CORD-19-Sentences  

CORD-19:12f9d385be20fc59e52070d0ce51daa580ec0f0c JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-160 Sentence denotes Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome * NIH Public Access NIH-PA Author Manuscript NIH-PA Author Manuscript
TextSentencer_T2 162-170 Sentence denotes Abstract
TextSentencer_T3 171-326 Sentence denotes Objective-The variant alleles in the mannose binding lectin-2 (MBL-2) gene have been associated with MBL deficiency and increased susceptibility to sepsis.
TextSentencer_T4 327-481 Sentence denotes We postulate that the variant MBL-2 genotypes are associated with increased susceptibility to and mortality in acute respiratory distress syndrome (ARDS).
TextSentencer_T5 482-515 Sentence denotes Design-Nested case-control study.
TextSentencer_T6 516-679 Sentence denotes Patients-Two hundred and twelve Caucasians with ARDS and 442 controls genotyped for the variant X, D, B, and C alleles of codon -221, 52, 54, and 57, respectively.
TextSentencer_T7 680-1032 Sentence denotes Measurements and Main Results-Patients homozygous for the variant codon 54B allele (54BB) had worse severity of illness on admission (p = .007), greater likelihood of septic shock (p = .04), and increased odds of ARDS (adjusted odds ratio, 6.7; 95% confidence interval, 1.5-31) when compared with heterozygotes and homozygotes for the wild-type allele.
TextSentencer_T8 1033-1184 Sentence denotes This association with ARDS was especially strong among the 311 patients with septic shock (adjusted odds ratio, 12.0; 95% confidence interval, 1.9-74).
TextSentencer_T9 1185-1374 Sentence denotes Among the patients with ARDS, the 54BB genotype was associated with more daily organ dysfunction (p = .01) and higher mortality (adjusted hazard rate, 4.0; 95% confidence interval, 1.6-10).
TextSentencer_T10 1375-1577 Sentence denotes Development of ARDS and outcomes in ARDS did not vary significantly with variant alleles of codon -221, 52, and 57, but the power to detect an effect was limited secondary to the low allele frequencies.
TextSentencer_T11 1578-1672 Sentence denotes Conclusions-The MBL-2 codon 54BB genotype may be important in ARDS susceptibility and outcome.
TextSentencer_T12 1673-1750 Sentence denotes Additional studies are needed to confirm these findings in other populations.
TextSentencer_T13 1752-1926 Sentence denotes Although clinical predictors for the development to acute respiratory distress syndrome (ARDS) are well recognized, a minority of patients with these risks develop ARDS (1) .
TextSentencer_T14 1927-2061 Sentence denotes Genetic susceptibility to acute lung injury may explain the observed interindividual differences in risk and in outcomes (2) (3) (4) .
TextSentencer_T15 2062-2248 Sentence denotes Mannose binding lectin (MBL) is a member of the collectin family important in the initiation of the lectin pathway of complement activation and opsonin-induced phagocytosis (5) (6) (7) .
TextSentencer_T16 2249-2339 Sentence denotes The MBL protein is encoded by the mannose binding lectin-2 (MBL-2) gene on chromosome 10 .
TextSentencer_T17 2340-2615 Sentence denotes It is now known that circulating MBL levels are due largely to three single nucleotide polymorphisms (SNPs) in codon 52 (db SNP ID rs5030737), 54 (db SNP ID rs1800450), and 57 (db SNP ID rs1800451) in exon 1 and a promoter SNP at codon -221 (MBLXY; db SNP ID rs7096206) (7) .
TextSentencer_T18 2616-2752 Sentence denotes The variant exon 1 alleles are known as D, B, and C, respectively, whereas the wild-type alleles are known collectively as the A allele.
TextSentencer_T19 2753-2954 Sentence denotes The variant alleles in exon 1 and the X allele in the MBLXY polymorphism have been found to be associated with serum MBL deficiency especially in individuals homozygous for the variant alleles (8, 9) .
TextSentencer_T20 2955-3222 Sentence denotes In clinical studies, variant MBL-2 alleles have been associated with increased susceptibility to meningococcemia (10) , invasive pneumococcal infection (11) , hepatitis B (12, 13) , severe acute respiratory syndrome (14) , and other infections (8, 9, (15) (16) (17) .
TextSentencer_T21 3223-3506 Sentence denotes In critical illnesses, two small studies have found an association between the variant MBL-2 alleles and increased incidence of systemic inflammatory syndrome from both infectious and noninfectious causes, increased severity of sepsis, and/or increased mortality in sepsis (18, 19) .
TextSentencer_T22 3507-3680 Sentence denotes In both studies, the variant alleles were associated with serum MBL deficiency with the lowest levels found among those patients who were homozygous for the variant alleles.
TextSentencer_T23 3681-3807 Sentence denotes Genes that are important in sepsis are likely to be relevant in ARDS because of the many common links between sepsis and ARDS.
TextSentencer_T24 3808-3849 Sentence denotes Sepsis is the leading cause of ARDS (1) .
TextSentencer_T25 3850-3967 Sentence denotes Most patients who die from ARDS die of refractory infection and sepsis, not from respiratory failure (20) (21) (22) .
TextSentencer_T26 3968-4037 Sentence denotes We describe a nested case-control study of patients at risk for ARDS.
TextSentencer_T27 4038-4260 Sentence denotes We hypothesized that the X allele of the MBLXY polymorphism and the variant D, B, and C alleles of the codon 52, 54, and 57 in the MBL-2 gene are associated with increased susceptibility to and increased mortality in ARDS.
TextSentencer_T28 4261-4329 Sentence denotes A schematic summary of the study design is illustrated in Figure 1 .
TextSentencer_T29 4330-4388 Sentence denotes Details of the study have been described previously (23) .
TextSentencer_T30 4389-4598 Sentence denotes Briefly, all admissions to the intensive care units (ICU) of the Massachusetts General Hospital (Boston, MA) were screened daily for study-defined clinical risk factor for ARDS as detailed in Table 1 (2, 23) .
TextSentencer_T31 4599-4836 Sentence denotes Exclusion criteria included age <18, diffuse alveolar hemorrhage, chronic lung diseases, directive to withhold intubation, immunosuppression except if secondary to corticosteroid, and treatment with granulocyte colony-stimulating factor.
TextSentencer_T32 4837-4946 Sentence denotes ICU admissions with one or more defined risks for ARDS and no exclusion criteria were eligible for the study.
TextSentencer_T33 4947-5485 Sentence denotes Enrolled patients were screened daily for the primary outcome of ARDS as defined by respiratory failure requiring intubation and fulfillment of American-European Consensus Conference criteria for ARDS as follows (23, 24) : a) presence of hypoxemia as evidenced by PaO 2 /FIO 2 ≤200 mm Hg; b) presence of bilateral infiltrates on chest radiographs; and c) absence of left atrial hypertension as evidenced by pulmonary arterial occlusion pressure ≤18 mm Hg or lack of notation for congestive heart failure as a problem in the progress note.
TextSentencer_T34 5486-5568 Sentence denotes Nested within the prospective cohort, a case-control study was designed (Fig. 1 ).
TextSentencer_T35 5569-5727 Sentence denotes All patients who did not develop ARDS during their hospitalization with no prior history of ARDS or prior enrollment into the study were selected as controls.
TextSentencer_T36 5728-5870 Sentence denotes The Human Subjects Committees approved the study, and informed written consent was obtained from all subjects or their appropriate surrogates.
TextSentencer_T37 5871-5952 Sentence denotes Baseline clinical information was collected for all subjects on admission to ICU.
TextSentencer_T38 5953-6124 Sentence denotes Vital signs and laboratory variables in the first 24 hrs after ICU admission were collected for calculation of Acute Physiology and Chronic Health Evaluation (APACHE) III.
TextSentencer_T39 6125-6339 Sentence denotes ARDS patients were followed for the secondary outcomes of all-cause 60-day mortality and daily multiple organ dysfunction score (MODS) for 28 days as defined according to Brussels Organ Dysfunction Score (23, 25) .
TextSentencer_T40 6340-6448 Sentence denotes Respiratory failure was not included in the calculation of the organ dysfunction score in the ARDS patients.
TextSentencer_T41 6449-6618 Sentence denotes Recollection and re-entry of the clinical data from 89 (13%) subjects selected at random revealed a data-entry error rate of 1% and a data collection error rate of 2.8%.
TextSentencer_T42 6619-6672 Sentence denotes Missing physiology data occurred in <13% of patients.
TextSentencer_T43 6673-6775 Sentence denotes Similar to the APACHE III study, missing physiology values were assumed to be within the normal range.
TextSentencer_T44 6776-6821 Sentence denotes All other missing data were coded as missing.
TextSentencer_T45 6822-6947 Sentence denotes All data were collected onto clinical data forms and entered into an ACCESS data-base at the Harvard School of Public Health.
TextSentencer_T46 6948-7039 Sentence denotes Blood (10 mL) was collected for DNA extraction and polymerase chain reaction amplification.
TextSentencer_T47 7040-7224 Sentence denotes Genotyping was done on the Sequenom MassARRAY for MBLXY and codon 57 and by polymerase chain reaction/restriction fragment length polymorphism for codon 54 (9) and Taqman for codon 52.
TextSentencer_T48 7225-7326 Sentence denotes The genotyping for a random 5% of samples was repeated using alternative methods for quality control.
TextSentencer_T49 7327-7398 Sentence denotes All genotyping results were interpreted by two separate research staff.
TextSentencer_T50 7399-7486 Sentence denotes Research personnel were blinded to the case-control status or genotype of the subjects.
TextSentencer_T51 7487-7762 Sentence denotes Haplotypes were generated from the genotype results using the Partition Ligation-Expectation Maximization (PL-EM) version 1.0 (26), as in other association studies (27) that reconstruct individual probabilities for individual phasing accuracy based on unphased genotype data.
TextSentencer_T52 7763-7879 Sentence denotes Only those 589 patients with complete genotyping data for the four MBL2 polymorphisms were used to infer haplotypes.
TextSentencer_T53 7880-8019 Sentence denotes Conformity to Hardy-Weinberg equilibrium and Lewontin's D' for linkage disequilibrium was determined using SAS/Genetics (version 9.0) (28).
TextSentencer_T54 8020-8130 Sentence denotes Univariate analysis was performed using Fisher's exact test, analysis of variance, or Wilcoxon rank-sum tests.
TextSentencer_T55 8131-8214 Sentence denotes Kaplan-Meier curves for 60-day ARDS survival were compared using the log-rank test.
TextSentencer_T56 8215-8392 Sentence denotes ARDS patients who were lost to follow-up, who were discharged home alive before 60 day, or who survived to 60 days were censored at discharge or at 60 days if known to be alive.
TextSentencer_T57 8393-8521 Sentence denotes Multivariate analyses included logistic regression for development of ARDS and Cox proportional hazard models for ARDS survival.
TextSentencer_T58 8522-8596 Sentence denotes Backward selection algorithms were used to determine possible confounders.
TextSentencer_T59 8597-8745 Sentence denotes The final multivariate model include the gene effect, results from backward elimination, and clinically relevant variables such as APACHE III score.
TextSentencer_T60 8746-8826 Sentence denotes A Hosmer-Lemeshow test was used to evaluate logistic regression model fit (29) .
TextSentencer_T61 8827-8944 Sentence denotes Interactions with the MBL-2 genotypes were tested with interaction terms, and no significant interactions were found.
TextSentencer_T62 8945-9149 Sentence denotes Only APACHE III scores deviated from proportional hazard assumption as indicated by time varying covariates (p = .04), so the final model for ARDS survival was stratified by APACHE III score by quartiles.
TextSentencer_T63 9150-9315 Sentence denotes Daily MODS after development of ARDS was compared using linear mixed effects models assuming an unstructured covariance matrix using the Proc Mixed procedure in SAS.
TextSentencer_T64 9316-9530 Sentence denotes The fixed factors included the polymorphisms and potential confounders such as age, trauma, baseline APACHE III scores, treatment with corticosteroids before admission, liver failure, transfusion, and septic shock.
TextSentencer_T65 9531-9613 Sentence denotes The number of days after development of ARDS was considered to be a random factor.
TextSentencer_T66 9614-9781 Sentence denotes To evaluate whether the MODS score varied significantly by genotype during the course of ARDS, an interaction term between genotype and time was included in the model.
TextSentencer_T67 9782-9933 Sentence denotes For patients discharged from the hospital within 28 days of ARDS, their last available MODS score before discharge was assigned to all subsequent days.
TextSentencer_T68 9934-10048 Sentence denotes For ARDS patients who died within 28 days of ARDS, the maximal score was assigned to all days subsequent to death.
TextSentencer_T69 10049-10124 Sentence denotes Ventilator-free days in ARDS were calculated as previously described (30) .
TextSentencer_T70 10125-10173 Sentence denotes All analyses were conducted using SAS version 9.
TextSentencer_T71 10174-10232 Sentence denotes A p value of .05 was considered statistically significant.
TextSentencer_T72 10233-10562 Sentence denotes Assuming an α-error of .05, 80% power, and genotype frequencies of 24% for the MBLXY X allele and 12%, 26%, and 3% for variant 52D, 54B, and 57C, respectively (9,31), a study with 212 cases and 442 controls would have a minimum detectable odds ratios of 1.6 for MBLXY and 1.9, 1.7, and 2.9 for codon 52, 54, and 57, respectively.
TextSentencer_T73 10563-10770 Sentence denotes Between September 9, 1999, and October 15, 2002, 752 patients were enrolled including 237 ARDS patients and 477 controls selected and genotyped for the MBL2 polymorphisms in the case-control study (Fig. 1 ).
TextSentencer_T74 10771-10865 Sentence denotes All subsequent analyses were restricted to the 212 Caucasian cases and 442 Caucasian controls.
TextSentencer_T75 10866-10979 Sentence denotes Clinical risk factors for ARDS and baseline characteristics on admission to the ICU are shown in Tables 2 and 3 .
TextSentencer_T76 10980-11133 Sentence denotes Variables in the final model for development of ARDS included direct pulmonary injury (p < .001), trauma (p < .001), age (p = .002), female gender (p = .
TextSentencer_T77 11134-11276 Sentence denotes 04), diabetes (p = .003), platelets ≤80,000/mm (p = .003), blood transfusion (p < .001), septic shock (p = .1), and APACHE III score (p = .6).
TextSentencer_T78 11277-11437 Sentence denotes The Hosmer-Lemeshow goodness-offit statistic for the final model was 9.3 with 8 degrees of freedom (p = .3), indicating no significant lack of fit of the model.
TextSentencer_T79 11438-11608 Sentence denotes The variant allele frequency in the study was 8% for codon 52, 15% for codon 54, 1.5% for codon 57, and 17% for MBLXY, which is similar to prior studies (8, 10, 11, 32) .
TextSentencer_T80 11609-11731 Sentence denotes Genotype failure for codon 52, 54, 57, and MBLXY occurred in 38 (6%), 0 (0%), 15 (2%), and 13 (2%) patients, respectively.
TextSentencer_T81 11732-11800 Sentence denotes Genotype frequencies among cases and controls are shown in Table 4 .
TextSentencer_T82 11801-11947 Sentence denotes Among the 212 patients with ARDS, the observed frequency for the codon 54BB genotype was higher than that predicted by Hardy-Weinberg equilibrium.
TextSentencer_T83 11948-12053 Sentence denotes However, this was not statistically significant (p = .4), given the smaller number of patients with ARDS.
TextSentencer_T84 12054-12183 Sentence denotes Among the 442 controls, the genotype frequency for codon 54 deviated from that predicted by Hardy-Weinberg equilibrium (p = .03).
TextSentencer_T85 12184-12280 Sentence denotes This is unlikely to be due to genotyping error as there was no discrepancy on repeat genotyping.
TextSentencer_T86 12281-12522 Sentence denotes However, controls in this study were not healthy, and patients homozygous for the codon 54B genotype were more likely to have septic shock on ICU admission as a predisposing injury for ARDS (eight of ten [80%] vs. 303 of 643 [47%]; p = .04).
TextSentencer_T87 12523-12675 Sentence denotes An association between the codon 54B genotype and the underlying condition among the controls may explain the deviation from Hardy Weinberg equilibrium.
TextSentencer_T88 12676-12932 Sentence denotes Among cases and controls, patients homozygous for the MBL-2 codon 54 variant B allele had significantly greater severity of illness, as indicated by APACHE III score, than patients homozygous or heterozygous for the wild-type A allele (p = .007) (Fig. 2) .
TextSentencer_T89 12933-13259 Sentence denotes Development of ARDS varied with the codon 54 genotype (p < .05), with patients who were homozygous for the variant codon 54B allele having an increased odds of developing ARDS compared with homozygotes or heterozygotes for the wild-type A allele (odds ratio [OR], 5.0, 95% confidence interval [CI], 1.3-20; p = .02) (Fig. 3) .
TextSentencer_T90 13260-13551 Sentence denotes On multivariate analyses after adjustment for age, gender, APACHE III, septic shock, trauma, direct pulmonary injury, hematologic and hepatic failure, and transfusion, the codon 54B genotype was still significantly associated with development of ARDS (OR adj , 6.7; 95% CI, 1.5-31; p = .01).
TextSentencer_T91 13552-13756 Sentence denotes When the analysis was restricted to the 311 patients admitted to the ICU with septic shock, the association between the 54BB genotype and ARDS was even stronger (OR adj , 12.0; 95% CI, 1.9 -74; p = .008).
TextSentencer_T92 13757-14052 Sentence denotes Because of the linkage between the MBLXY Y allele and the codon 54 variant B allele, patients homozygous for the MBL Y allele had higher APACHE III scores on admission to the ICU compared with patients who were homozygous or heterozygous for the X allele (mean 83 [SD 25] vs. 73 [25] ; p = .04).
TextSentencer_T93 14053-14262 Sentence denotes However, the frequency of the variant alleles of MBL XY, codon 52, or codon 57 on the MBL-2 gene did not vary significantly with ARDS ( The four polymorphisms are in complete linkage disequilibrium (D' = 1.0).
TextSentencer_T94 14263-14396 Sentence denotes Consistent with other reports (14, 18, 33) , the variant codon 54 B allele occurred only with the Y allele of the MBLXY polymorphism.
TextSentencer_T95 14397-14451 Sentence denotes Five haplotypes were identified with probability >99%.
TextSentencer_T96 14452-14508 Sentence denotes Haplotype analyses are similar to the preceding results.
TextSentencer_T97 14509-14588 Sentence denotes Only the ABAY haplotype was associated with the development of ARDS (Table 5) .
TextSentencer_T98 14589-14648 Sentence denotes The 60-day mortality was 46% (98 of 211) for ARDS patients.
TextSentencer_T99 14649-14776 Sentence denotes Clinical risks for ARDS and baseline characteristics between survivors and non-survivors of ARDS are shown in Tables 2 and 3 .
TextSentencer_T100 14777-14927 Sentence denotes Consistent with prior reports, survivors and nonsurvivors did not differ in Pao 2 /FIo 2 (p = .4), compliance (p = .4), or Lung Injury Score (p = .5).
TextSentencer_T101 14928-15075 Sentence denotes However, non-survivors had significantly fewer ventilator-free days than survivors (median 0 days [25-75% 0-0] vs. 7 days [25-75% 2-14]; p < .001).
TextSentencer_T102 15076-15209 Sentence denotes The 60-day mortality in ARDS varied significantly with the codon 54 genotype (p = .03) ( Table 4 ) and the ABAY haplotype (Table 5) .
TextSentencer_T103 15210-15435 Sentence denotes ARDS patients homozygous for the variant B allele had decreased survival compared with ARDS patients who were homozygous or heterozygous for the wild-type allele (hazard ratio [HR], 3.1; 95% CI, 1.4 -7.2; p = .007) (Fig. 4) .
TextSentencer_T104 15436-15706 Sentence denotes Among controls, the codon 54BB genotype was not significantly associated with ICU mortality (HR adj , 7.4; 95% CI, 0.90-61.3), although the power to determine an association was limited given that there were only three patients with the BB genotype who did develop ARDS.
TextSentencer_T105 15707-16005 Sentence denotes ARDS patients homozygous for the variant codon 54B allele had a nonsignificant trend to greater severity of illness on admission (p = .08) and significantly greater daily multiple organ dysfunction score after development of ARDS even after adjustment for potentially important variables (Fig. 5) .
TextSentencer_T106 16006-16217 Sentence denotes On multivariate analysis, the codon 54BB genotype remained associated with increased mortality compared with ARDS patients who were homozygous for the wild-type A allele (HR adj , 4.0; 95% CI, 1.6-10; p = .003).
TextSentencer_T107 16218-16429 Sentence denotes The 60-day mortality in ARDS did not vary significantly with the MBL-2 polymorphisms at MBLXY, codon 52, or codon 57 (Table 4 ) or when examined together as the variant O allele (HR adj , 1.0; 95% CI, 0.68-1.6).
TextSentencer_T108 16430-16780 Sentence denotes In a study of prospectively enrolled ICU patients with clearly defined ARDS risk factors, we found significant associations between the BB genotype of the MBL-2 codon 54 polymorphism and increased severity of illness on admission, increased development of ARDS, more multiple organ failures after development of ARDS, and increased mortality in ARDS.
TextSentencer_T109 16781-16818 Sentence denotes This study has a number of strengths.
TextSentencer_T110 16819-16960 Sentence denotes The prospective determination of ARDS using the American-European Consensus Conference definition helps minimize phenotype misclassification.
TextSentencer_T111 16961-17031 Sentence denotes In addition, clearly defined at-risk controls were used in this study.
TextSentencer_T112 17032-17169 Sentence denotes Using critically ill controls who have the opportunity to develop the outcome is more clinically relevant than using healthy individuals.
TextSentencer_T113 17170-17370 Sentence denotes Although this may bias the study toward the null, using at-risk controls also reduces the confounding from any possible association between the gene and the risk condition such as sepsis or pneumonia.
TextSentencer_T114 17371-17688 Sentence denotes Several other studies have found the variant O allele (codon 52D, codon 54B, or codon 57C allele) to be associated with infections, systemic inflammatory responses, or other disease states in a codominant (AO and OO vs. AA genotype) (8, 15, 18, 34, 35) or recessive model (OO vs. AO and AA genotype) (11, 10, 9, 36) .
TextSentencer_T115 17689-17801 Sentence denotes We did not find any associations between ARDS and the MBLXY X allele or the variant alleles for codon 52 and 57.
TextSentencer_T116 17802-17952 Sentence denotes However, it is important to note that, given the low variant allele frequency, our power to detect an association for the codon 52 and 57 was limited.
TextSentencer_T117 17953-18018 Sentence denotes Nevertheless, codon 54 may be very significant in the MBL-2 gene.
TextSentencer_T118 18019-18122 Sentence denotes The variant codon 54B allele is more prevalent than codon 52 and codon 57 in the Caucasian populations.
TextSentencer_T119 18123-18364 Sentence denotes Individuals with the codon 54B allele demonstrate even lower MBL protein concentration than individuals with the 52D allele (33) , and what MBL protein is produced was found to be incapable of activating the classic complement pathway (37) .
TextSentencer_T120 18365-18513 Sentence denotes Of the four polymorphisms, codon 54B has been independently found to be associated with increased susceptibility to infection (12, 14, 16, 17, 38) .
TextSentencer_T121 18514-18644 Sentence denotes It is not clear why patients with the codon 54 BB genotype may be at increased risk of developing and dying of ARDS in this study.
TextSentencer_T122 18645-18744 Sentence denotes Homozygotes for the variant MBL-2 alleles have been associated with a low circulating MBL (9, 18) .
TextSentencer_T123 18745-18863 Sentence denotes It is possible that patients with low MBL may be more susceptible to multilobar pneumonia or more severe septic shock.
TextSentencer_T124 18864-18992 Sentence denotes Alternatively, it is possible that MBL may influence the inflammatory response to the initial injury in critical illnesses (7) .
TextSentencer_T125 18993-19196 Sentence denotes MBL has been shown to decrease tumor necrosis factor release (39) and stimulate the production of anti-inflammatory cytokines such as interleukin-10 (40), but MBL modulation of TNF may be dose dependent.
TextSentencer_T126 19197-19297 Sentence denotes At low doses of MBL, increasing MBL concentration increases production of proinflammatory cytokines.
TextSentencer_T127 19298-19389 Sentence denotes But at higher concentrations, increasing MBL suppresses these inflammatory cytokines (41) .
TextSentencer_T128 19390-19636 Sentence denotes It is possible that in critically ill patients with the low or defective MBL-producing genotypes, circulating MBL may not be sufficiently high or effective enough to switch from enhancement to suppression of the proinflammatory cytokine response.
TextSentencer_T129 19637-19791 Sentence denotes Unfortunately, the functional significance of the MBL-2 polymorphisms and the inflammatory response of these patients in this study could not be examined.
TextSentencer_T130 19792-19932 Sentence denotes Additional studies are clearly needed to investigate the possible mechanisms by which MBL-2 genotypes may be important in acute lung injury.
TextSentencer_T131 19933-20078 Sentence denotes Among the controls in this study, the genotype frequency of the codon 54 polymorphism deviated from that predicted by Hardy-Weinberg equilibrium.
TextSentencer_T132 20079-20126 Sentence denotes This is unlikely to be due to genotyping error.
TextSentencer_T133 20127-20217 Sentence denotes The genotype frequencies found here compare well with those reported in other populations.
TextSentencer_T134 20218-20324 Sentence denotes In addition, repeat genotyping in a random subset of patients revealed no discrepancy in genotype results.
TextSentencer_T135 20325-20523 Sentence denotes It is more likely that deviation from Hardy-Weinberg occurred because of a possible association between the codon 54 polymorphism and the underlying condition requiring ICU admission such as sepsis.
TextSentencer_T136 20524-20670 Sentence denotes Indeed, patients in this study who were homozygous for the variant codon 54B allele were more likely to have septic shock on admission to the ICU.
TextSentencer_T137 20671-20836 Sentence denotes The association found between the codon 54 MBL-2 polymorphism and ARDS cannot be attributed to this association between 54B and septic shock, a risk factor for ARDS.
TextSentencer_T138 20837-20984 Sentence denotes The association between the 54BB genotype and ARDS was actually strengthened when the analyses were restricted to those patients with septic shock.
TextSentencer_T139 20985-21155 Sentence denotes Given the low allele frequency for codon 54, only ten patients were homozygous for the variant B allele in the study and no adjustment for multiple comparisons were made.
TextSentencer_T140 21156-21232 Sentence denotes However, the findings in this report are unlikely to be due to type I error.
TextSentencer_T141 21233-21375 Sentence denotes The polymorphism was chosen a priori as a candidate in ARDS based on previous studies supporting its role in infection and critical illnesses.
TextSentencer_T142 21376-21473 Sentence denotes The results are consistent with our hypothesis and with previous reports on infection and sepsis.
TextSentencer_T143 21474-21636 Sentence denotes Additionally, the findings are supported by results of secondary out-comes such as septic shock, severity of illness, and organ failure after development of ARDS.
TextSentencer_T144 21637-21758 Sentence denotes Nevertheless, as is true of all genetic association studies, our findings will need to be confirmed in other populations.
TextSentencer_T145 21759-21808 Sentence denotes We recognize some other limitations to our study.
TextSentencer_T146 21809-21896 Sentence denotes The functional significance of the MBL-2 polymorphisms was not evaluated in this study.
TextSentencer_T147 21897-22101 Sentence denotes Because of the study design, the results may not be generalizable to the community setting, to immunocompromised hosts or patients without risk factors for ARDS, or with different clinical risks for ARDS.
TextSentencer_T148 22102-22296 Sentence denotes In addition, the analyses were restricted to Caucasians, which reduces the possibility of confounding from ethnicity (42) but does not permit extrapolation of the results to other ethnic groups.
TextSentencer_T149 22297-22421 Sentence denotes We report an association between the MBL-2 codon 54 genotype and severity of illness, septic shock, and development of ARDS.
TextSentencer_T150 22422-22527 Sentence denotes The MBL-2 codon 54 genotype may also be associated with multiple organ dysfunction and mortality in ARDS.
TextSentencer_T151 22528-22629 Sentence denotes Additional studies are needed to confirm these findings in other populations with other risk factors.
TextSentencer_T152 22630-22704 Sentence denotes Flow diagram of study design and patient selection for case-control study.
TextSentencer_T153 22705-22773 Sentence denotes ICU, intensive care unit; ARDS, acute respiratory distress syndrome.
TextSentencer_T154 22774-22980 Sentence denotes Acute Physiology and Chronic Health Evaluation (APACHE) III score on admission to the intensive care unit by genotype for the mannose binding lectin-2 codon 54 polymorphism among all 654 cases and controls.
TextSentencer_T155 22981-23160 Sentence denotes The box denotes the interquartile range (25-75%), the horizontal line in the box indicates the median, + designates the mean, and error bars indicate the 95% confidence intervals.
TextSentencer_T156 23161-23306 Sentence denotes The mannose binding lectin-2 codon 54 genotype and the percentage of patients with acute respiratory distress syndrome (ARDS) with each genotype.
TextSentencer_T157 23307-23359 Sentence denotes The p value was calculated from Fisher's exact test.
TextSentencer_T158 23360-23763 Sentence denotes Daily Brussels multiple organ dysfunction score for each day after development of acute respiratory distress syndrome (ARDS) for the 212 patients with ARDS after adjustment for potentially important variables such as age, trauma as a risk factor for ARDS, Acute Physiology and Chronic Health Evaluation III scores, history of treatment with corticosteroids, liver failure, transfusion, and septic shock.
TextSentencer_T159 23764-23935 Sentence denotes Table 1 Study required risk factors for acute respiratory distress on admission to intensive care unit (24) 36 (17) 16 (14) 20 (20) Trauma 40 (9) 9 (4) .04 8 (7) 1 (1) .04
TextSentencer_T160 23936-23976 Sentence denotes Multiple transfusions 51 (12) 26 (12) .8
TextSentencer_T161 23977-23995 Sentence denotes 13 (11) 13 (13) .7
TextSentencer_T162 23996-24024 Sentence denotes Aspiration 34 (8) 24 (11) .1
TextSentencer_T163 24025-24044 Sentence denotes 13 (11) 11 (11) >.9
TextSentencer_T164 24045-24080 Sentence denotes >1 Risk for ARDS 48 (11) 29 (14) .3
TextSentencer_T165 24081-24100 Sentence denotes 16 (14) 13 (13) >.9
TextSentencer_T166 24101-24144 Sentence denotes Direct pulmonary injury b (26) 34 (16) .004
TextSentencer_T167 24145-24163 Sentence denotes 20 (18) 14 (14) .6
TextSentencer_T168 24164-24214 Sentence denotes History of alcohol abuse, n (%) 42 (10) 27 (13) .2
TextSentencer_T169 24215-24234 Sentence denotes 10 (9) 17 (17) . .4
TextSentencer_T170 24235-24281 Sentence denotes History of steroid use, n (%) 37 (8) 20 (9) .7
TextSentencer_T171 24282-24314 Sentence denotes 6 (5) 14 (14) . (25) 37 (38) .05
TextSentencer_T172 24315-24362 Sentence denotes Bilirubin <2.0 mg/dL, n (%) 53 (12) 39 (18) .03
TextSentencer_T173 24363-24382 Sentence denotes 14 (12) 25 (26) .02
TextSentencer_T174 24383-24453 Sentence denotes Hematologic failure (platelets ≤80,000/mm), n (%) 60 (14) 47 (22) .007
TextSentencer_T175 24454-24471 Sentence denotes 20 (18) 27 (28) .
TextSentencer_T176 24473-24491 Sentence denotes 17 (72) 14 (27) .4
TextSentencer_T177 24492-24522 Sentence denotes 10 (11) 18 (16) .1 19 (19) .03