scholarly journals Sequencing Alpha-1 MZ Individuals Shows Frequent Biallelic Mutations

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Kimberly E. Foil ◽  
M. Gwen Blanton ◽  
Chris Sanders ◽  
Joannah Kim ◽  
Haitham S. Al Ashry ◽  
...  
Keyword(s):  
Severity Score ◽  
Small Sample Size ◽  
Genetic Counselor ◽  
Familial Risk ◽  
Small Sample ◽  
Smoking History ◽  
Augmentation Therapy ◽  
Clinical Trial Registration ◽  
Increased Risk ◽  
Severity Scores

Rationale. Individuals with a single Z mutation in the SERPINA1 gene that codes for alpha-1 antitrypsin (AAT) are at increased risk for COPD if they have ever-smoked. Whether additional variants alter the risk for COPD in this population remains unknown. Objectives. To determine whether additional SERPINA1 variants impact COPD development in a previously identified MZ (carrier) cohort. Methods. Individuals with prior MZ results and AAT serum level <16uM were recruited from the Alpha-1 Coded Testing study and Alpha-1 Foundation Research Registry. Participants completed smoking history, demographics, and COPD Severity Score (Range 0-33) using REDCap data capture. At-home finger-stick tests were performed for next generation sequencing (NGS) at the Biocerna LLC laboratory. A genetic counselor reviewed records and interviewed participants with additional variants by NGS. A Wilcoxon Rank Sum test was used to assess correlation between variants and the COPD severity score. Results. A second SERPINA1 variant of known or possible significance was identified in 6 (5.8%) participants. One each of ZZ, SZ, FZ, ZSmunich, ZM2obernburg, and Z/c.922G>T genotypes were identified. ZZ, SZ, and FZ are known pathogenic genotypes. Smunich is a likely pathogenic variant. M2obernburg and c.922G>T are variants of uncertain significance. The ZZ individual was on augmentation therapy when determined MZ by protease inhibitor (Pi) phenotyping; the others had limited targeted genotyping with MZ results. These six participants with biallelic variants had positive COPD severity scores >1. Presence of additional variants was not significantly associated with COPD symptoms in this small sample size. Conclusions. Some diagnosed MZ individuals instead have biallelic variants. Larger studies are needed to determine COPD-risk liability of variants. Accurate diagnosis impacts medical management and familial risk assessment. Pi phenotyping can be confounded by augmentation therapy and liver transplantation. Because a normal M allele may be reported in the absence of tested mutation(s) in AATD genotyping, clinicians should consider clinical circumstances and laboratory methods when selecting and interpreting AATD tests. Advanced testing, including NGS, may be beneficial for select individuals with prior MZ results. Clinical Trial Registration. This study was registered with clinicaltrials.gov (NCT NCT02810327).

scholarly journals The incidence and prevalence of cardiovascular diseases in gout: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Peter Cox ◽  
Sonal Gupta ◽  
Sizheng Steven Zhao ◽  
David M. Hughes
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Random Effect ◽  
Small Sample ◽  
Future Research ◽  
Increased Risk

AbstractThe aims of this systematic review and meta-analysis were to describe prevalence of cardiovascular disease in gout, compare these results with non-gout controls and consider whether there were differences according to geography. PubMed, Scopus and Web of Science were systematically searched for studies reporting prevalence of any cardiovascular disease in a gout population. Studies with non-representative sampling, where a cohort had been used in another study, small sample size (< 100) and where gout could not be distinguished from other rheumatic conditions were excluded, as were reviews, editorials and comments. Where possible meta-analysis was performed using random-effect models. Twenty-six studies comprising 949,773 gout patients were included in the review. Pooled prevalence estimates were calculated for five cardiovascular diseases: myocardial infarction (2.8%; 95% confidence interval (CI)s 1.6, 5.0), heart failure (8.7%; 95% CI 2.9, 23.8), venous thromboembolism (2.1%; 95% CI 1.2, 3.4), cerebrovascular accident (4.3%; 95% CI 1.8, 9.7) and hypertension (63.9%; 95% CI 24.5, 90.6). Sixteen studies reported comparisons with non-gout controls, illustrating an increased risk in the gout group across all cardiovascular diseases. There were no identifiable reliable patterns when analysing the results by country. Cardiovascular diseases are more prevalent in patients with gout and should prompt vigilance from clinicians to the need to assess and stratify cardiovascular risk. Future research is needed to investigate the link between gout, hyperuricaemia and increased cardiovascular risk and also to establish a more thorough picture of prevalence for less common cardiovascular diseases.

scholarly journals Mediterranean Diet and Lifestyle Habits during Pregnancy: Is There an Association with Small for Gestational Age Infants? An Italian Single Centre Experience

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1941
Author(s):  
Rachele De Giuseppe ◽  
Manuela Bocchi ◽  
Silvia Maffoni ◽  
Elsa Del Bo ◽  
Federica Manzoni ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Mediterranean Diet ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Small Sample Size ◽  
Demographic Data ◽  
Small Sample ◽  
Activity Level ◽  
Lifestyle Habits ◽  
Increased Risk

Background. The small-for-gestational-age (SGA) in infants is related to an increased risk of developing Non-Communicable Diseases later in life. The Mediterranean diet (MD) is related to lower odds of being SGA. The study explored retrospectively the association between SGA, maternal MD adherence, lifestyle habits and other SGA risk factors during pregnancy. Methods. One hundred women (16–44 years) with a pregnancy at term were enrolled. Demographic data, parity, pre-gestational BMI, gestational weight gain, pregnancy-related diseases, and type of delivery were collected. The MD adherence (MEDI-LITE score ≥ 9), physical activity level, and smoking/alcohol consumption were registered. SGA neonates were diagnosed according to the neonatal growth curves. Results. Women were divided into “SGA group” vs. “non-SGA group”. The MD was adopted by 71% of women and its adherence was higher in the “non-SGA group” (p = 0.02). The prevalence of pregnancy-related diseases (gestational diabetes/pregnancy-induced hypertension) was higher in the “SGA group” (p = 0.01). The logistic regression showed that pregnancy-related diseases were the only independent risk factor for SGA. Conclusions. MD may indirectly reduce the risk of SGA since it prevents and exerts a positive effect on pregnancy-related diseases (e.g., gestational diabetes and hypertension). The small sample size of women in the SGA group of the study imposes a major limitation to the results and conclusions of this research, suggesting however that it is worthy of further investigation.

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

2021 ◽  
pp. 039156032110351
Author(s):  
Alessandro Uleri ◽  
Rodolfo Hurle ◽  
Roberto Contieri ◽  
Pietro Diana ◽  
Nicolòmaria Buffi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Advanced Disease ◽  
Independent Predictor ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Small Sample ◽  
Locally Advanced Disease ◽  
Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

scholarly journals Expanded CURB-65: a new score system predicts severity of community-acquired pneumonia with superior efficiency

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jin-liang Liu ◽  
Feng Xu ◽  
Hui Zhou ◽  
Xue-jie Wu ◽  
Ling-xian Shi ◽  
...  
Keyword(s):  
Severity Score ◽  
Community Acquired Pneumonia ◽  
Score System ◽  
Pneumonia Severity ◽  
Increased Risk ◽  
Severity Scores ◽  
Low Blood Pressure ◽  
Health Care Associated Pneumonia ◽  
Score Systems ◽  
Better Than

Abstract Aim of this study was to develop a new simpler and more effective severity score for community-acquired pneumonia (CAP) patients. A total of 1640 consecutive hospitalized CAP patients in Second Affiliated Hospital of Zhejiang University were included. The effectiveness of different pneumonia severity scores to predict mortality was compared, and the performance of the new score was validated on an external cohort of 1164 patients with pneumonia admitted to a teaching hospital in Italy. Using age ≥ 65 years, LDH > 230 u/L, albumin < 3.5 g/dL, platelet count < 100 × 109/L, confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, low blood pressure, we assembled a new severity score named as expanded-CURB-65. The 30-day mortality and length of stay were increased along with increased risk score. The AUCs in the prediction of 30-day mortality in the main cohort were 0.826 (95% CI, 0.807–0.844), 0.801 (95% CI, 0.781–0.820), 0.756 (95% CI, 0.735–0.777), 0.793 (95% CI, 0.773–0.813) and 0.759 (95% CI, 0.737–0.779) for the expanded-CURB-65, PSI, CURB-65, SMART-COP and A-DROP, respectively. The performance of this bedside score was confirmed in CAP patients of the validation cohort although calibration was not successful in patients with health care-associated pneumonia (HCAP). The expanded CURB-65 is objective, simpler and more accurate scoring system for evaluation of CAP severity, and the predictive efficiency was better than other score systems.

Abstract 13215: Gender-affirming Hormones Are Associated With Increased Risk of QT Prolongation in Transgender Females

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel Antwi Amoabeng ◽  
Ahmed Hanfy ◽  
Munadel Awad ◽  
Bryce D Beutler ◽  
Amneet Rai ◽  
...  
Keyword(s):  
Qt Interval ◽  
Small Sample Size ◽  
Qt Prolongation ◽  
Small Sample ◽  
Rank Test ◽  
Qt Interval Prolongation ◽  
Northern Nevada ◽  
Increased Risk ◽  
Before And After ◽  
Signed Rank Test

Introduction: Women have a longer QT interval than men. This sex-specific difference is attributed to hormones associated with the biological female sex. Male-to-female transgender individuals often take antiandrogens such as spironolactone or goserelin in addition to estrogens to suppress testosterone effects while increasing feminine features. Effects of gender-affirming hormone therapy (GHT) on the QT interval in these individuals remains to be elucidated. Hypothesis: We assessed the hypothesis that the use of GHT is associated with an increased risk for QT interval prolongation in transgender females. Methods: We identified 46 transgender females through a search of the electronic medical records of a Veterans Administration hospital in Northern Nevada. Patients with a diagnosis of congenital long QT syndrome were excluded. Of these, 13 patients had ECGs before and after initiation of GHT and were included. We adapted the Tisdale score using the auto-calculated corrected QT interval (QTc) to estimate the risk of QT prolongation. Age, QTc, and Tisdale scores before and after GHT initiation were compared using the Wilcoxon signed-rank test. All tests were performed as two-tailed at a 5% level of significance. Results: All 13 study patients were taking estrogens. Of these, 3 (23.1%) were taking goserelin and 9 (69.2%) were taking spironolactone. Mean ± SEM age at ECG acquisition was 45.0 ± 4.4 and 47.7 ± 4.7 years before and after the initiation of GHT respectively. Mean ± SEM QTc after initiation of GHT was significantly higher compared to the baseline (467.5 ± 12.8 ms vs. 428.2 ± 7.1 ms) (Figure 1A). The average baseline Tisdale score was significantly smaller on follow-up (1-point vs. 3 points) (Figure 1B). Conclusions: GHT appears to be associated with increased QTc in transgender women. This needs to be interpreted with caution owing to the very small sample size in this study. Further studies to investigate the strength of this association, if it exists, are warranted.

Discrepancy of blast percentage between the bone marrow aspirate and biopsy and its impact on survival outcomes in patients with myelodysplastic syndromes excess blast (MDS-EB).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7053-7053
Author(s):  
Meera Yogarajah ◽  
Phuong L. Nguyen ◽  
Rong He ◽  
Hassan Alkhateeb ◽  
Mithun Vinod Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Scoring System ◽  
Small Sample Size ◽  
Scoring Systems ◽  
Standard Of Care ◽  
Small Sample ◽  
International Prognostic Scoring System ◽  
Increased Risk ◽  
Significant Difference ◽  
Impact On Survival

7053 Background: The revised International Prognostic Scoring System (IPSS-R) aids in prognosticating MDS. The percentage (%) of blasts in the bone marrow is one of the major determinants of the scoring system. The aspirate blast % is utilized as the standard of care, but there could be discrepancies in the blast % reported by the aspirate and the biopsy. We aim to study the possible use of bone marrow biopsy blasts in MDS-EB in calculating IPSS-R. Methods: The MDS database was reviewed for cases of MDS-EB after due IRB approval. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and biopsy blast % (IPSS-RBx). The biopsy blast % was reported morphologically or by the CD34 stain. Whenever a range was reported the highest value was utilized as the blast %. Suboptimal aspirates were excluded from the study. The overall survival (OS) was determined by IPSS-RAsp, IPSS-RBx and IPSS-R highest blast (IPSS-RHi). OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno’s concordance statistic was used to compare all 3 risk scoring systems. Results: Of 1322 patients, 431 (33%) cases were identified with MDS-EB; out of which 173 cases had both blasts reported in the biopsy and the aspirate. Out of 173 cases, 35 (20%) had MDS-EB1, and 61 (35%) had MDS EB-2 based on both biopsy and aspirate (concordant cases). Seventy seven (45%) patients changed from EB-1 to EB2 or vice versa based on the biopsy blast (44/77 (57%) cases were upstaged). The OS outcomes based on the IPSS-RBx biopsy showed a clear and meaningful separation with median OS decreasing with increased risk but IPSS-RAsp and IPSS-RHi did not (Table). We compared the 3 models for observed OS differences using the Uno model and there was no statistically significant difference. Conclusions: IPSS-RBx (but not IPSS-RAsp and IPSS-RHi) identified prognostic groups for OS with median OS decreasing with increased risk. The small sample size may have led to an insignificant effect on model power by Uno model. This finding needs to be validated by other centers. [Table: see text]

scholarly journals Commonly Used Severity Scores Are Not Good Predictors of Mortality in Sepsis from Severe Leptospirosis: A Series of Ten Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Dimitrios Velissaris ◽  
Menelaos Karanikolas ◽  
Nikolaos Flaris ◽  
Fotini Fligou ◽  
Markos Marangos ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Multiorgan Failure ◽  
Good Condition ◽  
Case Series ◽  
Scoring Systems ◽  
Small Sample ◽  
University Hospital ◽  
Severity Scores ◽  
Retrospective Data Collection ◽  
Severe Leptospirosis

Introduction. Severe leptospirosis, also known as Weil's disease, can cause multiorgan failure with high mortality. Scoring systems for disease severity have not been validated for leptospirosis, and there is no documented method to predict mortality.Methods. This is a case series on 10 patients admitted to ICU for multiorgan failure from severe leptospirosis. Data were collected retrospectively, with approval from the Institution Ethics Committee.Results. Ten patients with severe leptospirosis were admitted in the Patras University Hospital ICU in a four-year period. Although, based on SOFA scores, predicted mortality was over 80%, seven of 10 patients survived and were discharged from the hospital in good condition. There was no association between SAPS II or SOFA scores and mortality, but survivors had significantly lower APACHE II scores compared to nonsurvivors.Conclusion. Commonly used severity scores do not seem to be useful in predicting mortality in severe leptospirosis. Early ICU admission and resuscitation based on a goal-directed therapy protocol are recommended and may reduce mortality. However, this study is limited by retrospective data collection and small sample size. Data from large prospective studies are needed to validate our findings.

Is increased screen time associated with the development of anxiety or depression in young people?

2017 ◽  
Vol 41 (S1) ◽  
pp. S530-S531 ◽  
Author(s):  
J. Khouja ◽  
M. Munafò ◽  
K. Tilling ◽  
N. Wiles ◽  
C. Joinson ◽  
...  
Keyword(s):  
Young People ◽  
Screen Time ◽  
Maternal Education ◽  
Small Sample Size ◽  
Small Sample ◽  
Anxiety And Depression ◽  
Parents And Children ◽  
Increased Risk ◽  
Before And After ◽  
Competing Interest

IntroductionEmerging evidence suggests that sedentary behaviour, specifically time spent taking part in screen-based activities, such as watching television, may be associated with mental health outcomes in young people [1]. However, recent reviews have found limited and conflicting evidence for both anxiety and depression [2].ObjectivesThe purpose of the study was to explore associations between screen time at age 16 years and anxiety and depression at 18.MethodsSubjects (n = 1958) were from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK-based prospective cohort study. We assessed associations between screen time (measured via questionnaire at 16 years) and anxiety and depression (measured in a clinic at 18 years using the Revised Clinical Interview Schedule) using ordinal logistic regression, before and after adjustment for covariates (including sex, maternal education, family social class, parental conflict, bullying and maternal depression).ResultsAfter adjusting for potential confounders, we found no evidence for an association between screen time and anxiety (OR = 1.02; 95% CI 0.95–1.09). There was weak evidence that greater screen time was associated with a small increased risk of depression (OR = 1.05, 95% CI 0.98–1.13).ConclusionsOur results suggest that young people who spend more time on screen-based activities may have a small increased risk of developing depression but not anxiety. Reducing youth screen time may lower the prevalence of depression. The study was limited by screen time being self-reported, a small sample size due to attrition and non-response, and the possibility of residual confounding. Reverse causation cannot be ruled out.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Investigation of factors relating to neuropsychological change following cardiac surgery

Perfusion ◽  
2007 ◽  
Vol 22 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Paul D Raymond ◽  
Michael Radel ◽  
Michael J Ray ◽  
Anton D Hinton-Bayre ◽  
Neville A Marsh
Keyword(s):  
Small Sample Size ◽  
Artery Bypass ◽  
Neuropsychological Test ◽  
Small Sample ◽  
Neuropsychological Impairment ◽  
Increased Risk ◽  
Computer Based ◽  
Computer Based Testing ◽  
Elderly Cohort ◽  
Discharge From Hospital

Background. An analysis of neuropsychological impairment following cardiopulmonary bypass was performed in 55 patients undergoing elective coronary artery bypass grafting. Methods. Neurocognitive function was measured preoperatively using the MicroCog: Assessment of Cognitive Functioning computer-based testing tool. Testing was repeated in the postoperative period immediately prior to discharge from hospital. Analysis of significant score decline was performed using the standardised regression-based technique. A patient was classified as overall impaired when ≥20% of test scores were significantly impaired. The proposed marker of neurological damage S-100β was also used. Prothrombin Fragment 1+2 (F1+2) was measured as a marker of thrombin development to test the hypothesis that excessive haemostatic activation may lead to thromboembolic damage to the brain. Results and Conclusions. 32.7% of patients were classified as significantly impaired. No relationship was detected between F1+2 and any neuropsychological test score; however, the study was limited due to small sample size. F1+2 levels were higher in patients undergoing prolonged bypass times. Neuropsychological decline was significantly correlated with patient age, suggesting a degree of caution is warranted when operating on an elderly cohort. An unexpected relationship was detected between higher heparin concentrations and increased risk of neuropsychological impairment; however, this requires re-evaluation. Perfusion (2007) 22, 27—33.

scholarly journals Modulation of Cardiac Injury by ACE inhibitor/ARB in Patients with Severe COVID-19

2020 ◽  
Author(s):  
Beibei Du ◽  
Daoyuan Si ◽  
Bo Yang ◽  
Guohui Liu ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Treatment Group ◽  
Small Sample Size ◽  
Cardiac Injury ◽  
Ventilatory Support ◽  
Small Sample ◽  
Clinical Trial Registry ◽  
Clinical Trial Registration ◽  
Significant Difference ◽  
Ctni Level

Abstract Introduction: Cardiac injury occurs in 7-22% of patient hospitalized with COVID-19 and an elevation in troponin is associated with a 4.2-fold increase in the risk of mortality. Preliminary data showed ACEi/ARB usage might not increase mortaily in COVID-19 patients. However, it is unknown if cardiac injury in patients with severe COVID-19 can be modulated by ACEi/ARB usage during evolution of the cardiac injury.Methods: In 154 COVID-19 patients with cardiac injury, the effect of ACEi/ARB treatment (17 patients) was compared with 137 patients without ACEi/ARB treatment. Cardiac injury was indicated by cTnI level.Results: In ACEi/ARB treatment group and no ACEi/ARB treatment group, peak cTnI level did not show significant difference (150.5 pg/ml [31.75-1179], vs 207 pg/ml [54.65-989.4], respectively, P = 0.21). Evolution of Cardiac injury (temporal change of cTnI at day 6, 9, 12, 15, 18, 21, 24, 27, 30, and 33) showed no statistical difference. Mortality (ACEi/ARB group vs no ACEi/ARB group; 52.9% vs 69.9%, P = 0.17), atrial arrhythmias (11.7% vs 24.4%, P = 0.36), requirement for invasive ventilatory support (29.4% vs 48.2%, P = 0.14) also showed no significant difference in two groups.Conclusions: ACEi/ARB usage during the COVID-19 was not associated with exacerbation of cardiac injury. These data should be interpreted as essentially hypothesis-generating due to small sample size.Clinical Trial Registration: This retrospective study was registered in Chinese clinical trial registry (ChiCTR 2000031301).

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