Comparisons of Mortality and Pre-discharge Respiratory Outcomes in Small-for-gestational-age and Appropriate-for-gestational-age Premature Infants.

BACKGROUND: There are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth. OBJECTIVE: To compare mortality and respiratory morbidity of SGA and AGA premature newborn infants. DESIGN/METHODS: A retrospective study was done of the 2,487 infants born without congenital anomalies at RESULTS: Controlling for GA, premature SGA infants were at a higher risk for mortality (Odds ratio 3.1, P = 0.001) and at lower risk of respiratory distress syndrome (OR = 0.71, p = 0.02) than AGA infants. However multivariate logistic regression modeling found that the odds of having respiratory distress syndrome (RDS) varied between SGA and AGA infants by GA. There was no change in RDS risk in SGA infants at GA 32 wk (OR = 0.41, 95% CI 0.27 - 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 - 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26-36 wks GA than AGA infants. CONCLUSIONS: Premature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at >/=32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.

What Sensory Signals are About

Kathleen Akins argues that "the traditional view" of sensory systems assumes too quickly that their function is detecting features of the outside environment. Instead, some systems are "narcissistic"--their signals tell their own states--and others may send signals that are not about anything at all. But Akins overlooks that "traditionalists" may argue, with Millikan, that the function of sensory systems may be steering motor routines. Aboutness comes in as how the systems have steered in ways evolution liked--by gearing steering to external features. Color vision and olfaction, for example, are thus, about external features.

The year-long unprecedented European heat and drought of 1540 – a worst case

The heat waves of 2003 in Western Europe and 2010 in Russia, commonly labelled as rare climatic anomalies outside of previous experience, are often taken as harbingers of more frequent extremes in the global warming-influenced future. However, a recent reconstruction of spring–summer temperatures for WE resulted in the likelihood of significantly higher temperatures in 1540. In order to check the plausibility of this result we investigated the severity of the 1540 drought by putting forward the argument of the known soil desiccation-temperature feedback. Based on more than 300 first-hand documentary weather report sources originating from an area of 2 to 3 million km2, we show that Europe was affected by an unprecedented 11-month-long Megadrought. The estimated number of precipitation days and precipitation amount for Central and Western Europe in 1540 is significantly lower than the 100-year minima of the instrumental measurement period for spring, summer and autumn. This result is supported by independent documentary evidence about extremely low river flows and Europe-wide wild-, forest- and settlement fires. We found that an event of this severity cannot be simulated by state-of-the-art climate models.

Development and Validation of a Symptom-Based Activity Index for Adults with Eosinophilic Esophagitis

BACKGROUND & Aims: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients' assessments of disease severity. We also evaluated relationships between patients' assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the US (69.4% male; median age, 43 years) via surveys (n = 135), focus groups (n = 27), and semi-structured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patients' assessment of EoE severity. The PRO instrument was prospectively used in 153 adult patients with EoE (72.5% male; median age, 38 years), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 years). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patients' assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity and PRO score was 0.13 (on a scale from 0 to 10). CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assesses symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome.

OBJECT Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. METHODS The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. CONCLUSIONS A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.

Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling.

Neutropenia is probably the strongest known predisposition to infection with otherwise harmless environmental or microbiota-derived species. Because initial swarming of neutrophils at the site of infection occurs within minutes, rather than the hours required to induce "emergency granulopoiesis," the relevance of having high numbers of these cells available at any one time is obvious. We observed that germ-free (GF) animals show delayed clearance of an apathogenic bacterium after systemic challenge. In this article, we show that the size of the bone marrow myeloid cell pool correlates strongly with the complexity of the intestinal microbiota. The effect of colonization can be recapitulated by transferring sterile heat-treated serum from colonized mice into GF wild-type mice. TLR signaling was essential for microbiota-driven myelopoiesis, as microbiota colonization or transferring serum from colonized animals had no effect in GF MyD88(-/-)TICAM1(-/-) mice. Amplification of myelopoiesis occurred in the absence of microbiota-specific IgG production. Thus, very low concentrations of microbial Ags and TLR ligands, well below the threshold required for induction of adaptive immunity, sets the bone marrow myeloid cell pool size. Coevolution of mammals with their microbiota has probably led to a reliance on microbiota-derived signals to provide tonic stimulation to the systemic innate immune system and to maintain vigilance to infection. This suggests that microbiota changes observed in dysbiosis, obesity, or antibiotic therapy may affect the cross talk between hematopoiesis and the microbiota, potentially exacerbating inflammatory or infectious states in the host.

VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children

BACKGROUND Despite substantial evidence supporting a pharmacogenetic approach to warfarin therapy in adults, evidence on the importance of genetics in warfarin therapy in children is limited, particularly for clinical outcomes. We assessed the contribution of CYP2C9/VKORC1/CYP4F2 genotypes and variation in other genes involved in vitamin K and coagulation pathways to warfarin dose and related clinical outcomes in children. PROCEDURE Clinical and genetic data for 93 children (age ≤ 18 years) who received warfarin therapy were obtained. DNA was genotyped for 93 selected single nucleotide polymorphisms using a custom assay. RESULTS With a median age of 4.8 years, our cohort included more young children than most previous studies. Overall, 76.3% of dose variability was explained by weight, indication, VKORC1-1639G/A and CYP2C9 *2/*3, with genotypes accounting for 21.1% of variability. There was a strong correlation (R(2) = 0.68; P < 0.001) between actual and predicted warfarin dose using a pediatric genotype-based dosing model. VKORC1 genotype had a significant impact on time to therapeutic international normalized ratio (INR) (P = 0.047) and time to over-anticoagulation (INR > 4; P = 0.024) during the initiation of therapy. CYP2C9*3 carriers were also at increased risk of major bleeding while receiving warfarin (adjusted OR = 11.28). An additional variant in CYP2C9 (rs7089580) was significantly associated with warfarin dose (P = 0.020) in a multivariate clinical and genetic model. CONCLUSIONS This study confirms the importance of VKORC1/CYP2C9 genotypes for warfarin dosing in a young pediatric cohort and demonstrates an impact of genetic factors on clinical outcomes in children. Furthermore, we identified an additional variant in CYP2C9 of potential relevance for warfarin dosing in children.

Extending resection and preserving function: modern concepts of glioma surgery

Recent studies have demonstrated that the improved prognosis derived from resection of gliomas largely depends on the extent and quality of the resection, making maximum but safe resection the ultimate goal. Simultaneously, technical innovations and refined neurosurgical methods have rapidly improved efficacy and safety. Because gliomas derive from intrinsic brain cells, they often cannot be visually distinguished from the surrounding brain tissue during surgery. In order to appreciate the full extent of their solid compartment, various technologies have recently been introduced. However, radical resection of infiltrative glioma puts neurological function at risk, with potential detrimental consequences for patients' survival and quality of life. The allocation of various neurological functions within the brain varies in each patient and may undergo additional changes in the presence of a tumour (brain plasticity), making intra-operative localisation of eloquent areas mandatory for preservation of essential brain functions. Combining methods that visually distinguish tumour tissue and detect tissues responsible for critical functions now enables resection of tumours in brain regions that were previously considered off-limits, and benefits patients by enabling a more radical resection, while simultaneously lowering the risk of neurological deficits. Here we review recent and expected developments in microsurgery for glioma and their respective benefits.

Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method

OBJECT The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4-2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated. METHODS The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r(2) = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11-20 mA, 13 patients; 6-10 mA, 8 patients; 4-5 mA, 17 patients; and 1-3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST. CONCLUSIONS Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study.

Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs.