scholarly journals Clinical value of a screening tool for tumor predisposition syndromes in childhood cancer patients (TuPS): a prospective, observational, multi-center study

2021 ◽  
Author(s):  
Floor A. M. Postema ◽  
Saskia M. J. Hopman ◽  
Corianne A. J. M. de Borgie ◽  
Cora M. Aalfs ◽  
Jakob K. Anninga ◽  
...  
Keyword(s):  
Screening Tool ◽  
Clinical Care ◽  
False Negative ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Variant Of Uncertain Significance ◽  
Multi Center Study ◽  
Center Study ◽  
Genetic Consultation

AbstractRecognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.

scholarly journals The Efficacy of Anti-Arrhythmic Drugs in Children With Idiopathic Frequent Symptomatic or Asymptomatic Premature Ventricular Complexes With or Without Asymptomatic Ventricular Tachycardia: a Retrospective Multi-Center Study

2021 ◽  
Author(s):  
Robin A. Bertels ◽  
Janneke A. E. Kammeraad ◽  
Anna M. Zeelenberg ◽  
Luc H. Filippini ◽  
Ingmar Knobbe ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Beta Blockers ◽  
Control Group ◽  
Premature Ventricular Complexes ◽  
Percentage Points ◽  
Asymptomatic Children ◽  
Group A ◽  
The Mean ◽  
Multi Center Study ◽  
Center Study

AbstractThe aim of the study is to compare the efficacy of flecainide, beta-blockers, sotalol, and verapamil in children with frequent PVCs, with or without asymptomatic VT. Frequent premature ventricular complexes (PVCs) and asymptomatic ventricular tachycardia (VT) in children with structurally normal hearts require anti-arrhythmic drug (AAD) therapy depending on the severity of symptoms or ventricular dysfunction; however, data on efficacy in children are scarce. Both symptomatic and asymptomatic children (≥ 1 year and < 18 years of age) with a PVC burden of 5% or more, with or without asymptomatic runs of VT, who had consecutive Holter recordings, were included in this retrospective multi-center study. The groups of patients receiving AAD therapy were compared to an untreated control group. A medication episode was defined as a timeframe in which the highest dosage at a fixed level of a single drug was used in a patient. A total of 35 children and 46 medication episodes were included, with an overall change in PVC burden on Holter of -4.4 percentage points, compared to -4.2 in the control group of 14 patients. The mean reduction in PVC burden was only significant in patients receiving flecainide (− 13.8 percentage points; N = 10; p = 0.032), compared to the control group and other groups receiving beta-blockers (− 1.7 percentage points; N = 18), sotalol (+ 1.0 percentage points; N = 7), or verapamil (− 3.9 percentage points; N = 11). The efficacy of anti-arrhythmic drug therapy on frequent PVCs or asymptomatic VTs in children is very limited. Only flecainide appears to be effective in lowering the PVC burden.

scholarly journals Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis

2020 ◽  
Author(s):  
René L. Warren ◽  
Inanç Birol
Keyword(s):  
In Silico ◽  
Statistical Significance ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Disease Prognosis ◽  
Increased Risk

ABSTRACTBackgroundThe Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants.MethodsBy combining the predictive power of multiple in silico HLA predictors, we have previously identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small cohorts at the COVID-19 pandemic onset. Since then, newer and larger patient cohorts with controls and associated demographic and clinical data have been deposited in public repositories. Here, we report on HLA-I and HLA-II alleles, along with their associated risk significance in one such cohort of 126 patients, including COVID-19 positive (n=100) and negative patients (n=26).ResultsWe recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes reveal nominally significant risk associations with A*11:01 (FET p=0.0078), C*04:01 (FET p=0.0087) and DQA1*01:02 (FET p=0.0121).ConclusionsWhile enrichment of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with the latter three alleles tend to fare worse overall. This is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0023), and may hold potential clinical value.

scholarly journals Increased Incidence of Perforated Appendicitis in Children During COVID-19 Pandemic in a Bavarian Multi-Center Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Frank-Mattias Schäfer ◽  
Johannes Meyer ◽  
Stephan Kellnar ◽  
Jakob Warmbrunn ◽  
Tobias Schuster ◽  
...  
Keyword(s):  
Open Surgery ◽  
Perforated Appendicitis ◽  
Control Group ◽  
Delayed Presentation ◽  
Perforation Rate ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Multi Center Study ◽  
Center Study

Introduction: Since early 2020 the COVID-19 pandemic and statutory preventive reorganization of treatment capacities with cancellation of elective surgery as well as curfew regulations led to vastly decreased utilization of primary health care.Materials and Methods: To assess whether there are negative effects on pediatric acute care in Bavaria during the spring 2020 lockdown a state-wide retrospective multi-center study was performed to analyze the rate of perforated appendicitis during lockdown. Children who have been operated on during the corresponding period in 2018/19 served as control group.Results: Overall, 514 patients (292 boys, 222 girls) were included (2020: 176 patients; 2019: 181 patients; 2018: 157 patients). Median age was 11.2 years. Four hundred thirty-nine patients (85.4%) underwent laparoscopic surgery, 69 (13.4%) open surgery and 1.2% underwent conversion from laparoscopic to open surgery. In 2020 a perforation rate of 27.8% (49/176 patients) was found, in 2018–2019 perforation rate was 20.7% (70/338 patients, p = 0.0359, Cochran-Mantel-Haenszel-Test). Subgroup analysis showed that in younger patients (≤ 11.2 years), in 2020 perforation rate was significantly higher with 37.6% (32/85 patients), while 22.2% (39/176) in 2018/2019 (p = 0.014, Fisher's exact test).In boys perforation rate was significantly higher in 2020 with 35.0% (35/100 patients) compared to 21.4% in 2018–2019 (p = 0.0165, Fisher's exact test).Conclusion: During the period of curfew regulations in Bavaria the rate of perforated appendicitis in childhood increased significantly, especially in younger children and boys. Potentially this has to be attributed to delayed presentation to pediatric surgery care. Because of potential long-term sequelae of perforated appendicitis these adverse effects during curfew have to be taken into account for future political decision making to ensure reasonable patient care and avoid collateral damage in near-future or on-going pandemic situations.

scholarly journals Early Tocilizumab Dosing is Associated with Improved Survival In Critically Ill Patients Infected With Sars-CoV-2

2020 ◽  
Author(s):  
Russell M. Petrak ◽  
Nicholas W. Van Hise ◽  
Nathan C. Skorodin ◽  
Robert M. Fliegelman ◽  
Vishnu Chundi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Markers ◽  
Standard Of Care ◽  
Control Group ◽  
Cytokine Storm ◽  
Novel Coronavirus ◽  
Multi Center Study ◽  
Center Study

AbstractBackgroundSARS-CoV-2 is a novel coronavirus that has rapidly expanded to become a pandemic, resulting in millions of deaths worldwide. The cytokine storm is caused by the release of inflammatory agents and results in a physiologic disruption. Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2.MethodsThis was a multi-center study of patients infected with SARS-CoV-2, admitted between 3/13/20 and 4/16/20, requiring mechanical ventilation. Parameters that were evaluated included age, sex, race, usage of steroids, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was utilized for comparison (untreated).FindingsWe studied 118 patients who required mechanical ventilation. Eighty-one (81) received tocilizumab, compared to 37 who were untreated. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p=0.003). Dosing tocilizumab late was associated with an increased mortality compared to the untreated group (p=0.006).InterpretationEarly tocilizumab administration was associated with decreased mortality in critically ill SARS-Co-V-2 patients, but a potential detriment was suggested by dosing later in a patient’s course.FundingThis work did not receive outside funding or sponsorship.

10 A Multi-center Study Analyzing Association of Vitamin D Deficiency and Replacement with Infectious Outcomes in Patients with Burn Injuries

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S12-S13
Author(s):  
Katelyn Garner ◽  
Sarah Zavala ◽  
Kate Pape ◽  
Todd A Walroth ◽  
Melissa A Reger ◽  
...  
Keyword(s):  
Vitamin D ◽  
Burn Injury ◽  
Graft Loss ◽  
Total Body Surface Area ◽  
Inhalation Injury ◽  
Control Group ◽  
Comfort Care ◽  
Increased Risk ◽  
Multi Center Study ◽  
Center Study

Abstract Introduction Vitamin D (25OHD) deficiency has been associated with poor outcomes in intensive care populations. A recent single-center, burn study found a high incidence of 25OHD deficiency. A difference was noted in infectious complications, but was underpowered. The primary objective of this multi-center study was to determine if 25OHD deficiency is associated with infectious outcomes in adult burn patients. Methods Adult patients were eligible for inclusion in this 7 center, retrospective study if admitted January 1, 2016 - July 25, 2019 and had a 25OHD concentration drawn within the first 7 days of admission. Patients were excluded if admitted for a non-burn injury, had total body surface area (TBSA) burned of less than 5%, a readmission, pregnant, incarcerated, or made comfort care or expired within 48 hours of admission. Expecting a 3:1 enrollment, goal was at least 250 total patients to be appropriately powered (β = 0.2; α = 0.05) to detect a 33% difference in composite infectious outcome (bacteremia, pneumonia, urinary tract infection, wound infection, graft loss, or death) between patients with 25OHD deficiency (&lt; 20 ng/mL) and control (≥ 20 ng/mL). Generalized linear mixed modelling was used to control for center effect, % TBSA, age, and presence of inhalation injury and find the most predictive model. Results A total of 1147 patients were initially included. After exclusions, 234 (56.8%) in the deficient and 178 in the control group remained. Patients in the control group had their concentration drawn earlier (p &lt; 0.001), were more likely to be male (p = 0.006), Caucasian (p &lt; 0.001), lower body mass index (p = 0.009), lower % TBSA burn (p = 0.002), and taking a 25OHD supplement prior to admission (p &lt; 0.001). Deficient patients were more likely to have an infectious outcome (52.1% vs 36.0%, p = 0.002), acute kidney injury requiring renal replacement therapy (p = 0.009), less ventilator free days in the first 28 days (p &lt; 0.001), and more days requiring vasopressors (p = 0.008). After controlling for center, % TBSA, age, and inhalation injury the best model also included presence of deficiency (odds ratio = 2.425 [1.035 - 1.252]), days until 25OHD supplement initiation (1.139 [1.035 - 1.252]), and choice of cholecalciferol over ergocalciferol 2.112 [1.151 - 3.877]). Conclusions Dilution concerns were controlled by including %TBSA in the regression model. Even if low 25OHD concentrations were an acute reaction to burn injury and not representative of true deficiency, low concentrations and delay in supplementation were independently associated with increased risk of an infectious outcome.

scholarly journals HLA alleles measured from COVID-19 patient transcriptomes reveal associations with disease prognosis in a New York cohort

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12368
Author(s):  
René L. Warren ◽  
Inanc Birol
Keyword(s):  
Statistical Significance ◽  
Severe Disease ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Hla Alleles ◽  
Disease Prognosis ◽  
Increased Risk

Background The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. Previously, we have identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small patient cohorts at the COVID-19 pandemic onset. Methods We have since analyzed a larger public patient cohort data (n = 126 patients) with controls, associated demographic and clinical data. By combining the predictive power of multiple in silico HLA predictors, we report on HLA-I and HLA-II alleles, along with their associated risk significance. Results We observe HLA-II DPA1*02:02 at a higher frequency in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p = 0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes, including admission to intensive care, reveal nominally significant risk associations with A*11:01 (FET p = 0.0078) and C*04:01 (FET p = 0.0087). The association with severe disease outcome is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0323). While prevalence of some of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with HLA-I C*04:01 tend to fare worse overall. This HLA allele may hold potential clinical value.

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