Neonatal intensive care admission for term neonates and subsequent childhood mortality: a retrospective linkage study.

BACKGROUND: Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality. METHODS: A single-center case-control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks' gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period. RESULTS: During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p < 0.001). For all term neonates, the mortality rate was 0.16% (n = 311); 47.9% (n = 149) of those had records of a NICU admission. The mortality rate by time points (ratio1:10,0000 births) related to the age at death during the follow-up period was as follows: 29, up to 7 days; 20, 7-28 days; 37, 28 days to 6 months; 21, 6 months to 1 year; 19, 1-2 years; 9, 2-3 years; 10, 3-4 years; and 27, 4 years and more. Following the exclusion of congenital malformations and chromosomal abnormalities, NICU admission remained the most significant risk factor associated with mortality of the study population, HRs, 364.4 [145.3; 913.3] for mortality in the first 7 days of life; 19.6 [12.1; 32.0] for mortality from 28 days through 6 months of life and remained markedly elevated after age 4 years; HR, 7.1 [3.0; 17.0]. The mortality risk related to the NICU admission event, adjusted for admission diagnoses remained significant; HR = 8.21 [5.43; 12.4]. CONCLUSIONS: NICU admission for term neonates is a pondering event for the risk of long-term childhood mortality. This group of term neonates may benefit from focused health care.

Detection of Global Brain Injury Using Point-of-Care Neonatal MRI Scanner.

BACKGROUND: Conventional magnetic resonance imaging (MRI) neuroimaging of infants is complicated by the need to transport infants outside the neonatal intensive care unit (NICU), often to distant areas of the hospital. PRIMARY OBJECTIVE: The main aim of this study was to evaluate and compare scoring of images from a novel 1T MRI, which enables neuroimaging within the NICU, with those from a conventional MRI. SECONDARY OBJECTIVE: The second aim of this study was to document improved expediency, and thereby greater patient safety, as reflected by decreased transport time. MATERIALS AND METHODS: Thirty premature infants (mean gestational age: 28.8 ± 2.1 weeks) were scanned consecutively on the novel 1T and 1.5T conventional scanners at term-equivalent age. Orthogonal T1- and T2-weighted images were acquired and reviewed. A global brain abnormality score (Kidokoro) was assigned independently to all images by two radiologists. Interrater agreement was evaluated using the kappa statistic and interscanner agreement was evaluated by Bland-Altman analysis. Transport time to and from both scanners was monitored and compared. RESULTS: Weighted kappas were 0.77 (standard error of measurement [SEM] 0.08; confidence interval [CI]: 0.62-0.92) and 0.86 (SEM: 0.07; CI: 0.73-1), for the 1T and 1.5T scanners, respectively, reflecting substantial interrater agreement. Bland-Altman analysis showed excellent agreement between the two scanners.Transport time was 8 ± 6 minutes for the 1T MRI versus 46 ± 21 minutes for the conventional MRI (p < 0.00001). No adverse events were recorded during transport. Standard transport times will vary from institution to institution. CONCLUSION: Kidokoro scores are similar when comparing images obtained from a 1T MRI with those of a conventional 1.5T MRI, reflecting comparable image quality. Transport time was significantly decreased using the 1T neonatal MRI.

Platelet Indices: Universally Available Clinical Adjunct for Diagnosing Necrotizing Enterocolitis.

OBJECTIVE: Platelet function parameters can be predictive of several adult diseases and their severity. However, few studies report on the association between platelet indices and neonatal diseases, specifically necrotizing enterocolitis (NEC). The objective of this study is to investigate whether platelet indices are associated with NEC diagnosis and NEC-related mortality. STUDY DESIGN: We retrospectively examined records from infants admitted to the neonatal intensive care unit with a diagnosis of NEC, verified by the presence of pneumatosis on X-ray or pathology at surgery. We compared them with an age-matched group of prematures without NEC. We investigated platelet count, mean platelet volume (MPV), platelet distribution width and red cell distribution width to platelet ratio (RPR) and delta platelets from birth to the time of NEC diagnosis or day of life 14 in the control group. RESULTS: Sixty-nine infants with NEC and 78 control infants were studied. Basic sociodemographic data were similar in both groups. All platelet parameters measured-except for MPV-were significantly associated with NEC diagnosis. Although MPV was not associated with the diagnosis of NEC (p = 0.800), it was significantly associated with NEC-related mortality (p < 0.001). Only total platelet count and RPR were significantly associated with both NEC diagnosis (p < 0.0001) and mortality (p = 0.04 and 0.01, respectively). On multivariable analysis only the change in platelet count from birth to time of diagnosis remained significant. CONCLUSION: While not definitive, this study demonstrates that these routinely available, inexpensive, and easily calculated platelet indices can provide a clinical adjunct in the often-elusive attempts to definitively diagnose NEC in preterm neonates. KEY POINTS: · Platelet indices were associated with NEC diagnosis.. · MPV was predictive of NEC-related mortality.. · Delta platelet count from birth was significantly related to NEC diagnosis..

Mildly Elevated Bilirubin Levels are Associated with Increased Magnetic Resonance Imaging Signal Intensity in the Basal Ganglia of Preterm Neonates.

OBJECTIVE: This study aimed to test whether mildly elevated bilirubin levels in preterm infants are associated with increased signal intensity (SI) on magnetic resonance imaging (MRI) of the basal ganglia (BG). STUDY DESIGN: MRI was performed at term equivalent age in 55 postpreterm infants using a neonatal MRI 1-T scanner. SI of the BG was correlated with mild hyperbilirubinemia. RESULTS: BG MRI SI was significantly increased in infants with mild hyperbilirubinemia on T1-weighted image (T1; p = 0.0393) and T2-weighted image (T2; p = 0.0309). We found no effect of gestational age or sepsis on BG MRI intensity; however, there was a significant effect of acidosis on T1 (p = 0.0223) but not on T2 (p = 0.2316). Infants with combined hyperbilirubinemia and acidosis had the most significant increase in SI on both T1 and T2 respectively (p = 0.0072 and 0.0195, respectively). CONCLUSION: We found a positive association between increased BG MRI SI and mildly elevated bilirubin levels. The effect was greatly strengthened when hyperbilirubinemia was associated with acidosis. KEY POINTS: · Excessive bilirubin is neurotoxic to the neonatal brain. It is deposited in the BG.. · BG MRI SI is increased with bilirubin deposition.. · The premature brain is more vulnerable to bilirubin associated MRI changes..

Hypercapnia: An Added Culprit in Gray Matter Injury in Preterm Neonates.

Over the last decade, there has been increased recognition of diverse forms of primary gray matter injury (GMI) in postpreterm neonates. In this study, we aimed to assess whether early neonatal hypercapnia in the preterm infant was associated with GMI on magnetic resonance imaging (MRI) at term equivalent age (TEA). All blood gases taken during the first 2 weeks of life were analyzed for hypercapnia. MRI was performed at TEA postpreterm infants using a unique neonatal MRI 1T scanner. The neonatal MRI scans were assessed using a standardized scoring system, the Kidokoro scoring system, a method used to assess abnormal brain metrics and the presence and severity of brain abnormalities. Subscores are assigned for different regions of the brain. Twenty-nine infants were studied, about half of whom had evidence of some gray matter abnormality. Fifteen of the infants were hypercapnic. The hypercapnic infants had significantly higher deep gray matter abnormality readings as compared with the nonhypercapnic infants (12 [11; 12] vs. 10 [8; 11], respectively; p = 0.0106). Correlations were observed between peak pCO2 over the first 2 weeks of life and the overall gray matter abnormality score (GMAS) at TEA, and between the percentage of hypercapnic blood gases during the first 2 weeks of life and the GMAS. All of the infants in our population who had severe GMI at TEA were hypercapnic in the first 2 weeks of life. In conclusion, our data show a correlation between early hypercapnia in preterm neonates and GMI at TEA.

Dual Therapy vs. Monotherapy for the Patent Ductus Arteriosus: A Systematic Review.

To evaluate the efficacy of dual patent ductus arteriosus (PDA) pharmacotherapy compared to monotherapy we searched Medline, Embase, Cochrane Library, and references of relevant articles through October 20, 2021 for randomized clinical trials (RCTs) and cohort studies comparing dual PDA treatment vs. monotherapy. Data were analyzed using a fixed effects model. The fixed effects model assumes that all studies included in a meta-analysis are estimating a single true underlying effect, that of ductal closure. Primary outcome was ductal closure; secondary outcome was surgical ligation. Of 170 articles retrieved, three cohort studies and two RCTs were included, totaling 470 patients: 384 babies received monotherapy and 86 dual therapy. Because of the small numbers, RCTs and cohort studies were pooled for analysis. Ductus closed in 67% of those who received combination compared with 58% those with monotherapy. Overall fixed effect shows an OR of 1.97 [1.10; 3.53; p = 0.023] favoring dual therapy. Dual pharmacologic treatment appears more effective than monotherapy. Future well-powered, high-quality, prospective RCTs are needed to further investigate this potential approach.

Neonatal Polycythemia and Hypoglycemia in Newborns: Are They Related?

OBJECTIVE: This study aimed to test whether neonatal hypoglycemia (NH) is more common in infants with neonatal polycythemia (NP). STUDY DESIGN: This is a retrospective study based on universal screening of NH and targeted screening for NP. Polycythemia was defined as venous hematocrit ≥ 65%. NH was defined as whole blood glucose (BG) concentration < 48 mg/dL (measured using a "point-of-care" analyzer [Accu-Chek]). RESULTS: The study population consisted of 119 consecutive term polycythemic infants and 117 controls. There were no significant differences between the two groups in perinatal characteristics, minimal BG concentration, and rate of hypoglycemia. In a stepwise backward multiple regression where NH was the dependent variable, only maternal gestational diabetes mellitus (p = 0.032) and toxemia (p = 0.001) remained significant, whereas NP was insignificant. CONCLUSION: NH is not more common in NP infants than in non-NP infants. We suggest that the occurrence of NH in infants with NP might be related to the common risk factors of the two morbidities.

The Saga of Pulse Oximetry Screening for Critical Congenital Heart Disease in Israel: A Historical Perspective.

BACKGROUND: Many countries have adopted a mandatory routine pulse oximetry screening of newborn infants to identify babies with otherwise asymptomatic critical congenital heart disease (CCHD). OBJECTIVES: To describe the current status of pulse oximetry CCHD screening in Israel, with a special emphasis on the experience of the Shaare Zedek Medical Center. METHODS: We review the difficulties of the Israeli Medical system with adopting the SaO2 screening, and the preliminary results of the screening at the Shaare Zedek Medical Center, both in terms of protocol compliance and CCHD detection. RESULTS: Large scale protocol cannot be implemented in one day, and regular quality assessment programs must take place in order to improve protocol compliance and identify the reasons for protocol failures. CONCLUSIONS: Quality control reviews should be conducted soon after implementation of the screening to allow for prompt diagnosis and quick resolution.

Elevated Nucleated Red Blood Cells in Neonates with Down Syndrome and Pulmonary Hypertension.

We report an association between higher absolute nucleated red blood cells and mean corpuscular volume and idiopathic persistent pulmonary hypertension of the newborn in neonates with Down syndrome. Elevation of these blood indicies should prompt echocardiographic studies to monitor pulmonary arterial pressures.

Normal Point of Care Glucose Values after Birth in the Well-Baby Nursery.

OBJECTIVE: Normal initial blood glucose values in healthy newborns are not well defined and are subject to controversy. Despite substantive research, there is no single initial value of glucose that can be used with certainty of safety in newborns, and thus various protocols and cutoffs have been proposed. STUDY DESIGN: We sought to characterize the normal values of blood glucose levels in a large cohort of neonates admitted to the well-baby nursery in Shaare Zedek Medical Center. The blood glucose levels were measured with a point of care (POC) glucometer (Accu-Chek Performa) within 180 minutes after birth. RESULTS: The study population included 3,912 newborns with a mean birth weight of 3,322 ± 439 g and a mean gestational age of 39.4 ± 1.3 weeks. Sampling was performed at a median age of 73 minutes (interquartile range [IQR], 55-92 minutes). Median glucose concentration was 58 (IQR, 51-67) mg/dL, and first, third, and fifth percentiles were 34, 39, and 41 mg/dL, respectively. CONCLUSION: Our data describe the normal range of POC blood glucose levels in healthy neonates on admission to the nursery. Extreme low levels were rare.

Wide Pulse Pressure Is Not Associated with Patent Ductus Arteriosus in the First Week of Life.

OBJECTIVES: Widened pulse pressure is generally associated with patent ductus arteriosus (PDA). Surprisingly, this is often not true for preterm infants during the first week of life when systolic and diastolic pressures are both reduced and pulse pressure may remain unchanged. STUDY DESIGN: This is a retrospective, observational review of individual blood pressure (BP) parameters preterm neonates <30 weeks' gestational age during the first week of life as correlated with ductal patency and severity. RESULTS: Sixteen preterm neonates had a closed ductus on initial echocardiogram during the first week of life; 30 had a PDA that was open but hemodynamically insignificant; and 16 were found to have a hemodynamically significant PDA. Pulse pressure showed no correlation (p = 0.266) with the degree of ductal patency, whereas diastolic BP was best correlated with ductal severity (p < 0.001). CONCLUSION: We found that low diastolic pressures are better correlated with ductal patency and severity than is pulse pressure in preterm neonates during the first week of life.

SMOFlipid Protects Preterm Neonates against Perinatal Nutrition-Associated Cholestasis.

OBJECTIVE: Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC. STUDY DESIGN: This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid. RESULTS: Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1-4.3) as compared with period 1; p = 0.018; NNT-14. CONCLUSION: SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.

Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

BACKGROUND: Neonatal asphyxia is often associated with hepatic injury. We hypothesized that this might lead to increased bilirubin concentrations. STUDY DESIGN: Term neonates admitted between January 2015 and April 2017 who remained hospitalized for ≥ 4 days and who had serial serum bilirubin concentrations recorded were divided into those with neonatal encephalopathy (NE) and controls. Serial serum bilirubin concentrations during the first days of life were compared between groups. RESULTS: Twenty-nine neonates with NE and 84 age-matched controls were identified. Mean total serum bilirubin concentrations of NE babies were significantly lower than those controls throughout the first days of life. At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for the control group. All of the NE babies remained below the 40th percentile of the Bhutani curve and none required phototherapy. CONCLUSION: Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant.

Pulse Oximetry with Two Infrared Wavelengths without Calibration in Extracted Arterial Blood.

Oxygen saturation in arterial blood (SaO2) provides information about the performance of the respiratory system. Non-invasive measurement of SaO2 by commercial pulse oximeters (SpO2) make use of photoplethysmographic pulses in the red and infrared regions and utilizes the different spectra of light absorption by oxygenated and de-oxygenated hemoglobin. Because light scattering and optical path-lengths differ between the two wavelengths, commercial pulse oximeters require empirical calibration which is based on SaO2 measurement in extracted arterial blood. They are still prone to error, because the path-lengths difference between the two wavelengths varies among different subjects. We have developed modified pulse oximetry, which makes use of two nearby infrared wavelengths that have relatively similar scattering constants and path-lengths and does not require an invasive calibration step. In measurements performed on adults during breath holding, the two-infrared pulse oximeter and a commercial pulse oximeter showed similar changes in SpO2. The two pulse oximeters showed similar accuracy when compared to SaO2 measurement in extracted arterial blood (the gold standard) performed in intensive care units on newborns and children with an arterial line. Errors in SpO2 because of variability in path-lengths difference between the two wavelengths are expected to be smaller in the two-infrared pulse oximeter.

Thiopurine S-methyltransferase (TPMT) activity is better determined by biochemical assay versus genotyping in the Jewish population.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is a key enzyme that deactivates thiopurines, into their inactive metabolite, 6-methylmercaptopurine. Intermediate and low TPMT activity may lead to leukopenia following thiopurine treatment. The aim of this study was to determine TPMT activity and TPMT alleles (genotype-phenotype correlation) in Jews, aiming to develop an evidence-based pharmacogenetic assay for this population. METHODS: TPMT activity was determined in 228 Jewish volunteers by high performance liquid chromatography. Common allelic variants in the Caucasian population [TPMT*2 (G238C), TPMT *3A (G460A and A719G), TPMT* 3B (G460A) and TPMT*3C (A719G)] were tested. Phenotype-genotype correlation was examined and discordant cases were fully sequenced to identify novel genetic variants. RESULTS: Mean TPMT activity was 15.4 ± 4 U/ml red blood cells (range 1-34). Intermediate activity was found in 33/228 (14%) subjects and absent activity was found in one sample (0.4%). Only eight individuals (3.5% of the entire cohort and 24% of those with intermediate/low activity) were identified as carriers of a TPMT genetic variant, all of whom had the TPMT*3A allele. Sequencing the entire TPMT coding region and splice junctions in the remainder of the discordant cases did not reveal any novel variants. CONCLUSION: Genotyping TPMT in Jews yields a much lower rate of variants than identified in the general Caucasian population. We conclude that a biochemical assay to determine TPMT enzymatic activity should be performed in Jews before starting thiopurine treatment in order to identify low activity subjects.

Scalloping is a reliable endoscopic marker for celiac disease.

BACKGROUND: Scalloping of duodenal folds noted on esophagogastroduodenoscopy (EGD) has been associated with various illnesses including celiac disease (CD). The aim of the present study was to examine the frequency of scalloping in pediatric patients undergoing EGD and to assess its significance in the diagnosis of CD. We also evaluated the association of scalloping with the histopathology and celiac serology in the subgroup of celiac patients. PATIENTS AND METHODS: All children (0-18 years) who underwent EGD at Shaare Zedek Medical Center for any reason during a 2.5-year period were retrospectively included, yielding a consecutive cohort without selection bias. Relevant data were obtained from the patient files. RESULTS: During the study period, 623 children underwent EGD of whom 149 (24%) were eventually diagnosed with CD. In 74/623children (12%), scalloping was seen and had a sensitivity of 48% (95% CI 0.40-0.57), specificity of 99% (0.98-0.99) and positive predictive value of 97% (0.9-0.99) to diagnose CD. The prevalence of scalloping increased with advancing stage of the Marsh classification from 33% (7/21) in Marsh 1 to 63% (34/54) in Marsh 3c (P < 0.001). Scalloping was associated with a significantly higher median tissue transglutaminase level (153 [IQR 98-168] versus 49 [IQR 11-143]; P = 0.011). CONCLUSION: The results suggest that the diagnosis of CD is almost certain if isolated scalloping is observed during EGD done to rule out CD. Thus, attention to this finding may serve as an additional tool in the diagnosis of CD.

Kernicterus on the Spectrum.

Kernicterus is the potential toxic sequela of extreme neonatal hyperbilirubinemia resulting from the passage of excess free, unconjugated bilirubin across the blood-brain barrier, irreversibly and selectively damaging vulnerable target brain cells including the basal ganglia, the cerebellum, and the auditory system. Kernicterus continues to plague the modern world. Not only does it continue to be uncontrolled in developing countries with underdeveloped medical systems, and health organizations rendered ineffective by the ravages of war, but it also remains prevalent in industrialized countries. In this review, we attempt to clarify the different and overlapping nomenclature used in the past to describe this entity and aim to offer a uniform approach to defining kernicterus spectrum disorder. We also discuss the different spectrum subtypes including motor-predominant kernicterus, auditory neural sensory dysfunction, subtle kernicterus, and kernicterus plus. In addition to reviewing several genetic factors that increase the risk of developing kernicterus, we also present some exciting potential therapeutic approaches.

Effect of maternal age on neonatal outcomes in very low birth weight singleton infants: a population-based study.

BACKGROUND: Little is known on the impact of maternal age (MA) on very low birth weight (VLBW) infants' outcomes. We tested the hypothesis that at both ends of MA there are increased adverse neonatal outcomes in VLBW infants. METHODS: We used the Israel National Neonatal Network VLBW (≤1500 g) database. Maternal age was stratified as: <20, 20-24, 25-34 (reference group), 35-39 and ≥40 years. Statistical analyses were univariate and multivariable logistic regression analysis. RESULTS: After adjustment, the infant outcomes of older mothers were similar to those of the reference group for mortality, RDS, severe ROP, NEC and sepsis. Mothers < 20 and 20-24 years old had higher odds of IVH grades 3-4 (OR 1.45, 95% CI 1.09-1.93 and OR 1.26, 95% CI 1.10-1.45, respectively), and BPD (OR 1.55, 95% CI 1.13-2.13 and OR 1.40, 95% CI 1.22-1.62, respectively). There were higher odds for PVL in infants of <20 year-old mothers (OR 1.83, 95% CI 1.26-2.65) and in infants of 35-39 year-old mothers (OR 1.38, 95% CI 1.12-1.69). Poor composite outcomes were significantly higher in the youngest maternal age categories (<20-year-old mothers (OR 1.63, 95% CI 1.28-2.08), and 20-24-year-old (OR 1.28, 95% CI 1.15-1.43). CONCLUSIONS: Neonatal outcomes differ in relation to maternal age among very low birth weight newborns, with adverse outcomes more predominant in infants of younger mothers.

Single nucleotide polymorphisms that increase expression of the guanosine triphosphatase RAC1 are associated with ulcerative colitis.

BACKGROUND & AIMS: RAC1 is a guanosine triphosphatase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases are associated with dysregulation of immune defenses. We studied the role of RAC1 in inflammatory bowel diseases using human genetic and functional studies and animal models of colitis. METHODS: We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 messenger RNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulfate sodium. RESULTS: We observed a genetic association between RAC1 with ulcerative colitis in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the single nucleotide polymorphisms rs10951982 (P(combined UC) = 3.3 × 10(-8), odds ratio = 1.43 [95% confidence interval: 1.26-1.63]) and rs4720672 (P(combined UC) = 4.7 × 10(-6), odds ratio = 1.36 [95% confidence interval: 1.19-1.58]). Patients with inflammatory bowel disease who had the rs10951982 risk allele had increased expression of RAC1 compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected against dextran sulfate sodium-induced colitis. CONCLUSIONS: Human studies and knockout mice demonstrated a role for the guanosine triphosphatase RAC1 in the development of ulcerative colitis; increased expression of RAC1 was associated with susceptibility to colitis.