The epidemiology series of brain-related disorders in Mongolia: nationwide registry-based epidemiological study on CNS tumours in Mongolia, 2015-2019.

No epidemiological study on central nervous system tumours is available for Mongolia. The aim of this study was to determine the incidence, mortality and survival of people diagnosed with central nervous system tumours in Mongolia. It reports cancer data for the entire population (3.3 million) during the period between 2015 and 2019. Data was obtained from the National Cancer Registry of Mongolia. Diagnosis of tumours was established according to the diagnostic criteria of the International Classification of Diseases-10 (ICD-10). Incidence and mortality rates were calculated as mean annual numbers per 100,000 population. Age-standardized incidence and age-standardized mortality rates were calculated from age-specific rates by weighting directly from the World Standard Population. The three-year survival from 2015 through 2017 was calculated between treatment types by the Kaplan-Meier survival analysis. It found 515 (adults: 83 %; children: 17%) newly diagnosed central nervous system tumour cases over the five year period. The national age-standardized incidence of central nervous system tumours for the entire population was 3.7 per 100,000. The rate was higher for males than females (4.2 versus 3.4 per 100,000, respectively). Only 23% of the diagnosed cases were confirmed histologically. The most common tumour was glioma (57.6% of histologically verified tumours). In children (age 0-19 years) the age-specified incidence rate of tumours was 1.4 per 100,000. Geographically, the age-standardized incidences of the Eastern region were higher than the country average rates for both genders. During the period, 381 deaths were registered with an age-standardized mortality rate of 3.0 per 100,000 population. Furthermore, the overall three-year survival rate was 40.6% (out of 283 patients, 115 survived). The five-year prevalence of tumours was 183 and the mean per 100,000 population was 5.5. In conclusion, the data from the National Cancer Registry indicate that the incidence and survival rates of central nervous system tumours in Mongolia are relatively low. The most common location of central nervous system tumours was the brain. Glioma was the most common tumour among histologically confirmed cases. Despite the limitations, data from this study should provide information for national health policy and health care assessment. To improve the diagnosis, prognosis and treatment of central nervous system tumours, expansion of the cancer registry through collecting data on non-malignant tumours, increasing the rate of histological verification, conducting studies on cancer epidemiology and the introduction of advanced treatment technologies for central nervous system tumours are recommended.

Factores asociados a la mortalidad en pacientes cirróticos / Factors associated with mortality in cirrhotic patients

Introducción: La cirrosis hepática representa en Perú el 9,1 por ciento de las causas de mortalidad. Existe poca evidencia sobre la influencia de variables epidemiológicas y clínicas en la mortalidad de pacientes con cirrosis hepática en Latinoamérica, en especial en países en vías de desarrollo, como Perú. Objetivo: Identificar los factores asociados a la mortalidad en pacientes cirróticos. Métodos: Estudio trasversal en pacientes cirróticos atendidos en el Hospital Cayetano Heredia, de Piura, Perú, en el año 2017. La variable dependiente fue la mortalidad hospitalaria y las variables independientes fueron las características epidemiológicas, clínicas y de laboratorio. Se utilizó la prueba exacta de Fisher y la prueba de t para estimar los factores asociados a la mortalidad. Resultados: De 52 pacientes, la frecuencia de mortalidad debido a cirrosis fue de 35,4 por ciento. Tener ascitis moderada (p = 0,004), grado de encefalopatía (p = 0,001), leucocitosis (p = 0,004), enfermedad descompensada según índice de Child Pugh (p = 0,023), índice de Meld entre 30-39 puntos (p < 0,001) y niveles de creatinina (p = 0,009) resultaron asociados a una mayor frecuencia de mortalidad. Conclusión: La presencia de ascitis moderada, grado de encefalopatía, leucocitosis, enfermedad descompensada según índice de Child Pugh, índice de Meld entre 30-39 y los niveles de creatinina, están asociados a la mortalidad en pacientes cirróticos(AU)

Introduction: Liver cirrhosis represents 9,1 percent of causes of mortality in Peru. There is little evidence on the influence of epidemiological and clinical variables on the mortality of patients with liver cirrhosis in Latin America, especially in developing countries such as Peru. Objective: To identify the factors associated with mortality in cirrhotic patients. Methods: Cross-sectional study in cirrhotic patients treated at the Cayetano Heredia Hospital in Piura, Peru, year 2017. The dependent variable was hospital mortality and the independent variables were epidemiological, clinical and laboratory characteristics. Fisher's exact test and the T test were used to estimate the factors associated with mortality. Results: Of 52 patients, the frequency of mortality due to cirrhosis was 35,4 percent. Have moderate ascites (p = 0,004), degree of encephalopathy (p = 0,001), leukocytosis (p = 0,004), decompensated disease according to the Child Pugh index (p = 0,023), Meld index between 30-39 points (p < 0,001) and creatinine levels (p = 0,009) were associated with a higher frequency of mortality. Conclusion: The presence of moderate ascites, degree of encephalopathy, leukocytosis, decompensated disease according to the Child Pugh index, Meld index between 30-39, creatinine levels are associated with mortality in cirrhotic patients(AU)

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh.

BACKGROUND: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. METHODS: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. FINDINGS: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

21st Century Early Adult (55-74) Deaths from Brain-Disease-Deaths Compared to All Other Cause Mortality in the Major Western Countries - Exposing a Hidden Epidemic.

OBJECTIVES: To examine early adult deaths (EAD) - people aged 55-74 due to brain disease deaths (BDD) compared to all other causes (AOC) in the 21st century in 21 major Western countries (MWC). METHOD: EAD are below MWCc average life expectancy. All mortality drawn from the latest WHO data. The three global BDD categories consist of mental and behaviour disorder, nervous diseases and Alzheimer and other dementias. Mortality rates per million are analysed for people 55-74 years and total age-standardised death rates (ASDR). BDD rates between 2000-2015 compared against AOC of deaths for EAD and ASDR. Confidence Intervals determine any significant difference AOC and BDD over the period 2000-15, plus an examination of EAD in six separate global mortality categories. RESULTS: EAD: The separate BDD categories for EAD significantly positively correlated, validating their combination as BDD. Every country's AOC 55-74 rates fell substantially, but fourteen country's BDD rose substantially (>20%) and all MWC countries BDD rose significantly more than AOC. ASDR: All nations total AOC fell substantially, whereas seventeen BDD rates rose substantially and every country's BDD significantly increased compared to AOC deaths. Six other EAD mortalities, circulatory, cancer, respiratory, compared to BDD produced Odds Ratios ranging from 1:1.54 to 1:2.36 such were the marked differences over the period. DISCUSSION: Positive news is that AOC are down across all investigated countries in the 21st century. However, the extent of the EAD rises in just 16 years indicates that these BDD conditions are starting earlier suggesting multiple interactive environmental factors impacting upon brain related diseases.

Encephalopathy at admission predicts adverse outcomes in patients with SARS-CoV-2 infection.

AIMS: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered. RESULTS: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001). CONCLUSIONS: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.

NK-lysin peptides ameliorate viral encephalopathy and retinopathy disease signs and provide partial protection against nodavirus infection in European sea bass.

Antimicrobial peptides (AMP) comprise a wide range of small molecules with direct antibacterial activity and immunostimulatory role and are proposed as promising substitutes of the antibiotics. Additionally, they also exert a role against other pathogens such as viruses and fungi less evaluated. NK-lysin, a human granulysin orthologue, possess a double function, taking part in the innate immunity as AMP and also as direct effector in the cell-mediated cytotoxic (CMC) response. This molecule is suggested as a pivotal molecule involved in the defence upon nervous necrosis virus (NNV), an epizootic virus provoking serious problems in welfare and health status in Asian and Mediterranean fish destined to human consumption. Having proved that NK-lysin derived peptides (NKLPs) have a direct antiviral activity against NNV in vitro, we aimed to evaluate their potential use as a prophylactic treatment for European sea bass (Dicentrarchus labrax), one of the most susceptible cultured-fish species. Thus, intramuscular injection of synthetic NKLPs resulted in a very low transcriptional response of some innate and adaptive immune markers. However, the injection of NKLPs ameliorated disease signs and increased fish survival upon challenge with pathogenic NNV. Although NKLPs showed promising results in treatments against NNV, more efforts are needed to understand their mechanisms of action and their applicability to the aquaculture industry.

Recognizing encephalopathy in immune checkpoint inhibitor therapy: A single-center experience.

BACKGROUND: In this pilot study, we examined the characteristics of patients with and without central nervous system (CNS) malignancies who developed immune checkpoint inhibitor (ICI)-induced encephalopathy. METHODS: We identified adult patients treated with ICIs between 1 January 2013 and 9 May 2018 at our tertiary care center who developed encephalopathy within 30 days of the last dose of ICI without other explained causes. Demographic and clinical features were compared between patients with primary and metastatic malignant CNS tumors and those without. RESULTS: Of the 480 patients treated with ICIs, 14 (2.9%) developed encephalopathy induced by nivolumab (8), pembrolizumab (4), and combined ipilimumab-nivolumab (2). Median age was 64.5 years. Patients with CNS malignancies tolerated more treatment cycles and developed encephalopathy later than patients without CNS lesions (20 and 32 days, respectively, p = 0.04) following ICI initiation. Four of seven patients with CNS tumors developed new contrast-enhancing lesions on brain imaging despite having no changes on imaging for a median of 61 (30-545) days. Electroencephalogram (EEG) revealed features of generalized dysfunction in patients in both cohorts. Two patients without and three with CNS malignancies were treated with steroids. Two thirds of patients without and 29% of those with CNS malignancies expired during ICI therapy or shortly thereafter. CONCLUSIONS: Lack of the uniform evaluation limits the definitive conclusion of the cause of encephalopathy in some patients but reflects the standard of care at the time of their assessment. ICI-associated neurotoxicity presenting with encephalopathy is an ominous complication of ICI therapy, especially if left untreated. Prompt recognition and involvement of multidisciplinary care, including neurologists, would facilitate timely administration of recommended therapies.

Severe Acute Neurologic Involvement in Children With Hemolytic-Uremic Syndrome.

BACKGROUND AND OBJECTIVES: Acute severe neurologic involvement is the most threatening complication in children with hemolytic-uremic syndrome (HUS). Our primary study objectives were to describe the association between acute neurologic manifestations (ANMs) and in-hospital mortality among children with HUS. METHODS: Using the Pediatric Health Information System database, in this retrospective multicenter cohort study, we identified the first HUS-related inpatient visit among children ≤18 years (years 2004-2018). Frequency of selected ANMs and combinations of ANMs, as well as the rate of mortality, was calculated. Multivariate logistic regression was used to identify the association of ANMs and the risk of in-hospital mortality. RESULTS: Among 3915 patients included in the analysis, an ANM was noted in 10.4% (n = 409) patients. Encephalopathy was the most common ANM (n = 245). Mortality was significantly higher among patients with an ANM compared with patients without an ANM (13.9% vs 1.8%; P < .001). Individuals with any ANM had increased odds of mortality (odds ratio [OR]: 2.25; 95% confidence interval [CI]: 1.29-3.93; P = .004), with greater risk (OR: 2.60; 95% CI: 1.34-5.06; P = .005) among patients with ≥2 manifestations. Brain hemorrhage (OR: 3.09; 95% CI: 1.40-6.82; P = .005), brain infarction (OR: 2.64; 95% CI: 1.10-6.34; P = .03), anoxic brain injury (OR: 3.92; 95% CI: 1.49-10.31; P = .006), and brain edema (OR: 4.81; 95% CI: 1.82-12.71; P = .002) were independently associated with mortality. CONCLUSIONS: In this study, the largest systematic assessment of ANMs among children with HUS to date, we identify differences in in-hospital mortality based on the type of ANM, with increased risk observed for patients with multiple ANMs.

Impact of Surgical and Medical Treatment on Survival of Patients with Cerebral Aspergillosis: Systematic Review of the Literature.

OBJECTIVE: Cerebral aspergillosis carries a high mortality. Rapid diagnosis and treatment can increase survival, but symptoms and imaging findings are nonspecific. The literature on cerebral aspergillosis consists mostly of case reports and case series and lacks large-scale review of data. METHODS: We performed a review of the literature using PubMed in March 2019. We recorded the year of publication, age and sex of patients, neurosurgical involvement, the antifungals administered, use of intrathecal antifungals, and the outcome of patients. The relationships among variables were tested using bivariant statics and linear regression. RESULTS: A total of 324 studies met the eligibility criteria, and 198 studies including 248 patients were included. Surgical resection (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.80; P < 0.01) and administration of voriconazole (OR, 0.32; 95% CI, 0.18-0.55; P < 0.001) or itraconazole (OR, 0.36; 95% CI, 0.16-0.72; P < 0.001) were shown to be significantly associated with survival. CONCLUSIONS: Given the significant survival benefits for patients who received voriconazole and surgical intervention, we suggest early antifungal medical treatment and resection.

Prognosis of Patients with Sepsis and Non-Hepatic Hyperammonemia: A Cohort Study.

BACKGROUND Hyperammonemia has been reported in some critically ill patients with sepsis who do not have hepatic failure. A significant proportion of patients with non-hepatic hyperammonemia have underlying sepsis, but the association between non-hepatic hyperammonemia and prognosis is unclear. MATERIAL AND METHODS Information about patients with sepsis and non-hepatic hyperammonemia was retrieved from the Medical Information Mart for Intensive Care-III database. Survival rates were analyzed using the Kaplan-Meier method. Multivariate logistic regression models were employed to identify prognostic factors. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of ammonia in terms of patient mortality. RESULTS A total of 265 patients with sepsis were enrolled in this study. Compared with the non-hyperammonemia group, the patients with hyperammonemia had significantly higher rates of hospital (59.8% vs. 43.0%, P=0.007), 30-day (47.7% vs. 34.8%, P=0.036), 90-day (61.7% vs. 43.7%, P=0.004), and 1-year mortality (67.3% vs. 49.4%, P=0.004). In the survival analysis, hyperammonemia was associated with these outcomes. Serum ammonia level was an independent predictor of hospital mortality. The area under the ROC curve for the ammonia levels had poor discriminative capacity. The hyperammonemia group also had significantly lower Glasgow Coma Scale scores (P=0.020) and higher incidences of delirium (15.9% vs. 8.2%, P=0.034) and encephalopathy (37.4% vs. 19.6%, P=0.001). Intestinal infection and urinary tract infection with organisms such as Escherichia coli may be risk factors for hyperammonemia in patients who have sepsis. CONCLUSIONS Higher ammonia levels are associated with poorer prognosis in patients with sepsis. Ammonia also may be associated with sepsis-associated encephalopathy. Therefore, we recommend that serum ammonia levels be measured in patients who are suspected of having sepsis.

A novel ITPA variant causes epileptic encephalopathy with multiple-organ dysfunction.

Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices (MIM:616647). ITPase plays an important role in purine metabolism. In this study, we identified two novel homozygous ITPA variants, c.264-1 G > A and c.489-1 G > A, in two unrelated consanguineous families. The probands had epilepsy, microcephaly with characteristic magnetic resonance imaging findings (T2 hyperintensity signals in the pyramidal tracts of the internal capsule, delayed myelination, and thin corpus callosum), hypotonia, and developmental delay; both died in early infancy. Our report expands the knowledge of clinical consequences of biallelic ITPA variants.

Clinical, molecular, and pathological findings in a Neu-Laxova syndrome stillborn: A Brazilian case report.

Neu-Laxova syndrome (NLS) is a lethal genetic multiple congenital anomaly syndrome of unknown prevalence representing the severe spectrum of serine biosynthesis defects associated with PHGDH, PSAT1, or PSP gene mutations. The purpose of this study was to describe clinical/molecular and pathologic features of a NLS case caused by novel heterozygous missense variant in PHGDH gene identified in his consanguineous parents.

Diabetic versus non-diabetic rhino-orbito-cerebral mucormycosis.

OBJECTIVE: To compare the characteristics and outcomes of rhino-orbito-cerebral mucormycosis (ROCM) in diabetic versus non-diabetic patients. METHOD: It is a retrospective comparative case series on consecutive patients with biopsy-proven ROCM. Systemic and ophthalmic manifestations, imaging, management and final outcomes were compared between diabetic versus non-diabetic ROCMs referred the eye clinic of a university-based hospital (2008-2016). RESULTS: Forty-three diabetics (55 eyes) with mean age of 54.6 (SD:12.5) years and 20 non-diabetics (24 eyes) with mean age of 57.5 (SD:13.8) years were enrolled. Patients' survival was observed in 51% of diabetics and 70% of non-diabetics (P = .1). The mortality rate was 7.4 times (CI95%: 1.85-29.96) higher in diabetic ROCM treated with non-liposomal amphotericin (P = .01). Exenteration did not significantly change the mortality rate in either group. Globe survival was 40% and 50% in diabetics and non-diabetics (P = 1), respectively. Vision survival was observed in 20% of diabetics and 37% of non-diabetics (P = .2). CONCLUSION: Patients', globe and vision survivals were not different between diabetic and non-diabetic patients with ROCM. They were 51%, 40% and 20% in diabetic and 70%, 50% and 37% in non-diabetic ROCM.

Scn8a Antisense Oligonucleotide Is Protective in Mouse Models of SCN8A Encephalopathy and Dravet Syndrome.

OBJECTIVE: SCN8A encephalopathy is a developmental and epileptic encephalopathy (DEE) caused by de novo gain-of-function mutations of sodium channel Nav 1.6 that result in neuronal hyperactivity. Affected individuals exhibit early onset drug-resistant seizures, developmental delay, and cognitive impairment. This study was carried out to determine whether reducing the abundance of the Scn8a transcript with an antisense oligonucleotide (ASO) would delay seizure onset and prolong survival in a mouse model of SCN8A encephalopathy. METHODS: ASO treatment was tested in a conditional mouse model with Cre-dependent expression of the pathogenic patient SCN8A mutation p.Arg1872Trp (R1872W). This model exhibits early onset of seizures, rapid progression, and 100% penetrance. An Scn1a +/- haploinsufficient mouse model of Dravet syndrome was also treated. ASO was administered by intracerebroventricular injection at postnatal day 2, followed in some cases by stereotactic injection at postnatal day 30. RESULTS: We observed a dose-dependent increase in length of survival from 15 to 65 days in the Scn8a-R1872W/+ mice treated with ASO. Electroencephalographic recordings were normal prior to seizure onset. Weight gain and activity in an open field were unaffected, but treated mice were less active in a wheel running assay. A single treatment with Scn8a ASO extended survival of Dravet syndrome mice from 3 weeks to >5 months. INTERPRETATION: Reduction of Scn8a transcript by 25 to 50% delayed seizure onset and lethality in mouse models of SCN8A encephalopathy and Dravet syndrome. Reduction of SCN8A transcript is a promising approach to treatment of intractable childhood epilepsies. Ann Neurol 2020;87:339-346.

Recent treatment patterns and variations for pediatric acute encephalopathy in Japan.

BACKGROUND: Treatments for pediatric acute encephalopathy are largely empiric with limited evidence to support. This study investigated recent trends in clinical practice patterns for pediatric acute encephalopathy at a national level. METHOD: Discharge records were extracted for children with acute encephalopathy for the fiscal years 2010-2015 using a national inpatient database in Japan. We ascertained the secular trends in medications, diagnostic and therapeutic procedures, healthcare costs, in-hospital mortality, and length of hospital stays (LOS), using mixed effect linear or logistic regression models. We also ascertained variations and clustering of the practice patterns across different hospitals using hierarchical cluster analyses. RESULTS: A total of 4692 eligible inpatients were identified. From 2010 to 2015, we observed increasing trends in hospitalization costs, corticosteroid and edaravone use and a decreasing trend in LOS. Despite changes in treatments, the rates of home respiratory support and in-hospital mortality were constant during the study period. Hierarchical cluster analyses showed that 6 hospital groups showed largely different therapeutic strategies to the same disease regardless of mortality rates. Hospitals with more intensive treatment practices were likely to have higher mortality, while hospitals with less intensive treatment practices were likely to have the lower mortality. However, hospitals in one group (group 1) had less intensive treatment practice even though they had the highest mortality. CONCLUSIONS: We provided novel insights into the recent trends in treatments for pediatric acute encephalopathy. Therapeutic strategies varied between hospitals, suggesting the importance of pursuing evidence-based treatment strategy and promoting standardized practices to pediatric acute encephalopathy.

Characteristics of Intracranial Group A Streptococcal Infections in US Children, 1997-2014.

BACKGROUND: Few data on intracranial group A Streptococcus (GAS) infection in children are available. Here, we describe the demographic, clinical, and diagnostic characteristics of 91 children with intracranial GAS infection. METHODS: Cases of intracranial GAS infection in persons ≤18 years of age reported between 1997 and 2014 were identified by the Centers for Disease Control and Prevention's population- and laboratory-based Active Bacterial Core surveillance (ABCs) system. Medical charts were abstracted using a active, standardized case report form. All available isolates were emm typed. US census data were used to calculate rates. RESULTS: ABCs identified 2596 children with invasive GAS infection over an 18-year period; 91 (3.5%) had an intracranial infection. Intracranial infections were most frequent during the winter months and among children aged <1 year. The average annual incidence was 0.07 cases per 100000 children. For 83 patients for whom information for further classification was available, the principal clinical presentations included meningitis (35 [42%]), intracranial infection after otitis media, mastoiditis, or sinusitis (34 [41%]), and ventriculoperitoneal shunt infection (14 [17%]). Seven (8%) of these infections progressed to streptococcal toxic shock syndrome. The overall case fatality rate was 15%. GAS emm types 1 (31% of available isolates) and 12 (13% of available isolates) were most common. CONCLUSIONS: Pediatric intracranial (GAS) infections are uncommon but often severe. Risk factors for intracranial GAS infection include the presence of a ventriculoperitoneal shunt and contiguous infections in the middle ear or sinuses.

Detailed clinical course of fatal acute encephalopathy in children.

OBJECTIVE: Although the mortality among previously healthy children with acute encephalopathy (AE) is approximately 5%, their detailed clinical course has not been clarified. The objective of the present study was to describe the detailed clinical course, in minutes, of fatal AE. METHODS: We retrospectively reviewed the medical records of five patients (from 6 months to 14 years of age) who previously had no neurological disorders and were diagnosed with brain death due to AE between 2002 and 2018 at Kobe Children's Hospital. RESULTS: The initial clinical symptoms were convulsion in three cases and impaired consciousness in two. The earliest noted brain imaging abnormality was 7.5 h after neurological symptom detection. Liver enzymes and creatinine levels increased at initial examination, and sodium elevated gradually. All patients met the criteria of systemic inflammatory response syndrome, disseminated intravascular coagulation, and shock within 14 h of symptom detection. High dose steroids and targeted temperature management were initiated 3.5-14 h after onset. Despite these therapies, patients were diagnosed with brain death from 16 h to 4 days after initial neurological symptoms. AE diagnoses were made between 4 h 29 min and 4 days after initial neurological symptoms and included hemorrhagic shock and encephalopathy syndromes, Reye-like syndrome, and acute necrotizing encephalopathy in two, two, and one patient(s), respectively. CONCLUSIONS: We revealed the time series' of clinical events (e.g. SIRS, shock, DIC, AE diagnosis, brain death, and treatments) and laboratory findings relative to initial neurological symptom in fatal AE.

Sudden Infant Death After Vaccination: Survey of Forensic Autopsy Files.

Sudden infant deaths might be attributable to adverse reaction to vaccination, but separating them from coincidental occurrences is difficult. This study retrospectively investigated vaccination-related details and postmortem findings for 57 cases of sudden death in children 2 years or younger. Data were extracted from autopsy files at the Department of Forensic Medicine, Tokai University School of Medicine. Vaccination histories were available in 50 cases based on the maternity passbook. Of the 32 cases in which any vaccines were administered, 7 infants (21.9%) had received immunization within 7 days of death. The most frequent vaccine cited as the last immunization before death was Haemophilus influenzae B. Although a temporal association of vaccines with sudden death was present for two 3-month-old and one 14-month-old infants in whom death occurred within 3 days of receiving the H. influenzae type b and other vaccinations, a definitive relationship between the vaccine and death could not be identified. Histopathological examinations revealed pneumonia and upper respiratory infection as contributing to death in their cases. Moreover, all 3 cases showed hemophagocytosis in the spleen and lymph nodes, which are similar features to hemophagocytic lymphohistiocytosis. Judgment of the disorders as truly related to vaccination is difficult, but suspicious cases do exist. Forensic pathologists must devote more attention to vaccination in sudden infant death cases.

Outcomes associated with hospital admissions for accidental opioid overdose in British Columbia: a retrospective cohort study.

OBJECTIVES: To study the association between accidental opioid overdose and neurological, respiratory, cardiac and other serious adverse events and whether risk of these adverse events was elevated during hospital readmissions compared with initial admissions. DESIGN: Retrospective cohort study. SETTING: Population-based study using linked administrative data in British Columbia, Canada. PARTICIPANTS: The primary analysis included 2433 patients with 2554 admissions for accidental opioid overdose between 2006 and 2015, including 121 readmissions within 1 year of initial admission. The secondary analysis included 538 patients discharged following a total of 552 accidental opioid overdose hospitalizations and 11 040 matched controls from a cohort of patients with ≥180 days of prescription opioid use. OUTCOME MEASURES: The primary outcome was encephalopathy; secondary outcomes were adult respiratory distress syndrome, respiratory failure, pulmonary haemorrhage, aspiration pneumonia, cardiac arrest, ventricular arrhythmia, heart failure, rhabdomyolysis, paraplegia or tetraplegia, acute renal failure, death, a composite outcome of encephalopathy or any secondary outcome and total serious adverse events (all-cause hospitalisation or death). We analysed these outcomes using generalised linear models with a logistic link function. RESULTS: 3% of accidental opioid overdose admissions included encephalopathy and 25% included one or more adverse events (composite outcome). We found no evidence of increased risk of encephalopathy (OR 0.57; 95% CI 0.13 to 2.49) or other outcomes during readmissions versus initial admissions. In the secondary analysis, <5 patients in each cohort experienced encephalopathy. Risk of the composite outcome (OR 2.15; 95% CI 1.48 to 3.12) and all-cause mortality (OR 2.13; 95% CI 1.18 to 3.86) were higher for patients in the year following overdose relative to controls. CONCLUSIONS: We found no evidence that risk of encephalopathy or other adverse events was higher in readmissions compared with initial admissions for accidental opioid overdose. Risk of serious morbidity and mortality may be elevated in the year following an accidental opioid overdose.