Feasibility of ketogenic diet therapy variants for refractory epilepsy in neonates to infants under 2 years old.

BACKGROUND: Ketogenic diet Therapy (KDT) has been reported as a possible beneficial management strategy for controlling seizures in infants aged <2 years, but the safety and efficacy of this therapy remain to be investigated. We investigated the achievability, tolerability, efficacy, and safety of KDT for patients under 2 years old. MATERIALS AND METHODS: Infants younger than 2 years old with pharmacoresistant epilepsy were enrolled in this prospective study. We divided cases into three age groups: I) neonates; II) infants aged 1-12 months; III) infants aged 12-24 months. KDT initiation protocol were administration through parenteral route, enteral route or oral feeding. Seizure reduction rate, physical growth, and adverse effects were assessed at monthly visit. RESULTS: Thirteen patients who completed 6 months of KDT were recruited. There was one neonate in group I, 9 infants in group II, and 3 infants in group III. Eleven of them (11/13, 84.6%) were responders to KDT. All infants with underlying genetic etiology were seizure free after treating with KDT. The starting keto ratio was 1.1 mmol/L in group I, 2.3 mmol/L in group II, and 2.8 mmol/L in group III, which gradually approached 3:1-4:1 over 5-7 days. There were no symptomatic adverse effects or growth retardation in any of the study subjects. CONCLUSIONS: KDT is a promising alternative therapy with high feasibility, safety, and efficacy for pharmacoresistant epilepsy in infants under 2 years old, especially for those with genetic etiology. The starting keto ratio should be lower, and the keto ratio titration period should be longer than for children older than 2 years.

Effects of Mindfulness-Based Therapy for Cancer Patients: A Systematic Review and Meta-analysis.

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD - 3.48, CI - 4.07, - 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD - 0.42, CI - 0.70, - 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD - 0.64, CI - 1.09, - 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages.

Music-Based Intervention Ameliorates Mecp2-Loss-Mediated Sociability Repression in Mice through the Prefrontal Cortex FNDC5/BDNF Pathway.

Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in mecp2 null/y mice as an experimental RTT model. Male mecp2 null/y mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. BDNF, TrkB receptor motif, and FNDC5 expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. mecp2 null/y mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the mecp2-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of BDNF signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in mecp2 null/y mice, whereas TrkB signaling was not significantly changed in either region. FNDC5 expression in the prefrontal cortex region in mecp2 null/y mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve mecp2-loss-induced social dysfunction. BDNF and FNDC5 signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention.

Developing an Integrated Electronic Medication Reconciliation Platform and Evaluating its Effects on Preventing Potential Duplicated Medications and Reducing 30-Day Medication-Related Hospital Revisits for Inpatients.

The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1-November 30, 2015) and post-intervention (October 1-December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68-1.74; p < .001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03-0.53; p < .01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit.

The impact of a medication reconciliation programme at geriatric hospital admission: A pre-/postintervention study.

AIMS: The aim of this study was to improve medication reconciliation and reduce the occurrence of duplicate prescriptions by pharmacists and physicians within 72 hours of hospital admission using an intelligent prescription system combined with the National Health Insurance PharmaCloud system to integrate the database with the medical institution computerized physician order entry (CPOE) system. METHODS: This 2-year intervention study was implemented in the geriatric ward of a hospital in Taiwan. We developed an integrated CPOE system linked with the PharmaCloud database and established an electronic platform for coordinated communication with all healthcare professionals. Patients provided written informed consent to access their PharmaCloud records. We compared the intervention effectiveness within 72 hours of admission for improvement in pharmacist medication reconciliation, increased at-home medications documentation and decreased costs from duplicated at-home prescriptions. RESULTS: The medication reconciliation rate within 72 hours of admission increased from 44.0% preintervention to 86.8% postintervention (relative risk = 1.97, 95% confidence interval [CI]: 1.69-2.31; P < .001). The monthly average of patients who brought and took home medications documented in the CPOE system during hospitalization increased by 7.54 (95% CI 5.58-20.49, P = .22). The monthly average of home medications documented increased by 102.52 (95% CI 38.44-166.60; P = .01). Savings on the monthly average prescription expenditures of at-home medication increased by US$ 2,795.52 (95% CI US$1310.41-4280.63; P < .01). CONCLUSION: Integrating medication data from PharmaCloud to the hospital's medical chart system improved pharmacist medication reconciliation, which decreased duplicated medications and reduced in-hospital medication costs.

The effectiveness of music therapy for individuals with Rett syndrome and their families.

BACKGROUND: Patients with Rett syndrome (RTT) present characteristic regression in communication and hand skills, which eventually leads to intellectual and physical disability. Moreover, caregivers of patients with RTT face stressors related to patients' medical and developmental concerns. Given the indications from case reports, this pilot study investigated the effectiveness of music therapy on RTT patients, as well as on parental stress for families of children with RTT. METHODS: Families in the study group were enrolled in a twice-weekly 120-minute music therapy program for 24 weeks (n = 11), whereas families in the control group did not receive music therapy (n = 12). Participants were administered the Vineland Adaptive Behavior Scales, Rett Syndrome Clinical Severity Scale, Rett Syndrome Motor Behavioral Assessment, and Parenting Stress Index for caregivers of RTT children before and after the music therapy program. RESULTS: Music therapy improved receptive language, verbal and non-verbal communication skills, and social interaction for RTT patients. In addition, purposeful hand function, breathing patterns, and eye contact were significantly improved. Of note, music therapy also decreased the frequency of epileptic seizures. Lastly, caregivers in the study group exhibited significantly lower stress following the program. CONCLUSION: The 24-week music therapy program was effective in improving social interaction, communication skills, eye contact, hand function, and reducing seizure frequency among RTT patients. Additionally, music therapy was effective in relieving parenting stress, which may help healthcare providers initiate early intervention strategies that can prevent parenting stress and reduce the risk of depression.

Thyroxin Protects White Matter from Hypoxic-Ischemic Insult in the Immature Sprague⁻Dawley Rat Brain by Regulating Periventricular White Matter and Cortex BDNF and CREB Pathways.

BACKGROUND: Periventricular white-matter (WM) injury is a prominent feature of brain injury in preterm infants. Thyroxin (T4) treatment reduces the severity of hypoxic-ischemic (HI)-mediated WM injury in the immature brain. This study aimed to delineate molecular events underlying T4 protection following periventricular WM injury in HI rats. METHODS: Right common-carotid-artery ligation, followed by hypoxia, was performed on seven-day-old rat pups. The HI pups were injected with saline, or 0.2 or 1 mg/kg of T4 at 48⁻96 h postoperatively. Cortex and periventricular WM were dissected for real-time (RT)-quantitative polymerase chain reactions (PCRs), immunoblotting, and for immunofluorescence analysis of neurotrophins, myelin, oligodendrocyte precursors, and neointimal. RESULTS: T4 significantly mitigated hypomyelination and oligodendrocyte death in HI pups, whereas angiogenesis of periventricular WM, observed using antiendothelium cell antibody (RECA-1) immunofluorescence and vascular endothelium growth factor (VEGF) immunoblotting, was not affected. T4 also increased the brain-derived neurotrophic factors (BDNFs), but not the nerve growth factor (NGF) expression of injured periventricular WM. However, phosphorylated extracellular signal regulated kinase (p-ERK) and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) concentrations, but not the BDNF downstream pathway kinases, p38, c-Jun amino-terminal kinase (c-JNK), or Akt, were reduced in periventricular WM with T4 treatment. Notably, T4 administration significantly increased BDNF and phosphorylated CREB in the overlying cortex of the HI-induced injured cortex. CONCLUSION: Our findings reveal that T4 reversed BNDF signaling to attenuate HI-induced WM injury by activating ERK and CREB pathways in the cortex, but not directly in periventricular WM. This study offers molecular insight into the neuroprotective actions of T4 in HI-mediated WM injury in the immature brain.

Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats.

Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats.

Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14-21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

Therapeutic effects of extracorporeal shock wave therapy on patients with spastic cerebral palsy and Rett syndrome: clinical and ultrasonographic findings.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases. MATERIAL AND METHODS: Patients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography. RESULTS: Fifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT. CONCLUSION: Our study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult. Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx .

Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats.

Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear. Maternal HFD causes microbiota dysbiosis. In this study, we find that the plasma level of butyrate, a major metabolite of microbiota, is significantly decreased in the adult female maternal HFD offspring. In these rats, GPR43, a butyrate receptor was downregulated in the hippocampus. Moreover, the expressions of mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) were downregulated in the hippocampus. The decreases of these functional proteins were reversed by fructooligosaccharides (FOS, a probiotic) treatment in adulthood. Astrocytes are critical for energy metabolism in the brain. Primary astrocyte culture from female maternal HFD offspring indicated that GPR43 and the mitochondrial biogenesis were significantly suppressed, which was reversed by supplemental butyrate incubation. The oxygen consumption rate (OCR) was reduced in the HFD group and rescued by butyrate. Intriguingly, the nuclear histone deacetylase 4 (HDAC4) was enhanced in the HFD group, suggesting an inhibitory role of butyrate on histone deacetylase activity. Inhibition of HDAC4 effectively restored the OCR, bioenergetics, and biogenesis of mitochondria. Together, these results suggested that the impaired butyrate signaling by maternal HFD could underlie the reduced mitochondrial functions in the hippocampus via HDAC4-mediated epigenetic changes.

Thyroxin treatment protects against white matter injury in the immature brain via brain-derived neurotrophic factor.

BACKGROUND AND PURPOSE: Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. METHODS: Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. RESULTS: On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. CONCLUSIONS: T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

Cerebral sinovenous thrombosis associated with mastoiditis due to recurrent otitis media.

Cerebral sinovenous thrombosis (CSVT) in childhood is a rare reported. In this era of widespread antibiotic use for acute otitis media, the incidence of otogenic CSVT has markedly declined but has not been completely prevented. The current therapies for CSVT include anticoagulation, thrombolysis, hydration, surgery, and supportive care that were based on adult studies, pediatric case studies, and expert opinion. We describe the case of a 3-year-old boy who presented with manifestations of CSVT associated with mastoiditis secondary to otitis media. He completed a 3-month course of combination antibiotic and anticoagulation therapy; the CSVT was recanalized, and the mastoiditis had partially improved.

Hypoxic-ischemic retinal injury in rat pups.

BACKGROUND: Visual loss associated with brain damage, especially hypoxic-ischemic (HI) encephalopathy, is the most common cause of visual impairment in children in developed countries. We hypothesized that HI insults can cause long-term damage in immature eyes. METHODS: In postnatal day 7 rat pups, HI was induced by unilateral common carotid artery ligation followed by hypoxia. Retina damage was assessed by electroretinography (ERG) and cell counting. Neuronal injury and astrogliosis were evaluated by terminal deoxynucleotidyl transferase nick-end labeling, cleaved caspase 3, ED1, and glial fibrillary acidic protein immunostaining. RESULTS: We observed rapid and persistently extensive injuries in the ganglia cell layer (GCL), inner plexiform layer, and inner nuclear layer (INL) in ipsilateral retinas after HI injury, corresponding to the marked alteration in ERG. HI insult caused prominent microglial and Muller cell activation in ipsilateral inner retinas. Neuronal death in the GCL and INL after HI injury was mainly apoptotic, involving caspase-dependent pathways. CONCLUSION: Our study demonstrated the first evidence of HI retinal damage at both the pathological and functional level using the Vannucci model in neonatal rats. Because retinal damage is often associated with HI injury, it is important to demonstrate that a particular neuroprotective strategy effectively preserves the retina in addition to the brain.

Graph Theory-Based Electroencephalographic Connectivity via Phase-Locking Value and Its Association with Ketogenic Diet Responsiveness in Patients with Focal Onset Seizures.

Ketogenic diets (KDs) are a promising alternative therapy for pediatric refractory epilepsy. Several predictors of KD responsiveness have been identified, including biochemical parameters, seizure types, and electroencephalography (EEG) examinations. We hypothesized that graph theory-based EEG functional connectivity could explain KD responses in patients presenting focal onset seizure (FOS). A total of 17 patients aged 0-30 years old with focal onset seizures (FOS) were recruited as a study group between January 2015 and July 2021. Twenty age-matched children presenting headache with no intracranial complications nor other medical issues were enrolled as a control group. Data were obtained at baseline and at 12 months after initiating KD therapy (KDT) using the child behavior checklist (CBCL) and brain functional connectivity parameters based on phase-locking value from 19 scalp EEG signals, including nodal strength, global efficiency, clustering coefficient, and betweenness centrality. Compared with age-matched controls, patients presenting FOS with right or bilateral EEG lateralization presented higher baseline functional connectivity, including parameters such as global efficiency, mean cluster coefficient and mean nodal strength in the delta and beta frequency bands. In patients presenting FOS with right or bilateral EEG lateralization, the global efficiency of functional connectivity parameters in the delta and theta frequency bands was significantly lower at 12 months after KDT treatment than before KDT. Those patients also presented a significantly lower mean clustering coefficient and mean nodal strength in the theta frequency band at 12 months after KDT treatment. Changes in brain functional connectivity were positively correlated with social problems, attention, and behavioral scores based on CBCL assessments completed by parents. This study provides evidence that KDT might be beneficial in the treatment of patients with FOS. Graph theoretic analysis revealed that the observed effects were related to decreased functional connectivity, particularly in terms of global efficiency. Our findings related to brain connectivity revealed lateralization to the right (non-dominant) hemisphere; however, we were unable to define the underlying mechanism. Our data revealed that in addition to altered brain connectivity, KDT improved the patient's behavior and emotional state.

Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Graph Theory-Based Electroencephalographic Connectivity and Its Association with Ketogenic Diet Effectiveness in Epileptic Children.

Ketogenic diet therapies (KDTs) are widely used treatments for epilepsy, but the factors influencing their responsiveness remain unknown. This study aimed to explore the predictors or associated factors for KDTs effectiveness by evaluating the subtle changes in brain functional connectivity (FC) before and after KDTs. Segments of interictal sleep electroencephalography (EEG) were acquired before and after six months of KDTs. Analyses of FC were based on network-based statistics and graph theory, with a focus on different frequency bands. Seventeen responders and 14 non-responders were enrolled. After six months of KDTs, the responders exhibited a significant functional connectivity strength decrease compared with the non-responders; reductions in global efficiency, clustering coefficient, and nodal strength in the beta frequency band for a consecutive range of weighted proportional thresholds were observed in the responders. The alteration of betweenness centrality was significantly and positively correlated with seizure reduction rate in alpha, beta, and theta frequency bands in weighted adjacency matrices with densities of 90%. We conclude that KDTs tended to modify minor-to-moderate-intensity brain connections; the reduction of global connectivity and the increment of betweenness centrality after six months of KDTs were associated with better KD effectiveness.

Comorbidities associated with genetic abnormalities in children with intellectual disability.

Intellectual disability (ID) has emerged as the commonest manifestation of underlying genomic abnormalities. Given that molecular genetic tests for diagnosis of ID usually require high costs and yield relatively low diagnostic rates, identification of additional phenotypes or comorbidities may increase the genetic diagnostic yield and are valuable clues for pediatricians in general practice. Here, we enrolled consecutively 61 children with unexplained moderate or severe ID and performed chromosomal microarray (CMA) and sequential whole-exome sequencing (WES) analysis on them. We identified 13 copy number variants in 12 probands and 24 variants in 25 probands, and the total diagnostic rate was 60.7%. The genetic abnormalities were commonly found in ID patients with movement disorder (100%) or with autistic spectrum disorder (ASD) (93.3%). Univariate analysis showed that ASD was the significant risk factor of genetic abnormality (P = 0.003; OR 14, 95% CI 1.7-115.4). At least 14 ID-ASD associated genes were identified, and the majority of ID-ASD associated genes (85.7%) were found to be expressed in the cerebellum based on database analysis. In conclusion, genetic testing on ID children, particularly in those with ASD is highly recommended. ID and ASD may share common cerebellar pathophysiology.

Vagus nerve stimulation in pediatric patients with failed epilepsy surgery.

Adequate control of pharmacoresistant epilepsy continues to be a challenge. Multiple studies have reported the benefits of epilepsy surgery and vagus nerve stimulation for children with pharmacoresistant epilepsy. Little is known about the role of vagus nerve stimulation for children with failed epilepsy surgeries. The aim of this study was to examine the effects of vagus nerve stimulation on seizure frequency reduction for children with failed epilepsy surgeries. We retrospectively reviewed 85 children with pharmacoresistant epilepsy who underwent vagus nerve stimulation. Six of these patients underwent epilepsy surgery before vagus nerve stimulation (group I) and 79 patients received only vagus nerve stimulation (group II). We recorded seizure frequency at 3, 12, 24 and 36 months after vagus nerve stimulator implantation. Both groups had reduced seizure frequencies at the 3-, 12-, 24- and 36-month follow-up (p = 0.044 for group I trends and 0.008 for group II trends). Vagus nerve stimulator implantations significantly improve seizure frequency for children with or without previous epilepsy surgery at 3, 12, 24 and 36 months. These findings suggest that vagus nerve stimulation should be considered an alternative therapy for pediatric patients with previous failed surgeries.