scholarly journals AB1010 CLINICAL SPECTRUM AND IMMUNE ANALYSIS OF PATIENTS WITH CRYOPYRIN-ASSOCIATED AUTOINFLAMMATORY SYNDROME IN TAIWAN

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1798.1-1798
Author(s):  
C. Y. Wu ◽  
P. S. Chu ◽  
H. Y. Yang

Background:Cryopyrin-associated periodic syndromes (CAPS) are emerging autoinflammatory diseases with available treatment. No reports have yet been reported from Taiwan.Objectives:We reviewed cases suspected with CAPS to identify its existence in Taiwan.Methods:Genomic DNA from one hundred and ten cases with symptom signs suggestive of CAPS(1) between 2016-2019 were sent for NLRP3 gene analysis. Clinical presentations, laboratory data, treatment regimens, as well as inflammasome activities were analyzed among those treated in a tertiary medical center in northern Taiwan.Results:Among the 110 cases sequenced, 16 of them were found to carry missense mutations within the NLRP3 gene. Fourteen cases harbored known pathogenic genetic variants (c.1316C>T; c.1574A>T; and c.907G>C) and two carried novel NLRP3 missense mutations (c.210G>A, c.1371G>T)(2) with unknown pathophysiological roles. Through chart review, chronic urticarial, systemic juvenile idiopathic arthritis, Behcet’s disease and refractory Kawasaki disease were most likely diagnosed before genetic analysis were arranged. As compared to chronic infantile neurological, cutaneous and articular syndrome (CINCA) and Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) was the most frequently observed clinical presentation. Plasma serumamyloidA (SAA) and IL-1b were both significantly elevated among the cases diagnosed with CAPS as compared to the controls (p<0.05). IL-18, on the other hand, showed no significant differences between the groups. While the presence of LPS without ATP significantly increased the level of IL-1b in the PBMC stimulation test, IL-18 were significantly elevated in the confirmed CAPS with or without ATP upon LPS stimulation (all p<0.05). Caspase 1 activity were also tested positive among the cases with CAPS. Furthermore, we compared the immune profiles between those CAPS cases harboring pathogenic mutations with the 2 harboring unreported NLRP3 missense mutations and discovered that the PBMC stimulation test in cases with c.210G>A and c.1371G>T mutation did not differ from the healthy controls.Conclusion:The number of NLRP3 gene alterations among patients suspected with CAPS in Taiwan is not low. In order to identify potential patients for proper medical intervention in the future, physician awareness, genetic testing as well as functional analysis are important.References:[1]Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942-7.[2]Van Gijn ME, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, et al. New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018;55(8):530-7Disclosure of Interests:Chao-Yi Wu Speakers bureau: Abbvie, Boehringer Ingelheim International GmbH, Nestle, Pi-Shuang Chu: None declared, Huang-Yu Yang: None declared

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Seung Won Choi ◽  
Yeri Lee ◽  
Kayoung Shin ◽  
Harim Koo ◽  
Donggeon Kim ◽  
...  

AbstractPTEN is one of the most frequently altered tumor suppressor genes in malignant tumors. The dominant-negative effect of PTEN alteration suggests that the aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hotspot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that overexpress these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties regarding their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.


2019 ◽  
Vol 45 (4) ◽  
pp. 442-449 ◽  
Author(s):  
Ashley S. Dexter ◽  
Janet F. Pope ◽  
Dawn Erickson ◽  
Catherine Fontenot ◽  
Elizabeth Ollendike ◽  
...  

Purpose The purpose of the study was to evaluate a 12-week cooking education class on cooking confidence, dietary habits, weight status, and laboratory data among veterans with prediabetes and diabetes. Methods The sample for this study included 75 veterans within the Overton Brooks Veteran Affairs Medical Center who completed the 12-week class in an in-person group setting in Shreveport, Louisiana, or via Clinical Video Telehealth (CVT) in Longview, Texas. Veterans were referred to the Healthy Teaching Kitchen by their primary care provider or primary care dietitian. Enrollment in the class was on a volunteer basis. The cooking and nutrition education classes included topics such as carbohydrate counting, safety and sanitation, meal planning, and creating budget-friendly recipes. Participants completed 2 questionnaires for assessment of healthy dietary habits and confidence related to cooking. Changes in body weight, lipid panel, and hemoglobin A1C were assessed. Differences in class settings were tested via independent samples t tests. Paired samples t tests were completed to compare changes in mean laboratory results, weight, and questionnaire responses. Results Subjects lost a mean 2.91 ± 5.8 lbs ( P < .001). There was no significant difference in percent change in laboratory data and weight between subjects participating via CVT and subjects in the live class. Overall, there was significant improvement in the confidence questionnaire ratings and Healthy Habits Questionnaire responses. Conclusions Cooking and nutrition education can increase cooking confidence and dietary quality. These results provide support for the need for further research on the long-term effects of nutrition cooking education and for the benefits of using CVT software to provide education to remote facilities.


Kardiologiia ◽  
2021 ◽  
Vol 61 (9) ◽  
pp. 33-39
Author(s):  
A. V. Svarovskaya ◽  
M. B. Arzhanik ◽  
O. N. Ogurkova ◽  
E. A. Kuzheleva ◽  
A. E. Baev ◽  
...  

Aim      To reveal a relationship between preprocedural laboratory data and adverse cardiac outcomes (CO) in patients with stable ischemic heart disease (IHD) following elective endovascular revascularization (ER).Material and methods  This study included 225 patients with IHD admitted for treatment to the Research Institute of Cardiology of the Tomsk National Research Medical Center. The study included patients with documented IHD and hemodynamically significant coronary stenoses requiring elective ER. Patients were divided into groups based on the presence of complications: group 1, 98 patients with adverse CO and group 2, 127 patients without adverse CO. Besides evaluation of complaints, history, and objective status, general clinical and biochemical tests were performed for all patients. Concentration of glycated hemoglobin (НbА1с) was measured by immunoturbidimetry (DiaSys Diagnostic Systems). Serum concentrations of insulin, interleukin-6 (IL-6), endothelin 1 (ET-1), and homocysteine were measured by enzyme immunoassay. Blood lipid profile was determined by enzymatic colorimetry (DiaSys). Content of non-high-density lipoprotein (non-HDL) cholesterol (CS) was calculated as: CS – HDL CS. Insulin resistance (IR) was assessed by the HOMА-IR index. IR was diagnosed at the index of 2.77. Statistical analyses were performed with Statistica 10.0 and Medcalc 19.2.6 software.Results A one-way regression analysis identified predictors for adverse CO following ER. The most significant predictors were fibrinogen (odds ratio (OR), 1.430; 95 % confidence interval (CI), 1.027–1.990), HbA1c (OR 1.825; 95 % CI, 1.283–2.598), homocysteine (OR, 1.555; 95 % CI, 1.348–1.794), ET-1 (OR, 94.408; 95 % CI, 16.762–531.720), triglycerides (TG)/glucose ratio (OR 1.815; 95 % CI, 1.155–2.853). Based on selected factors, logistic regression models were constructed. However, not all models had a high prognostic power. Only concentrations of ET-1 and homocysteine showed a high prognostic capability in respect of the adverse outcome (88.3 and 85.7 %, respectively).Conclusion      For patients with IHD, the prognostic capability of ET-1 and homocysteine with respect of the risk for adverse CO following ER was the highest compared to other markers. The results of the study are completely consistent with data of literature and can be successfully used in clinical practice for optimizing the medical care of patients after elective ER. 


Author(s):  
Rachel Chava Rosenblum ◽  
Orit Twito ◽  
Liat Barzilay-Yoseph ◽  
Erez Ramaty ◽  
Noa Klein ◽  
...  

Abstract Context Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate, which is not indicated for this condition. Objective To evaluate the efficacy and safety of pamidronate for moderate-to-severe PTHRH. Design Retrospective case-control study. Setting Tertiary care medical center. Patients Adults hospitalized with serum calcium levels ≥12mg/dL, 29/10/2013–17/12/2019. Interventions Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with pamidronate (PTHRH-Pam+) were compared to pamidronate-untreated counterparts (PTHRH-Pam-). Results Thirty-four patients with 37 hospitalizations for PTHRH (pamidronate-treated and untreated) met the inclusion criteria. Pamidronate was given in 24/37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- (14.4mg/dL vs. 13.0mg/dL, p=0.005). Median total pamidronate dose was 60mg (range 30–180mg) in the treated group. Serum calcium decreased 3.5mg/dL for PTHRH-Pam+ vs. 1.6mg/dL for PTHRH-Pam- (p=0.003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs. PTHRH-Pam- group (1.7mg/dL vs. 2.4mg/dL, respectively, p=0.005). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received pamidronate within 28 days preoperatively. Post-operatively, 4 developed hypocalcemia and 3 hypophosphatemia. Conclusions This study demonstrates that pamidronate is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of pamidronate and other potent bisphosphonates in moderate-to-severe PTHRH.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S725-S725
Author(s):  
Fernando H Centeno ◽  
Asim A Ahmed ◽  
David K Hong ◽  
Sudeb Dalai ◽  
Laila Woc-Colburn

Abstract Background Rickettsia typhi typically causes a nonspecific syndrome characterized by fever, rash, and headache but can rarely progress to severe disease. R. typhi is transmitted by the rat flea and there has been an increased incidence in Houston, TX. Establishing the diagnosis can be challenging and is often made by serological studies. Prompt therapy with doxycycline is important especially in severe disease. Methods Karius Test results from the prior 2 years (Redwood City, CA) were reviewed for detections of R. typhi. The Karius Test is a CLIA-certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human sequences are removed and remaining sequences are aligned to a curated pathogen database of >1,000 organisms. Organisms present above a statistical threshold are reported. Chart review was conducted on the cases of R. typhi identified by the Karius Test. Results The Karius Test detected R. typhi in 6 adult patients, 4 women and 2 men, from a medical center in Houston, TX. In 2 patients, R. typhi mcfDNA was present in the raw sequencing data but at an abundance below validated statistical thresholds. R. typhi mcfDNA was not found in negative controls run simultaneously with the samples. All patients presented with fever, 4 presented with headache, 3 presented with gastrointestinal symptoms, 3 developed rash, one presented with hypotension. Laboratory data were available for 5 patients. Four patients developed thrombocytopenia, 5 had anemia, 4 patients had WBC < 5, 4 had transaminase elevation and 3 developed hyponatremia. 3 out of 5 had R. typhi serologies sent; all 3 were positive (including two of the patients with R. typhi mcfDNA levels below threshold). In the two other patients the Karius test was the means of establishing the diagnosis. 3 out of 5 patients where data were available were treated with doxycyline. Conclusion The Karius test was able to detect R. typhi in a cluster of 6 patients in one medical center in Houston, TX. NGS for mcfDNA offers a rapid means of detecting R. typhi infection. Accurate, rapid diagnosis of R. typhi has important public health implications given its vector-borne mechanism of transmission. Disclosures All authors: No reported disclosures.


2020 ◽  
pp. 088506662091300 ◽  
Author(s):  
Tolga Dittrich ◽  
Stephan Marsch ◽  
Stephan Rüegg ◽  
Gian Marco De Marchis ◽  
Sarah Tschudin-Sutter ◽  
...  

Background/Objective: Data regarding delirium in patients presenting with infections of the central nervous system, such as meningitis and/or encephalitis (ME), are scarce. We aimed to determine the frequency and early predictors of delirium in the acute phase of ME. Methods: We assessed clinical, radiologic, and laboratory data of patients with ME at a Swiss academic medical center from 2011 to 2017. The highest Intensive Care Delirium Screening Checklist (ICDSC) score was assessed within 24 hours around lumbar puncture. Multivariable logistic regression was performed to identify predictors of delirium (ICDSC ≥4). Results: Among 330 patients with ME, infectious pathogens were identified in 41%. An ICDSC >1 was found in 28% with and 19% without identified infectious pathogens. Delirium was diagnosed in 18% with and 14% without infectious pathogens and significantly associated with prolonged in-hospital treatment and mechanical ventilation, more frequent administration of neuroleptics and anesthetics (in 96% with delirium vs 35% without), complications, and less recovery to premorbid functional baseline. Low serum albumin at presentation was the only independent predictor of delirium (area under the receiver–operating curve [AUROC] = 0.792) in patients with pathogens. In patients with infections, the AUROC was smallest for encephalitis (AUROC = 0.641) and larger for patients with meningeal infections (meningitis AUROC = 0.807; meningoencephalitis AUROC = 0.896). Conclusions: Delirium in the context of ME is seen in almost every fifth patient and linked to prolonged treatment, complications, and incomplete recovery. Among clinical, radiologic, and laboratory parameters, the good calibration and discrimination of low albumin serum concentrations for the prediction of delirium in patients with ME seem promising, especially if meninges are affected.


2020 ◽  
Vol 21 (21) ◽  
pp. 8318
Author(s):  
Caspar Mewes ◽  
Tessa Alexander ◽  
Benedikt Büttner ◽  
José Hinz ◽  
Ayelet Alpert ◽  
...  

Background: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. Methods: Patients with sepsis (n = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. Results: Kaplan–Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, p = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, p = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and Staphylococcus epidermidis infections, and rs10515746 CC homozygotes presented more Staphylococcus epidermidis infections. Conclusion: The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis.


2019 ◽  
Vol 6 ◽  
pp. 2333794X1988481
Author(s):  
Benetta Collins-Andrews ◽  
Patricia McQuilkin ◽  
Kanagasabai Udhayashankar ◽  
Eric Adu ◽  
Ann Moormann

Malaria is endemic in Liberia with a prevalence rate of up to 60% in some regions, and it has been a major cause of death in children under 5 years of age. Prior to the recent Ebola epidemic, we undertook a prospective, hospital-based pilot study at the National Referral Hospital in Monrovia, to characterize the presentation, accuracy of diagnosis, and treatment outcomes of children presenting for treatment of malaria. From June 2013 to May 2014, we recruited children 5 years and under who presented to the JFK Medical Center with suspected malaria. We collected both clinical and laboratory data on admission and on discharge. We enrolled 477 patients with an average age of 1.6 years. Demographic factors associated with testing negative for malaria included regular bed net use and prior treatment for malaria. The most common presenting symptoms of severe malaria in this population were headache and seizures. Of 246 patients admitted and treated for severe malaria, 33% tested negative by rapid diagnostic test and blood smear for malaria. The case fatality rate was higher for the patients who tested negative for malaria (4.9%) versus those who tested positive (0.6%). Three children who tested negative for malaria showed evidence of undiagnosed Salmonella typhi infection. These results suggest that malaria may be overdiagnosed and that the diagnoses of other infectious diseases, which present in a similar fashion, may be neglected. These findings underscore the need to develop rapid diagnostic tests to screen for alternative causes of febrile illness.


Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 918-924
Author(s):  
David Roh ◽  
Glenda L Torres ◽  
Chunyan Cai ◽  
Christopher Zammit ◽  
Alexandra S Reynolds ◽  
...  

Abstract BACKGROUND There are radiographic and clinical outcome differences between patients with deep and lobar intracerebral hemorrhage (ICH) locations. Pilot studies suggest that there may be functional coagulation differences between these locations detectable using whole blood coagulation testing. OBJECTIVE To confirm the presence of interlocation functional coagulation differences using a larger cohort of deep and lobar ICH patients receiving whole blood coagulation testing: thromboelastography (TEG; Haemonetics). METHODS Clinical and laboratory data were prospectively collected between 2009 and 2018 for primary ICH patients admitted to a tertiary referral medical center. Deep and lobar ICH patients receiving admission TEG were analyzed. Patients with preceding anticoagulant use and/or admission coagulopathy (using prothrombin time/partial thromboplastin time/platelet count) were excluded. Linear regression models assessed the association of ICH location (independent variable) with TEG and traditional plasma coagulation test results (dependent variable) after adjusting for baseline hematoma size, age, sex, and stroke severity. RESULTS We identified 154 deep and 53 lobar ICH patients who received TEG. Deep ICH patients were younger and had smaller admission hematoma volumes (median: 16 vs 29 mL). Adjusted multivariable linear regression analysis revealed longer TEG R times (0.57 min; 95% CI: 0.02-1.11; P = .04), indicating longer clot formation times, in deep compared to lobar ICH. No other TEG parameter or plasma-based coagulation differences were seen. CONCLUSION We identified longer clot formation times, suggesting relative coagulopathy in deep compared to lobar ICH confirming results from prior work. Further work is required to elucidate mechanisms for these differences and whether ICH location should be considered in future coagulopathy treatment paradigms for ICH.


2018 ◽  
Vol 9 (3) ◽  
pp. 36-40 ◽  
Author(s):  
Rakesh Kumar Mandal ◽  
Primo B. Valenzuela

Background: Neutrophil-Lymphocyte count ratio (NLCR), a readily accessible biomarker, has become increasingly useful as predictive and prognostic tools in patients with various medical conditions. NLCR has also been reported to represent disease severity effectively.Aims and Objectives: To investigate NLCR on admission as a prognostic marker of bacteremia and in-hospital mortality in patients diagnosed with Sepsis and Septic Shock.Materials and Methods: This cross-sectional, retrospective study involves one-hundred twenty (120) adult patients with Sepsis and Septic Shock admitted to the IMCU and ICU from January 2015 to December 2016. Laboratory data and clinical outcomes were retrieved and documented from the laboratory and patients’ charts. A cut-off point of >10 was used to be a marker for bacteremia and hence, patients were stratified into two groups based on this cut-off. Out of 120, 78 patients (with mean age of 60) has NLCR of at least 10 while only 42 patients (with mean age of 55) has NCLR of at most 10.Results: A significant, strong and positive association between NLCR and in-hospital mortality was found (P=0.0001) indicating that an increased rate of mortality is observed for patients with persistently high NCLR. Results also indicated that NLCR is a significant predictor (P=0.0002) of in-hospital mortality via a logistic model. The receiver-operating characteristic (ROC) curve for NLCR predicting in-hospital mortality showed an area under the curve (AUC) of 0.8007 which is an indicative of high predictive power. Its sensitivity and specificity is calculated to be 97.37% and 93.18, respectively. Overall, the performance of NCLR as a predictor based on its computed hit rate is found to be approximately 93.33%.Conclusion: Increased NLCR levels were independently associated with unfavorable clinical prognosis in patients with sepsis. A high NLCR (>10) is significantly associated with in- hospital mortality. NCLR predicts in-hospital mortality with high accuracy, high precision and small misclassification.Asian Journal of Medical Sciences Vol.9(3) 2018 6-9


Sign in / Sign up

Export Citation Format

Share Document