Robotic-assisted endoscopic onlay repair (R-ENDOR) for concomitant ventral hernias and diastasis recti: initial results and surgical technique.

BACKGROUND: The surgical management of midline ventral hernias complicated by concomitant diastasis recti presents a significant clinical challenge. The Endoscopic Onlay Repair (ENDOR) offers a minimally invasive solution, effectively addressing both conditions. This study focuses on describing the adaptation of ENDOR to a robotic platform, termed R-ENDOR, aiming to report initial outcomes along with other established robotic surgical approaches. METHODS: This retrospective case series study included consecutive adult patients who underwent R-ENDOR approach from October 2018 to April 2023, performed by a single surgeon. A comprehensive description of the surgical technique is included. Patient demographics, operative, and hernia-specific characteristics, as well as clinical outcomes are described. RESULTS: A total of 15 patients undergoing R-ENDOR for ventral hernia repair with diastasis recti plication were included. The median age was 59 years (IQR 42-63), with 60% (n = 9) female patients. The majority (86%, n = 13) had an ASA score of ≤ 2, and the median BMI was 24 kg/m2, with 20% (n = 3) classified as obese. Median hernia size was 2 cm (IQR 2-2.25), with a median diastasis length of 19 cm (IQR 15-21.5) and width of 4 cm (IQR 3-6). The median operative time was 129 min (IQR 113-166). Most repairs (93%, n = 14) were reinforced with mesh, predominantly self-fixating (73.3%, n = 11). Eighty percent of patients (n = 12) were discharged on the same day, with a median follow-up of 153 days (IQR 55-309). Notable complications included clinically significant seromas in 20% of patients (n = 3), long-term hypoesthesia in 40% (n = 6), and readmission in one patient (6.6%) for surgical site infection (SSI) requiring IV antibiotic therapy. CONCLUSION: Midline ventral hernias associated to diastasis recti can be managed robotically by ENDOR with safe and consistent 90-day outcomes in a carefully selected group of patients.

Early role for a Na+,K+-ATPase (ATP1A3) in brain development.

Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function catalyzed by the Na+,K+-ATPase α-subunit. Here, we describe ATP1A3 variants encoding dysfunctional α3-subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we built an ATP1A3 transcriptional atlas of fetal cortical development using mRNA in situ hybridization and transcriptomic profiling of ∼125,000 individual cells with single-cell RNA sequencing (Drop-seq) from 11 areas of the midgestational human neocortex. We found that fetal expression of ATP1A3 is most abundant to a subset of excitatory neurons carrying transcriptional signatures of the developing subplate, yet also maintains expression in nonneuronal cell populations. Moving forward a year in human development, we profiled ∼52,000 nuclei from four areas of an infant neocortex and show that ATP1A3 expression persists throughout early postnatal development, most predominantly in inhibitory neurons, including parvalbumin interneurons in the frontal cortex. Finally, we discovered the heteromeric Na+,K+-ATPase pump complex may form nonredundant cell-type-specific α-ß isoform combinations, including α3-ß1 in excitatory neurons and α3-ß2 in inhibitory neurons. Together, the developmental malformation phenotype of affected individuals and single-cell ATP1A3 expression patterns point to a key role for α3 in human cortex development, as well as a cell-type basis for pre- and postnatal ATP1A3-associated diseases.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Impact of previous macrolide use on invasive pneumococcal disease due to erythromycin-resistant serotypes in adults over 59 years of age.

The major goals of the study were to describe the invasive pneumococcal disease (IPD) cases due to erythromycin-resistant serotypes and to evaluate the association between these cases and recent macrolide use in individuals aged over 59 years. We selected cases of IPD reported between 2007 and 2016 in persons aged over 59 years living in the Community of Madrid (CM). We followed the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The explanatory variables (age, sex, year of onset of symptoms, clinical presentation, serotypes, vaccination status) were taken from the Mandatory Notification System for Infectious Diseases System and from the Vaccination Information System. The cases were classified as either included in the 13-valent pneumococcal conjugate vaccine (PCV13) or not (nonPCV13). Associations between cases due to erythromycin-resistant serotypes and previous macrolide use (total, long and short-term) were adjusted with a logistic regression multivariate analysis. A total of 1,831 cases were identified, of whom 408 were erythromycin-resistant serotypes. PCV13 cases were associated with previous macrolide use (OR: 5.07), particularly long-acting types (OR: 8.61). NonPCV13 cases were associated with the use of total macrolides (OR: 3.48) and long-acting macrolides (OR: 4.26) suggesting that PCV13 did not reduce the IPD cases in patients with previous use of macrolides. Our results confirmed that previous macrolide consumption was associated with the presence of IPD due to erythromycin-resistant serotypes. The risk was higher with the use of long-term macrolides.

Ultrasound Computed Tomography.

This chapter presents theoretical, numerical, and experimental frameworks for the use of Ultrasound Computed Tomography (USCT) for cortical bone tissue imaging. Most of the research conducted on this topic concerns adult bone, although some work presented in this chapter is specific to the study of child bone. USCT is recognized as a powerful method for soft tissue imaging. In bone imaging, the difficulties arise from the very high impedance contrast between tissues which alters the propagation of the ultrasonic waves and limits the linear inversion algorithms used. Solutions consist in optimally assessing non-linear effects in an iterative approach aiming at local linearization. When the problem can be reduced to the study of a fluid-like cavity buried in an elastic cylinder surrounded by water, the signal processing and/or compound algorithms can be added as an extension to the linear algorithms. The main limitation of these methods is the heavy experimental costs involved. We have then suggested the introduction of purely numerical non-linear full-waveform inversion algorithms. The performances and the limitations of these linear and non-linear methods applied to cortical bone tissue imaging problems are overviewed and discussed.

Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis.

A peptide from the P0 acidic ribosomal protein (pP0) of ticks conjugated to keyhole limpet hemocyanin from Megathura crenulata has shown to be effective against different tick species when used in host vaccination. Turning this peptide into a commercial anti-tick vaccine will depend on finding the appropriate, technically and economically feasible way to present it to the host immune system. Two conjugates (p64K-Cys1pP0 and p64K-ßAla1pP0) were synthesized using the p64K carrier protein from Neisseria meningitidis produced in Escherichia coli, the same cross-linking reagent, and two analogues of pP0. The SDS-PAGE analysis of p64K-Cys1pP0 showed a heterogeneous conjugate compared to p64K-ßAla1pP0 that was detected as a protein band at 91kDa. The pP0/p64K ratio determined by MALDI-MS for p64K-Cys1pP0 ranged from 1 to 8, being 3-5 the predominant ratio, while in the case of p64K-ßAla1pP0 this ratio was 5-7. Cys1pP0 was partially linked to 35 out of 39 Lys residues and the N-terminal end, while ßAla1pP0 was mostly linked to the six free cysteine residues, to the N-terminal end, and, in a lesser extent, to Lys residues. The assignment of the conjugation sites and side reactions were based on the identification of type 2 peptides. Rabbit immunizations showed the best anti-pP0 titers and the highest efficacy against Rhipicephalus sanguineus ticks when the p64K-Cys1pP0 was used as vaccine antigen. The presence of high molecular mass aggregates observed in the SDS-PAGE analysis of p64K-Cys1pP0 could be responsible for a better immune response against pP0 and consequently for its better efficacy as an anti-tick vaccine. Graphical abstract.

In-solution buffer-free digestion allows full-sequence coverage and complete characterization of post-translational modifications of the receptor-binding domain of SARS-CoV-2 in a single ESI-MS spectrum.

Subunit vaccines based on the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 provide one of the most promising strategies to fight the COVID-19 pandemic. The detailed characterization of the protein primary structure by mass spectrometry (MS) is mandatory, as described in ICHQ6B guidelines. In this work, several recombinant RBD proteins produced in five expression systems were characterized using a non-conventional protocol known as in-solution buffer-free digestion (BFD). In a single ESI-MS spectrum, BFD allowed very high sequence coverage (≥ 99%) and the detection of highly hydrophilic regions, including very short and hydrophilic peptides (2-8 amino acids), and the His6-tagged C-terminal peptide carrying several post-translational modifications at Cys538 such as cysteinylation, homocysteinylation, glutathionylation, truncated glutathionylation, and cyanylation, among others. The analysis using the conventional digestion protocol allowed lower sequence coverage (80-90%) and did not detect peptides carrying most of the above-mentioned PTMs. The two C-terminal peptides of a dimer [RBD(319-541)-(His)6]2 linked by an intermolecular disulfide bond (Cys538-Cys538) with twelve histidine residues were only detected by BFD. This protocol allows the detection of the four disulfide bonds present in the native RBD, low-abundance scrambling variants, free cysteine residues, O-glycoforms, and incomplete processing of the N-terminal end, if present. Artifacts generated by the in-solution BFD protocol were also characterized. BFD can be easily implemented; it has been applied to the characterization of the active pharmaceutical ingredient of two RBD-based vaccines, and we foresee that it can be also helpful to the characterization of mutated RBDs.

Ultrasonic Imaging of High-contrasted Objects Based on Full-waveform Inversion: Limits under Fluid Modeling.

Quantitative ultrasound techniques have been previously used to evaluate biological hard tissues, characterized by a large acoustic impedance contrast. Here, we are interested in the imaging of experimental data from different test-targets with high acoustic impedance contrast, using the Full Waveform Inversion (FWI) method to solve the inverse problem. This method is based on high-resolution numerical modeling of the forward problem of interaction between waves and medium, considering the full time series. To reduce the complexity of the numerical implementation, the model considers a fluid medium. Therefore, the aim is to evaluate the precision of the reconstruction under this assumption for materials with a different level of attenuation of shear waves, to study the limits of this hypothesis. Images of the sound speed obtained using the experimental data are presented, and the precision of the reconstruction is evaluated. Future work should include viscoelastic materials.

Insulin-Like Growth Factor 1 in the Cardiovascular System.

Non-communicable diseases, such as cardiovascular diseases, are the leading cause of mortality worldwide. For this reason, a tremendous effort is being made worldwide to effectively circumvent these afflictions, where insulin-like growth factor 1 (IGF1) is being proposed both as a marker and as a central cornerstone in these diseases, making it an interesting molecule to focus on. Firstly, at the initiation of metabolic deregulation by overfeeding, IGF1 is decreased/inhibited. Secondly, such deficiency seems to be intimately related to the onset of MetS and establishment of vascular derangements leading to atherosclerosis and finally playing a definitive part in cerebrovascular and myocardial accidents, where IGF1 deficiency seems to render these organs vulnerable to oxidative and apoptotic/necrotic damage. Several human cohort correlations together with basic/translational experimental data seem to confirm deep IGF1 implication, albeit with controversy, which might, in part, be given by experimental design leading to blurred result interpretation.

Is insulin-like growth factor-1 involved in Parkinson's disease development?

Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence: (1) IGF-1 decreases with age, while aging is the major risk for PD establishment and development; (2) numerous basic and translational data have appointed direct protective and homeostasis IGF-1 roles in all brain cells; (3) estrogens seem to confer women strong protection to PD via IGF-1; and (4) clinical correlations in PD cohorts have confirmed elevated IGF-1 levels at the onset of the disease, suggesting an ongoing compensatory or "fight-to-injury" mechanism.

Both gain-of-function and loss-of-function de novo CACNA1A mutations cause severe developmental epileptic encephalopathies in the spectrum of Lennox-Gastaut syndrome.

OBJECTIVE: Developmental epileptic encephalopathies (DEEs) are genetically heterogeneous severe childhood-onset epilepsies with developmental delay or cognitive deficits. In this study, we explored the pathogenic mechanisms of DEE-associated de novo mutations in the CACNA1A gene. METHODS: We studied the functional impact of four de novo DEE-associated CACNA1A mutations, including the previously described p.A713T variant and three novel variants (p.V1396M, p.G230V, and p.I1357S). Mutant cDNAs were expressed in HEK293 cells, and whole-cell voltage-clamp recordings were conducted to test the impacts on CaV 2.1 channel function. Channel localization and structure were assessed with immunofluorescence microscopy and three-dimensional (3D) modeling. RESULTS: We find that the G230V and I1357S mutations result in loss-of-function effects with reduced whole-cell current densities and decreased channel expression at the cell membrane. By contrast, the A713T and V1396M variants resulted in gain-of-function effects with increased whole-cell currents and facilitated current activation (hyperpolarized shift). The A713T variant also resulted in slower current decay. 3D modeling predicts conformational changes favoring channel opening for A713T and V1396M. SIGNIFICANCE: Our findings suggest that both gain-of-function and loss-of-function CACNA1A mutations are associated with similarly severe DEEs and that functional validation is required to clarify the underlying molecular mechanisms and to guide therapies.

Prognostic Role of Hyponatremia in Heart Failure Patients Depending on Renal Disease: Clinical Evidence.

AIM: Hyponatremia is very often associated with renal disease in patients with heart failure (HF) and, when present, determines a poor outcome. We investigated the role of hyponatremia in HF patients in whom the presence or absence renal insufficiency was accurately predefined. METHODS: This was a cohort study based on the Spanish National Registry on Heart Failure (RICA), a multicenter, prospective registry that enrolls patients admitted for decompensated HF who were subsequently followed up for 1 year. We classified patients into 4 groups according to the presence or absence of renal disease defined by the hematocrit, urea, and gender formula (HUGE) and then according to the presence of hyponatremia (Na ≤135 mEq/L). RESULTS: A total of 3,478 patients were included. Hyponatremia was more prevalent in the group with renal disease (22.1%) than without (18.4%). During admission, both groups with hyponatremia had more complications than those with normal serum sodium. During the 1-year follow-up, patients with hyponatremia and renal disease had a significantly worse outcome (HF mortality and readmission), HR 1.87, 95% CI 1.54-2.29, p < 0.001, compared to those with hyponatremia without renal disease, HR 1.01, 95% CI 0.79-1.3, p = 0.94. CONCLUSIONS: Hyponatremia is more prevalent in patients with renal insufficiency, and outcome is poorest when both renal disease and hyponatremia coexist. Patients with hyponatremia without renal disease show no differences in outcome compared to those without hyponatremia.

Effect of a Therapeutic Strategy Guided by Lung Ultrasound on 6-Month Outcomes in Patients with Heart Failure: Randomized, Multicenter Trial (EPICC Study).

INTRODUCTION AND OBJECTIVES: Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound has shown to be highly sensitive for detecting PC in HF. The aim of this study is to evaluate whether lung ultrasound-guided therapy improves 6-month outcomes in patients with HF compared with conventional treatment. MATERIALS AND METHODS: Randomized, multicenter, single-blind clinical trial in patients discharged from Internal Medicine Departments after hospitalization for decompensated HF. Participants will be assigned 1:1 to receive treatment guided according to the presence of lung ultrasound signs of congestion (semi-quantitative evaluation of B lines and the presence of pleural effusion) versus clinical assessment of congestion. The primary outcome is the combination of cardiovascular death and readmission for HF at 6 months. CONCLUSIONS: The results of this study will provide more evidence about the impact of lung ultrasound on treatment monitoring in patients with chronic HF.

Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. METHODS: We retrospectively evaluated HRV in epilepsy patients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. RESULTS: The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. SIGNIFICANCE: These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk.

Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45.

Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta-propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female. Six presented with DEE and 1 with early onset focal seizures and profound regression. Median seizure onset was 12 months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients had magnetic resonance susceptibility-weighted imaging; blooming was noted in the globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years, consistent with iron accumulation. We show that de novo pathogenic variants are associated with a range of developmental and epileptic encephalopathies with profound developmental consequences.

Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation.

Synaptic plexi of U-fibre layer beneath focal cortical dysplasias: Role in epileptic networks.

AIMS: The purpose is to demonstrate heterotopic neurones and their synaptic plexi within the U-fibre layer beneath focal cortical dysplasias (FCD). MATERIALS AND METHODS: This prospective qualitative neuropathological study included 23 patients, ages from 3 months to 17 years: resections at epileptogenic foci in 10 FCD Ia; 6 FCD IIa,b; 2 FCD IIIa,d; 3 HME; 2 TSC; 8 controls. TECHNIQUES: immunoreactivities for synaptophysin, NeuN, MAP2, SMI32, calretinin, GFAP, vimentin, α-B-crystallin. Bielschowsky silver; LFB; mitochondrial enzyme histochemistry (frozen sections). RESULTS: Subcortical white matter in FCD exhibited neuronal dispersion within U-fibres in FCD I, II and also deep white matter neuronal clusters in FCD II, HME, TSC. Neurones reacted for NeuN, MAP2; few for calretinin. Synaptophysin well demonstrated elaborate U-fibre plexi including axones between U-fibre neurones and projecting to overlying cortex. Deep white matter axones interconnected heterotopia but did not penetrate U-fibres to reach cortex. Mitochondrial enzymatic activity was intense in some neurones, normal in others. Glial α-B-crystallin served as a marker of epileptogenic zones identified electrographically. CONCLUSION: U-fibre synaptic plexi contribute to excitatory circuitry in the cortex and thus to epileptic networks. Deep white matter neurones form local, less integrated plexi except transmantle dysplasias continuous with cortex. U-fibres may be a barrier to axonal penetration from deep heterotopia. Hypermetabolic neurones suggest repetitive ictogenic depolarizations. Gyral resections should include the U-fibre layer. Neuropathology reports should describe subcortical plexi. Synaptophysin immunoreactivity is a valuable supplement for this purpose.
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Introduction of Continuous Video EEG Monitoring into 2 Different NICU Models by Training Neonatal Nurses.

BACKGROUND: Continuous video electroencephalographic (EEG) (cvEEG) monitoring is emerging as the standard of care for diagnosis and management of neonatal seizures. However, cvEEG is labor-intensive and the need to initiate and interpret studies on a 24-hour basis is a major limitation. PURPOSE: This study aims at establishing consistency in monitoring of newborns admitted to 2 different neonatal intensive care units (NICUs) managed by the same neurocritical care team. METHODS: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues, and identify amplitude-integrated EEG abnormalities. Guidelines, checklists, and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. A cohort of 100 infants with moderate to severe hypoxic-ischemic encephalopathy before and after the training program was compared. RESULTS: During the study period, 192 cvEEGs were obtained. The time to initiate brain monitoring decreased by 31.5 hours posttraining; this, in turn, led to an increase in electrographic seizure detection (20% before vs 34% after), decrease in seizure clinical misdiagnosis (65% before and 36% after), and reduction in antiseizure medication burden. IMPLICATIONS FOR PRACTICE: Training experienced NICU nurses to set up, start, and monitor cvEEGs can decrease the time to initiate cvEEGs, which may lead to better seizure diagnosis and management. IMPLICATIONS FOR RESEARCH: Further understanding of practice bundles for best supporting infants at risk and being treated for seizures needs to be evaluated for integration into practice.Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Neuropsychological Outcome in Perinatal Stroke Associated With Epileptiform Discharges in Sleep.

BACKGROUND: Patients with arterial perinatal stroke often suffer long-term motor sequelae, difficulties in language, social development, and behaviour as well as epilepsy. Despite homogeneous lesions, long-term behavioural and cognitive outcomes are variable and unpredictable. Sleep-related epileptic encephalopathies can occur after early brain injury and are associated with global developmental delays. We hypothesized that sleep-potentiated epileptiform abnormalities are associated with worse developmental outcomes after perinatal stroke. METHODS: Participants were identified from a population-based cohort (Alberta Perinatal Stroke Project). Inclusion criteria were magnetic resonance imaging-confirmed arterial perinatal stroke, age 4 to 18 years, electroencephalogram (EEG) including sleep, and comprehensive neuropsychological evaluation. Sleep-related EEG abnormalities were categorized by an epileptologist blinded to the cognitive outcome. Associations between EEG classification and neuropsychological outcomes were explored (t tests, Bonferroni correction for multiple comparisons). RESULTS: Of 128 potentially eligible participants, 34 (53% female) had complete EEG (mean age, 8.1 years; range, 0.2-16.4) and neuropsychology testing (mean age, 9.8 years; range 4.4-16.7). Twelve (35%) were classified as having electrical status epilepticus in sleep. Patients with abnormal EEGs were more likely to have statistically worse scores when corrected for multiple comparisons, in receptive language (median, 1st percentile; IQR 1-7th percentile; p<0.05), and externalizing behaviours (median, 82nd percentile; IQR, 79-97th percentile; p<0.05). CONCLUSIONS: Developmental outcome in language and behaviour in children with arterial perinatal stroke is associated with electrical status epilepticus in sleep. Increased screening with sleep EEG is suggested, whereas further studies are necessary to determine if treatment of EEG abnormalities can improve outcome.

Maternal obesity associated with increase in natural killer T cells and CD8+ regulatory T cells in cord blood units.

BACKGROUND: One of the major limitations of umbilical cord blood (UCB) as hematopoietic stem cell source is its restricted cell number. In mothers who are candidates for stem cell donation, there are variables that affect the quantity and quality of UCB units. The aim of this study was to determine if obstetric, maternal, and fetal factors modify the number of lymphocyte subsets in UCB units. STUDY DESIGN AND METHODS: This was a prospective, observational study. In UCB units, the numbers of CD34, NK, NKT, iNKT, Type 1 dendritic cells (DCs), Type 2 DCs, T γδ, T CD4+, T CD8+ lymphocytes, CD4+CD25+FoxP3+, and CD8+CD25+FoxP3+ T regulatory (Treg) cells were quantified by flow cytometry. RESULTS: Fifty-four UCB units were included; the donors' mean weight was 75 kg (range, 52 to 102 kg) and they had a mean body mass index (BMI) of 30 kg/m(2) (range 22 to 40 kg/m(2) ), of which 12 (22%) had a normal BMI, 14 (26%) were overweight, and 28 (52%) were obese. The mean number of CD34+ cells was 4.45 × 10(6) (range, 0.7 × 10(6) to 20.5 × 10(6) ). The number of NKT, CD3+, CD4+, CD8+, and CD8+CD25+FoxP3+ Treg cells was significantly higher in overweight or obese mothers; CD34+ cells were decreased in the same group. The number of iNKT and CD34+ cells was decreased in newborns weighing above the average. CONCLUSIONS: Maternal factors such as BMI, and fetal factors such as weight at birth, should be added to the selection criteria of UCB donors.