Single Course Of Dexamethasone Research Articles

Effects of dexamethasone on short-term and long-term outcomes in late preterm infants with twin pregnancy: an observational study

Objective: To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy. Methods: A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared. Results: (1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups (H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant (P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age (OR=0.884, 95%CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I (OR=2.967, 95%CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion: Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.

Effect of dexamethasone on newborn survival at different administration-to-birth intervals: A secondary analysis of the WHO ACTION (Antenatal CorticosTeroids for Improving Outcomes in Preterm Newborn)-I trial.

The WHO ACTION-I trial demonstrated that dexamethasone significantly reduced neonatal mortality when administered to women at risk of early preterm birth in low-resource countries. We conducted a secondary analysis to determine how these benefits can be optimised, by evaluating the effect of dexamethasone compared to placebo on newborn mortality and severe respiratory distress outcomes at different administration-to-birth intervals, and identifying the interval with the greatest benefits. The WHO ACTION-I trial was a multi-country, individually-randomised, parallel-group, double-blind, placebo-controlled trial. It was conducted in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. Women with a viable singleton or multiple pregnancy who presented to participating hospitals at a gestational age of 26 weeks 0 days-33 weeks 6 days and who were at risk of imminent preterm birth were eligible. In this secondary analysis, 2638 women and their newborns treated with single course of dexamethasone or placebo were analysed. Multivariate logistic regression was used to assess the effect of dexamethasone versus placebo on neonatal death, stillbirth or neonatal death, and severe respiratory distress at 24h and at 168h, by administration-to-birth interval (from 0 through 28 days), adjusting for gestational age at first dose. We used relative risks to identify the administration-to-birth interval with the greatest benefits of dexamethasone compared to placebo on the newborn outcomes. Between 24 December 2017 and 21 November 2019, 2852 women and their 3070 babies were enrolled in the WHO ACTION-I trial; 1332 women (1464 babies) in the dexamethasone group and 1306 women (1440 babies) in the placebo group were included in this secondary analysis. Neonatal mortality risk was lower with increasing time between initiating dexamethasone and birth, achieving peak mortality reduction by days 13 and 14 and then diminishing as the interval approached 28 days, regardless of gestational age at administration. For other outcomes, the overall pattern of risk reduction extending into the second week was consistent with that of neonatal death. In women at risk of preterm birth prior to 34 weeks' gestation, the neonatal benefits of antenatal dexamethasone appear to increase with longer administration-to-birth intervals than previously thought. This knowledge can support clinical assessment and estimation of the risks of adverse preterm newborn outcomes at the time of birth, and the potential benefits of antenatal dexamethasone treatment for a known administration-to-birth interval. Bill and Melinda Gates Foundation; World Health Organization.

Effects of a single course versus repeated courses of antenatal corticosteroids on fetal growth, placental morphometry and the differential regulation of vascular endothelial growth factor.

To investigate the impact of antenatal exposure to a single course or repeated courses of dexamethasone (DEX) on neonatal anthropometrics, placental morphometry and potential effect on maternal plasma levels and placental expression of vascular endothelial growth factor (VEGF). Pregnant women between 27 and 32 weeks of gestation who delivered between 28 and 40 weeks and received a single course (n = 38) or repeated courses (n = 33) of DEX were compared to gestational age-matched controls (n = 30). Maternal blood samples were obtained, and placental biopsy was taken. Area percent of VEGF immunostaining and villous capillarization index were evaluated using image analysis. Infants exposed to repeated courses of DEX were significantly associated with decreased birthweight, body length, head circumference and placental weight compared with controls (P = 0.011, P < 0.001, P = 0.004, P < 0.001, respectively) and with the group that received a single course of DEX (P = 0.021, P = 0.020, P = 0.049, P = 0.010, respectively). There was a significant decrease in maternal VEGF plasma levels and percentage of VEGF immunostained area after repeated courses of DEX compared with controls (P < 0.001 and P = 0.001, respectively) or a single course (P = 0.028 and P = 0.002, respectively). Notably, repeated courses of DEX impaired normal increase in villous capillarization index compared with controls or a single course (P = 0.001 and P = 0.041, respectively). Repeated antenatal courses of DEX compromised fetal and placental growth compared with a single course of DEX, and these effects were potentially mediated by altered maternal plasma levels and placental expression of VEGF with consequent decrease in placental vascularization. Because of continuing uncertainties, several key messages for clinicians are provided.

Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults

AbstractImmune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ≥30 × 109/L platelets. Four patients relapsed. Complete response at 6 months (platelets ≥100 × 109/L) was achieved in 50% of patients and response at 6 months (platelets ≥30 <100 × 109/L) was achieved in another 25%; relapse-free survival was 66.7% at 12 months (median response duration of 8.3 months). In conclusion, eltrombopag/dexamethasone is a feasible frontline therapy for ITP. This trial is registered at www.clinicaltrials.gov as NCT01652599.

Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months

To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants. Preterm infants born ≤32 weeks gestational age were recruited during 2001-2004 from a single neonatal intensive care unit. Resting salivary cortisol was collected at least once at 3, 8 and 18 months corrected age in a longitudinal cohort. A mixed-effects repeated measures analysis was used to accommodate cases with less than complete follow-up. One hundred and thirty three infants were included in the present study, contributing 266 cortisol samples. Of these, 107 infants had been exposed to a single course of antenatal dexamethasone and 26 not exposed to antenatal steroids. There was no significant main effect of antenatal steroids on resting cortisol at any age. This result was not altered after adjusting for gestational age at birth, neonatal cumulative pain, morphine exposure, mechanical ventilation days and post-natal steroid exposure. No effect of a single course of dexamethasone on resting salivary cortisol, an indicator of hypothalamic-pituitary-adrenal axis function, was found in infancy up to 18 months corrected age in infants born very preterm.

Standard Dose Rituximab Plus 2–4 Cycles of Pulse Dexamethasone Is Effective and Tolerable in Treatment of Immune Thrombocytopenia (ITP)

Abstract 1166▪▪This icon denotes a clinically relevant abstract Background:70–80% of patients with ITP respond to initial corticosteroid-based treatment, but almost all experience recurrent thrombocytopenia requiring further therapy. Rituximab is effective in inducing responses in about 50% of patients with ITP, but most do not experience sustained remission. Strategies to improve the efficacy of rituximab would be of value. Cheng and colleagues have shown that a single 4 day course of dexamethasone is effective in newly diagnosed ITP, and GIMEMA demonstrated that multiple courses are even more efficacious. Zaja and colleagues reported that the combination of rituximab with a single course of dexamethasone is superior to dexamethasone alone in previously untreated patients. Given the activity of these two drugs, patients at Weill Cornell Medical College (WCMC) with ITP have been treated with a combination of standard rituximab and 2–4 cycles of pulse dexamethasone (R+Dex) given at 2 week intervals. We preliminarily reported results of 14 patients treated with this combination; we have expanded this cohort to 34 patients to obtain a broader evaluation of efficacy and safety of this therapeutic approach in ITP. Methods:Patients who had received rituximab concurrently with multiple courses of pulse dexamethasone were retrospectively identified. Response was initially assessed at 8 weeks after initiation of therapy. Complete remission (CR) was defined as platelet count greater than or equal to 100×109/L, and partial remission (PR) as platelet count of 50–100×109/L. Variables were compared either by chi-square or fisher exact test including duration of ITP at greater or less than one year, age of patients, prior therapy, and lymphocyte subsets. The study was approved by the WCMC Institutional Review Board. Results:Thirty-four ITP patients received concurrent rituximab and pulse dexamethasone. All patients were treated for platelet count less than 30 or inability to discontinue chronic therapy such as corticosteroids or thrombopoietin receptor agonist. Median age was 21 years (range 2–63 years), and median time since diagnosis of ITP was 12 months (range 1–180 months). All patients but one had previously been treated, with median of 2 prior therapies (range 0–7). Thirty-two of 34 patients received 4 infusions of standard dose rituximab (the other 2 received 2 and 3 infusions). All patients received between one and 4 cycles of dexamethasone, with most (22/34) receiving 3 cycles. Twenty-four patients responded at 8 weeks from start of therapy or later (71% ORR). Best response was CR in 20 patients (59%) and PR in 4 (12%). Two responding patients relapsed to no response at 3 and 6 months, and 3 additional patients relapsed from CR but maintained PR at last follow up. At median follow up of 8 months, 22 patients (65%) remain in response: CR in 47% and PR in 18%. None of the variables tested was predictive of response; there was a trend toward increased response rate in adults (p=0.13). Adverse events related to R+Dex were mostly mild, with most common toxicities including fatigue, headache, infusion-related events, and gastrointestinal upset. Dexamethasone was often poorly tolerated. One patient experienced colitis requiring hospitalization. That patient and one other interrupted therapy for AE’s. Conclusion:Rituximab plus multiple courses of dexamethasone is active with manageable toxicity in patients with ITP. This regimen merits further exploration in a prospective trial. Disclosures:Elstrom:Genentech: Speakers Bureau. Off Label Use: Rituximab is approved for use in NHL, CLL and RA. Bussel:Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding.

Long Term Follow up Analysis Following Front Line Therapy with Dexamethasone or Dexamethasone Plus Rituximab in Adults with Primary Immune Thrombocytopenia.

Abstract 2415Poster Board II-392We previously reported that in adults with primary immune thrombocytopenia (ITP) the addition of four weekly administrations of rituximab 375 mg/m2 to a single course of dexamethasone (40 mg daily for four days) improves the rate of sustained response (SR, i.e. platelet count 3 50 × 109/L at month 6 from the beginning of treatment) if compared with dexamethasone alone (63% vs 36%, P= 0.004, 95% C.I.: [0.079-0.455]) (ML18542 study, Zaja et al. Blood 2008; 112:Abstract 1). Moreover, the rate of SR in 27 patients receiving dexamethasone plus rituximab salvage therapy because of primary refractoriness or relapse after dexamethasone monotherapy was 56%. In order to better address the impact of therapy beyond month 6, a subsequent observational follow-up study up which lasted from month 6 up to month 36 was planned. Participating centers were asked to continue to monitor the patients enrolled in the ML18542 study at least every 4 months up to the end of year 3 from accrual, documenting the occurrence of delayed side effects, the response status and the need for further treatment. We considered as efficacy parameters the duration of response (RD), i.e. the interval between achievement of SR and relapse, the relapse rate (number of patients who lost their SR status) and the need of further specific anti ITP therapy after month 6 (TFS). Eighty out of the original 101 patients enrolled in the ML18542 study, 15 treated with the dexamethasone monotherapy arm, 41 with the dexamethasone plus rituximab arm and 24 who received dexamethasone plus rituximab salvage therapy, were systematically followed-up beyond month 6 for a median overall period of observation of 20 months (range: 4-40 months). Twenty-one patients could not be valuable, most of them because lost at follow up during the study period. As far as the safety profile, we documented one single case of Herpes Zoster reactivation at month 22 in a patient initially allocated to the dexamethasone arm who further received dexamethasone plus rituximab salvage therapy. No other infectious, delayed toxic events or deaths were registered. Fifty-three out 80 patients who achieved a SR according to the study protocol could be evaluated for long term efficacy. This group included 13 patients from the dexamethasone monotherapy arm who were observed after month 6 for a median period of 20 months (range: 12-28 months), 26 of dexamethasone plus rituximab arm observed for a median period of 24 months (range: 8-40 months), and 14 from the dexamethasone plus rituximab salvage therapy group observed for a median period of 20 months (range: 12-34). The rate of relapse in the three groups was 23% (3/13), 23% (6/26), and 14% (2/14) respectively (Fisher test, P= 0.824). The 30 months estimated probability of RD within each of the three treatment groups was 77%, 71%, and 85% (Log-rank test, P= 0.755), respectively. The time of SR loss was comprised between month 4 and 30 in the dexamethasone monotherapy arm, month 4 and 40 in the experimental arm, and month 8 and 34 in the salvage therapy arm. In these three groups, the use of further specific anti ITP therapy after month 6 was registered in 33%, 29% and 36% of patients (Fisher test, P= 1), respectively. Overall, in this period of observation 4 out 80 (5%) valuable patients underwent splenectomy. In conclusion the results of this study indicate: i) similar and very low pattern of long term toxicity between ITP patients treated either with single course of dexamethasone or dexamethasone plus rituximab; ii) no significant differences in the relapse rate, RD and TFS among patients who achieved SR after dexamethasone monotherapy or dexamethasone plus rituximab, either front line or salvage therapy, suggesting that relapse rate may be a possible surrogate of SR, rather than of the initial therapeutic choice. Disclosures:Zaja:Roche: Honoraria, Research Funding, financial support for the costs of travel to the ASH annual meeting. Off Label Use: Rituximab in ITP.

Maternal glucocorticoid exposure alters tight junction protein expression in the brain of fetal sheep

We examined the expression of tight junction (TJ) proteins in the cerebral cortex, cerebellum, and spinal cord of fetuses after maternal treatment with single and multiple courses of dexamethasone. Ewes received either single courses of four 6-mg dexamethasone or placebo injections every 12 h for 48 h between 104 and 107 days or the same treatment once a week between 76-78 and 104-107 days of gestation. TJ protein expression was determined by Western immunoblot analysis on tissue harvested at 105-108 days of gestation. Blood-brain barrier permeability has been previously quantified with the blood-to-brain transfer constant (K(i)) with alpha-aminoisobutyric acid (39). After a single course of dexamethasone, claudin-5 increased (P < 0.05) in the cerebral cortex, occludin and claudin-1 increased in the cerebellum, and occludin increased in the spinal cord. After multiple dexamethasone courses, occludin and zonula occludens (ZO)-1 increased in the cerebral cortex, and occludin and claudin-1 increased in the cerebellum. Junctional adhesion molecule-A and ZO-2 expressions did not change. Linear regression comparing K(i) to TJ proteins showed inverse correlations with claudin-1 and claudin-5 in the cerebral cortex after a single course and ZO-2 in the spinal cord after multiple courses and direct correlations with ZO-1 in the cerebellum and spinal cord after multiple courses. We conclude that maternal glucocorticoid treatment increases the expression of specific TJ proteins in vivo, patterns of TJ protein expression vary after exposure to single and multiple glucocorticoid courses, and decreases in blood-brain barrier permeability are associated with increases in claudin-1, claudin-5, and ZO-2 expression and decreases in ZO-1 expression. In utero glucocorticoid exposure alters the molecular composition of the barrier and affects fetal blood-brain barrier function.

The effects of antenatal corticosteroids and surfactant replacement on neonatal respiratory distress syndrome.

The goal of this study was to determine the effects of antenatal corticosteroids and surfactant replacement on the severity and frequency of Respiratory Distress Syndrome (RDS) in a cohort of premature infants born in Sarajevo, Bosnia and Herzegovina, from 2005 to 2007. The cohort consisted of 172 premature neonates with estimated gestational age between 26 and 34 weeks. Babies with IUGR, babies of diabetic mothers and babies with major congenital defects were excluded. Out of 172 neonates, 80 were treated antenatally with corticosteroids (single course of dexamethasone) and 92/172 were not. There was no statistical difference (p>0,5) in average gestational age (31,2 vs. 31,0 GW) and male/female ratio between investigated groups; there were significantly more male patients (p<0,05) in both groups. Frequency of RDS was significantly lower in the corticosteroid group (24/80) in relation to the control group (54/92) (p<0,001). Severe RDS was significantly (p<0,01) more frequent in the control group 34/53 (62,96%) then in the corticosteroid group 6/24 (25,0%). Bovine surfactant (Survanta) was given as a rescue therapy to 78 babies with clinical and radiological signs of RDS who required FiO2>0,40 and mechanical ventilation. Early surfactant administration within six hours after birth appeared to be effective at reducing mortality then later surfactant administration (p<0,005). In the group of babies requiring FiO2> or =0,6 at the time of surfactant replacement, the mortality rate was significantly higher (p<0,05). In conclusion, we confirm the efficacy of antenatal corticosteroid treatment and early surfactant treatment in a cohort of premature infants born in Sarajevo.

Single and multiple courses of antenatal steroids regulate connexin 36 abundance in the ovine fetal brain

Connexin 36 (Cx 36) forms gap junctions (GJ). GJ facilitate intercellular communication and are important in neuronal differentiation during development. Cx 36 is the main GJ between neurons, increases during rodent development and is up regulated by dexamethasone (DEX) in pancreatic islets. The effects of steroids on GJ proteins have not been examined in fetal brain. We examined the effects of single and multiple courses of DEX on Cx 36 abundance in the cerebral cortex (CC), cerebellum (CL) and cervical spinal cord (SP), and differences in Cx 36 protein abundance among fetal brain regions. Ovine fetuses at 70% of gestation were examined after a single course of four 6 mg DEX or placebo (PL) injections were given every 12 h for 48 h to the ewes, or the same DEX or PL given course once a wk for 5 wks. Regional brain tissue was frozen after the last DEX or PL dose. Cx 36 protein expression was determined by Western immunoblot. A single course of DEX increased (P &lt; 0.05) Cx 36 protein abundance compared with PL in the CC and SP, and multiple courses increased Cx 36 in SP, but not in CC or CL. Cx 36 was higher in SP than CL. Maternal DEX treatment regulates Cx 36 proteins in vivo in the fetal CC and SP, but not in CL. Different DEX regimens regulate Cx 36 protein abundance in specific brain regions. The greater abundance of Cx 36 protein in SP than CL may suggest the presence of more functional channels in SP in the premature fetal brain.

Na+,K+-ATPase Activity and Subunit Isoform Protein Abundance: Effects of Antenatal Glucocorticoids in the Frontal Cerebral Cortex and Renal Cortex of Ovine Fetuses

We examined the effects of single and multiple maternal glucocorticoid courses on cerebral cortical (CC) and renal cortical (RC) Na(+),K(+)-ATPase activity and protein isoform abundance in fetal sheep. Ewes received four dexamethasone or placebo injections in the single course (SC) groups, and the same treatment once a week for five-weeks in the multiple course (MC) groups. CC Na(+),K(+)-ATPase a(2)-abundance was higher (P<0.05) and beta(2)-abundance lower in the SC dexamethasone than placebo group, but Na(+),K(+)-ATPase activity did not change. CC Na(+),K(+)-ATPase activity, a(1)-, beta(1) -, and beta(2)-abundance were lower in the MC dexamethasone than placebo group, but a(2)- and a(3)-abundance did not change. Both dexamethasone courses did not affect CC cell number. RC Na(+),K(+)-ATPase activity, a(1)- and beta(1) -abundance were higher in the MC dexamethasone than placebo group, but did not change in the SC dexamethasone group. We conclude MC, but not a SC of dexamethasone, affect fetal cerebral and renal Na(+),K(+)-ATPase, and MC result in differential effects on Na(+),K(+)-ATPase in these organs.

Effects of maternal antenatal glucocorticoid treatment on apoptosis in the ovine fetal cerebral cortex

We examined the effects of single and multiple maternal glucocorticoid courses on apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single dexamethasone or placebo courses at 104-106 or 133-135 days or multiple courses between 76-78 and 104-106 days gestation. In the single-course groups, ewes received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr. Multiple-course groups received the same treatment once per week for 5 weeks. Neuronal and nonneuronal apoptotic cell numbers per square millimeter were determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01) nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were 40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at 70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after multiple dexamethasone than placebo courses, but apoptotic cell number did not differ. We conclude that nonneuronal apoptosis represents the major form of apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal cells decreases with maturity and after a single course of dexamethasone at 70%, but not at 90%, gestation and not after multiple courses at 70% gestation. We speculate that a single course of glucocorticoids exerts maturational changes on the rate of apoptosis in the cerebral cortex of preterm ovine fetuses.

A Prospective Randomized Study of Rituximab and Dexamethasone vs Dexamethasone Alone in ITP.

Previous uncontrolled studies have highlighted the potential activity of Rituximab in patients with idiopathic thrombocytopenic purpura (ITP) relapsed or refractory to standard treatments. To better address this effect, a prospective randomized, multicenter, phase III study comparing treatment with Dexamethasone alone (arm A) vs Dexamethasone plus Rituximab (arm B) was started in July 2005 for adult patients with ITP according to the ASH guidelines. Main inclusion criteria were: age ≥ 18 years, untreated ITP, platelet (PLT) count ≤ 20 x109/L, HIV- HCV-HbsAg negativity, informed consent. Patients randomized to arm A received a single course of Dexamethasone 40 mg po on days +1, +2, +3, +4, while patients randomized to arm B received Dexamethasone (as in arm A) in association with Rituximab 375 mg/m2 iv on days +7, +14, +21, +28. Patients in arm A who failed to achieve a sustained response (SR) could be rescued with arm B treatment. The primary objective of the study was to compare SR, i.e. PLT ≥ 50 x 109/L at month + 6 of treatment. The secondary objectives were: the initial overall (OR= PLT ≥ 50 x109/L) and complete response (CR= PLT ≥ 100 x 109/L) by day 30 after starting treatment, respectively; the toxic profile. The statistical plan considered three interim analyses, after the first 50, 100 and 150 enrolled patients, with an estimated sample size of 198 patients (99 per arm). Table 1 summarizes the main demographic data and the results of efficacy and toxicity according to an intention to treat analysis of the first interim analysis. The toxic profile was characterized by only grade 3 adverse events (AE); no patient died during the study period. 16 patients of arm A were rescued with arm B. For this group SR was 81% and no patient experienced SAE or ≥ grade 3 AE. In accordance with the initial statistical plan of the study, which stated that patients' recruitment would ceased if a ≥ 50% difference in sustained response was demonstrated, enrolment has been stopped in June 2007 with a total number of 103 randomized patients. This preliminary report indicates a significantly higher SR for arm B of treatment with no difference in toxicity profile. A final report will be prepared when the results on the entire study group will be available.Table 1TherapyArm AArm BStatisticsPatients2426Male/female11/1310/16p = NSAge (median ± SD)54.54 ± 18.7848.65 ± 15.10p = NSInitial OR15 (62.5%)18 (69%)p = NSInitial CR10 (42%)16 (61%)p = NSSR7 (29%)21 (81%)p = 0.0001SAE or grade 3 AE3 (12.5%)2 (8%)p = NS

Maternal steroid enhancement of fetal rabbit gastrointestinal motility

The purpose of the present study was to determine the potential maturational effects of maternal dexamethasone administration on fetal upper gastrointestinal motility. Nineteen pregnant rabbits were randomized into two groups (DEX and CONT) and studied on either day 24, 27 or 30 of pregnancy (term 31 days). The DEX group received intramuscular dexamethasone (DEX) 2 days before study and the controls received saline. Under ultrasound guidance, a needle was percutaneously inserted into each fetal stomach and fluorescein, labeled with color-coded microspheres, was injected. Two hours later, the length of fluorescein travel throughout the small intestine was measured. The percent motility was calculated by dividing the length of fluorescein travel by the total fetal small intestinal length x 100%. All maternal and fetal rabbits survived. On day 24 the length of fluorescein travel and the percent motility of the DEX group were significantly longer than controls. There were no differences on either day 27 or 30. Fetal growth was significantly suppressed by a single course of DEX at all gestational ages. Fetal rabbit gastrointestinal motility is significantly increased after prenatal steroids are given early in the last trimester (day 24 of a 31-day gestation). Although beneficial in end-organ maturation, the timing of prenatal steroid administration is crucial to minimize its potential detrimental effects on fetal somatic growth.