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Objectives: This study aims to determine the current state of CDD diagnosis and epilepsy treatment in an upper‐middle‐income country. Methods: Forty‐seven families of the Brazilian CDD Association were invited to participate in an online survey to gather information about the diagnosis and treatment of epilepsy. Results: Forty‐three families (91.5%) of unrelated patients with confirmed genetic diagnosis of CDD participated. The median age was 7 years (ranging from 1.3–25 years) and the male: female ratio was 1:6. Early and severe epilepsy started during infancy in 74.4%. Seizures occurred daily in 61.9% and 83.7% had clusters of seizures. The mean age of diagnosis was 3.3 years (ranging from 37 days to 16 years), and younger patients had an earlier diagnosis (p < 0.001). Patients were seen by an average of 4.4 physicians (1–15) before the diagnosis. The most relevant obstacles to genetic testing were cost (55.8%) and late requests by physicians (27.9%). At the moment of the assessment, patients received a mean of 3.6 ASMs/day (ranging from 1 to 5). Thirty‐four (79.1%) caregivers reported side effects throughout life, including life‐threatening events in 16.3%. Significance: Based on our findings, a sense of urgency for genetic assessment implementation is evident since the delay in the diagnosis with unnecessary use of resources and excessive polytherapy with serious side effects cause a higher burden to the healthcare system, caregivers, and patients. Plain Language Summary: In this study, we assessed the diagnosis and treatment of patients with genetically confirmed DEE‐CDKL5 from the Brazilian Association of CDD with an online survey. Caregivers reported a long delay in the diagnosis associated with cost and late referral to genetic testing, considered the last resource for one‐third of the patients. Patients received a high number of ASM, mainly under polytherapy, with serious side effects. Although it is promising that younger patients received earlier diagnosis, public policies for genetic testing are needed to improve CDD patients' care. [ABSTRACT FROM AUTHOR]

Background/Objectives: Epilepsy is a major public health issue in Sub-Saharan Africa, particularly among children, due to limited healthcare resources, socioeconomic inequalities, and cultural stigma that often result in underdiagnosis and undertreatment. This review examines pediatric epilepsy's diagnosis, classification, and management in this setting, highlighting the need for culturally appropriate interventions to improve care quality and address these challenges. Methods: A review of the literature was conducted using MEDLINE, Embase, Scopus, and Web of Science databases to identify pertinent studies published between 2013 and 2024. This review included studies examining the epidemiology, seizure classification and etiologies of epilepsy among children in Sub-Saharan Africa. Results: This review revealed higher incidence and prevalence of epilepsy in Sub-Saharan Africa compared to high-income countries, primarily attributable to factors such as infectious diseases, perinatal injuries, and limited diagnostic resources. The most frequently reported types of epilepsy were generalized and focal seizures, with significant etiological contributions from structural and infectious causes, including nodding syndrome and HIV-related epilepsy. The treatment gap remains considerable, with up to 80% of children not receiving appropriate antiseizure medications. Conclusions: The diagnosis and treatment of epilepsy in pediatric populations in Sub-Saharan Africa is complicated by several factors, including cultural stigma and the lack of adequate healthcare infrastructure. There is an urgent need for culturally tailored diagnostic tools, improved access to affordable treatments, and public health initiatives aimed at reducing stigma. Addressing these gaps through enhanced research, improved healthcare access, and targeted educational campaigns is crucial for improving the quality of life for children with epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To develop a high‐throughput sequencing panel for the diagnosis of developmental and epileptic encephalopathy in Tunisia and to clarify the frequency of disease‐causing genes in this region. Methods: We developed a custom panel for next‐generation sequencing of the coding sequences of 116 genes in individuals with developmental and epileptic encephalopathy from the Tunisian population. Segregation analyses and in silico studies have been conducted to assess the identified variants' pathogenicity. Results: We report 12 pathogenic variants in SCN1A, CHD2, CDKL5, SZT2, KCNT1, GNAO1, PCDH19, MECP2, GRIN2A, and SYNGAP1 in patients with developmental and epileptic encephalopathy. Five of these variants are novel: "c.149delA, p.(Asn50MetfsTer26)" in CDKL5; "c.3616C > T, p.(Arg1206Ter)" in SZT2; "c.111_113del, p.(Leu39del)" in GNAO1; "c.1435G>C, p.(Asp479His)" in PCDH19; and "c.2143delC, p.(Arg716GlyfsTer10)" in SYNGAP1. Additionally, for four of our patients, the genetic result facilitated the choice of the appropriate treatment. Significance: This is the first report of a custom gene panel to identify genetic variants implicated in developmental and epileptic encephalopathy in the Tunisian population as well as the North African region (Tunisia, Egypt, Libya, Algeria, Morocco) with a diagnostic rate of 30%. This high‐throughput sequencing panel has considerably improved the rate of positive diagnosis of developmental and epileptic encephalopathy in the Tunisian population, which was less than 15% using Sanger sequencing. The benefit of genetic testing in these patients was approved by both physicians and parents. [ABSTRACT FROM AUTHOR]

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored. [ABSTRACT FROM AUTHOR]

We report on a unique case of a 7-year-old girl with new onset ocular myasthenia gravis shortly after recovery from multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2 infection. The diagnosis of myasthenia gravis was based on suggestive symptoms of fatigable bilateral orbital ptosis, diplopia, positive ocular cold compression test and serum acetylcholine receptor antibody positivity, as well as a favourable treatment response to pyridostigmine. The addition of corticosteroids and methotrexate resulted in complete resolution of the ocular signs. [ABSTRACT FROM AUTHOR]

Syringomyelia associated with tuberculous meningitis (TBM) is an extremely rare condition. Only a few adult cases have been reported. A 12-year-old woman, who previously suffered TBM at the age of 6 months, presented with a long-standing history of right upper limb panhypertrophy, dissociate anaesthesia, frequent headaches, scoliosis and acquired macrocephaly. MRI demonstrated hydrocephalus, descent of the cerebral tonsils and an intramedullary syrinx extending from C2 to L1. Endoscopic third ventriculostomy (ETV) leads to reduction in the size of the syringomyelia and resolution of the thermoanaesthesia. This case highlights a very rare long-term complication associated with childhood TBM and the potential benefit offered by ETV. [ABSTRACT FROM AUTHOR]

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In recent years, the affordability and availability of genetic testing have led to its increased use in clinical care. The increased frequency of testing has led to STXBP1 variants being identified as one of the more common variants associated with neurological disorders. In this review, we aim to summarize the common clinical phenotypes associated with STXBP1 pathogenic variants, provide an overview of their known natural history, and discuss current research into the genotype to phenotype correlation. We will also provide an overview of the suspected normal function of the STXBP1-encoded Munc18-1 protein, animal models, and experimental techniques that have been developed to study its function and use this information to try to explain the diverse phenotypes associated with STXBP1-related disorders. Finally, we will explore current therapies for STXBP1 disorders, including an overview of treatment goals for STXBP1-related disorders, a discussion of the current evidence for therapies, and future directions of personalized medications for STXBP1-related disorders. [ABSTRACT FROM AUTHOR]

Background: Early infantile epileptic encephalopathy (EIEE) is a group of highly heterogeneous diseases, both phenotypically and genetically. Usually, it starts early on and manifests as intractable epilepsy, abnormal electroencephalogram, and growth retardation/intellectual impairment. With the advent of next‐generation sequencing (NGS), its genetic etiology has attracted increasing clinical attention. This study aimed to investigate the genetic characteristics and clinical phenotypes of patients with EIEE from a central hospital in Eastern China. Methods: This study retrospectively included the gene variants from 24 EIEE‐positive patients admitted between January 2021 and January 2022 to a hospital in Anhui Province, China. The genetic diagnosis was performed in all cases by trio‐based whole‐exome sequencing (WES). Additionally, Video electroencephalogram (VEEG) and neuroimaging examinations were performed. Results: A total of 24 children were included. The average age at the first seizure was approximately 5 months. About 42% of children had developmental retardation of varying degrees, 43% had brain structural abnormalities, and 64% had VEEG abnormalities. In addition, other phenotypes, including endocrine metabolism and cardiac structural abnormalities, have been independently reported. In total, fifteen pathogenic gene variants were identified in 24 patients. The main pathogenic genes identified were SCN1A (25%, 6/24), KCNQ2 (8.3%, 2/24), and TBC1D24 (8.3%, 2/24). We also found an extremely rare case of EIEE84 type caused by biallelic UGDH gene variants, predicting that this variant might affect the stability of the protein structure. Conclusions: SCN1A pathogenic variants are the main factor leading to EIEE, similar to previously published cohort reports. NGS is useful for accurate clinical diagnoses and precise treatment choices. We also reported a rare case of EIEE84 caused by variants in the UGDH gene in a Chinese patient. This study further enriches the known spectrum of pathogenic EIEE genes. [ABSTRACT FROM AUTHOR]

We herein report a case of a child with tuberculous meningitis and COVID-19 coinfection complicated by hydrocephalus, arterial ischaemic stroke and extensive cerebral sinus venous thrombosis. Both conditions induce a proinflammatory cytokine drive resulting, among others, in a prothrombotic state. The disruption of the coagulation system in this case was supported by elevated D-dimers, fibrinogen and ferritin levels, consistent with thrombotic complications reported in some adult patients infected with COVID-19. The child also exhibited prolonged viral shedding that suggests severe disease. [ABSTRACT FROM AUTHOR]

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits. [ABSTRACT FROM AUTHOR]

COVID-19 infection has had a profound impact on society. During the initial phase of the pandemic, there were several suggestions that COVID-19 may lead to acute and protracted neurologic sequelae. For example, peripheral neuropathies exhibited distinctive features as compared to those observed in critical care illness. The peripheral nervous system, lacking the protection afforded by the blood--brain barrier, has been a particular site of sequelae and complications subsequent to COVID-19 infection, including Guillain-Barre syndrome, myasthenia gravis, and small fiber neuropathy. We will discuss these disorders in terms of their clinical manifestations, diagnosis, and treatment as well as the pathophysiology in relation to COVID-19. [ABSTRACT FROM AUTHOR]

To analyze the efficacy of using honey to treat acute cough in children. Systematic review, synthesis without meta-analysis. We searched PubMed, Scopus, CENTRAL, CINAHL, and Web of Science databases on August 15, 2022, for words honey and cough. Randomized controlled trials conducted in children were included. Risk-of-bias and evidence quality were assessed. Studies were not pooled due to lack of key information. Instead, we provided the range of observed effects for the main outcomes. Three hundred ninety-six papers were screened, and 10 studies were included. Two studies had high risk-of-bias and six had some concerns. Honey seemed to decrease cough frequency more than placebo/no treatment (range of observed effect 0.0–1.1 points) and cough medication (0.2–0.9 points). Sleep improved more often in the honey group (range of effect was 0.0–1.1) compared to placebo/no treatment and (− 0.2–1.1 points) compared to cough medication. Quality of the evidence was low to very low. Conclusion: We found low quality evidence that honey may be more effective than cough medication or placebo/no treatment in relieving symptoms and improving sleep in children with acute cough. Better quality randomized, placebo-controlled blinded trials are needed to confirm the effectiveness of honey in treating acute cough in children. Trial registration: CRD42022369577. What is Known: • Honey has been suggested to be effective as a symptomatic treatment in acute cough. • Prior randomized trials have had conflicting results and thus an overview of the literature was warranted. What is New: • Based on low quality evidence honey may be more effective than placebo or over-the-counter medications for acute symptom reliwef in cough. • Future studies with better reporting are needed to confirm the results. [ABSTRACT FROM AUTHOR]

Background: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). Methods: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 − Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. Results: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48–84 HOL (AUC 0.71–0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42–66 HOL (AUC 0.8–0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). Conclusions: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Honey is a nutritious, healthy, and natural food, to which antioxidant, anti-inflammatory, and antimicrobial properties have been attributed, mainly due to its content of phenolic compounds. The aim of this review is to analyze the available evidence of the effect of honey on humans. Forty-eight clinical trials published between 1985 and 2022 were analyzed, with a total of 3655 subjects. More beneficial effects of honey intake than no or negative effects on different cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, cough in children and wound healing, among others have been observed. Although the number of studies conducted to date is limited and the different investigations are not standardized, beneficial effects of honey intake have been observed, especially when its intake replaces the intake of other sweeteners. In addition, honey could be a safe adjuvant to be administered alongside drugs used for certain diseases. [ABSTRACT FROM AUTHOR]

Background: Tuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further. Methods: Among those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. "Tuberculous meningitis" and "cerebral venous thrombosis" were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition. Results: Among 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent. Conclusions: CVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. Methods: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. Results: A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43–13.88; p = 0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70–6.00; p < 0.001), and radiological infarction (aOR: 3.47; 95%CI: 1.87–6.45; p < 0.001) were associated with a poor developmental outcome. Left hemispherical (single and multiple) stroke and bilateral stroke were associated with poor developmental outcomes. Conclusion: Certain neurological signs as well as radiological infarct characteristics are important predictors of poor developmental outcome. Anticipation of the likely level of cognitive impairment at diagnosis allows more accurate prognostication and prompt institution of supportive and rehabilitative measures, after the acute illness. [ABSTRACT FROM AUTHOR]

Advances in disease-related gene discovery have led to tremendous innovations in the field of epilepsy genetics. Identification of genetic mutations that cause epileptic encephalopathies has opened new avenues for the development of targeted therapies. Clinical testing using extensive gene panels, exomes, and genomes is currently accessible and has resulted in higher rates of diagnosis and better comprehension of the disease mechanisms underlying the condition. Children with developmental disabilities have a higher risk of developing epilepsy. As our understanding of the mechanisms underlying encephalopathies and epilepsies improves, there may be greater potential to develop innovative therapies tailored to an individual's genotype. This article provides an overview of the significant progress in epilepsy genomics in recent years, with a focus on developmental and epileptic encephalopathies in children. The aim of this review is to enhance comprehension of the clinical utilization of genetic testing in this particular patient population. The development of effective and precise therapeutic strategies for epileptic encephalopathies may be facilitated by a comprehensive understanding of their molecular pathogenesis. [ABSTRACT FROM AUTHOR]

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers. [ABSTRACT FROM AUTHOR]

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as an early acute kidney injury (AKI) biomarker in the neonatal population. Our goal is to describe this biomarker behavior in this high-risk population, in absence of AKI as confirmed by inulin clearance. Materials and methods: Prospective study including 42 preterm newborns (mean gestational age: 30.7 ± 2.3 weeks) with a urinary NGAL collection between day 1 and 6 of life. Results: Median urinary neutrophil gelatinase-associated lipocalin (uNGAL) value is 122.8 ng/ml (7–1981.5 ng/ml). Statistically significant higher uNGAL values are found in female. uNGAL median values are decreasing when comparing extremely, very, and late preterm groups (812.2 ng/ml [75.8–1453.9] vs. 124.4 ng/ml [31.4–1981.5] vs. 65.3 ng/ml [7.1–1091]). There is a statistically significant inverse correlation between gestational age and uNGAL values (Pearson's coefficient r= −0.37). uNGAL median values are higher in groups exposed to gentamicin, neonatal asphyxia, early onset sepsis, or patent ductus arteriosus. Median inulin clearance is 18.8 ml/min/1.73 m2 [14.8–25.5 ml/min/1.73 m2]. There is no correlation between uNGAL values and inulin clearance results (Pearson's coefficient r=–0. 29, p:.06). Conclusions: In this preterm newborn's series without AKI, the median uNGAL and its high variability are in accordance with published reference ranges. Correlation between uNGAL and gestational age exists, as well as gender impact. Newborns exposed to different renal insults present higher uNGAL values, suggesting potential undetected tubular toxicity or reflecting NGAL production in case of inflammatory or ischemic processes. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis, like COVID-19, is most often a pulmonary disease. The COVID-19 pandemic has severely disrupted tuberculosis services in myriad ways: health facility closures, lockdowns, travel bans, overwhelmed healthcare systems, restricted export of antituberculous drugs, etc. The effects of the shared risk on outcomes of the two diseases is not known, particularly for the first year of the pandemic, during the period before COVID-19 vaccines became widely available. Objective: We embarked on a systematic review to elucidate the consequences of tuberculosis on COVID-19 outcomes and of COVID-19 on tuberculosis outcomes during the pre-vaccination period of the pandemic. Methods: The systematic review protocol is registered in PROSPERO. We conducted an initial search of PubMed, Embase, Web of Science, WHO coronavirus database, medRxiv, bioRxiv, preprints.org, and Google Scholar using terms relating to COVID-19 and tuberculosis. We selected cohort and case–control studies for extraction and assessed quality with the Newcastle-Ottawa scale. Results and Conclusion: We identified 2108 unique abstracts published between December 2019 and January 2021. We extracted data from 18 studies from 8 countries. A total of 650,317 persons had a diagnosis of COVID-19, and 4179 had a diagnosis of current or prior tuberculosis. We explored links between tuberculosis and COVID-19 incidence, mortality, and other adverse outcomes. Nine studies reported on mortality and 13 on other adverse outcomes; results on the association between tuberculosis and COVID-19 mortality/adverse outcomes were heterogenous. Tuberculosis outcomes were not fully available in any studies, due to short follow-up (maximum of 3 months after COVID-19 diagnosis), so the effects of COVID-19 on tuberculosis outcomes could not be assessed. Much of the rapid influx of literature on tuberculosis and COVID-19 during this period was published on preprint servers, and therefore not peer-reviewed. It offered limited examination of the effect of tuberculosis on COVID-19 outcomes and even less on the effect of COVID-19 on tuberculosis treatment outcomes. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has set back the global tuberculosis (TB) response by several years. In 2020, access to TB prevention and care declined sharply, with TB notifications dropping by 18% compared to 2019. Declines were more pronounced in children, with a 24% drop in 0–14 year-olds and a 28% drop in 0–4 year-olds. As a result, in 2020 the number of deaths due to TB increased to 1.5 million across all ages, reversing a decade-long declining trend. Progress toward the UN High Level Meeting targets for 2022 is at risk, including the targets related to children for TB and drug-resistant TB treatments, and TB preventive therapy. Nonetheless, ending TB by 2030 as envisaged in the Sustainable Development Goals (SDGs) is still possible, but requires increased investments in accelerated case detection, subclinical TB, preventive therapy and an effective vaccine. Investing in TB could prepare the world better for fighting a future airborne pandemic. [ABSTRACT FROM AUTHOR]

Our study evaluates the effects of aminophylline in the reduction of NGAL levels in perinatal asphyxia. Term neonates with hypoxic ischaemic encephalopathy who were divided into two groups, the treatment and placebo. Urine NGAL levels were measured on day one and four of the treatment using BIOPORTO kits in both the groups. Day 1 NGAL levels were not statistically different in either group irrespective of the age, gender and the mode of delivery. on 4th day, NGAL in treatment group significantly decreased as compared to day 1 levels and placebo day-4 levels. significant differences were seen between first and fourth day NGAL levels among children with normal and caesarean birth and among female and male neonates. Following the treatment with aminophylline, NGAL levels in asphyxiated neonates are likely to reduce. Further studies based on other kidney dysfunction parameters can lead to the better and accurate conclusions. [ABSTRACT FROM AUTHOR]

Emerging cases of coinfection of coronavirus disease 2019 (COVID-19) and tuberculosis (TB), although rare, have attracted the attention of health systems around the world and have arisen many concerns about the diagnosis, treatment, and prognosis of this coinfection especially in high TB burden countries. Here, we report a rare case and, to the best of our knowledge, the first reported case in Morocco of simultaneous diagnosis of an active pulmonary TB infection and a COVID-19 pneumonia. We present a case of a sixty-seven-year-old male patient who was admitted to our COVID-19 emergency department with a diagnosis of COVID-19 pneumonia, confirmed by nasopharyngeal swab's polymerase chain reaction (PCR) for detection of SARS-CoV-2. The atypical radiological findings suggested a TB coinfection which was later confirmed by sputum cultures and Xpert MTB/Rif assay. The patient also presented some complications including thrombosis of the left leg, pulmonary embolism and inaugural ketosis. Treatment was administered as per local protocols: broad spectrum antibiotics, corticosteroids, fixed dose-combination of antituberculosis treatment along with hydration and insulin therapy for ketosis treatment and anticoagulation. The patient was discharged after twenty-three days of hospitalization. Due to the currently limited data, further studies are necessary to establish any possible correlation between COVID-19 infection and the progression of a latent and/or the severity of an active TB infection. [ABSTRACT FROM AUTHOR]

Introduction: Viral infection such as coronavirus disease 2019 (COVID-19) can exacerbate and aggravate neurological disorders due to autoimmune etiology like myasthenia gravis (MG). Experimental therapies used in COVID-19 are also factors that can cause the worsening of MG symptoms. This review aimed to assess and conclude the research-based study systematically to analyze the relationship of MG and COVID-19. Method: This study was conducted in accordance to Cochrane handbook for systematic reviews and the guideline of preferred reporting items for systematic review and meta-analysis (PRISMA) and synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. Inclusion criteria in this review were primary studies of every design, articles published in English around January 2000–October 2021, and the study used human as subject. A systematic literature finding was applied in 15 electronic scientific resources. The authors evaluated the study quality and risk of bias of each retrieved article. Results: The authors found the study through electronic scientific resources that met inclusion and exclusion criteria. The authors evaluated 362 articles identified in literature searching, 22 articles met the criteria for this review and then underwent the evaluation of study quality and risk of bias. Conclusion: COVID-19 infection can increase the risk of new-onset MG, myasthenic crisis, respiratory failure, and mortality rate due to cytokine storm in MG patients. The management of COVID-19 patients with MG is tailored to each person and based on national guidelines and local expert recommendations. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 19 (COVID-19) and Mycobacterium tuberculosis (MTB) are among the top ongoing health crises globally. Both cause respiratory diseases, and the clinical presentations are similar. There is no summarized information about cases of COVID-19 patients with concomitant TB infection from different settings. Therefore this review aimed to summerize the clinical features and treatment outcomes of coronavirus and tuberculosis co-infected patients. Methods: An electronic search of case reports published between 2020 and 2021 was conducted using Google Scholar, PubMed, Scopus, and ScienceDirect. From eligible reports, data were collected for the selected variables. We analyzed the collected information using SPSS version 27 software. Descriptive statistics were computed for the selected variables. Results: A total of 83 patient histories were collected from 47 case reports. The majority (80%) of the cases were reported for male patients. The mean age was 42.6 years (3 months to 84 years, SD=17.3). Fever was reported in 80% of cases, followed by cough (73.3%) and hypotension (37.1%). Blood cell parameters revealed lymphopenia (52%), lower hemoglobin (30%), elevated CRP (70%), elevated ferritin (28%), and increased D-dimer (23.4%). Treatment outcome is significantly associated with blood cell count results (p-0.044) and a rise in blood inflammatory cytokines(p-0.041). The mean days for viral clearance or negative PCR was 23 days (Range 5– 82 days) and the overall mean duration of hospitalization was 27 days. The total death rate was 22.4%. Recovery was reported for 76.6% of cases. Survival status (p-0.613) and disease severity (p-0.68) are not significantly associated with the gender of the participants. Conclusion: An alteration in blood cell parameters is associated with an unfavorable treatment outcome. There is a higher death rate in COVID-19/TB co-infection. The death is associated with older age, smoking or smoking history, drug abuse, and co-morbidity of non-communicable diseases. Conversely, there is a lower death rate in HIV patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is an infectious disease that poses severe threats to global public health and significant economic losses. The COVID-19 global burden is rapidly increasing, with over 246.53 million COVID-19 cases and 49.97 million deaths reported in the WHO 2021 report. People with compromised immunity, such as tuberculosis (TB) patients, are highly exposed to severe COVID-19. Both COVID-19 and TB diseases spread primarily through respiratory droplets from an infected person to a healthy person, which may cause pneumonia and cytokine storms, leading to severe respiratory disorders. The COVID-19-TB coinfection could be fatal, exacerbating the current COVID-19 pandemic apart from cellular immune deficiency, coagulation activation, myocardial infarction, and other organ dysfunction. This study aimed to assess the pathogenesis of SARS-CoV-2- Mycobacterium tuberculosis coinfections. We provide a brief overview of COVID19-TB coinfection and discuss SARS-CoV-2 host cellular receptors and pathogenesis. In addition, we discuss M. tuberculosis host cellular receptors and pathogenesis. Moreover, we highlight the impact of SARS-CoV-2 on TB patients and the pathological pathways that connect SARS-CoV-2 and M. tuberculosis infection. Further, we discuss the impact of BCG vaccination on SARS-CoV-2 cases coinfected with M. tuberculosis , as well as the diagnostic challenges associated with the coinfection. [ABSTRACT FROM AUTHOR]

We present a rare case of cerebral venous sinus thrombosis in a COVID-19-positive, 2-month-old infant, to this day the youngest described patient with this rare combination of findings. He was hospitalized with focal seizures. The first brain imaging showed subdural hematoma and focal ischemic changes. The subdural hematoma was successfully evacuated. The control imaging, done due to lethargy, showed an extensive cerebral venous sinus thrombosis. The thrombosis was managed with low molecular weight heparin leading to clinical and radiological improvement. With this case report, we would like to add to the information pool of COVID-19 neurological manifestations in children, particularly those younger than 1 year. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is still one of the most important causes of death worldwide. The lack of timely attention on TB diagnosis and treatment during the coronavirus disease 2019 (COVID-19) pandemic is a potential threat to health issues and may have severe consequences for patients and health systems. There is not much information on the management of TB during this period. Here, we reviewed the current literature to evaluate the rate of Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 coinfections and interactions between these infectious agents. Methods: Several databases, including Web of Science, Scopus, and MEDLINE (via PubMed), were searched for original articles addressing TB and COVID-19 diseases published from December 2019 to April 2021. Results: Of 3,879 articles, 57 articles were included in this study, and among 106,033 patients affected by COVID-19, 891 also had TB. Overall, investigators found a consistent increase in C-reactive protein, D-dimer (especially in patients with severe clinical manifestation), erythrocyte sedimentation rate, lactate dehydrogenase, alanine aminotransferase, and a reduction of lymphocytes. The respiratory symptoms of TB/COVID-19 patients were similar to those of TB patients, but the risk of developing pulmonary TB increased in COVID-19 patients. Also, the mortality rate in TB/COVID-19 patients was higher than that in patients affected only by COVID-19 or TB. Conclusion: Some reports indicated worsening respiratory symptoms and even activation of latent TB after COVID-19 or vice versa. It seems that both active and previously treated TB constituted a risk factor for COVID-19 in terms of severity and mortality, regardless of other underlying diseases and patient status. Health systems should not neglect TB during this era of the ongoing COVID-19 pandemic by setting up appropriate diagnostic and clinical management algorithms. [ABSTRACT FROM AUTHOR]

Background and purpose: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease‐2019 (COVID‐19). Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases to identify cases of COVID‐19–associated CVT. The search period spanned 1 January 2020 to 1 December 2020, and the review protocol (PROSPERO‐CRD42020214327) followed Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Identified studies were evaluated for bias using the Newcastle‐Ottawa scale. A proportion meta‐analysis was performed to estimate the frequency of CVT among hospitalized COVID‐19 patients. Results: We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, and the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37%, and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS‐CoV‐2 infection were present in 31%. In‐hospital mortality was 40%. Using data from 34,331 patients, the estimated frequency of CVT among patients hospitalized for SARS‐CoV‐2 infection was 0.08% (95% confidence interval [CI]: 0.01–0.5). In an inpatient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID‐19 (cohort of 406 patients, 95% CI: 1.47–11.39). Conclusions: Cerebral venous thrombosis in the context of SARS‐CoV‐2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, because the diagnosis of this potentially life‐threatening condition in COVID‐19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID‐19–associated CVT. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients. [ABSTRACT FROM AUTHOR]

Honey is a natural product that has been used as medication since the ancient times for its nutritive and therapeutic value. Despite these properties, honey use has been limited in evidence-based medicine due to the lack of evidence in clinical settings, particularly in paediatric population. An increasing interest has grown towards honey during the last years. The aim of this article is to examine the possible role of honey as a therapeutic tool in paediatrics. We performed a literature search to summarise the highest quality evidences, analysed articles regarding honey's nutritional properties and therapeutic value. The state of the art is represented by evidences related to beneficiary effects of honey on respiratory, gastroenterological and oncohaematologic diseases. Many other uses could promisingly come from in vitro studies or clinical trial based on adult samples. Honey shows an excellent risk-benefit profile and can be safely administrated in children older than 12 months. In conclusion, honey does not only represent a grandma's remedy, but is a real useful tool in different clinical settings, including paediatrics practice. However, there is a need for high-quality, large randomised controlled trials confirming effectiveness and practical application of honey in paediatric population. [ABSTRACT FROM AUTHOR]

Neurologic manifestations associated with Covid-19 are increasingly reported, especially stroke and acute cerebrovascular events. Beyond cardiovascular risk factors associated with age, some young adults without medical or cardiovascular history had stroke as a presenting feature of Covid-19. Suggested stroke mechanisms in this setting are inflammatory storm, subsequent hypercoagulability, and vasculitis. To date, a handful of pediatric stroke cases associated with Covid-19 have been reported, either with a cardioembolic mechanism or a focal cerebral arteriopathy. We report the case of an adolescent who presented with febrile meningism and stupor. Clinical, biological, and radiological features favored the diagnosis of Lemierre syndrome (LS), with Fusobacterium necrophorum infection (sphenoid sinusitis and meningitis) and intracranial vasculitis. The patient had concurrent SARS-CoV-2 infection. Despite medical and surgical antimicrobial treatment, stroke prevention, and venous thrombosis prevention, he presented with severe cerebrovascular complications. Venous thrombosis and stroke were observed, with an extension of intracranial vasculitis, and lead to death. As both F. necrophorum and SARS-CoV-2 enhance inflammation, coagulation, and activate endothelial cells, we discuss how this coinfection may have potentiated and aggravated the usual course of LS. The potentiation by SARS-CoV-2 of vascular and thrombotic effects of a bacterial infection may represent an underreported cerebrovascular injury mechanism in Covid-19 patients. These findings emphasize the variety of mechanisms underlying stroke in this disease. Moreover, in the setting of SARS-CoV-2 pandemic, we discuss in what extent sanitary measures, namely, lockdown and fear to attend medical facilities, may have delayed diagnosis and influenced outcomes. This case also emphasizes the role of clinical assessment and the limits of telemedicine for acute neurological condition diagnosis. [ABSTRACT FROM AUTHOR]

Most children with SARS-CoV-2 infection have relatively mild clinical symptoms without fever or pneumonia, although severe cases with multiple-organ failure have been reported. Neurological symptoms, which have been mainly reported in adults, are very rare in children. This article will review 2 different aspects of neurological involvement related to this infection in children. In the first part, we will review the neurological abnormalities reported in children caused by this viral infection. Adults frequently report muscle pain, headache, anosmia, dysgeusia, and occasionally more severe central or peripheral nervous system damage. Neurological involvement seems infrequent in children, although some cases have been reported. In the second part, we will discuss the COVID-19 pandemic impact on the healthcare system of some countries, causing collateral damage to general pediatric care and in particular to those children affected with chronic diseases, mainly neurological conditions, including autism, intellectual disability, attention deficit and hyperactivity disorder (ADHD), neuromuscular disorders, cerebral palsy, and epilepsy, and patients needing neurosurgical procedures. [ABSTRACT FROM AUTHOR]

There is growing evidence that neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. The objective of this meta-analysis is to determine the accuracy of serum and urinary NGAL in the detection of acute kidney injury in neonates with perinatal asphyxia. Medline (1966-2018), Scopus (2004-2018), EMBASE (1980-2018), Clinicaltrials.gov (2008-2018), and Google Scholar (2004-2018) databases, along with the reference lists of the electronically retrieved articles, were systematically searched. Eleven studies were included, with a total number of 652 neonates. The summary sensitivity of serum NGAL was 0.818 (95% CI [0.668, 0.909]), the specificity 0.870 (95% CI [0.754, 0.936]), and the area under the curve 0.912. Regarding urinary NGAL, pooled sensitivity was calculated at 0.897 (95% CI [0.829, 0.940]), specificity at 0.729 (95% CI [0.561, 0.850]), and area under the curve at 0.899.Conclusion: Serum and urinary NGAL represent candidate biomarkers with high performance in the prediction of acute kidney injury in newborns with perinatal asphyxia. Before NGAL can be widely used in clinical practice, future large prospective studies are needed to define the optimal cutoffs and accurately determine which levels are suggestive of post-asphyxial acute kidney injury. What is Known: • Acute kidney injury is a major cause of morbidity and mortality in perinatal asphyxia. • Current markers are insufficient in predicting post-asphyxial acute kidney injury. What is New: • Area under the curve for serum and urinary neutrophil gelatinase-associated lipocalin is 0.818 and 0.899, respectively. • Neutrophil gelatinase-associated lipocalin is a useful marker for detecting asphyxiated neonates at risk of developing acute kidney injury. [ABSTRACT FROM AUTHOR]

Persistent cough is one of the most common reasons for parents to seek pediatric care for their children. The prevalence of the use of antitussive drugs in childhood is high and their administration is not always guided by a doctor. Evidence from clinical studies shows that centrally acting antitussives and antihistamines do not appear to be superior to placebo, while studies on mucolytics are few. A variety of natural substances (e.g., honey) have been shown to exhibit an efficient antitussive effect, while some studies even document that a placebo may alleviate cough. It should be noted that dosage guidelines for a series of antitussive drugs are based on studies conducted exclusively in adult populations. [ABSTRACT FROM AUTHOR]

Background and objective: We conducted a prospective double-blind randomized study assessing bupivacaine end-of-surgery wound infiltration for pain relief in thyroid surgery.Methods: Patients were randomly divided into two groups: Group S, local wound infiltration with saline solution; Group B, bupivacaine 0.5% was administered. Pain perception was measured using visual analogue scale (VAS) during post-anaesthetic care unit (PACU) stay every 10 min and during the 24 postoperative hours admission at 2, 4, 6, 12, and 24 h after surgery. The total consumption of analgesics (morphine and nefopam) was recorded.Results: Sixty patients were studied. The VAS scores were significantly lower in the bupivacaine administered group in the post-anaesthetic care unit (PACU) at 0, 10, 20, 30, 40, 50 and 60 min, and during the hospital stay at hours 6, 12, 18 and 24. The number of patients who required postoperative opioid rescue was significantly lower in group B. No patient in group B developed neurological or cardiological complications after infiltration.Conclusion: Bupivacaine application is effective in decreasing postoperative pain and analgesic requirement during the hospital stay for patients with thyroidectomy. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA).Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria.Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p < 0.001,p <0.001,p  <0.02,p  <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p = 0.002,p  <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p = 0.004) compared to those without AKI.Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients. [ABSTRACT FROM PUBLISHER]

Background: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid emulsion workgroup was therefore established by the American Academy of Clinical Toxicology to review the evidence on the effect of ILE for LA toxicity.Methods: We performed a systematic review of the literature published through 15 December 2014. Relevant articles were determined based on pre-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded.Results: We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 healthy volunteers. The subclinical LA toxicity design did not show a difference in the effects of ILE versus saline. There was one case series and 73 case reports of ILE use in the context of toxicity (83 patients) including CNS depression or agitation (n = 45, 54%), seizures (n = 49, 59%), hypotension, hypertension, EKG changes, arrhythmias (n = 39, 47%), cardiac arrest (n = 18, 22%), cardiopulmonary resuscitation, and/or requirement for endotracheal intubation and/or mechanical ventilation (n = 35, 42%). There were 81 (98%) survivors including 63 (76%) with no reported sequelae from the LA poisoning or ILE, although the presence or absence of sequelae was not reported in 15 (18%) cases. Animal studies included 29 randomized controlled studies, three observational studies, five case series, and one case report; bupivacaine was used in 29 of these reports (76%). Of 14 controlled experiments in animals, eight showed improved survival or time to return of spontaneous circulation and five no benefit of ILE versus saline or non-ILE treatments. Combining ILE with epinephrine improved survival in five of the six controlled animal experiments that studied this intervention. The studies were heterogeneous in the formulations and doses of ILE used as well as the doses of LA. The body of the literature identified by this systematic review yielded only a very low quality of evidence.Conclusion: ILE appears to be effective for reversal of cardiovascular or neurological features in some cases of LA toxicity, but there is currently no convincing evidence showing that ILE is more effective than vasopressors or to indicate which treatment should be instituted as first line therapy in severe LA toxicity. [ABSTRACT FROM AUTHOR]