Neurological Comorbidities Research Articles

INNV-17. SAME-DAY DISCHARGE AFTER LASER INTERSTITIAL THERMAL THERAPY: A PROSPECTIVE COHORT PILOT STUDY WITH A MATCHED CONTROL GROUP

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for intracranial pathologies, offering precision and control over tissue damage. With implementation of enhanced recovery after surgery (ERAS) protocols within neurosurgery, identifying patients amenable for same-day discharge (SDD) is an important step towards streamlining perioperative care following LITT, and correspondingly, we aim to summarize our initial experience. METHODS We conducted a prospective study at the University of Miami Hospital of 7 patients who underwent LITT for intracranial pathologies and were discharged on the same day of ablation (post-ablation day 0, PAD0). We then performed a retrospective case-control study against a historic matched PAD1 cohort comparing categorical and continuous variables for statistical significance. RESULTS The mean age of the PAD0 cohort was 55 years with 71% males. Preoperative neurological status and comorbidities did not differ significantly between the PAD0 and PAD1 cohorts for KPS (median [IQR]: 80 [80-90] vs. 90 [80-90], p=0.40), mFI-5 (median [IQR]: 1 [1.5] vs. 0 [1], p=0.54), and mFI-11 (median [IQR]: 1 [1.5] vs. 1 [1], p=0.52). PAD0 outcomes demonstrated no immediate complications, neurosurgical readmissions, or significant neurological deficits within 6 months post-procedure and were non-significantly different than PAD1 patients. No PAD0 patient experienced intracranial hemorrhage or vasogenic edema following LITT that necessitated further intervention. CONCLUSIONS Our study demonstrates the safety and feasibility of same-day discharge following LITT for intracranial pathologies in the appropriately selected patient. Through meticulous patient selection and optimized perioperative protocols, expedited recovery without compromising patient outcomes was achieved. This approach holds potential for substantial cost savings and resource optimization within healthcare systems. Further research and quality improvement initiatives are warranted to refine patient selection criteria and maximize the benefits of same-day discharge in LITT practice.

Somatic and neurological comorbidities in COVID-19 with fatal outcome

Introduction. Although the risk of emerging coronavirus infection may seem to have disappeared at first glance, SARS-COV-2 has complex and poorly understood effects on many organ systems, including the nervous system. Disease progression and unfavorable outcome COVID-19 are not only due to lung damage, elderly age, concomitant pathology: hypertension, diabetes mellitus, etc. have a significant impact.Aim. To study the structure of mortality in a new coronavirus infection COVID-19, caused by delta strain of coronavirus SARS- CoV-2, taking into account the nature of concomitant therapeutic and neurological pathology, the degree of comorbidity, fatal complications, and sex and age characteristics.Materials and methods. A postmortem analysis of pathological and anatomical conclusions of 209 patients with COVID-19 with comorbid somatic and neurological pathology who received inpatient treatment in covid hospitals of the Republic of Mordovia in 2021 was performed. The severity of the underlying disease, concomitant therapeutic and neurological pathology, and comorbidity were analysed. The coincidence of the final clinical and pathological diagnoses, fatal complications were assessed. The presented data allowed to identify the main factors of unfavourable outcome.Results and discussion. In unfavourable outcome of the disease, concomitant pathology is represented by hypertension, ischemic heart disease, chronic heart failure, chronic cerebral ischemia. In women, cases of diabetes mellitus and atherosclerosis were more frequent, in men - hypertension and chronic heart failure.Conclusions. New coronavirus COVID-19 infection associated with delta strain of SARS-COV-2 virus is characterised by severe and extremely severe course in elderly patients with comorbid somatic and neurological pathology.

Rett syndrome.

Rett syndrome (RTT) is a severe, progressive, neurodevelopmental disorder, which affects predominantly females. In most cases, RTT is associated with pathogenic variants in MECP2. MeCP2, the protein product of MECP2, is known to regulate gene expression and is highly expressed in the brain. RTT is characterized by developmental regression of spoken language and hand use that, with hand stereotypies and impaired ambulation, constitute the four core diagnostic features. Affected individuals may present multiple other neurological impairments and comorbidities, such as seizures, breathing irregularities, anxiety and constipation. Studies employing neuroimaging, neuropathology, neurochemistry and animal models show reductions in brain size and global decreases in neuronal size, as well as alterations in multiple neurotransmitter systems. Management of RTT is mainly focused on preventing the progression of symptoms, currently improved by guidelines based on natural history studies. Animal and cellular models of MeCP2 deficiency have helped in understanding the pathophysiology of RTT and guided the development of trofinetide, an IGF1-related compound, which is an approved drug for RTT, as well as of other drugs and gene therapies currently under investigation.

Health status and quality of life before critical illness: Northern Finland Birth Cohort 1966 study.

Previous findings support the claim intensive care unit (ICU) patients have a higher rate of comorbidities and reduction of health- and functional status compared with the normal population. In this prospective observational study, our aim was to determine those health-related factors at the age of 31 years which were associated with a later critical illness among previously un-hospitalized individuals by exploring data obtained from the Northern Finland Birth Cohort 1966 (NFBC1966). NFBC1966 is a Finnish birth cohort, which includes 12,058 live births with expected dates of delivery during 1966. The study was conducted among cohort participants who had not been hospitalized for any reason before the cohort follow-up visit at the age of 31. The study group included NFBC1966 participants who were admitted to the ICU of the Oulu University Hospital. The control group included participants who were treated for any reason in regular hospital wards. The data considering the participants' health status and behavior at the age of 31 were collected from the NFBC1966 database. The gathering of ICU and hospitalization data was concluded on December 31, 2016. 849 NFBC1966 participants met the inclusion criteria: 69 were treated in the ICU (study group) and 780 on regular hospital wards (controls). In the study group, the rate of neurological diseases (26% vs. 16%, 95% CI: -21.8%, -0.2%), malignancy (3% vs. 0.7%, 95% CI: -9.7%, 0.0%), alcohol abuse (4.5% vs. 1%, 95% CI: -11.5%, -0.3%) and smoking (77% vs. 65%, 95% CI: -21.6%, -0.3%) were higher compared with the control group. The patients in the ICU group were also more prone to violent injuries, (17% vs. 7%, 95% CI: -20.2%, -1.9%), practiced less hard physical activity (65% vs. 78%, 95% CI: 2.1%, 25.3%) and had lower maximal muscle strength according to the hand grip test (30 vs. 34 kg, 95% CI: -8.2, 8.6 kg). In this study examining previously un-hospitalized patients, the main factors associated with future critical illness were neurological comorbidities, malignancy, alcohol misuse, smoking, low maximum muscle strength, and less frequent physical exercise compared with those with hospitalization not requiring ICU admission.

Tobacco Smoke Exposure in Children and Adolescents: Prevalence, Risk Factors and Co-Morbid Neuropsychiatric Conditions in a US Nationwide Study.

Tobacco smoke exposure (TSE) is a major public health concern, impacting not only smokers but also those around them, particularly children and adolescents. TSE is linked to various neuropsychiatric conditions and significantly impacts quality of life. This study examines the prevalence, socio-demographic factors, and the impact of TSE on the severity of neurological and psychiatric co-morbidities. Data from the National Survey of Children's Health (NSCH) in the US from 2020 to 2021 were used in this study. We included 91,404 children and adolescents aged between 0 to 17 years for the TSE prevalence and socio-demographic analysis, and 79,182 children and adolescents aged between 3 and 17 years for the neuropsychiatric co-morbidities analysis. The mean age of these individuals was 8.7 (standard deviation: 5.3), and 11,751 (12.9%) had confirmed TSE. Our analysis showed that TSE is more common in males (53%) than females (47%). Additionally, the odds of TSE were higher in families with a lower income level and with American Indian/Native Alaska racial descent. We found that 36.4% of youths with TSE developed at least one co-morbid condition. The most common neuropsychiatric co-morbidities were anxiety problems (15.7%), Attention-Deficit Hyperactivity Disorder (ADHD) (15.5%), behavioral and conduct problems (13.7%), and learning disability (12%). Females had lower odds of co-morbid anxiety (OR: 0.3, p = 0.02) and Autism Spectrum Disorder (ASD) (OR: 0.9, p = 0.04) than males. Asians showed lower odds of co-morbid ADHD (OR: 0.3, p-value: 0.001), anxiety problems (OR: 0.4, p-value: 0.003), speech/other language disorder (OR: 0.4, p-value: 0.001), developmental delay (OR: 0.4, p-value: 0.001), behavioral and conduct problems (OR: 0.4, p-value: 0.003), and learning disability (OR: 0.5, p-value: 0.004). Conversely, American Indian children and adolescents had higher odds of co-morbid headaches (OR: 3, p-value: 0.005). TSE co-occurring with Tourette's Syndrome (TS) (OR: 4.4, p < 0.001), ADHD (OR: 1.3, p < 0.001), developmental delay (OR: 1.3, p < 0.001), behavioral problems (OR: 1.3, p < 0.001), headaches (OR: 1.3, p = 0.005), depression (OR: 1.2, p = 0.02), anxiety (OR: 1.2, p < 0.01), ASD (OR: 1.2, p < 0.001), and learning disability (OR: 1.2, p = 0.03) may contribute to a more severe manifestation. ADHD, behavioral/conduct problems, and learning disabilities were the most prevalent co-occurring conditions with TSE. Our findings show that 36.4% of youths with TSE had at least one neuropsychiatric comorbidity. Screening for these conditions in youths exposed to TSE is crucial for early detection and interventions to increase their mental health and well-being.

Pattern and Predictors of Neurologic Comorbidities Among African Children with Epilepsy

Abstract Background Epilepsy is the most common neurologic disorder affecting children in Nigeria. It is often associated with other neurologic comorbidities in addition to epileptic seizures, such as attention deficit hyperactivity disorder (ADHD) and cognitive, visual, and hearing impairments, which can be unrecognized while focusing on the seizures. Methods This cross-sectional study assessed the prevalence, pattern, and predictors of neurologic comorbidities among 100 children with epilepsy (CWE) attending the pediatric neurology clinic of Jos University Teaching Hospital, Jos, Nigeria, and age- and sex-matched controls selected consecutively. Data were summarized using frequencies and proportions. Chi-squared and Mann–Whitney U tests were used to test the categorical values, while logistic regression was used to determine the predictive factors for neurologic comorbidities. Results The prevalence of neurologic comorbidities among CWE versus controls was 65 vs. 15% (p &lt; 0.001). Factors associated with neurologic comorbidities in CWE include younger age at onset of epileptic seizures (p &lt; 0.003), severity of seizures (p &lt; 0.001), history of status epilepticus (p &lt; 0.044), background history of intracranial infections (p &lt; 0.029), and the use of combination antiepileptic drugs (p &lt; 0.001). Predictors of comorbidities in CWE were treatment with sodium valproate and polytherapy. Conclusion Neurologic comorbidities are more frequent among CWE than controls; therefore, screening for neurologic comorbidities should be routine when assessing and managing CWE.

S1151 Prevalence of Neurologic Co-Morbidities in Patients with IBD compared to IBS and RA: A Multi-Network Population Based Study

S1151 Prevalence of Neurologic Co-Morbidities in Patients with IBD compared to IBS and RA: A Multi-Network Population Based Study

Design and implementation of a multicenter protocol to obtain impulse oscillometry data in preterm children

ABSTRACTImportanceObjective measures of lung function are critical for assessing respiratory outcomes of prematurity. Among extremely low gestational age neonates (ELGANs) (&lt; 29 weeks gestational age), high rates of neurodevelopmental impairment may interfere with lung function testing. Impulse oscillometry (IOS) is a noninvasive test of respiratory system mechanics not requiring forced expiration.ObjectiveTo describe a multicenter study design for respiratory follow‐up testing in a cohort with a high rate of extreme prematurity.MethodsSchool‐age children enrolled in two prior trials of ELGANs and term controls were assessed by IOS at five centers. Groups consisted of children with prematurity with a high incidence of bronchopulmonary dysplasia, children with prematurity with no or minimal lung disease, and healthy term children. A rigorous centralized review process reviewed IOS studies for technical acceptability. Approach to design and implementation, rates of feasibility and success, and characteristics of participants are described.ResultsA total of 243 children were recruited, of whom 239 (98%) attempted oscillometry. There were high rates of technical acceptability across all three cohorts (85%–90% of attempted tests), and across all five centers (80%–94% of attempted tests). Respiratory and neuromotor clinical factors associated with testing failure included a higher number of days on ventilation during neonatal intensive care, a history of intraventricular hemorrhage grade 3 or 4, and gross motor functional impairment.InterpretationWe report high rates of feasibility and success of oscillometry in a large multicenter ELGAN population, in whom neurological and developmental comorbidities likely play a confounding role.

Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions.

Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals. This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models. Of 168 patients with MS (median [interquartile range (IQR)] age 47.0 [21.7] years; 101 women; 6,898 WMLs, 775 CLs) and 103 healthy individuals (age 33.0 [10.5] years, 57 women), 108 and 62 were followed for a median of 2 years, respectively (IQR 0.1; 5,030 WMLs, 485 CLs). At baseline, WMLs had lower myelin (median 0.025 [IQR 0.015] parts per million [ppm]) and iron (0.017 [0.015] ppm) than the corresponding NAWM (myelin 0.030 [0.012]; iron 0.019 [0.011] ppm; both p < 0.001). After 2 years, both myelin (0.027 [0.014] ppm) and iron had increased (0.018 [0.015] ppm; both p < 0.001). Younger age (p < 0.001, b = -5.111 × 10-5), lower disability (p = 0.04, b = -2.352 × 10-5), and relapsing-remitting phenotype (RRMS, 0.003 [0.01] vs primary progressive 0.002 [IQR 0.01], p < 0.001; vs secondary progressive 0.0004 [IQR 0.01], p < 0.001) at baseline were associated with remyelination. Increment of myelin correlated with clinical improvement measured by EDSS (p = 0.015, b = -6.686 × 10-4). χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.

Preoperative neurologic comorbidity and unanticipated early postoperative reintubation: a multicentre cohort study

BackgroundThe risk of respiratory complications is highest in the first 72 h post-surgery. Postoperative respiratory events can exacerbate pre-existing respiratory compromise and lead to reintubation of the trachea, particularly in patients with neurologic disorders. This study examined the association between neurologic comorbidities and unanticipated early postoperative reintubation in children. MethodsThis multicentre, 1:1 propensity score-matched study included 420 096 children who underwent inpatient, elective, noncardiac surgery at National Surgical Quality Improvement Program reporting hospitals in 2012–22. The primary outcome was unanticipated early postoperative reintubation within 72 h after surgery. The secondary outcome was prolonged postoperative mechanical ventilation, defined as ventilator use >72 h. We also evaluated 30-day mortality in patients requiring reintubation. ResultsCerebral palsy was associated with the highest risk of early reintubation (adjusted relative risk [RRadj]: 1.97, 95% confidence interval [CI]: 1.44–2.69; P<0.01), followed by seizure disorders (RRadj: 1.87, 95% CI: 1.50–2.34; P<0.01), neuromuscular disorders (RRadj: 1.76, 95% CI: 1.41–2.19; P<0.01), and structural central nervous system abnormalities (RRadj: 1.35, 95% CI: 1.13–1.61; P<0.01). Unanticipated early postoperative reintubation was associated with an eight-times increased risk of 30-day mortality (adjusted hazard ratio: 8.1, 95% CI: 6.0–11.1; P<0.01). Risk of prolonged postoperative mechanical ventilation was also increased with neurologic comorbidities, particularly seizure disorders (RRadj: 1.73, 95% CI: 1.55–1.93; P<0.01). ConclusionsChildren with neurologic comorbidities have an increased risk of unanticipated early postoperative reintubation and prolonged mechanical ventilation. Given the high mortality risk associated with these outcomes, children with neurologic comorbidities require heightened monitoring and risk assessment.

Adolescents and Young Adults With Respiratory Failure in U.S. PICUs: A Pediatric Health Information System Database Study, 2011–2022

Objectives: To examine the clinical characteristics, outcomes, and resource use of adolescents and young adults (AYAs) admitted to PICUs in the United States with respiratory failure. Design: Retrospective cohort study. Setting: De-identified data from 48 U.S. children’s hospitals contributing to the Pediatric Health Information System (PHIS) database. Patients: All patients older than 30 days old with respiratory failure, defined as encounters with clinical transaction codes for noninvasive or invasive mechanical ventilation, admitted to PHIS database PICUs from January 2011 to December 2022. Patients were categorized into five cohorts (&lt; 15, 15–18, 19–21, 22–25, and &gt; 25 yr old). Interventions: None. Measurements and Main Results: A total of 430,238 patients were identified. AYA (≥ 15 yr old) accounted for 15% (65,740) of all PICU admissions with respiratory failure. Forty-nine percent (32,232/65,740) of AYA older than 25 years had medical technology dependence compared with 39% in those younger than 15 years (p &lt; 0.001). Sixty-one percent of AYA older than 25 years had a cardiovascular comorbidity compared with 35% of those younger than 15 years (p &lt; 0.001). Forty percent of AYA older than 25 years had a neurologic comorbidity, and 27% a gastrointestinal comorbidity, compared with 27% and 31%, respectively, in those younger than 15 years (all p &lt; 0.001). Compared with those younger than 15 years, AYA median hospital crude mortality rate was higher at 7.7% compared with 5.2%, as were median hospital charges per encounter at $163K (interquartile range [IQR], $77K–$350K) vs. $121K (IQR, $53K–$278K; all p &lt; 0.001). Median ventilator days and hospital length of stay in survivors were similar for all age cohorts. Conclusions: AYA represent a substantial proportion of patients admitted to the PICU with respiratory failure. These individuals have unique comorbidities and are at risk for increased mortality and resource utilization compared with younger patients during hospitalization. Medical complexity and sequelae of pediatric illness may delay the transition of AYA to adult care, necessitating collaboration between adult and pediatric critical care physicians to increase research across the age spectrum and develop and implement appropriate evidence-based guidelines.

Dysphagia is a strong predictor of revision supraglottoplasty in pediatric laryngomalacia

BackgroundThere is growing research on the association between swallowing dysfunction and laryngomalacia. Supraglottoplasty is the surgical intervention used to treat laryngomalacia, however a portion of patients who undergo this procedure will require a revision surgery. Predictive risk factors for revision supraglottoplasty in patients with laryngomalacia are not well understood, and previous studies failed to evaluate swallowing systematically. HypothesisWe predict a significant association between swallowing dysfunction and revision supraglottoplasty for patients with laryngomalacia. MethodsThis was a retrospective cohort study of consecutive patients between 2013 and 2023 at a tertiary pediatric care centre (Stollery Children's Hospital). All patients had an endoscopic diagnosis of laryngomalacia by a staff otolaryngologist and at minimum a systematic clinical swallowing assessment by a speech language pathologist, with an instrumental assessment as needed. Patients with genetic or neurological comorbidities, lack of follow up information, or age of >3 years were excluded. Clinical and instrumental swallow data, demographic information, surgical outcomes and revision surgeries were documented and collected. Univariate analysis was done to determine associations between variables and revision supraglottoplasty. Binary logistic regression was done to determine independent predictors of revision supraglottoplasty. Results214 patients met the inclusion criteria and were analyzed in the study. 24 patients (11 %) required revision supraglottoplasty. 118 out of the 214 patients (55 %) had an instrumental assessment completed (FEES or VFSS). Of those, 92 (78 %) had abnormal findings on instrumental assessments. Univariate analysis showed Type 2 laryngomalacia (P = 0.017), presence of aspiration (P=<0.001), presence of cyanosis (P = 0.002) and abnormal findings on an instrumental assessment (P = 0.013) to be significantly associated with the need for revision supraglottoplasty. Binary regression analysis showed aspiration (OR = 5.6 {2.087–14.889}, P=<0.001) and cyanosis (OR = 5.3 {1.852–15.181}, P = 0.002) to be the only independent predictors of revision supraglottoplasty. ConclusionPresence of aspiration is a strong predictive factor for revision supraglottoplasty in patients with laryngomalacia, when swallowing is evaluated systematically. More prospective research is needed to understand the relationship between swallowing dysfunction, laryngomalacia and surgery.

Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder: a retrospective cohort study of electronic health records.

Intermittent Explosive Disorder (IED) is an understudied psychiatric condition that presents with repeated episodes of impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities will allow for enhanced screening, diagnosis, and treatment of patients. To investigate prevalence and associations of IED with psychiatric, neurological, and somatic disorders using real-world data. Matched cohorts of patients with or without IED diagnosis were identified using data from the TriNetX Research Network (until January 31, 2024). Cox proportional hazard models were used to estimate and compare the probabilities of acquiring other diagnoses using patients' available medical records. Analysis of electronic medical records from two patient populations. 30,357 individuals with IED and equal number of demographically matched individuals without IED from the TriNetX Research. IED diagnosis identified through the associated ICD codes. The main outcomes were ICD-10-CM diagnostic categories and root codes for disorders and health conditions in both cohorts. Main measures are total numbers and proportions of patients who had the diagnostic codes, as well as adjusted hazard ratios for IED diagnosis. Although only 0.03% of the total patient population had an IED diagnosis, we found extensive and widespread comorbidities with psychiatric, neurological and somatic conditions. A significant 95.7% of the individuals with IED had another psychiatric diagnosis. All psychiatric sub-categories and 95% of the psychiatric diagnoses were significantly associated with IED, with HRs ranging from 2 to 77. Among neurological conditions, neurodegenerative diseases and epilepsy had the highest HRs, followed by extrapyramidal and movement disorders, cerebral palsy and other paralytic syndromes, and sleep disorders. Notable associations with IED also includes conditions such as obesity, hyperlipidemia, hypertension, and GERD. Our findings illuminate the extensive comorbid relationships between IED and psychiatric, neurological, and somatic disorders. This underscores the necessity for an integrated diagnostic and treatment approach that addresses both the psychological and physical health aspects of IED. Additionally, our work highlights the need for more accurate and inclusive diagnosis of IED in patients with mental disorders.

Clinical, Biochemical, and Molecular Characteristics of Filipino Patients with Tyrosinemia Type 1.

Hereditary tyrosinemia type I (HT1), or hepatorenal tyrosinemia, is an amino acid disorder which may cause hepatic failure as well as renal and neurologic comorbidities. Early detection of this disorder is possible with newborn screening (NBS). The objective of this study is to describe the clinical, biochemical, and molecular characteristics of Filipino patients diagnosed with HT1 through the expansion of the Philippine NBS program in 2014. There were a total of 16 patients with confirmed HT1 from then until September 2022. Clinical and biochemical data during confirmation and initial evaluation, as well as molecular data, were obtained from the patients' medical records. The cohort included children between the ages of 18 and 54 months at the time of data collection. The mean age at treatment initiation was 26.8 days. The mean succinylacetone level from dried blood spot sampling using tandem mass spectrometry (MS) was 11.1 µmol/L. Biochemical confirmatory tests via plasma amino acid analysis showed mean levels of tyrosine, phenylalanine, and methionine of 506.1 µmol/L, 111.5 µmol/L, and 125.4 µmol/L, respectively. Upon urine organic acid (UOA) analysis, succinylacetone was detected in all except for one patient, who was managed prior to UOA analysis. The most common clinical characteristics were abnormal clotting times (62.5%), elevated alpha fetoprotein (37.5%), anemia (31.3%), and metabolic acidosis (31.3%). The most common genotype was homozygous c.122T>C p.Leu41Pro in 64.3% of patients. The allelic frequency of this pathogenic variant is 71.4%. The inclusion of HT1 in the Philippine NBS program allowed early diagnosis and management of HT1 patients.

Patient factors associated with positive respiratory cultures following tracheostomy in pediatric patients

ObjectivesAn increasing number of pediatric patients undergo tracheostomy placement annually. Despite advances in care, these patients remain at high risk for postoperative complications, including respiratory infections. The risk factors for positive respiratory cultures and the impact of culture positivity on overall morbidity and mortality in this population is not fully characterized. Study design and settingRetrospective cross-sectional analysis of all patients within a single tertiary care institution who underwent tracheostomy placement from January 1, 2019 to 12/31/2021. MethodsWe collected patient demographic information, comorbidities, primary indication for tracheostomy placement, and respiratory culture information preoperatively and postoperatively. The primary outcome measure was positive bacterial respiratory culture with speciation within 1, 3, or 6 months of tracheostomy placement. The secondary outcome measure was all-cause mortality within the study period. ResultsA total of 180 patients with median (IQR) age of 5.2 (3.4–31.0) months at time of tracheostomy placement were included in the study. Nearly half of patients had a positive culture within 1 month (n = 81,47.4 %) while 63.7 % of patients were positive within 6 months of tracheostomy placement (n = 109). Risk factors included respiratory and/or cardiac comorbidities. Positive respiratory cultures within 6 months of surgery and cardiac and/or neurologic comorbidities were associated with increased all-cause mortality following tracheostomy placement. ConclusionsPositive respiratory cultures are common following tracheostomy placement, more so in patients with cardiac and pulmonary comorbid conditions. Positive cultures are associated with increased all-cause mortality. More work is necessary to determine optimal screening frequency and treatment protocols for positive cultures in this population.

The benefit of sentinel lymph node biopsy in elderly patients with melanoma: A retrospective analysis of SEER Medicare data (2010-2018)

BackgroundSentinel lymph node status is critical for melanoma staging and treatment. However, the factors influencing SLNB and its oncologic benefits in elderly patients are unclear. MethodsWe conducted a retrospective analysis of patients aged ≥65 with clinically node-negative melanoma and Breslow depth ≥1 ​mm, using Surveillance, Epidemiology, and End Results Medicare database (2010–2018). Multivariable logistic regression assessed SLNB likelihood by demographic and clinical factors, and Cox-proportional hazard models evaluated overall and melanoma-specific mortality (MSM) for SLNB recipients versus non-recipients. ResultsOf 13,160 melanoma patients, 62.29 ​% underwent SLNB. SLNB was linked to reduced all-cause mortality (HR: 0.65 [95%CI 0.61–0.70]) and MSM (HR: 0.76 [95%CI 0.67–0.85]). Older age, non-White race, male sex, and unmarried status was associated with decreased SLNB likelihood, while cardiopulmonary, neurologic, and secondary cancer comorbidities were associated with increased SLNB likelihood. ConclusionsThough less frequently performed, SLNB is associated with lower mortality in elderly melanoma patients. Advanced age alone should not contraindicate SLNB.

The implementation of EMI-Heart, a family-tailored early motor intervention in infants with complex congenital heart disease, in practice: a feasibility RCT

BackgroundChildren with congenital heart disease (CHD) who undergo open-heart surgery are at risk of developmental impairment, including motor delay, which contributes to parental concerns. Additionally, parents experience prolonged stress associated with their child’s disease. There is a lack of early motor interventions in infants with CHD accounting for parental burdens. We developed a family-tailored early motor intervention (EMI-Heart), aiming to promote motor development in infants with CHD and family well-being. The primary aim was to evaluate the feasibility of the study design and the intervention. The secondary aim was to evaluate differences between the intervention and the control group in motor outcomes and family well-being at baseline (3–5 months), post-treatment (6–8 months), and at follow-up (12 months).MethodIn this single-centre feasibility randomized control trial (RCT), infants with CHD after open-heart surgery without genetic or major neurological comorbidities were randomly allocated to EMI-Heart or the control group (standard of care). EMI-Heart’s key elements promote postural functional activities and encourage parental sensitivity to infants’ motor and behaviour cues. Infants assigned to EMI-Heart received nine sessions of early motor intervention at home, in the hospital, and online for a duration of 3 months by a paediatric physiotherapist. We performed descriptive statistics for feasibility and secondary outcomes.ResultsThe recruitment rate was 59% (10/17), all participating families completed the study (10/10), and the intervention duration was 3.9 months (± 0.54), including nine intervention sessions per family. Median acceptability to parents was 3.9 (1 = not agree–4 = totally agree, Likert scale). The paediatric physiotherapist considered the intervention as feasible. The comparison of motor outcomes did not show differences between groups. However, we detected improved reliable change scores in family well-being outcomes for families of the intervention group compared to the controls.ConclusionsOur research indicates that EMI-Heart is a feasible intervention for infants with CHD after open-heart surgery. The intervention was highly acceptable both to parents and to the paediatric physiotherapist. Online treatment sessions offer a valuable alternative to home and hospital visits. This feasibility RCT provides a foundation for a future full trial.Trial registrationClinicalTrials.gov, NCTT04666857. Registered 23.11.2020.

“Sigma-1 receptor modulation by clemastine highlights its repurposing as neuroprotective agent against seizures and cognitive deficits in PTZ-kindled rats”

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures alongside other neurological comorbidities. Cognitive impairment is the most frequent comorbidity secondary to progressive neurologic changes in epilepsy. Sigma 1 receptors (σ1 receptors) are involved in the neuroprotection and pathophysiology of both conditions and targeting these receptors may have the potential to modulate both seizures and comorbidities. The current research demonstrated the effect of clemastine (10 mg/kg, P.O.), a non-selective σ1 receptor agonist, on pentylenetetrazol (PTZ) (35 mg/kg, i.p., every 48 h for 14 doses)-kindling rats by acting on σ1 receptors through its anti-inflammatory/antioxidant capacity. Clemastine and phenytoin (30 mg/kg, P.O.) or their combination were given once daily. Clemastine treatment showed a significant effect on neurochemical, behavioural, and histopathological analyses through modulation of σ1 receptors. It protected the kindling animals from seizures and attenuated their cognitive impairment in the Morris water maze test by reversing the PTZ hippocampal neuroinflammation/oxidative stress state through a significant increase in inositol-requiring enzyme 1 (IRE1), x-box binding protein 1 (XBP1), along with a reduction of total reactive oxygen species (TROS) and amyloid beta protein (Aβ). The involvement of σ1 receptors in the protective effects of clemastine was confirmed by their abrogation when utilizing NE-100, a selective σ1 receptor antagonist. In light of our findings, modulating σ1 receptors emerges as a compelling therapeutic strategy for epilepsy and its associated cognitive impairments. The significant neuroprotective effects observed with clemastine underscore the potential of σ1 receptor-targeted treatments to address both the primary symptoms and comorbidities of neurological disorders.

Responsive neurostimulation in pediatric epilepsy: a systematic review and individual patient meta-analysis supplemented by a single institution case series in 105 aggregated patients.

To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations. A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran's Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher's exact, and chi-squared tests. This systematic review was not registered. Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient's sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality. RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.

Cognition trajectory in Duchenne muscular dystrophy

BackgroundDuchenne muscular dystrophy (DMD) is an X-linked recessive disease brought on by genetic changes that alter the dystrophin (DYS) protein. There has been growing evidence that children with DMD have been at higher risk of developing symptoms of neurodevelopmental disorders. We aimed at defining the cognitive difficulties and their categories in patients with DMD, compared to healthy controls, and assessing their relation with the functional severity. This work was a multi-center, observational, case–control study conducted on DMD patients. Age and sex-matched healthy subjects with no neurologic, psychiatric, or medical comorbidities were included as normal controls.ResultsThere was a statistically significant difference in cognitive patterns between the studied groups. We have observed a significant relationship between cognitive difficulties and functional severity assessment in our patients. There was a statistically significant difference between the studied cases regarding basic characteristics and correlation between cognitive functions and demographic data.ConclusionsThe decline in cognitive functions in DMD patients compared to healthy controls was established. Education was the most affected domain in patients, with more speech delay and dropping out of school. Therefore, it was recommended to establish cognitive screening as a routine in the evaluation and follow-up of DMD children.