ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

Microsatellite-primed PCR and random primer amplification polymorphic DNA for the identification and epidemiology of dermatophytes.

This study demonstrates the capacity of the one-step polymerase chain reaction (PCR) fingerprinting method using the microsatellite primers (GACA)4 or (GTG)5 (MSP-PCR) to identify six of the most frequent dermatophyte species causing cutaneous mycosis. PCR with (GACA)4 was a suitable method to recognise Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton interdigitale among 82 Argentinian clinical isolates, producing the most simple and reproducible band profiles. In contrast, the identification of Trichophyton mentagrophytes and Trichophyton tonsurans was achieved using PCR with (GTG)5. In this way, the sequential application of PCR using (GACA)4 and (GTG)5 allowed the successful typification of clinical isolates which had not been determined by mycological standard techniques. In this work, the intraspecies variability among 33 clinical isolates of M. canis was detected using random amplification of polymorphic DNA (RAPD-PCR) with the primers OPI-07 and OPK-20. The genetic variations in the isolates of M. canis were not associated with clinical features of lesions or pet ownership, but a geographical restriction of one genotype was determined with OPK-20, suggesting a clonal diversity related to different ecological niches in certain geographical areas. The results of this work demonstrate that the detection of intraspecies polymorphisms in M. canis by RAPD-PCR may be applied in future molecular epidemiological studies to identify endemic strains, the route of infection in an outbreak or the coexistence of different strains in a single infection.

Sterile water moisturizer of the skin of extremely low birth weight infants.

OBJECTIVE: To assess the feasibility of sterile water application to the skin of the extremely low birth weight (ELBW) newborns in the first week of life and examine its effects on their skin integrity and outcomes. DESIGN: Pilot randomized controlled trial. SETTING: Open-bay, 18 bed Level III NICU in the Eastern United States. PARTICIPANTS: Twenty-eight ELBW neonates. Two newborns expired, sixteen newborns remained in the intervention group and twelve newborns in the control group. METHODS: ELBW neonates were either assigned to receive frequent sterile water wash to skin or not during care for the first week of life. Using the Neonatal Skin Condition Scale (NSCS), assessments were performed twice a day during the first week. Fluid intake, serum electrolytes, culture proven sepsis and other morbidities, and length of stay (LOS) were compared while controlling for confounding variables using multiple regression analysis. RESULTS: There was no difference in the demographic or clinical characteristics between both groups. Sterile water wash application to skin was not associated with differences in skin health indices or fluid intake. However, it was associated with higher median sodium level and with early regression of bilirubin level when compared to controls. CONCLUSION: Frequent skin washes with sterile water are feasible and safe. However, they may not be associated with improved skin integrity or fluid intake.

Interobserver Reliability of an MR Imaging Scoring System in Infants with Hypoxic-Ischemic Encephalopathy.

BACKGROUND AND PURPOSE: MR imaging has a key role in predicting neurodevelopmental outcomes following neonatal hypoxic-ischemic encephalopathy (HIE). A novel MR imaging scoring system for hypoxic-ischemic brain injury was used in our patient population with the aim of assessing interobserver variability and developing subcategories for the severity of brain injury. MATERIALS AND METHODS: We evaluated brain MR images of 252 infants who underwent hypothermia for HIE between 2014 and 2019. First, 40 infants were selected randomly to test interobserver variability. Discrepancies were identified during the assessment of the first 20 MR images. The remaining 20 MR images were scored after adjusting the scoring system. Second, we determined cutoff values for the severity of injury that were based on the percentiles of the total scores in the full cohort. RESULTS: The interobserver reliability showed excellent agreement for the total score both before (intraclass correlation coefficient = 0.96; 95% CI 0.89-0.99) and after the adjustment (intraclass correlation coefficient = 0.96; 95% CI, 0.89-0.98). The average of the differences and the agreement interval between the 2 readers decreased after the adjustment. Subcategories of brain injury were the following: We considered a total score of ≤4 (≤75%) as normal, 5-10 (76%-90%) as mild, 11-15 (91%-95%) as moderate, and >15 (>95%) as severe brain injury. The agreement on the classification of brain injury improved in the second epoch (weighted κ = 0.723 versus 0.887). CONCLUSIONS: The adjusted scoring system may lead to a higher degree of interrater agreement. The presented cutoff values may be used to determine the severity of brain injury in future clinical studies including infants with mild hypoxia-ischemia.

Bedside and laboratory neuromonitoring in neonatal encephalopathy.

Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome. Simultaneous use of these monitoring modalities may improve our ability to provide meaningful prognostic information regarding ongoing treatments. Evidence will be summarized in this review for each of these modalities, by describing (1) the methods, (2) the clinical evidence in context of NE both before and with hypothermia, and (3) the research and future directions.

Early exit from neonatal therapeutic hypothermia: A single institution experience using MRI to guide decision-making.

BACKGROUND: To evaluate the feasibility of a protocol using combined magnetic resonance imaging (MRI), clinical data, and electroencephalogram (EEG) to identify neonates with mild neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH) who are eligible for "early exit". METHODS: Retrospective chart review of TH cases at a single Level III NICU over a 5-year period was used to describe the demographic, clinical, and outcome data in neonates that received early exit in contrast to 72 hour TH treatment. RESULTS: Two hundred and eight TH cases, including 18 early exit cases (9%) and 9 cases (4%) evaluated for early exit with MRI but continued on 72 hours of TH, were identified. Early exit and 72 hour treatment groups did not differ in demographics or cord gas measures, although early exit neonates had a shorter length of stay (p < 0.05). Consistent with the early exit protocol, no early exit infants had evidence of moderate or severe encephalopathy on EEG or evidence of hypoxic ischemic injury on MRI at 24 hours of life. Neurology follow up between age 1 and 18 months was available for 10 early exit infants, 8 of whom had a normal examination. CONCLUSIONS: Early MRI at 24 hours of age, alongside clinical and EEG criteria, is feasible as part of a protocol to identify neonates eligible for early exit from therapeutic hypothermia.

[Bortezomib-induced acute neutrophilic dermatosis]. / Dermatose neutrophilique aiguë induite par le bortezomib.

INTRODUCTION: Bortezomid is a potent proteasome inhibitor used in patients with relapsing or refractory multiple myeloma and provides a 35% response with a median duration of response of 12 months. Numerous adverse effects are known, mainly comprising haematological and neurological complications. A wide variety of cutaneous complications have also been described in 10 to 20% of patients. CASE REPORT: We report a case of bortezomib-induced Sweet syndrome. The diagnostic criteria required for drug-induced Sweet syndrome were present. DISCUSSION: The importance of this description is that this induced Sweet syndrome may not necessarily require cessation of bortezomid since administration of corticosteroids prevents its recurrence.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis.

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.

Factores asociados a mayor sobrevida en pacientes con cáncer de páncreas tratados mediante pancreatoduodenectomía. Estudio de casos y controles

Introducción: El cáncer de páncreas (CP) tiene un pronóstico ominoso a pesar de los avances en técnica quirúrgica y en los cuidados peri/postoperatorios. Nuestro objetivo fue identificar factores asociados a mayor sobrevida en pacientes con CP tratados mediante pancreatoduodenectomía (PD). Material y Método: Estudio de casos y controles de pacientes con CP tratados mediante PD en el Hospital Clínico de la Universidad Católica entre 2002-2015. Se definió como caso al paciente con sobrevida ≥ 3 años y como control a aquel con sobrevida inferior a ese plazo. Se comparó entre casos y controles datos biodemográficos, clínicos, histopatológicos, de morbilidad y mortalidad mediante regresión logística. Resultados: Se analizaron 70 pacientes, con una edad media de 62 ± 11 años; 40 (57%) mujeres. Hubo morbilidad en 26 enfermos (37,1%); Clavien-Dindo ≥ Illa en 8 (11,4%). La mediana (rango) de días de hospitalización fue 12 (7-84). La sobrevida actuarial a 1, 3 y 5 años fue 77%, 32% y 22% respectivamente. Se identificaron 21 casos (30%) y 49 controles (70%). En el análisis univariable, la resección R0, los ganglios regionales negativos, la ausencia de infiltración perineural, los estadios más precoces (IA, IB y IIA) y la ausencia de diabetes mellitus (DM2) al momento del diagnóstico, fueron variables asociadas a sobrevida ≥ 3 años (p 100 U/mL) y los tratamientos complementarios no se asociaron a diferencias significativas en sobrevida. En el análisis multivariable, se identificó la ausencia de DM2 (OR ajustado: 12; IC95% 1,7-84,3), la ausencia de infiltración perineural (OR ajustado: 7; IC95% 1,3-36,3) y los estadios precoces IA, IB y IIA (OR ajustado: 10,3; IC95% 2,1-49,1) como los factores independientes asociados a sobrevida mayor a 3 años. Conclusión: Los pacientes no diabéticos, con etapas precoces del CP sin infiltración perineural, resecados R0 mediante PD pueden obtener una sobrevida mayor a 3 años.

Introduction: Pancreatic cancer (PC) remains one of the most lethal malignancies, despite developments in surgical and non-surgical therapies. Significant improvements in long-term survival have not been achieved. Only radical surgical resection has obtained a moderate extension in survival. We aim to identify factors associated with longer survival in patients with PC treated by pancreatoduodenectomy (PD). Material and Method: We designed a case-control study of patients with PC treated by PD in our center between 2002-2015. We compare patients who survived ≥ 3 years (case) with those not achieving it (control). Bio-demographic, clinical, histopathological, morbidity and mortality data were compared between cases and controls using logistic regression. Results: Seventy patients were analyzed; mean age 62 ± 11 years; 40 (57%) women. Morbidity was found in 26 patients (37.1%); Clavien-Dindo ≥ Illa in 8 (11.4%). The median (range) of hospitalization days was 12 (7-84). The actuarial 1, 3, and 5 years survival was 77%, 32%, and 22%, respectively, for the entire series. Twenty-one cases (30%), and 49 controls (70%) were identified. In the univariate analysis, R0 resection, negative regional lymph nodes, the absence of perineural infiltration, the earliest stages (IA, IB, and IIA) and the absence of diabetes mellitus (DM) at time of diagnosis were variables associated with survival ≥ 3 years (p 100 U / mL), and neo/adjuvant treatments, did not significantly show differences in survival. In the multivariate analysis, no DM at diagnosis (adjusted OR: 12; 95% CI 1.7 - 84.3), no perineural infiltration (adjusted OR: 7; 95% CI 1.3 - 36.3) and early stages IA, IB, and IIA (adjusted OR: 10.3; 95% CI 2.1 - 49.1) were identified as independent factors associated with survival > 3 years. Conclusion: Nondiabetic patients with early stages PC without perineural infiltration, resected R0 by PD can achieve survival over 3 years.

[Effectiveness of a health network in secondary prevention among coronary patients]. / Efficacité d'un réseau pour la prévention secondaire chez les patients coronariens.

OBJECTIVE: To improve the secondary prevention, particularly hypertension management among coronary patients. METHODS: In 2004-2005, out of 175 coronary patients having taken part in a cycle of the Educoeur center of the health network Rivarance, 131 (75%) aged between 32-79 years of age (an average of 61 years with 11% women, 52% hypertensive, 24% smokers, 10% diabetics and 72% with unbalanced dyslipidemia (LDL>1g/l)) were re-examined within 12 months and were compared with a French cohort of the EuroAspire II study (365 patients - Lancet 2001). 56% were treated by angioplasty, 24% by coronary bypass and 20% by medical treatment. The 4-week ambulatory educational program consisted of a physical education with 22 meetings of cardiac rehabilitation (ergo cycle, carpet, segmentary muscular work, steps and balneotherapy) and a therapeutic and dietetic education (18 courses and cooking workshops, supermarket visits and self BP measurement). These 131 patients were re-examined 3, 6 and 12 months after by the paramedical team. The GP and nurses were taught recommendations on CV risk factors management. The patients were followed by a computerized medical file. BP (average of 3 measurements by OMRON M4), total cholesterol (CT), weight, physical activity (insufficient if less than 3 walks of 30 min per week), smoking and drugs intake were analyzed on J0 then at one year and were compared with the French results of EuroAspire II. [table: see text] CONCLUSION: The education and the follow-up of the patient in a network of health improve CV risk factors and particularly hypertension management of these coronary patients but this decreases with time.

[Control of cardiovascular risk factors in coronary patients one year after cardiac rehabilitation]. / Contrôle des facteurs de risque chez les patients coronariens un an après une réadaptation cardiaque.

OBJECTIVE: To assess risk factors monitoring in coronary patients one year after cardiac rehabilitation. METHOD: From 2015 to 2015, cardiac morbidity, total mortality and risk factors data were collected from a 4-week ambulatory cardiac rehabilitation program with a control one year later and were compared with the results of Euroaspire and Reach studies. RESULTS: Out of 1091 (87%) coronary patients, 746 (68%) were re-examined 12months later (aged 60years (ranging from 20 to 85years), 15% women, 44% hypertensive, 36% smokers, 17% diabetics, 74% with dyslipidemia). At the end of the program, management of CV risk factors was improved (BP ≤ 140/90mmHg and BMI > 30: 80 and 20% vs 65 and 25% at the beginning of the program; LDL < 0.7g/L: 42% and smoking: 4% vs 18% when hospitalized for their cardiac event). Unfortunately, this benefit decreased significantly at one year (BP ≤ 140/90mmHg: 63%, LDL < 0.7g/L: 27%; smoking: 6%) but it remains better than in Euroaspire IV study: 57, 20 et 16% respectively). While 54% had insufficient physical activity before cardiac rehabilitation, they were only 23% at 1-year vs 60% in Euroaspire study. We reported a total mortality of 0.6% vs 2.9% in Reach study and 12% cardiac hospitalization (53% for a new coronary event). CONCLUSION: Participation of coronary patients in a cardiac rehabilitation program significantly improves management of CV risk factors, morbidity and mortality. However, the control obtained at the end of the program decreases at one year.

Patent ductus arteriosus in premature infants: to treat or not to treat?

OBJECTIVE: Closing patent ductus arteriosus (PDA) is a widely accepted approach in the management of very low birth weight (VLBW) infants. Our objective is to test the hypothesis that conservative management (no treatment) of PDA will not affect survival without chronic lung diseases (CLD). STUDY DESIGN: This retrospective study utilizes a prospectively collected database to compare two cohorts of VLBW infants. Infants in the first group (2001 to 2009) had their PDA treated with pharmacological and if necessary with surgical ligation. PDA in the second group (2010 to 2014) was not treated with medical or surgical intervention. The primary outcome was survival without oxygen requirement at 36 weeks. Pulmonary and non-pulmonary morbidities were also compared. Logistic regression analyses were performed to control for confounders. RESULTS: This study included 643 VLBW infants, of them 415 infants in the Treat group and 228 in the No-Treat group. The rate of survival without CLD did not differ between Treat and No-Treat groups (78.4% vs 83.9%, respectively; adjusted odds ratio (aOR)=1.72, confidence interval (CI): 0.92 to 3.23, P=0.09). Mortality declined in No-Treat group (15.2% vs 10.5%, aOR=0.51, CI: 0.25 to 0.99, P=0.049), but the two groups did not differ in the incidence of CLD among survivors (5.8% vs 5.0%,=P0.47). Pulmonary complications and non-pulmonary morbidities did not differ between groups. CONCLUSIONS: Conservative management (no treatment) of PDA may not compromise survival without CLD and is not associated with increased morbidities in VLBW infants. Prospective physiological studies are needed to determine the sector of VLBW infants, if any, who could benefit from PDA treatment.

Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.

[What are the etiological medical therapies in amyotrophic lateral sclerosis?]. / Quelles sont les thérapeutiques médicamenteuses étiologiques?

The increasing knowledge about Amyotrophic Lateral sclerosis (ALS) led to the development of the first and only available treatment: riluzole. The efficacy of this drug has been demonstrated in two controlled clinical trials. The data showed that riluzole increases the rates of survival in patients suffering from ALS. This increase was about 25 percent over a period of 12 months of treatment. Since its marketing, the clinical efficacy of riluzole was confirmed in several epidemiological studies. Tested initially because of its anti-glutamates qualities, the exact mechanisms of action responsible for the efficacy of Riluzole in ALS remains unknown. Furthermore, despite a strong rational based on important literature, several other anti-glutamates drugs failed to demonstrate efficacy in ALS, nor did numerous anti-oxydant, neurotrophics, immunomodulators, and favoring mitochondrial metabolism drugs. Despite the low rate of patients showing an increase of liver enzymes, a strict control of liver functions is necessary with a treatment by riluzole. its dose should be increased gradually in case of important fatigue, a change of the general state, or respiratory incapacity. Because of the neuroprotectrives qualities of riluzole, early neuronal death in ALS, the difficulty to confirm early the diagnosis, and the evident interest to treat in the first stage, the treatment of the suspected forms of the disease becomes justifiable. The perspectives of treatment of ALS will depend on our capacity to understand better the physiopathology, the reasons of failures in the past, and to develop new biomarkers. They will depend also on our capacity to include in clinical trials and to follow up over a long time, an important number of patients. Different new methods, as the cellular therapy are in development, and represent a real hope for the future.

Ex-vivo liver perfusion for organ preservation: Recent advances in the field.

Liver transplantation is the optimal treatment for end-stage liver disease but is limited by the severe shortage of donor organs. This shortage has prompted increased utilization of marginal grafts from DCD and extended criteria donors, which poorly tolerate cold storage in comparison to standard criteria grafts. Ex-vivo liver perfusion (EVLP) technology has emerged as a potential alternative to cold storage for organ preservation, but there is no consensus regarding the optimal temperature or conditions for EVLP. Herein, we review recent advances in both pre-clinical and clinical studies, organized by perfusion temperature (hypothermic, subnormothermic, normothermic).

Maternal juvenile rheumatoid arthritis may be associated with preterm birth but not poor fetal growth.

OBJECTIVE: Adverse pregnancy outcomes in mothers with juvenile rheumatoid arthritis (JRA) are not known. The objective of this study was to examine the risk of preterm birth and restricted fetal growth in pregnant mothers diagnosed with JRA, and to examine the impact of race/ethnicity and maternal age on this association. STUDY DESIGN: Hospital discharge records for mothers who gave birth in 2011 and 2012 were examined in the National Inpatient Sample (NIS) database. JRA, preterm birth (<37 weeks of gestation), birth weight that is small for gestational age (SGA) and other demographic and clinical variables were identified using ICD-9 (International Classification of Disease--9th revision) diagnostic codes. The associations of JRA with preterm birth and restricted fetal growth were examined controlling for confounding variables. RESULT: The sample included 8,273,987 birthing mothers, of these 1236 (0.01%) had JRA. The prevalence of preterm birth and SGA was 6.08% and 2.34%, respectively. Preterm birth in mothers with JRA was 12.9% compared with 6.1% in mothers without JRA with an adjusted odds ratio (OR) of 2.1 (confidence interval (CI): 1.74 to 2.42, P<0.001). The incidence of SGA in infants born to mothers with JRA was 3.34% compared with 2.34% in non-JRA mothers, which was not statistically significant. Adjusted OR for preterm birth in association with JRA among White mothers was 1.78 (CI: 1.41 to 2.24, P<0.001). However, Hispanic mothers with JRA (12%) were the ethnicity to suffer the most from preterm birth with an adjusted OR of 4.43 (CI: 2.97 to 6.62, P<0.001). Preterm birth among advanced maternal age (AMA) mothers with JRA was 25% compared with 7% in those without JRA with an adjusted OR of 5.42 (CI: 3.51 to 8.35, P<0.001). CONCLUSION: JRA is associated with preterm birth but not with SGA. This association is significantly influenced by race/ethnicity and maternal age. More studies are needed to examine these findings in relation to medications used, severity of the disease and exacerbation during pregnancy to understand the genetic/socioeconomic factors behind these racial/ethnic differences.

EEG maturation and stability of cerebral oxygen extraction in very low birth weight infants.

OBJECTIVE: Fractional cerebral tissue oxygen extraction (FTOE) can be continuously monitored by simultaneous near-infrared spectroscopy (NIRS) and pulse oximetry. The objective of this study is to test the hypothesis that in very low birth weight (VLBW) infants, the more mature EEG activity is, the less variable FTOE is. STUDY DESIGN: A prospective study was conducted on VLBW infants (< 1500 g and ⩽ 34 weeks gestation) without significant brain injury. Simultaneous continuous two-channel electroencephalography (EEG), NIRS and pulse oximetry were recorded. Absolute and relative powers of EEG in the delta, theta, alpha, beta and total frequency bands have been calculated. FTOE variability was calculated on two scales: short scales (3 to 20 s) and long scales (20 to 150 s). FTOE variability was examined against changes in relative spectral power of different EEG bands. RESULT: We evaluated 67 studies performed on 46 VLBW infants. Average study duration was 21.3 ± 5.5 h. Relative power of delta band positively correlated with FTOE short- and long-scale variability (r=0.45, P<0.001; r=0.44, P<0.001, respectively). Relative power of alpha bands negatively correlated with FTOE short- and long-scale variability (r=-0.38, P=0.002; r=-0.42, P<0.001, respectively). These correlations continued to be significant when controlling for sex, small for gestational age, postmenstrual age, being on respiratory support, hemoglobin concentration, systemic oxygen saturation and transcutaneous carbon dioxide tension. CONCLUSION: Increased maturation of EEG activity is associated with decreased variability in cerebral oxygen extraction. The implications of increased variability in FTOE on brain injury in premature infants need further exploration.

rHuEpo before high-dose therapy allows autologous peripheral stem-cell transplantation without red blood cell transfusion: a pilot study.

To decrease red blood cell (RBC) transfusion requirements during high-dose therapy (HDT) for hematological malignancies, we conducted a pilot study to assess the effect of recombinant human erythropoietin (rHuEpo) given during chemotherapy before HDT and autologous peripheral stem-cell transplantation (APSCT). The transfusion histories of 15 HDT and APSCT for hematological disease performed in 11 consecutive patients who received rHuEpo (10 000 U subcutaneously three times/week) were compared to those of 22 HDT and ASCT performed in 17 consecutive historical controls matched for hematological parameters. rHuEpo increased the hemoglobin (Hb) level from 10.3+/-2.3 g/dl at diagnosis to 12.9+/-2.2 g/dl at the time of HDT in 11 patients; no major adverse effects occurred. Compared to historical controls (95%, 21/22), RBC transfusion requirements were significantly lower for rHuEpo recipients (26%, 4/15) (P=0.00001) and rHuEpo responders (15%, 2/13) (P=0.000002). After HDT and APSCT, fewer RBC transfusions were needed: 3.3, 1.2 and 0.3 RBC units for controls, rHuEpo recipients and rHuEpo responders, respectively (P=0.006 and 0.00002). Therefore, rHuEpo should be administered before, and not after HDT and APSCT, to lower RBC transfusion requirements after HDT and APSCT.