft related outcomes compared to patients with quiescent disease. Normalized ESR is not a good predictor of quiescent disease.

Effective treatment of TNF\u03b1 inhibitors in Chinese patients with Blau syndrome

ObjectivesBlau syndrome (BS) is a rare dominantly inherited autoinflammatory disorder associated with mutations in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Biologic therapy of BS yielded diverse results. We aimed to evaluate clinical features and outcomes of Chinese patients with BS who were treated with tumor necrosis factor (TNF)α inhibitors.MethodsA total of four patients with BS were diagnosed and treated with infliximab (IFX) at the Peking Union Medical College Hospital during 2015 to 2018 and were followed up for 18 months. All patients were systematically studied for treatment outcomes including the clinical manifestations and inflammatory markers. We also conducted a comprehensive literature review about TNFα inhibitor therapy in BS.ResultsFour BS patients were all Chinese Han, and three were women. The mean age of disease onset was 4 ± 3.5 years, and the mean time of diagnosis delay was 19 ± 11 years. All patients received IFX plus methotrexate, and all achieved clinical remission of skin lesions and polyarthritis rapidly, as well as normalization of erythrocyte sedimentation rate and C-reactive protein and improvements in inflammatory cytokines, patient visual analogue scale, physician global assessment, and Short Form (SF)-36, at the first follow-up of 6 months. The disease relapsed in two patients after they lengthened the interval of IFX and discontinued methotrexate. According to the 38 English-language publications, 62 patients with BS were reported who underwent TNFα inhibitor therapy, including IFX used in 31, adalimumab in 24, and etanercept in 7. IFX was well tolerated in 27 patients, while 2 still had uveitis, and the other 2 experienced an adverse drug reaction.ConclusionsEarly recognition and effective treatment of BS are very important to avoid irreversible organ damage. TNFα inhibitors such as IFX may be a promising approach for BS patients who have unsatisfactory response to corticosteroids and traditional disease-modifying antirheumatic drugs.

2644 ACE Inhibitor-Induced Visceral Angioedema - A Rare Phenomenon

INTRODUCTION: Angiotensin Converting enzyme (ACE) inhibitors are widely used to treat hypertension and congestive heart failure. Common adverse reactions include cough, hypotension and dizziness. Angioedema is a rare reaction that occurs in less than 1% of patients. Most cases of angioedema are involving the lips, tongue, face and airway. More rarely, visceral angioedema can also occur with jejunal involvement. CASE DESCRIPTION/METHODS: A 24-year-old female with recently diagnosed hypertension treated with lisinopril presented for evaluation of abdominal pain, vomiting, and diarrhea. On examination, she had moderate epigastric tenderness with normal bowel sounds and no organomegaly. Labs revealed white blood cells 20 k/mm3, elevated C-reactive protein 34.2 mg/L and normal erythrocyte sedimentation rate 7 mm/hr. Complement levels including C1 esterase inhibitor, C1q and C4 were found to be normal. Stool culture also remained negative. Computed tomography (CT) of the abdomen revealed moderate ascites, marked mucosal thickening of jejunal and ileal loops with adjacent mesenteric edema (Figure 1). Magnetic Resonance Enterography did not reveal any pathological process. A paracentesis was performed with the ascetic fluid analysis revealing a low serum-ascites albumin gradient without infection. Endoscopy with small bowel enteroscopy revealed normal duodenum and jejunum (Figure 2). Jejunal biopsy returned negative for an infectious or inflammatory process. Due to negative diagnostic workup, a diagnosis of ACE inhibitor-induced visceral angioedema was suspected. Patients symptoms quickly improved 24 hours after cessation of lisinopril and she was discharged home. On follow up 4 weeks later, the patient remained symptom-free. DISCUSSION: Visceral angioedema is a rare side effect of ACE inhibitors most commonly affecting the small bowel. The jejunum is most often affected followed by ileum and duodenum. High levels of bradykinin can cause increased vascular permeability within the bowel mucous membrane causing edema. Symptoms commonly include abdominal pain, anorexia, vomiting and diarrhea. Symptoms typically begin 72 hours after starting the ACE inhibitor. Imaging studies show circumferential small bowel thickening with mesenteric edema and ascites. Endoscopic examination is usually normal. Diagnosis is made by exclusion of other etiologies and improvement of symptoms within 48 hours of drug cessation. Treatment includes discontinuation of the offending drug and supportive therapy until symptoms are resolved.

Obez çocuklarda alkolik olmayan yağlı karaciğer hastalığı ve eşlik eden diğer karaciğer hastalıkları

Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) in children increased parallel to the increment of childhood obesity. Also, NAFLD may be the presenting feature of different liver diseases in non-obese children. We aimed to determine whether there were co-existing liver diseases in overweight and obese children with NAFLD. Material and Methods: Pediatric gastroenterology outpatient clinic records of obese and overweight patients, aged between 5-18 years, were retrospectively reviewed. Seventy patients who had liver steatosis on ultrasonography, and alanine aminotransferase (ALT) levels were higher than 1.5 times the upper limit of normal were recruited to the study. The demographic findings, laboratory tests for infectious, metabolic, and autoimmune causes, abdominal ultrasonography and liver biopsy findings of patients were recorded. Results: At presentation, 94.2% of the patients (n: 66) had mild transaminase elevation. All patients were negative for viral hepatitis, anti-tissue transglutaminase immunoglobulin (Ig) A, anti-liver-kidney-microsome type 1 and anti-smooth muscle antibody. They had normal erythrocyte sedimentation rate (ESR) , C-reactive protein (CRP), ceruloplasmin, and total IgG levels . O nly one patient with low alpha-1 antitrypsin levels had heterozygotes of the PiMZ phenotype. Three (4.3%) patients had antinuclear antibody ( ANA) positivity. 44.7% of patients were given ursodeoxycholic acid treatment. On follow-up, normalization of ALT was achieved in 31 (44.2%) patients at mean 6.1 ±4.6 (2-19) months, but no relation was found between normalization and ursodeoxycholic acid treatment. A patient with ANA positivity had increased ALT, ESR , CRP , IgG levels and ANA titers o n follow-up, and she was diagnosed with autoimmune hepatitis with the support of liver biopsy. Under prednisolone and azathioprine treatment, ESR and IgG levels were normalized, ALT and ANA titers decreased. Conclusion: Other causes of chronic hepatitis should be screened in obesity-related non-alcoholic fatty liver disease and the development of autoimmune hepatitis should be kept in mind in the presence of ANA.

Mean Corpuscular Volume to White Blood Cell Ratio for Thiopurine Monitoring in Pediatric Inflammatory Bowel Disease.

Thiopurines, commonly used to treat inflammatory bowel disease, cause lymphopenia and red blood cell macrocytosis, requiring therapeutic monitoring. Mean corpuscular volume/white blood cell (MCV/WBC) ratio has been proposed as a surrogate for therapeutic monitoring. Our aim was to investigate MCV/WBC ratio for assessing clinical response to thiopurines among pediatric patients with inflammatory bowel disease. We performed a retrospective cross-sectional study at a tertiary care center using laboratory results and standardized physician global assessments (PGA) among pediatric patients taking thiopurines. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, and 6-thioguanine nucleotides were assessed when available. The primary outcome was association between MCV/WBC ratio and clinical remission assessed by ESR, CRP, calprotectin, or PGA. We also used a composite outcome requiring all available data to be normal. Analyses were limited to 1 occurrence per patient, >60 days after starting thiopurine, and comparators were required to be within 14 days of one another. A total of 471 patients met inclusion criteria. MCV/WBC ratio poorly predicted quiescent disease as defined by PGA (area under receiver operating characteristic curve [AuROC] 0.55, 95% confidence interval [CI] 0.43-0.66). MCV/WBC ratio better predicted quiescent disease defined as normal CRP (AuROC 0.64, 95% CI 0.58-0.70) or normal ESR (AuROC 0.59, 95% CI 0.52-0.66). When the composite outcome measure was used, MCV/WBC ratio had an AuROC of 0.65 (95% CI 0.59-0.70), indicating it is reasonably accurate in discriminating between clinical remission and active disease. MCV/WBC ratio is a noninferior, easy, and low-cost alternative to thiopurine metabolite monitoring.

Temporal Value of C-Reactive Protein and Erythrocyte Sedimentation Rate after Total Knee Arthroplasty in Patients with Elevated Preoperative C-Reactive Protein: A Matched-Pair Analysis.

Background:We aimed to determine whether temporal values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) after total knee arthroplasty (TKA) differ between patients with and without elevated preoperative CRP. We hypothesized that temporal pattern of CRP and ESR change would differ between the two groups.Materials and Methods:This retrospective study included 30 TKAs with a diagnosis of osteoarthritis with elevated preoperative CRP (>1 mg/dl) without clinical signs and symptoms of infection before surgery (elevated CRP group). Patients without elevated preoperative CRP were matched in a 1:10 fashion according to age, sex, number of comorbidities and whether TKA was unilateral or bilateral (nonelevated CRP group). The temporal values of CRP and ESR after TKA were compared between the two groups until 2 months after surgery.Results:The mean peak values of CRP and ESR after surgery were similar between the two groups in both unilateral and bilateral TKAs. In the unilateral TKA, mean values of CRP and ESR and the proportions of the knees with normal CRP and ESR at 2 months after surgery were similar in the two groups. However, in the bilateral TKA, mean values of CRP and ESR were higher and the proportions of the knees with normal CRP and ESR at 2 months after surgery were lower in the elevated CRP group compared to the nonelevated CRP group.Conclusions:When performing TKA in patients with elevated preoperative CRP, the fact that the levels of CRP and ESR may not be normalized until 2 months after surgery should be considered during followup.

Hematologic disorders during essential hypertension

BackgroundBesides the traditional risk factors, hematological changes may be involved in the development of arterial hypertension and in its pathogenesis. MethodsThe study, conducted on a sample of 545 subjects, 215 with hypertension and 330 witnesses, were evaluated for peripheral blood parameters in western Algeria; Logistic regression analysis was used to predict hypertension with hematological parameters. ResultsThe characters studied related significantly; lower red blood cell levels have a three-and-a-half-fold risk of developing hypertension compared to those who have normal red blood cell counts (OR = 3.64, 95% CI = 1.37–9.65, p < 0.05). Subjects who have mean corpuscular volume rate below 80 fl are more exposed to hypertension (OR = 13.58, 95% CI = 4.68–39.41, p = 0.000). The mean corpuscular hemoglobin concentration reveals that subjects who have a lower than normal (<27 pg) are once less exposed to hypertension (OR = 0.04, 95% CI = 0.01–0.13, p = 0.000). Subjects who have lower platelet count than normal are twelve times more exposed to hypertension (OR = 12.13, 95% CI = 1.45–101.18, P = 0.021). Finally, the increase in sedimentation rate at one hour increases the risk of hypertension by 56.63 times compared to subjects with normal sedimentation rate (OR = 56.63, 95% CI = 3.37–597.33, P = 0.001). ConclusionsHematological profile associated with essential hypertension retained Red blood cells ratio, mean corpuscular volume, mean corpuscular hemoglobin concentration, platelet ratio, and sedimentation rate at one hour.

Hands as cold as ice

A healthy 24-year-old woman presented with a 1-year history of discolouration, paraesthesia and pain predominantly affecting the middle and ring fingers of both hands. Symptoms were attributed to cold exposure...

Analysis and Hierarchical Clustering of Blood Results Before Diagnosis in Pediatric Inflammatory Bowel Disease.

Pediatric inflammatory bowel disease (PIBD) is associated with a diagnostic delay. Blood tests are a routine part of the work-up in children with chronic abdominal symptoms (pain, diarrhea). Normal blood tests cannot exclude PIBD. We analyzed blood results at diagnosis over a 5-year period. Patients diagnosed from 2013 to 2017 were identified from the Southampton-PIBD database. Results were obtained up to 100 days before diagnostic endoscopy. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, hemoglobin, platelets, packed cell volume (PCV), white cell count (WCC), and alanine transferase (ALT) were analyzed. Hierarchical clustering was applied to normalized results. Two hundred fifty-six patients were included (Crohn's disease [CD], 151; ulcerative colitis [UC], 95; IBD-unclassified, 10; median age, 13.48 years; 36.7% female). Hierarchical clustering of patients revealed novel groupings enriched for CD and UC, characterized by specific patterns of results. In PIBD, 9% presented with all normal blood tests, 21.9% with normal CRP and ESR. Abnormal results were seen in all tests (ESR, 56.4% of patients; CRP, 53.4%; albumin, 28%; hemoglobin, 61.9%; platelets, 55.6%; PCV, 64.6%; WCC, 22.7%; and ALT, 7.2%). Normal inflammatory markers were more common in UC compared with CD (UC, 34%; CD, 15.8%; P = 0.0035). UC (14.4% normal) presented with all normal results more frequently than CD (CD, 5.3%; P = 0.02). CRP, ESR, and platelets were significantly higher in CD compared with UC. Albumin and hemoglobin were significantly lower. Most cases of PIBD present with >1 abnormal blood result, although 1/11 patients presents with normal blood tests and 1/5 present with normal inflammatory markers. Hierarchical clustering offers the potential to produce novel groupings to inform disease categorization and best management.

C-reactive protein or erythrocyte sedimentation rate results reliably exclude invasive bacterial infections

BackgroundClinicians utilize inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), to identify febrile children who may have an occult serious illness or infection. ObjectivesOur objective was to determine the relationship between invasive bacterial infections (IBIs) and CRP and ESR in febrile children. MethodsWe performed a retrospective cross-sectional study of 1460 febrile children <21 years of age, who presented to a single Emergency Department (ED) between 2012 and 2014 for evaluation of fever of <14 days' duration, who had both CRP and ESR obtained. Our primary outcome was IBI, defined as growth of pathogenic bacteria from a culture of cerebrospinal fluid or blood. We reviewed all ED encounters that occurred within three days of the index visits for development of IBI. We examined the negative predictive value (NPV) of CRP and ESR for IBI. ResultsOf the 1460 eligible ED encounters, the median patient age was 5.3 years [interquartile range (IQR) 2.4–10.0 years] and 762 (50.4%) were hospitalized. The median duration of fever was 4 days (IQR 1–7 days). Overall, 20 had an IBI (20/1460; 1.4%, 95% confidence interval (CI) 0.9–2.1%). None of those with a normal CRP (NPV 273/273; 100%, 95% CI 98.6–100%) or a normal ESR (NPV 486/486; 100%, 95% CI 99.2–100%) had an IBI. ConclusionsIn our cross-sectional study of febrile children, IBI was unlikely with either a normal CRP or ESR. Inflammatory markers could be used to assist clinical decision-making while awaiting results of bacterial cultures.

Relevance of erythrocyte sedimentation rate and C-reactive protein in patients with active uveitis

PurposeTo relate erythrocyte sedimentation rates (ESR) and C-reactive protein (CRP) values to different uveitis entisties.MethodsA retrospective study of patients with a first episode of active uveitis visiting the Erasmus University Medical Center, uveitis clinic, Rotterdam, the Netherlands, was performed. Levels of ESR and CRP were determined within 2 weeks and 1 week after onset of uveitis, respectively. Uveitis had to be of unknown origin at that moment. The specific etiologic groups were related to ESR and CRP values.ResultsThe majority of patients with uveitis had ESR and/or CRP values within the normal limits and no association of ESR and/or CRP with the specific cause of uveitis was observed. However, elevation of ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L was mostly seen in patients with systemic immune-mediated diseases (8/59, 14% of all with immune-mediated diseases) or systemic infectious causes (7/38, 18% of all infectious uveitis). Patients with ocular toxoplasmosis typically exhibited normal ESR and CRP (9/11, 82%) while patients with endogenous endophthalmitis had elevated ESR and/or CRP in 6/7, 86%. Sarcoidosis-associated uveitis showed predominantly elevated ESR (13/24, 54%; range 20–59 mm/h in 11/13, 85%). Human immunodeficiency virus–positive patients had more often elevated ESR values when compared to the remainder of patients (9/11, 82% vs. 64/163, 39%, 18%, P = 0.009). The cause of uveitis was established in 19/20 (95%) of patients with ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L.ConclusionsThe majority of patients with first attack of uveitis had ESR and CRP within the normal limits. Elevated levels of ESR and CRP reflected systemic involvement and high levels of both values were associated with established uveitis cause.

Early detection of multiple myeloma in primary care using blood tests: a case-control study in primary care.

BackgroundMultiple myeloma is a haematological cancer characterised by numerous non-specific symptoms leading to diagnostic delay in a large proportion of patients.AimTo identify which blood tests are useful in suggesting or excluding a diagnosis of myeloma.Design and settingA matched case–control study set in UK primary care using routinely collected data from the Clinical Practice Research Datalink.MethodSymptom prevalence and blood tests were analysed up to 5 years before diagnosis in 2703 cases and 12 157 matched controls. Likelihood ratios (LR) were used to classify tests or their combinations as useful rule-in tests (LR+ = ≥5), or rule-out tests (LR− = ≤0.2).ResultsRaised plasma viscosity (PV) had an LR+ = 2.0, 95% confidence interval [CI] = 1.7 to 2.3; erythrocyte sedimentation rate (ESR) 1.9, 95% CI = 1.7 to 2.0; and C-reactive protein (CRP) 1.2, 95% CI = 1.1 to 1.4. A normal haemoglobin had an LR− = 0.42, 95% CI = 0.39 to 0.45; calcium LR− = 0.81, 95% CI = 0.78 to 0.83; and creatinine LR− = 0.80, 95% CI = 0.77 to 0.83. The test combination with the lowest LR− was all normal haemoglobin with calcium and PV, which had an LR− = 0.06, 95% CI = 0.02 to 0.18, though the LR− for normal haemoglobin and PV together was 0.12 (95% CI = 0.07 to 0.23).ConclusionPlasma viscosity and ESR are better for both ruling in and ruling out the disease compared with C-reactive protein. A combination of a normal ESR or PV and normal haemoglobin is a simple rule-out approach for patients currently being tested in primary care.

A Mutation Outside the Dimerization Domain Causing Atypical STING-Associated Vasculopathy With Onset in Infancy.

Mutations in the gene encoding stimulator of interferon genes (STING) underlie a type I interferon (IFN) associated disease, STING-associated vasculopathy with onset in infancy (SAVI). Patients suffer cutaneous vasculopathy and interstitial lung disease, but are not known to suffer life-threatening infection. We describe a child who presented with Pneumocystis jirovecii pneumonia in early life, from which he recovered. He went on to suffer failure to thrive, developmental delay, livedo reticularis, and vesicular rash, but without cutaneous vasculitis, and with normal C-reactive protein and erythrocyte sedimentation rates. At 3 years of age, he developed life-threatening pulmonary hypertension. Whole genome sequencing (WGS) was performed using the Illumina HiSeqX10 platform and the Seave platform was used for bioinformatic analysis. mRNA expression of IFN-stimulated genes and inflammatory cytokines from peripheral blood mononuclear cells was determined by quantitative polymerase chain reaction. Luciferase assay was used to model IFNβ and NF-κB activity in vitro. WGS revealed a de novo mutation p.Arg284Ser in STING at an amino acid previously associated with SAVI. Although this mutation did not fall in the dimerization domain (DD), mRNA analysis revealed constitutive IFN-gene activation consistent with an interferonopathy, which correlated to STING activation in vitro. The patient was treated with corticosteroids and the JAK inhibitor Ruxolitinib, resulting in a rapid improvement of pulmonary hypertension, general well-being, and resolution of the IFN gene signature. However, he did go on to evolve a nasal septal erosion suggesting incomplete control of disease. This case provides molecular evidence to support the p.Arg284Ser variant in STING exerting pathogenicity through a gain-of-function mechanism. The lack of cutaneous vasculitis or elevated systemic inflammatory markers, and the occurrence of an opportunistic infection are notable, and raise the possibility that variants outside the STING DD may potentially manifest with an atypical SAVI phenotype. Nevertheless, there was an objective clinical improvement in response to JAK inhibition.