Sparrow Hospital

Human herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. iMCD accounts for one third to one half of all cases of MCD and can occur in individuals of any age. Accurate diagnosis is challenging, because no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders. An international working group comprising 34 pediatric and adult pathology and clinical experts in iMCD and related disorders from 8 countries, including 2 physicians that are also iMCD patients, was convened to establish iMCD diagnostic criteria. The working group reviewed data from 244 cases, met twice, and refined criteria over 15 months (June 2015 to September 2016). The proposed consensus criteria require both Major Criteria (characteristic lymph node histopathology and multicentric lymphadenopathy), at least 2 of 11 Minor Criteria with at least 1 laboratory abnormality, and exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. Characteristic histopathologic features may include a constellation of regressed or hyperplastic germinal centers, follicular dendritic cell prominence, hypervascularization, and polytypic plasmacytosis. Laboratory and clinical Minor Criteria include elevated C-reactive protein or erythrocyte sedimentation rate, anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, renal dysfunction or proteinuria, polyclonal hypergammaglobulinemia, constitutional symptoms, hepatosplenomegaly, effusions or edema, eruptive cherry hemangiomatosis or violaceous papules, and lymphocytic interstitial pneumonitis. iMCD consensus diagnostic criteria will facilitate consistent diagnosis, appropriate treatment, and collaborative research.

BACKGROUND: Cardiac pacemakers are limited by device-related complications, notably infection and problems related to pacemaker leads. We studied a miniaturized, fully self-contained leadless pacemaker that is nonsurgically implanted in the right ventricle with the use of a catheter. METHODS: In this multicenter study, we implanted an active-fixation leadless cardiac pacemaker in patients who required permanent single-chamber ventricular pacing. The primary efficacy end point was both an acceptable pacing threshold (≤2.0 V at 0.4 msec) and an acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 months. The primary safety end point was freedom from device-related serious adverse events through 6 months. In this ongoing study, the prespecified analysis of the primary end points was performed on data from the first 300 patients who completed 6 months of follow-up (primary cohort). The rates of the efficacy end point and safety end point were compared with performance goals (based on historical data) of 85% and 86%, respectively. Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the total cohort). RESULTS: The leadless pacemaker was successfully implanted in 504 of the 526 patients in the total cohort (95.8%). The intention-to-treat primary efficacy end point was met in 270 of the 300 patients in the primary cohort (90.0%; 95% confidence interval [CI], 86.0 to 93.2, P=0.007), and the primary safety end point was met in 280 of the 300 patients (93.3%; 95% CI, 89.9 to 95.9; P<0.001). At 6 months, device-related serious adverse events were observed in 6.7% of the patients; events included device dislodgement with percutaneous retrieval (in 1.7%), cardiac perforation (in 1.3%), and pacing-threshold elevation requiring percutaneous retrieval and device replacement (in 1.3%). CONCLUSIONS: The leadless cardiac pacemaker met prespecified pacing and sensing requirements in the large majority of patients. Device-related serious adverse events occurred in approximately 1 in 15 patients. (Funded by St. Jude Medical; LEADLESS II ClinicalTrials.gov number, NCT02030418.).

AIMS: Atrial tachyarrhythmias (ATs) detected by implanted devices are often atrial fibrillation or flutter (AF) associated with stroke. We hypothesized that introduction and termination of anticoagulation based upon AT monitoring would reduce both stroke and bleeding. METHODS AND RESULTS: We randomized 2718 patients with dual-chamber and biventricular defibrillators to start and stop anticoagulation based on remote rhythm monitoring vs. usual office-based follow-up with anticoagulation determined by standard clinical criteria. The primary analysis compared the composite endpoint of stroke, systemic embolism, and major bleeding with the two strategies. The trial was stopped after 2 years median follow-up based on futility of finding a difference in primary endpoints between groups. A total of 945 patients (34.8%) developed AT, 264 meeting study anticoagulation criteria. Adjudicated atrial electrograms confirmed AF in 91%; median time to initiate anticoagulation was 3 vs. 54 days in the intervention and control groups, respectively (P < 0.001). Primary events (2.4 vs. 2.3 per 100 patient-years) did not differ between groups (HR 1.06; 95% CI 0.75-1.51; P = 0.732). Major bleeding occurred at 1.6 vs. 1.2 per 100 patient-years (HR 1.39; 95% CI 0.89-2.17; P = 0.145). In patients with AT, thromboembolism rates were 1.0 vs. 1.6 per 100 patient-years (relative risk -35.3%; 95% CI -70.8 to 35.3%; P = 0.251). Although AT burden was associated with thromboembolism, there was no temporal relationship between AT and stroke. CONCLUSION: In patients with implanted defibrillators, the strategy of early initiation and interruption of anticoagulation based on remotely detected AT did not prevent thromboembolism and bleeding. CLINICAL TRIAL REGISTRATION: IMPACT ClinicalTrials.gov identifier: NCT00559988 ( http://clinicaltrials.gov/ct2/show/NCT00559988?term=NCT00559988&rank=1 ).

The purpose of the Society of Anesthesia and Sleep Medicine guideline on preoperative screening and assessment of adult patients with obstructive sleep apnea (OSA) is to present recommendations based on the available clinical evidence on the topic where possible. As very few well-performed randomized studies in this field of perioperative care are available, most of the recommendations were developed by experts in the field through consensus processes involving utilization of evidence grading to indicate the level of evidence upon which recommendations were based. This guideline may not be appropriate for all clinical situations and all patients. The decision whether to follow these recommendations must be made by a responsible physician on an individual basis. Protocols should be developed by individual institutions taking into account the patients' conditions, extent of interventions and available resources. This practice guideline is not intended to define standards of care or represent absolute requirements for patient care. The adherence to these guidelines cannot in any way guarantee successful outcomes and is rather meant to help individuals and institutions formulate plans to better deal with the challenges posed by perioperative patients with OSA. These recommendations reflect the current state of knowledge and its interpretation by a group of experts in the field at the time of publication. While these guidelines will be periodically updated, new information that becomes available between updates should be taken into account. Deviations in practice from guidelines may be justifiable and such deviations should not be interpreted as a basis for claims of negligence.

OBJECTIVES: To summarize the literature on mortality rates and prevalences of major neurodevelopmental disabilities and to examine trends of these outcomes over time in extremely premature neonates. DATA SOURCES: MEDLINE was used to search the English literature for studies published since 1970 reporting on both mortality and disability in infants born at or before 26 weeks' gestation (extremely immature [EI] cohort), with a birth weight of 800 g or less (extremely small [ES] cohort), or subgroups of these. STUDY SELECTION: Studies were included in the analysis if all of the following were reported: mortality; direct examination of 75% or more of the survivors; and the proportion of patients with at least 1 of the following disabilities: cerebral palsy, mental retardation, blindness, and deafness. Studies reporting cohorts included as a subset of cohorts in another study were excluded. Forty-two studies providing mortality and disability data for 20 cohorts of 4116 EI infants and 38 cohorts of 4345 ES infants born after 1972 met the inclusion criteria. DATA EXTRACTION: Data were abstracted from all studies that met these criteria by two of us (J.M.L. and D.E.W.), independently; the data were then cross-checked to ensure accuracy. RESULTS: Survival averaged 41% for EI infants and 30% for ES infants, and it increased significantly with time. In contrast to mortality, the prevalences of major neurodevelopmental disabilities among survivors have not changed over time. The most common major disability was mental retardation, found in 14% of EI and ES survivors. Cerebral palsy was found in 12% of EI survivors and 8% of ES survivors, blindness was found in 8% of EI and ES survivors, and deafness was found in 3% of EI and ES survivors. Overall, 22% of EI survivors and 24% of ES survivors were classified as having at least 1 major disability. Each 100 EI or ES livebirths yielded 7 children with major disabilities; this prevalence was correlated with survival across cohorts. CONCLUSIONS: The prevalence of disabilities had not changed among EI or ES survivors with increasing survival. However, increasing survival of these infants has resulted in a steadily increasing prevalence of children with disabilities.

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients.

BACKGROUND: The intestinal microbiome represents a complex network of microbes that are important for human health and preventing pathogen invasion. Studies that examine differences in intestinal microbial communities across individuals with and without enteric infections are useful for identifying microbes that support or impede intestinal health. RESULTS: 16S rRNA gene sequencing was conducted on stool DNA from patients with enteric infections (n = 200) and 75 healthy family members to identify differences in intestinal community composition. Stools from 13 patients were also examined post-infection to better understand how intestinal communities recover. Patient communities had lower species richness, evenness, and diversity versus uninfected communities, while principle coordinate analysis demonstrated close clustering of uninfected communities, but not the patient communities, irrespective of age, gender, and race. Differences in community composition between patients and family members were mostly due to variation in the abundance of phyla Proteobacteria, Bacteroidetes, and Firmicutes. Patient communities had significantly more Proteobacteria representing genus Escherichia relative to uninfected communities, which were dominated by Bacteroides. Intestinal communities from patients with bloody diarrhea clustered together in the neighbor-joining phylogeny, while communities from 13 patients' post-infection had a significant increase in Bacteroidetes and Firmicutes and clustered together with uninfected communities. CONCLUSIONS: These data demonstrate that the intestinal communities in patients with enteric bacterial infections get altered in similar ways. Furthermore, preventing an increase in Escherichia abundance may be an important consideration for future prevention strategies.

BACKGROUND: A placental microbiome, which may be altered in gestational diabetes mellitus (GDM), has been described. However, publications raising doubts about the existence of a placental microbiome that is different than contaminants in DNA extraction kits and reagents ("kitomes") have emerged. The aims of this study were to confirm the existence of a placental microbiome distinct from contaminants and determine if it is altered in GDM mothers. RESULTS: We first enrolled normal weight, obese and GDM mothers (N = 17) at term elective cesarean section delivery in a pilot case control study. Bacterial DNA was extracted from placental parenchyma, maternal and cord blood, maternal vaginal-rectal swabs, and positive and negative controls with the standard Qiagen/MoBio Power Soil kit. Placentas had significantly higher copies of bacterial 16S rRNA genes than negative controls, but the placental microbiome was similar in all three groups and could not be distinguished from contaminants in blank controls. To determine the source and composition of the putative placental bacterial community identified in the pilot study, we expanded the study to 10 subjects per group (N = 30) and increased the number and variety of negative controls (N = 53). We modified our protocol to use an ultraclean DNA extraction kit (Qiagen QIAamp UCP with Pathogen Lysis Tube S), which reduced the "kitome" contamination, but we were still unable to distinguish a placental microbiome from contaminants in negative controls. We noted microbial DNA from the high biomass vaginal-rectal swabs and positive controls in placental and negative control samples and determined that this resulted from close proximity well-to-well cross contamination or "splashome". We eliminated this source of contamination by repeating the sequencing run with a minimum of four wells separating high biomass from low biomass samples. This reduced the reads of bacterial 16S rRNA genes in placental samples to insignificant numbers. CONCLUSIONS: We identified the problem of well-to-well contamination ("splashome") as an additional source of error in microbiome studies of low biomass samples and found a method of eliminating it. Once "kitome" and "splashome" contaminants were eliminated, we were unable to identify a unique placental microbiome.

BACKGROUND: Studies of the relationship between ultrasound images from preterm newborns and developmental delay most often are based on small samples defined by birth weight and exclude infants not testable with standardized assessments. METHODS: We evaluated associations between ultrasound-defined lesions of the brain and developmental delays at 24 months' corrected age in 1017 children born before the 28th postmenstrual week. Brain ultrasound scans were read for concordance on 4 lesions: intraventricular hemorrhage, moderate/severe ventriculomegaly, white matter echodense/hyperechoic lesions, and white matter echodense/hypoechoic lesions and 2 diagnoses-periventricular leukomalacia and periventricular hemorrhagic infarction. Certified examiners, who were not aware of the infants' ultrasound findings, administered the Bayley Scales of Infant Development-Second Edition. Children with an impairment (eg., blindness) that precluded testing with the Bayley Scales and those for whom >2 test items were omitted were classified using the Vineland Adaptive Behavior Scales Motor Skills Domain instead of the Psychomotor Development Index and the Adaptive Behavior Composite instead of the Mental Development Index. RESULTS: Fully 26% of all of the children had delayed mental development (ie, Mental Development Index < 70), and 31% had delayed psychomotor development (ie, Psychomotor Development Index < 70). Ultrasound abnormalities were more strongly associated with low Psychomotor Development Index than with low Mental Development Index. Children without cranial ultrasound abnormality had the lowest probability (23% and 26%) of delayed mental or psychomotor development. Moderate/severe ventriculomegaly was associated with a more than fourfold increase in the risk of psychomotor delay and an almost threefold increase in the risk of mental delay. Echolucency was the next best predictor of delayed mental and psychomotor development. The probability of low scores varied with the number of zones involved and with the location of echolucency. At particularly high risk were infants with bilateral cerebellar hemorrhage, co-occurring ventriculomegaly and echolucency bilateral echolucency, or echolucency located posteriorly. CONCLUSIONS: Focal white matter damage, as characterized by echolucent/hypoechoic lesion, and diffuse damage, as suggested by late ventriculomegaly, are associated with delayed mental and psychomotor development.

BACKGROUND: Based on the hypothesis that cancer cells may not be able to metabolize ketones as efficiently as normal brain cells, the ketogenic diet (KD) has been proposed as a complementary or alternative therapy for treatment of malignant gliomas. CASE PRESENTATION: We report here our experience in treating two glioma patients with an IRB-approved energy-restricted ketogenic diet (ERKD) protocol as monotherapy and review the literature on KD therapy for human glioma patients. An ERKD protocol was used in this pilot clinical study. In addition to the two patients who enrolled in this study, we also reviewed findings from 30 other patients, including 5 patients from case reports, 19 patients from a clinical trial reported by Rieger and 6 patients described by Champ. A total of 32 glioma patients have been treated using several different KD protocols as adjunctive/complementary therapy. The two patients who enrolled in our ERKD pilot study were monitored with twice daily measurements of blood glucose and ketones and daily weights. However, both patients showed tumor progression while on the ERKD therapy. Immunohistochemistry reactions showed that their tumors had tissue expression of at least one of the two critical mitochondrial ketolytic enzymes (succinyl CoA: 3-oxoacid CoA transferase, beta-3-hydroxybutyrate dehydrogenase 1). The other 30 glioma patients in the literature were treated with several different KD protocols with varying responses. Prolonged remissions ranging from more than 5 years to 4 months were reported in the case reports. Only one of these patients was treated using KD as monotherapy. The best responses reported in the more recent patient series were stable disease for approximately 6 weeks. No major side effects due to KD have been reported in any of these patients. CONCLUSIONS: We conclude that 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in controlling the progression of some gliomas; and 4. further studies are needed to determine factors that influence the effectiveness of KD, whether as a monotherapy, or as adjunctive or supplemental therapy in treating glioma patients. TRIAL REGISTRATION: ClinicalTrials.gov# NCT01535911.

Importance: Several studies have examined the role of warfarin in preventing strokes in patients with atrial fibrillation and end-stage renal disease; however, the results remain inconclusive. Objective: To assess recently published studies to examine the outcomes of the use of warfarin among patients with atrial fibrillation and end-stage renal disease. Data Sources: A literature search was performed using the terms warfarin and atrial fibrillation and end-stage renal disease and warfarin and atrial fibrillation and dialysis in the MEDLINE, Embase, and Google Scholar databases from January 1, 2008, to February 28, 2019. Study Selection: The studies included were those with patients with end-stage renal disease and atrial fibrillation who were receiving warfarin and with hazard ratios (HRs) of at least 1 primary outcome. The studies excluded were those with a lack of information on outcomes and unreliable 95% CIs of the results. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in selecting studies. Collected data were also scrutinized for reliable 95% CIs. Finally, studies were examined for perceived biases, their limitations, and the definitions of the outcomes. Main Outcomes and Measures: The HRs and 95% CIs were calculated for the incidence of ischemic stroke, hemorrhagic stroke, major bleeding, and mortality among patients receiving anticoagulants and those not receiving anticoagulants. Results: Study selection yielded 15 studies with a total of 47 480 patients with atrial fibrillation and end-stage renal disease. Of these patients, 10 445 (22.0%) were taking warfarin. With a mean (SD) follow-up period of 2.6 (1.4) years, warfarin use was associated with no significant change for the risk of ischemic stroke (HR, 0.96; 95% CI, 0.82-1.13), with a significantly higher risk of hemorrhagic stroke (HR, 1.49; 95% CI, 1.03-1.94), with no significant difference in the risk of major bleeding (HR, 1.20; 95% CI, 0.99-1.47), and with no change in overall mortality (HR, 0.95; 95% CI, 0.83-1.09). Conclusions and Relevance: In the studies reviewed, warfarin use appears to have been associated with no change in the incidence of ischemic stroke in patients with atrial fibrillation and end-stage renal disease. However, from the studies reviewed, it does appear to be associated with a significantly higher risk of hemorrhagic stroke, with no significant difference in the risk of major bleeding, and with no change in mortality.

A series of the changes are being wrought on a range of IHRM functions – recruitment, global staffing, management development and careers, and rewards – by the process of globalization highlighting the difference between globally standardized, optimized or localized HR processes. However, our theoretical understanding of the issues involved is still driven by concepts rooted in global staffing strategies based on the management of small cadres of international managers, such as expatriates. The fragmentation of international employee populations and the changing structure and role of international HR functions has raised three important questions. The first concerns the study of globalization processes at functional level (staffing) and whether this can provide useful insights for the IHRM literature. The second concerns the indicators that best evidence globalization of staffing at the functional level, and whether these might form the basis of useful future research. The third concerns the patterns or strategies within the global HR recruitment activity of organizations across domestic and overseas labour markets and whether these patterns can be explained by existing theory. This paper reports on a study of firm-level developments in international recruitment and selection, drawing upon an analysis of four case studies each conducted in four theoretically derived contexts of centralized or decentralized control and co-ordination, and focus on domestic or overseas markets. It examines the disparities between policy and practice through interview of HR actors at corporate level and in country operations.

Manganese (Mn) toxicity is a potential limitation to plant growth on acidic and poorly drained soils. Five laboratory experiments using such soils were conducted to examine the influence of soil temperature, pH and water potential on the redox reactions of Mn and the potential for Mn toxicity. The microbial inhibitor sodium azide was used in some experiments to assess the role of microorganisms in these reactions. The reduction of Mn oxides (MnOx) during waterlogging was faster at 20°C and 30°C than at 10°C or 4°C. Sodium azide slowed the reduction of Mn oxides at 20°C and 30°C during waterlogging but had little effect at 4°C and 10°C, suggesting that microbial MnOx reduction during waterlogging was minimal at the lower temperatures. Re-oxidation of Mn2+ in soil drained after severe waterlogging was only observed in soil not treated with sodium azide, indicating that even when very high concentrations of Mn2+ were present, Mn2+ oxidation was still microbial. Prior liming of aerobic soil established lower starting concentrations of water-soluble plus exchangeable (WS+E) Mn2+ and slowed the reduction of Mn oxides during subsequent waterlogging. After drainage, rapid re-oxidation of Mn2+ was observed in all lime treatments but was fastest at the two highest lime rates. In the fourth and fifth experiments, interactions between temperature and water potential were observed. When waterlogged soils were drained to –5 and –10 kPa, re-oxidation of Mn2+ occurred at both 10°C and 20°C. At –1 kPa, there was no net change in WS+E Mn2+ at 10°C, whereas at 20°C, the concentration of WS+E Mn2+ increased, possibly due to the lower concentration of O2 in the soil water at the higher temperature. In the fifth experiment, at 4°C and 10°C there was little or no effect on Mn reactions of varying water potential from –1 to –1500 kPa, but at 20°C and especially at 30°C, both Mn2+ oxidation and Mn oxide reduction were slowed at –1500 kPa compared with the higher water potentials. Overall, the experiments show that a delicate balance between the microbial oxidation of Mn2+ and the reduction of Mn oxides can exist, and that it can be shifted by small changes in soil water potential along with changes in temperature and pH.

BACKGROUND: Amnioinfusion is thought to dilute meconium present in the amniotic fluid and so reduce the risk of meconium aspiration. OBJECTIVES: To assess the effects of amnioinfusion for meconium-stained liquor on perinatal outcome. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013). SELECTION CRITERIA: Randomised trials comparing amnioinfusion with no amnioinfusion for women in labour with moderate or thick meconium staining of the amniotic fluid. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed eligibility and trial quality, and extracted data. MAIN RESULTS: Fourteen studies of variable quality (4435 women) are included.Subgroup analysis was performed for studies from settings with limited facilities to monitor the baby's condition during labour and intervene effectively, and settings with standard peripartum surveillance.Settings with standard peripartum surveillance: there was considerable heterogeneity for several outcomes. There was no significant reduction in the primary outcomes meconium aspiration syndrome, perinatal death or severe morbidity, and maternal death or severe morbidity. There was a reduction in caesarean sections (CSs) for fetal distress but not overall. Meconium below the vocal cords diagnosed by laryngoscopy was reduced, as was neonatal ventilation or neonatal intensive care unit admission, but there was no significant reduction in perinatal deaths or other morbidity. Planned sensitivity analysis excluding trials with greater risk of bias resulted in an absence of benefits for any of the outcomes studied.Settings with limited peripartum surveillance: three studies were included. In the amnioinfusion group there was a reduction in CS for fetal distress and overall; meconium aspiration syndrome (three studies, 1144 women; risk ratio (RR) 0.17, 95% confidence interval (CI) 0.05 to 0.52); perinatal mortality (three studies, 1151 women; RR 0.24, 95% CI 0.11 to 0.53) and neonatal ventilation or neonatal intensive care unit admission. In one of the studies, meconium below the vocal cords was reduced and, in the other, neonatal encephalopathy was reduced. AUTHORS' CONCLUSIONS: Amnioinfusion is associated with substantive improvements in perinatal outcome only in settings where facilities for perinatal surveillance are limited. It is not clear whether the benefits are due to dilution of meconium or relief of oligohydramnios.In settings with standard peripartum surveillance, some non-substantive outcomes were improved in the initial analysis, but sensitivity analysis excluding trials with greater risk of bias eliminated these differences. Amnioinfusion is either ineffective in this setting, or its effects are masked by other strategies to optimise neonatal outcome.The trials reviewed are too small to address the possibility of rare but serious maternal adverse effects of amnioinfusion.

OBJECTIVE: The objective of this study was to compare the primary and secondary outcomes of very low birth weight infants before and after participation in the Breathsavers Group of the Vermont Oxford Network-sponsored Neonatal Intensive Care Quality Collaborative. METHODS: Hospitals that participated in the Breathsavers Group contributed clinical data on the outcomes of their very low birth weight infants to the Vermont Oxford Network using standardized clinical definitions, data forms, and inclusion criteria. Outcomes from the last year of the collaborative, 2003, were compared with those from the baseline year, 2001. Models for treatment practices and outcomes measures were adjusted for within-hospital correlation (clustering) and standard risk factors that were present at birth. RESULTS: Bronchopulmonary dysplasia dropped significantly in 2003 compared with the baseline year. Survival improved but not significantly. In addition, severe retinopathy of prematurity, severe intraventricular hemorrhage, and supplemental oxygen at discharge dropped significantly. The use of conventional ventilation at any time during the initial hospitalization, postnatal steroids, and time to first dose of surfactant all decreased significantly. The use of nasal continuous positive airway pressure at any time during hospitalization increased. The use of high-frequency ventilation, delivery room intubation, and surfactant at any time during hospitalization did not change. CONCLUSIONS: The Breathsavers Group improved both clinical care processes and clinical outcomes during the Neonatal Intensive Care Quality Collaborative.

BACKGROUND: Recent studies in animal models, based on the hypothesis that malignant glioma cells are more dependent on glycolysis for energy generation, have shown promising results using ketogenic diet (KD) therapy as an alternative treatment strategy for malignant glioma, effectively starving glioma cells while providing ketone bodies as an energy source for normal neurons and glial cells. In order to test this treatment strategy in humans, we investigated the relative expression of several key enzymes involved in ketolytic and glycolytic metabolism in human anaplastic glioma (WHO grade III) and glioblastoma (GBM, WHO grade IV). METHODS: Immunohistochemistry was performed on formalin fixed paraffin embedded sections from 22 brain biopsies (17 GBM, 3 anaplastic astrocytoma and 2 anaplastic oligoastrocytoma) using antibodies raised against glycolytic and ketolytic enzymes. The glycolytic enzymes included hexokinase-II (HK2) and pyruvate kinase M2 isoform (PKM2). The ketone body metabolic enzymes included: succinyl CoA: 3-oxoacid CoA transferase (OXCT1), 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and BDH2), and acetyl-CoA acetyltransferase 1 (ACAT1). The immunoreactivities were graded using a semi-quantitative scale based on the percentage of positive cells: POS (>20%), LOW (5-20%), and very low (VLOW) (<5%). Focal non-neoplastic "normal" brain tissue within the biopsy specimens served as internal controls. RESULTS: The rate limiting mitochondrial ketolytic enzymes (OXCT1 and BDH1) were either LOW or VLOW, concordantly in 14 of the 17 GBMs and in 1 of 5 anaplastic gliomas, whereas at least one of the glycolytic enzymes was POS in 13 of these 17 GBMs and all 5 anaplastic gliomas. Cytosolic BDH2 and mitochondrial ACTAT1 were, surprisingly, POS in most of these tumors. CONCLUSION: Our results showing that malignant gliomas have differential expression of ketolytic and glycolytic enzymes are consistent with previous studies that have shown that these are genetically heterogeneous tumors. It seems reasonable to hypothesize that patients with low or very low expression of key ketolytic enzymes in their malignant gliomas may respond better to the KD therapy than those patients with positive expression of these enzymes. Further studies in animal models and/or a large-scale clinical trial would be needed to test this hypothesis.

An 18-year-old Thoroughbred gelding was evaluated because of sudden onset of ventricular tachycardia and signs of colic. Three years earlier, a diastolic decrescendo murmur, consistent with aortic regurgitation, had been detected, but the horse continued to perform well and compete successfully. Cardiac ultrasonographic examination revealed a defect in the interventricular septum below the aortic root, and serum concentrations of cardiac troponin I (cTnI) were higher than those measured in clinically normal horses. Repeated development of tachyarrhythmia during hospitalization prompted a decision to euthanatize the horse. A ruptured endocardial jet lesion below the aortic valve with formation of a cleft into the interventricular septum was found on necropsy. This report of increased serum cTnI concentrations in a horse with myocardial disease and our other findings suggest that assessment of cardiac troponin concentrations may be a useful tool in the evaluation of horses with suspected myocardial disease.

The development of the human skin from intrauterine to extrauterine life is a balletic interplay of maturing layers and interlocking structures. We discuss this transition and then branch out to touch on issues of premature infant as well as neonatal skin care. Disruption of the barrier function due to toxins and development errors are expounded upon. Staph scalded skin syndrome, collodion membrane, bullous congenital ichthyosiform erythroderma, autosomal recessive ichthyosis (lamellar and congenital ichthyosiform erythroderma), and harlequin fetus are used as examples of these disruptions. Discussion of therapy with the authors' experience highlights each disease.

OBJECTIVES: Improvements in neonatal care have resulted in increasing survival of extremely premature infants whose hospital course often runs into weeks or months. Some interventions during the acute care of these neonates, such as umbilical catheterization and use of steroids, not infrequently result in elevation of blood pressure (BP). It is, therefore, essential that these infants be monitored accurately for possible hypertension during their convalescence. Unfortunately, normative data on BP in this population are scant and comparison of data from various studies is hampered by methodologic differences in design. Studies in adults address the necessity for a restful state, adopting a comfortable position, and attempts to reduce the startle response to initial cuff inflation. Studies in the newborn using the oscillometric technique have not addressed these concerns. A standard BP measurement protocol was studied to determine the effect of ensuring a restful state, startle response to cuff inflation, and infant position on BP in clinically stable low birth weight infants after the first week of life. STUDY DESIGN: The Dianamap oscillometer was used to measure BP in infants with a birth weight <2500 g between 7 and 42 days postnatal age. Each infant was studied only once when they were clinically stable. BP was measured in two positions, prone and supine, in random order. Infants were studied at least 11/2 hours after their last feeding or medical intervention. An appropriate sized cuff was applied to the right upper arm and the infant was positioned according to randomization. The infant was then left undisturbed for at least 15 minutes or until the infant was sleeping or in a quiet awake state. Three successive BP recordings were taken at 2-minute intervals. The infant's position was then reversed and another 15 minutes of quiet time was allowed. Thereafter, a second set of three successive BP recordings were obtained. The most recent routine nursing BP measurement was also recorded. Data were analyzed using analysis of variance and are presented as means and standard errors of the mean. RESULTS: Sixty-four infants were studied. Birth weights ranged from 901 to 2423 g and gestational ages from 26 to 37 weeks. Overall, mean BP was significantly lower in the prone than supine positions (45.7 +/- 0.7 vs 47.8 +/- 0.8 mm Hg, P < .002). In either position, the first measurement was significantly higher than the third (average difference was 3 mm Hg, P < .003). In general, the relationships among position and order of measurement were similar for systolic and diastolic BP. Mean BPs obtained by routine nurse measurements were significantly higher than those in either position using our standard protocol (54.4 vs 47.0 or 49.1 mm Hg, P < .003). Moreover, the routine nurse measurements varied more widely than did those obtained using the standard protocol. The standard deviation for the routine mean BP measurements by nurses was 11.4 compared with 6.8 and 8.2 for the first measurements in the prone and supine positions, respectively, with the standard protocol. The mean BP measurements made in the supine position (the highest measurements obtained) using the standard protocol were also significantly lower than published values: 57 of 64 measurements were less than the average mean BP for age described by Tan (J Pediatr. 1988; 112:266-270). CONCLUSION: The statistically significant difference between the prone and supine position and among successive measurements in each position are not clinically relevant. The clinically significant differences between measurements obtained with this standard protocol and routine nursing measurements or published data are the result of ensuring a restful state after cuff application. We believe that measurements thus obtained are more representative of true resting BPs in these infants. (ABSTRACT TRUNCATED)

BACKGROUND: Bioprosthetic (BP) valves have been increasingly used for aortic valve replacement over the last decade. Due to their limited durability, patients presenting with failed BP valves are rising. Valve in Valve - Transcatheter Aortic Valve Implantation (ViV-TAVI) emerged as an alternative to the gold standard redo-Surgical Aortic Valve Replacement (redo-SAVR). However, the utility of ViV-TAVI is poorly understood. METHODS: A systematic electronic search of the scientific literature was done in PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov. Only studies which compared the safety and efficacy of ViV-TAVI and redo-SAVR head to head in failed BP valves were included. RESULTS: Six observational studies were eligible and included 594 patients, of whom 255 underwent ViV- TAVI and 339 underwent redo-SAVR. There was no significant difference between ViV-TAVI and redo- SAVR for procedural, 30 day and 1 year mortality rates. ViV-TAVI was associated with lower risk of permanent pacemaker implantation (PPI) (OR: 0.43, CI: 0.21-0.89; P = 0.02) and a trend toward increased risk of paravalvular leak (PVL) (OR: 5.45, CI: 0.94-31.58; P = 0.06). There was no significant difference for stroke, major bleeding, vascular complications and postprocedural aortic valvular gradients more than 20 mm-hg. CONCLUSION: Our results reiterate the safety and feasibility of ViV-TAVI for failed aortic BP valves in patients deemed to be at high risk for surgery. VIV-TAVI was associated with lower risk of permanent pacemaker implantation with a trend toward increased risk of paravalvular leak.