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1.
World J Pediatr Congenit Heart Surg ; : 21501351241232075, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454620

ABSTRACT

Background: The Ross-Konno procedure is a technically demanding surgical option to treat multilevel left ventricular outflow tract obstruction. Methods: A systematic review with pooled analyses was conducted according to PRISMA criteria on studies published between January 2000 and May 2022 that assessed outcomes following the Ross-Konno intervention in children. Individual patient data were extracted from published Kaplan-Meier curves using digitalization software. Overall survival and freedom from reintervention were assessed by time-to-event approaches. Determinants of one-year survival were investigated by meta-regression analyses. Results: Ten studies with a total population of 274 patients were included. The overall pooled early (≤30 days) survival rate was 86.9% (95% CI [87.6%-78.4%]). Five-year survival rates in patients without and with (N = 50 [18.2%] of 274 total patients) concomitant mitral valve surgery were 82.5% (95% CI [87.6%-77.4%]) versus 56.1% (95% CI [74.1%-38.1%]), hazard ratio 2.67, 95% CI (1.44-4.93), P < .0001. Five- and ten-year freedom from pulmonary autograft reoperation rates were 93.5% and 90.9%, respectively. Five- and ten-year freedom from right ventricular outflow tract reoperation rates were 74.3% and 57.3%, respectively. By meta-regression analysis, resection of endocardial fibroelastosis (N = 32 [11.7%] of 274 total patients) was associated with superior one-year survival (P = .027). Conclusion: The Ross-Konno procedure is associated with substantial early mortality and gradual attrition thereafter. Mortality is higher in patients with concomitant mitral valve surgery. Resection of endocardial fibroelastosis is associated with superior survival. Right ventricular outflow tract reinterventions are common.

2.
Lancet ; 403(10421): 44-54, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38096892

ABSTRACT

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).


Subject(s)
Uterine Rupture , Pregnancy , Female , Humans , Uterine Rupture/epidemiology , Uterine Rupture/etiology , Uterine Rupture/prevention & control , Canada , Cesarean Section/adverse effects , Delivery, Obstetric/adverse effects , Morbidity
3.
Vaccines (Basel) ; 11(11)2023 Nov 11.
Article in English | MEDLINE | ID: mdl-38006043

ABSTRACT

The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6-16.4%) and 5.1% (95% CI: 3.2-6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5-20.8%) and 10.7% (8.2-13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.

4.
JTCVS Open ; 15: 454-467, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37808065

ABSTRACT

Objective: This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery. Methods: Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death. Results: One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P = .49). Conclusions: In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results.

5.
Open Forum Infect Dis ; 10(7): ofad288, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37496607

ABSTRACT

Background: Few head-to-head comparisons have been performed on the real-world effectiveness of coronavirus disease 2019 (COVID-19) booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 vs BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against any medically attended, outpatient, and hospitalized COVID-19. Methods: A data set linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients age ≥18 years vaccinated with a primary series between February and October 2021 (Part 1) and a homologous mRNA booster between October 2021 and January 2022 (Part 2). Adjusted hazard ratios (HRs) were derived from 1:1 matching adjusted across potential covariates. rVE was (1 - HRadjusted) × 100. Additional analysis was performed across regions and age groups. Results: Following adjustment, Part 1 rVE for mRNA-1273 vs BNT162b2 was 23% (95% CI, 22%-25%), 23% (95% CI, 22%-25%), and 19% (95% CI, 14%-24%), while the rVE for mRNA-1273 vs Ad26.COV2.S was 50% (95% CI, 48%-51%), 50% (95% CI, 48%-52%), and 57% (95% CI, 53%-61%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 vs BNT162b2 was 14% (95% CI, 10%-18%), 13% (95% CI, 8%-17%), and 19% (95% CI, 1%-34%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically attended COVID-19 was higher in adults age ≥65 years (35%; 95% CI, 24%-47%) than in those age 18-64 years (13%; 95% CI, 9%-17%) after the booster. Conclusions: In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following a primary series during the Delta-dominant period and more effective than BNT162b2 as a booster during the Omicron-dominant period.

6.
J Pediatr Surg ; 58(1): 82-88, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36357227

ABSTRACT

BACKGROUND: The aim of this study was to establish the feasibility and safety of the use of indocyanine green technology during pediatric intestinal resections. While indocyanine green fluorescence angiography (ICG-FA) has been advocated as an imaging technique to assess bowel perfusion in adults, few studies have evaluated this technology in a pediatric context. METHODS: A prospective clinical trial was conducted. Patients 16 years old or younger undergoing a surgery potentially requiring an intestinal resection were eligible. Patients received a standardized intravenous injection of indocyanine green and intestinal perfusion was evaluated. The study endpoints included safety, impact on bowel resection and feasibility and acceptance of ICG-FA in this population. RESULTS: From May 2020 to March 2021, 30 consecutive patients were included in this trial. Final analysis was done on 28 patients with a median age of 15.00 [6.36,85.00] weeks and weight of 5.58 [3.64,11.70] kg at surgery. Adequate fluorescence was achieved in less than one minute for all cases with an average dose of 0.14 mg/kg. No adverse event related to indocyanine green occurred. ICG-FA versus standard assessment of potential resection sites differed in 62% (95% IC 0.41-0.82) of our cases. Qualitative analysis demonstrated that 95% of the surgical team agreed that ICG-FA was safe. CONCLUSIONS: The use of ICG-FA is feasible and safe for pediatric intestinal resections. Introduction of ICG-FA was simple and acceptance rates were high within the surgical team. This fluorescence imaging may be a valuable imaging technology for intestinal resections in pediatric surgery.


Subject(s)
Digestive System Surgical Procedures , Fluorescein Angiography , Indocyanine Green , Adolescent , Child , Humans , Infant , Digestive System Surgical Procedures/methods , Fluorescein Angiography/adverse effects , Fluorescein Angiography/methods , Prospective Studies , Child, Preschool
7.
Pediatr Crit Care Med ; 24(1): e9-e19, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36053070

ABSTRACT

OBJECTIVE: Healthcare constraints with decreasing bed availability cause strain in acute care units, and patients are more frequently being discharged directly home. Our objective was to describe the population, predictors, and explore PICU readmission rates of patients discharged directly home from PICU, compared with those discharge to the hospital ward, then home. DESIGN: An observational cohort study. SETTING: Children admitted to the PICU of CHU Sainte-Justine, between January 2014 and 2020. PATIENTS: Patients less than 18 years old, who survived their PICU stay, and were discharged directly home or to an inpatient ward. Patients discharged directly home were compared with patients discharged to the ward using descriptive statistics. Logistic regression was used to identify factors associated with home discharge. Propensity scores were used to compare PICU readmission rates in patients discharged directly home to those discharged to the ward. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 5,531 admissions included, 594 (10.7%) were discharged directly home from the PICU. Patients who were more severe ill (odds ratio [OR], 0.93; 95% CI, 0.90-0.97), had invasive ventilation (OR, 0.70; 95% CI, 0.53-0.92), or had vasoactive agents (OR, 0.70; 95% CI, 0.53-0.92) were less likely to be discharged directly home. Diagnoses associated with discharge directly home were acute intoxication, postoperative ear-nose-throat care, and shock states. There was no difference in the rate of readmission to PICU at 2 (relative risk [RR], 0.20 [95% CI, 0.02-1.71]) and 28 days (RR, 1.20 [95% CI, 0.61-3.36]) between propensity matched patients discharged to the ward for 2 or less days, compared with those discharged directly home. CONCLUSION: Discharge directly home from the PICU is increasing locally. The population includes less severely ill patients with rapidly resolving diagnoses. Rates of PICU readmission between patients discharged directly home from the PICU versus to ward are similar, but safety of the practice requires ongoing evaluation.


Subject(s)
Patient Discharge , Patient Readmission , Child , Humans , Adolescent , Retrospective Studies , Cohort Studies , Intensive Care Units, Pediatric , Length of Stay
8.
Pediatrics ; 150(1)2022 07 01.
Article in English | MEDLINE | ID: mdl-35652296

ABSTRACT

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.


Subject(s)
Docosahexaenoic Acids , Lactation , Child Development , Dietary Supplements , Double-Blind Method , Female , Gestational Age , Humans , Infant , Infant, Newborn
9.
Vox Sang ; 117(4): 545-552, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34820856

ABSTRACT

BACKGROUND AND OBJECTIVES: Hospital-acquired infections (HAIs) are an important problem in critically ill children. Studies show associations between the transfusion of non-leukoreduced red blood cell units (RBC) and increased HAI incidence rates (IRs). We hypothesize that transfusing pre-storage leukoreduced RBC is also associated with increased HAI IR. We aim to evaluate the associations between (1) a leukoreduced RBC restrictive transfusion strategy and HAI IR, (2) leukoreduced RBC transfusions and HAI IR, and (3) the number or volume of leukoreduced RBC transfusions and HAI IR in critically ill children. MATERIALS AND METHODS: This post hoc secondary analysis of the "Transfusion Requirement in Paediatric Intensive Care Units" (TRIPICU) randomized controlled trial (637 patients) used quasi-Poisson multivariable regression models to estimate HAI incidence rate ratios (IRRs) and 95% confidence intervals (CI). RESULTS: A restrictive transfusion strategy yielded an IRR of 0.88 (95% CI 0.67, 1.16). The association between transfusing leukoreduced RBCs (IRR 1.25; 95% CI 0.73, 2.13) and HAI IR was not statistically significant. However, we observed significant associations between patients who received >20 cc/kg volume of leukoreduced RBC transfusions (IRR 2.14; 95% CI 1.15, 3.99) and ≥3 leukoreduced RBC transfusions (IRR 2.40; 95% CI 1.15, 4.99) and HAI IR. CONCLUSION: Exposing critically ill children to >20 cc/kg or ≥3 leukoreduced RBC transfusions were associated with higher HAI IR, suggesting dose-response patterns.


Subject(s)
Critical Illness , Erythrocyte Transfusion , Child , Critical Illness/therapy , Erythrocyte Transfusion/adverse effects , Hospitals , Humans
10.
Transfus Med ; 31(6): 467-473, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34585466

ABSTRACT

OBJECTIVE: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children. BACKGROUND: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. METHODS: In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). RESULTS: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long-stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). CONCLUSION: Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children.


Subject(s)
Blood Preservation , Critical Illness , Child , Critical Illness/therapy , Erythrocytes , Hospitals , Humans , Intensive Care Units, Pediatric
11.
Vaccines (Basel) ; 9(8)2021 Aug 05.
Article in English | MEDLINE | ID: mdl-34451987

ABSTRACT

MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose trivalent inactivated influenza vaccine (HD-IIV3) elicit an enhanced immune response in older adults compared to standard, quadrivalent inactivated influenza vaccines (IIV4). We sought to determine the relative vaccine effectiveness (rVE) of aIIV3 versus IIV4 and HD-IIV3 in preventing influenza-related medical encounters in this retrospective cohort study involving adults ≥65 years with ≥1 health condition during the 2017-2018 and 2018-2019 influenza seasons. Data were obtained from primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was determined using the formula (% rVE = 1 - ORadjusted) × 100. Analysis sets included 1,755,420 individuals for the 2017-2018 season and 2,055,012 for the 2018-2019 season. Compared to IIV4, aIIV3 was 7.1% (95% confidence interval 3.3-10.8) and 20.4% (16.2-24.4) more effective at preventing influenza-related medical encounters in the 2017-2018 and 2018-2019 seasons, respectively. Comparable effectiveness was observed with HD-IIV3 across both seasons. Our results support improved effectiveness of aIIV3 vs IIV4 in a vulnerable population of older adults at high risk of influenza and its complications.

12.
Open Forum Infect Dis ; 8(7): ofab167, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34327253

ABSTRACT

BACKGROUND: Higher rates of influenza-related morbidity and mortality occur in individuals with underlying medical conditions. To improve vaccine effectiveness, cell-based technology for influenza vaccine manufacturing has been developed. Cell-derived inactivated quadrivalent influenza vaccines (cIIV4) may improve protection in seasons in which egg-propagated influenza viruses undergo mutations that affect antigenicity. This study aimed to estimate the relative vaccine effectiveness (rVE) of cIIV4 versus egg-derived inactivated quadrivalent influenza vaccines (eIIV4) in preventing influenza-related medical encounters in individuals with underlying medical conditions putting them at high risk of influenza complications during the 2018-2019 US influenza season. METHODS: An integrated dataset, linking primary care electronic medical records with claims data, was used to conduct a retrospective cohort study among individuals aged ≥4 years, with ≥1 health condition, vaccinated with cIIV4 or eIIV4 during the 2018-2019 season. Adjusted odds ratios (ORs) were derived using a doubly robust inverse probability of treatment-weighting (IPTW) model, adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness was estimated by (1 - OR) × 100 and presented with 95% confidence intervals (CIs). RESULTS: The study cohort included 471 301 cIIV4 and 1 641 915 eIIV4 recipients. Compared with eIIV4, cIIV4 prevented significantly more influenza-related medical encounters among individuals with ≥1 health condition (rVE, 13.4% [95% CI, 11.4%-15.4%]), chronic pulmonary disease (rVE, 18.7% [95% CI, 16.0%-21.3%]), and rheumatic disease (rVE, 11.8% [95% CI, 3.6%-19.3%]). CONCLUSIONS: Our findings support the use of cIIV4 in individuals ≥4 years of age at high risk of influenza complications and provide further evidence supporting improved effectiveness of cIIV4 compared with eIIV4.

13.
J Pediatr Hematol Oncol ; 43(6): e867-e872, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33661168

ABSTRACT

In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver. In this retrospective cross-sectional case-control study, 16 patients with SCD were matched to 50 patients without SCD on known busulfan clearance's covariates (glutathione-S-transferase alpha1 polymorphisms, age, weight). Clearance of the first dose of busulfan was not significantly different independently of genetic or anthropometric factors in patients with or without SCD.


Subject(s)
Anemia, Sickle Cell/metabolism , Busulfan/pharmacokinetics , Immunosuppressive Agents/pharmacokinetics , Adolescent , Adult , Anemia, Sickle Cell/therapy , Busulfan/metabolism , Case-Control Studies , Child , Child, Preschool , Cross-Sectional Studies , Female , Hematopoietic Stem Cell Transplantation , Humans , Immunosuppressive Agents/metabolism , Male , Metabolic Networks and Pathways , Retrospective Studies , Transplantation Conditioning , Young Adult
14.
J Cyst Fibros ; 20(6): e93-e99, 2021 11.
Article in English | MEDLINE | ID: mdl-33277205

ABSTRACT

BACKGROUND: YKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease. METHODS: A prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters. RESULTS: We found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic. CONCLUSION: Our study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile.


Subject(s)
Chitinase-3-Like Protein 1/genetics , Cystic Fibrosis/genetics , Adult , Biomarkers/blood , Chitinase-3-Like Protein 1/blood , Cystic Fibrosis/blood , Female , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Prospective Studies , Severity of Illness Index
15.
J Thromb Haemost ; 18(12): 3309-3315, 2020 12.
Article in English | MEDLINE | ID: mdl-32898930

ABSTRACT

BACKGROUND: International guidelines recommend using the Villalta score (VS) to diagnose the postthrombotic syndrome (PTS). However, a high proportion of PTS detected with VS could just reflect the presence of preexisting primary venous insufficiency (PVI). Furthermore, it is unclear whether the contralateral VS (cl-VS) can be used to assess for preexisting PVI. OBJECTIVES: To estimate whether cl-VS can be used to assess for preexisting PVI, and to assess the proportion of PTS that could be attributable to preexisting PVI. METHODS: Subanalysis of the SOX multicenter randomized trial focusing on patients with a first unilateral proximal deep vein thrombosis (DVT) followed for up to 2 years. PVI was defined as a baseline cl-VS > 4, and PTS as VS > 4 in the leg ipsilateral to DVT starting 6 months after DVT. RESULTS: Among 680 patients, mean cl-VS remained stable over time: 1.23 (standard deviation [SD] ±2.49) at baseline and 1.17 (±2.20), 1.59 (±2.81), 1.54 (±2.50), 1.65 (±2.82), and 1.55 (±2.63) at the 1-, 6-, 12-, 18-, and 24-month visits, respectively. Baseline cl-VS and ipsilateral VS measured during follow-up were mildly correlated (Pearson correlation = 0.13-0.25). This association disappeared after subtracting the cl-VS measured at the same visit from the ipsilateral VS. Overall, 48.8% of patients developed PTS of whom 12.8% had baseline cl-VS > 4. CONCLUSION: In our study of patients with a first unilateral proximal DVT, the proportion of patients with PTS who had a cl-VS > 4 is modest. However, cl-VS appears to be stable over time. Its assessment could constitute a simple way of documenting preexisting PVI and help to classify patients as having PTS.


Subject(s)
Postthrombotic Syndrome , Venous Insufficiency , Venous Thrombosis , Humans , Postthrombotic Syndrome/diagnosis , Risk Factors , Time Factors , Venous Insufficiency/diagnosis , Venous Thrombosis/diagnosis
16.
J Crit Care ; 59: 23-31, 2020 10.
Article in English | MEDLINE | ID: mdl-32485439

ABSTRACT

PURPOSE: End-stage kidney disease (ESKD) causes bleeding diathesis; however, whether these findings are extrapolable to acute kidney injury (AKI) remains uncertain. We assessed whether AKI is associated with an increased risk of bleeding. METHODS: Single-center retrospective cohort study, excluding readmissions, admissions <24 h, ESKD or kidney transplants. The primary outcome was the development of incident bleeding analyzed by multivariate time-dependent Cox models. RESULTS: In 1001 patients, bleeding occurred in 48% of AKI and 57% of non-AKI patients (p = .007). To identify predictors of incident bleeding, we excluded patients who bled before ICU (n = 488). In bleeding-free patients (n = 513), we observed a trend toward higher risks of bleeding in AKI (22% vs. 16%, p = .06), and a higher risk of bleeding in AKI-requiring dialysis (38% vs. 17%, p = .01). Cirrhosis, AKI-requiring dialysis, anticoagulation, and coronary artery disease were associated with bleeding (HR 3.67, 95%CI:1.33-10.25; HR 2.82, 95%CI:1.26-6.32; HR 2.34, 95%CI:1.45-3.80; and HR 1.84, 95%CI:1.06-3.20, respectively), while SOFA score and sepsis had a protective association (HR 0.92 95%CI:0.84-0.99 and HR 0.55, 95%CI:0.34-0.91, respectively). Incident bleeding was not associated with mortality. CONCLUSIONS: AKI-requiring dialysis was associated with incident bleeding, independent of anticoagulant administration. Studies are needed to better understand how AKI affects coagulation and clinical outcomes.


Subject(s)
Acute Kidney Injury/therapy , Critical Care/methods , Hemorrhage/epidemiology , Hemorrhage/etiology , Renal Dialysis/adverse effects , Aged , Anticoagulants/adverse effects , Coronary Artery Disease/complications , Critical Illness , Female , Follow-Up Studies , Hemorrhage/mortality , Humans , Incidence , Length of Stay , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sepsis/complications , Treatment Outcome
17.
Pediatr Nephrol ; 35(5): 843-850, 2020 05.
Article in English | MEDLINE | ID: mdl-31932958

ABSTRACT

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury. METHODS: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up. RESULTS: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed. CONCLUSIONS: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.


Subject(s)
Complement Membrane Attack Complex/analysis , Glomerular Mesangium/pathology , Glomerulonephritis, IGA/diagnosis , IgA Vasculitis/diagnosis , Immunosuppressive Agents/therapeutic use , Adolescent , Biomarkers/analysis , Biopsy , Child , Child, Preschool , Complement Membrane Attack Complex/immunology , Complement Pathway, Alternative/drug effects , Complement Pathway, Alternative/immunology , Complement Pathway, Mannose-Binding Lectin/drug effects , Complement Pathway, Mannose-Binding Lectin/immunology , Feasibility Studies , Female , Follow-Up Studies , Glomerular Mesangium/immunology , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/pathology , Humans , IgA Vasculitis/drug therapy , IgA Vasculitis/immunology , IgA Vasculitis/pathology , Immunoglobulin A/immunology , Immunosuppressive Agents/pharmacology , Male , Prognosis , Retrospective Studies , Treatment Outcome
20.
Healthcare (Basel) ; 7(1)2019 Jan 02.
Article in English | MEDLINE | ID: mdl-30609712

ABSTRACT

Several children receiving palliative care experience dyspnea and pain. An order protocol for distress (OPD) is available at Sainte-Justine Hospital, aimed at alleviating respiratory distress, pain and anxiety in pediatric palliative care patients. This study evaluates the clinical use of the OPD at Sainte-Justine Hospital, through a retrospective chart review of all patients for whom the OPD was prescribed between September 2009 and September 2012. Effectiveness of the OPD was assessed using chart documentation of the patient's symptoms, or the modified Borg scale. Safety of the OPD was evaluated by measuring the time between administration of the first medication and the patient's death, and clinical evolution of the patient as recorded in the chart. One hundred and four (104) patients were included in the study. The OPD was administered at least once to 78 (75%) patients. A total of 350 episodes of administration occurred, mainly for respiratory distress (89%). Relief was provided in 90% of cases. The interval between administration of the first protocol and death was 17 h; the interval was longer in children with cancer compared to other illnesses (p = 0.02). Data from this study support the effectiveness and safety of using an OPD for children receiving palliative care.

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