Onset Cases Research Articles

Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve

BackgroundBicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated...

Glucocorticoids in IgA vasculitis

IgA vasculitis (IgAV) is an immune complex vasculitis affecting small vessels characterized by IgA1 immune deposits. IgA vasculitis typically resolves spontaneously in most cases, especially in pediatric cases but may have more severe outcomes in adults and the optimal treatment for IgAV remains controversial. Although glucocorticoids are the mainstay of treatment, studies are investigating the role of alternative immunosuppressive agents and biologics, particularly in adult onset, severe or resistant cases. The efficacy of glucocorticoids appears to vary according to the specific manifestations and severity of IgAV. They may be effective in treating complications when combined with immunosuppressive agents but glucocorticoids should not be used prophylactically as they do not prevent complications.

Utility of Tau PET in the diagnostic work up of neurodegenerative dementia among Indian patients

Background and objectivesTau PET is being increasingly appraised as a novel diagnostic modality for dementia work up. Given limited data among South Asians, we assessed the frequency, patterns, phenotypic associations and incremental value of positive Tau PET scans in clinically diagnosed neurodegenerative dementia. MethodsThis cross-sectional study recruited consecutive patients of Alzheimer's disease (AD) and non-AD syndromes (September 2021 to October 2022, India). Participants underwent clinical interview, cognitive assessment, MRI brain and tau PET scan ([F-18]ML-104). Visual read in a priori regions of interest was used to identify patterns of tau deposition in the brain. ResultsWe recruited 54 participants (mean age: 63.2 ± 9.2 years, 70.4 % men, 77.8 % dementia, 70.4 % early onset cases, 37.8 % APOE4+). The analysis identified abnormal tau uptake in 40/54 (74.1 %) participants; with uptake in AD signature areas in 27/40 (67.5 %) cases [cortical subtype (74.1 %), limbic (14.8 %), combined cortical/limbic (11.1 %)], and patterns not conforming to AD in 13/40 (32.5 %) cases. Tau PET substantiated the diagnosis of AD among 17/19 (89.5 %) cases with clinically diagnosed AD dementia, 8/23 (34.8 %) cases with suspected non-AD cause, and 2/12 (16.7 %) cases with mild cognitive impairment. A trend for increasing proportion of early onset cases, and worsening cognition, behavior and functional ability was seen, from ‘limbic’ to ‘combined cortical/limbic’ to ‘cortical’ subgroups. ConclusionTau PET is a useful modality to differentiate AD dementia from other neurodegenerative causes in the Indian setting where amyloid biomarkers are not widely available. Biological subtypes of AD map well onto clinical phenotypes and need study in larger cohorts.

Age as a Predictor of Overall Survival in Colorectal Cancer.

The diagnosis of colorectal cancer (CRC) at early ages has become a challenging trend for oncology due to high rates of mortality worldwide. The correlation of clinical features with young-age prognosis in CRC remains unclear. Therefore, we aimed to describe the clinicopathological features and their impact on the overall survival of young Mexican adults diagnosed with CRC treated in the National Cancer Institute. This was a retrospective, observational study. The included patients were treated at the National Cancer Institute between 2004 and 2020. The statistical analyses comprised the X2 and t tests, Kaplan-Meier, log rank, and Cox regression. Statistical significances were assessed when p was bilaterally < 0.05. A total of 3652 patients diagnosed with CRC attended the National Cancer Institute. Cases of early onset of CRC increased over the 16 years under study, with significant differences between the median age, from 57 in 2004 to 55 years old in 2020 (F = 5.49; gl: 12 p = 0.019). For this analysis, the population was divided in three groups: young (≤30 years), adults (31-70), and elderly (>70). The young population was mostly composed of men (62%; (n = 63), (p = 0.020), with high rates of metastatic disease (44%) (p = 0.001) and right-side tumors (57%), (p = 0.046), and with 44% with a moderate grade (p = 0.750). According to the overall survival (OS) analysis, the median OS was 29 months for young, versus 170 months for adult and 56 months for elderly patients (p <0.001, HR 1.53, 95% CI 1.11-2.10). A sub-analysis was performed considering only patients with metastatic disease. The median OS was 12 months for young, versus 17 and 9 months for adults and elderly (p = 0.08, HR 1.27, 95% CI 1.02-1.46). CRC diagnosis in the young population is increasing due unhealthy lifestyle habits and lack of screening. This population have clinical features of bad prognosis, such as left side, poor grade differentiation, and metastatic disease, precluding prognosis and OS.

A case of acute idiopathic maculopathy in both eyes with peripheral vascular occlusion

BackgroundThis study aimed to present a case of bilateral symmetric onset of acute idiopathic maculopathy after high fever with peripheral vascular occlusion.Case presentationA 54-year-old yellow female experienced acute binocular visual acuity decrease after 1 day of high fever, and binocular visual acuity decreased to index or anterior. OCT in the external hospital showed dome-shaped cortical detachment in the symmetrical macular area of both eyes with subretinal fluid, discontinuity in the ellipsoid zone and the chimera. The patient autonomously administered antibiotics and non-steroidal anti-inflammatory agents, including amoxicillin and ibuprofen. Following a three-day period, the patient’s visual acuity demonstrated significant improvement. Additionally, macular edema demonstrated a notable reduction as indicated by optical coherence tomography, while the presence of peripheral retinal vascular occlusions was also observed on fluorescein fundus angiography. At the onset of 6 days, oral hormone therapy was given in the outside hospital, with no significant improvement in visual acuity.23 days after the onset of the disease, the patient was admitted to our hospital, and was finally diagnosed as acute idiopathic maculopathy combined with the imaging findings of FFA, ICGA and OCT. During the follow-up, the visual acuity of both eyes improved spontaneously.ConclusionsThis case is a rare acute idiopathic macular lesion with bilateral involvement, accompanied by highly symmetrical peripheral retinal vascular occlusion in both eyes, which deepens our understanding of acute idiopathic maculopathy with a view to providing guidance for subsequent clinical practice.

Increased Survival in Contemporary Parkinson’s Disease: A 47-Year Autopsy Study

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The main clinical features are bradykinesia, rigidity, and resting tremor. Other neurodegenerative disorders such as progressive supranuclear palsy and multiple system atrophy share some of these clinical manifestations. All those disorders are collectively known as parkinsonism or Parkinson syndrome (PS). Definite diagnosis of PD requires brain autopsy. There is no known cure for PD. Since its discovery in the 1960s, levodopa (LD) has remained the best and most widely used medication in PD. The impact of that is important to understanding the neuroepidemiology of PD. The incidence of PD rises with advancing age. In the last six decades, life expectancy in the general population has increased resulting in a larger pool of at-risk persons. Onset age of PD is the most reliable indicator of PD survival as older onset cases have shorter survival. We report on survival in autopsy-confirmed PD cases with onset age <70 years treated with LD and compare that with similar onset-age cases of PD before the discovery of LD. Material and Methods: The Saskatchewan Movement Disorders Program (SMDP) has operated uninterrupted since 1968. Long follow-up and autopsy studies are a special interest of the SMDP. All PS cases followed by the SMPD during 47 years (1968–2015) that came to autopsy were considered. Those with autopsy-confirmed PD and onset <70 years were included and were compared with pre-LD cases of similar age of onset. Results: Overall, 392 PS cases were seen in our clinic between 1968 and 2015 and had brain pathology studies. A total of 314 (80%) of those had PD. Overall, 128 (41%) of the PD cases had onset <70 years and were included in this study. Their median survival was 18 years. Conclusion: Prior to widespread use of LD, nearly all PD cases had onset <70 years and mean survival was 9.4 years. Longer survival in our study is attributed primarily to modern treatment. Increased survival has resulted in a larger number of older, chronically treated, higher comorbidity, and complicated PD patients. These changes present new challenges. It requires a larger and increasingly diverse workforce for patient care and research.

Un caso di FPIES in paziente alimentata con latte di formula per galattosemia

Soy-derived proteins are a known trigger for Food Protein Induced Enterocolitis Syndrome. The authors present the case of a sly onset of chronic FPIES in a newborn fed by soy-based formula. The baby’s nutrition was switched to infant formula to avoid human milk, as she was found positive for galactosemia by the extended neonatal screening (the diagnosis was later confirmed by genetic testing).

Machine-learning-based prediction of cardiovascular events for hyperlipidemia population with lipid variability and remnant cholesterol as biomarkers.

Dyslipidemia poses a significant risk for the progression to cardiovascular diseases. Despite the identification of numerous risk factors and the proposal of various risk scales, there is still an urgent need for effective predictive models for the onset of cardiovascular diseases in the hyperlipidemic population, which are essential for the prevention of CVD. We carried out a retrospective cohort study with 23,548 hyperlipidemia patients in Shenzhen Health Information Big Data Platform, including 11,723 CVD onset cases in a 3-year follow-up. The population was randomly divided into 70% as an independent training dataset and remaining 30% as test set. Four distinct machine-learning algorithms were implemented on the training dataset with the aim of developing highly accurate predictive models, and their performance was subsequently benchmarked against conventional risk assessment scales. An ablation study was also carried out to analyze the impact of individual risk factors to model performance. The non-linear algorithm, LightGBM, excelled in forecasting the incidence of cardiovascular disease within 3years, achieving an area under the 'receiver operating characteristic curve' (AUROC) of 0.883. This performance surpassed that of the conventional logistic regression model, which had an AUROC of 0.725, on identical datasets. Concurrently, in direct comparative analyses, machine-learning approaches have notably outperformed the three traditional risk assessment methods within their respective applicable populations. These include the Framingham cardiovascular disease risk score, 2019 ESC/EAS guidelines for the management of dyslipidemia and the 2016 Chinese recommendations for the management of dyslipidemia in adults. Further analysis of risk factors showed that the variability of blood lipid levels and remnant cholesterol played an important role in indicating an increased risk of CVD. We have shown that the application of machine-learning techniques significantly enhances the precision of cardiovascular risk forecasting among hyperlipidemic patients, addressing the critical issue of disease prediction's heterogeneity and non-linearity. Furthermore, some recently-suggested biomarkers, including blood lipid variability and remnant cholesterol are also important predictors of cardiovascular events, suggesting the importance of continuous lipid monitoring and healthcare profiling through big data platforms.

First bipolar episode following booster dose of COVID-19 vaccination

Introduction and importance: The interactions between the susceptibility of the host and some of the COVID-19 vaccine components happened. Viral infections, including COVID-19, are related to the pathogenesis of bipolar disorder (BD). These findings could trigger an initial bipolar episode. Case presentation: A 48-year-old Syrian married female, presented to the out-clinic of Modern Medical Centre Hospital, in July 2022 for episodes of sub-maniac/mania episodes, which began within 15 days after the booster dose of COVID-19 vaccination, preceded by depressive mood. Both family and personal past psychiatric and/or trauma history were negatives. Initiation of carbamazepine 600 mg/day showed significant improvement within 3 days; 3 months later, carbamazepine dose was decreased to 200 mg/day, as there were no clinical symptoms. Clinical discussion: mRNA vaccines of COVID-19 increase the levels of type I interferon (INF), an inflammatory cytokine that creates a signal leading to the expression of interleukins, INF, and tumor necrosis factor-alpha. The pathology of BD is also unclear. Genetic predisposition, immunological effects, and the classification of BD, itself, as an autoimmune disease play a role. Although rapid improvement following treatment, prolonged and maintenance treatment by essentially mood stabilizer should be considered in bipolar episodes initiated by COVID-19 vaccination. Rare data are available about maniac episodes after COVID-19 infection, but to our knowledge, we reported the first case of bipolar onset after the booster vaccination of COVID-19. Conclusion: Bipolar disease can present following a booster dose of COVID-19 vaccination in previously healthy people.

Validity and Reliability of Self-Reported Prevalent and Incident Cardiovascular Disease Among Asian Adults.

Cardiovascular disease (CVD) is the leading cause of death in Asians. We aimed to examine the validity and reliability of self-reported (SR) CVD in 6762 Chinese, Malay, and Indian adults aged 40-80 years who attended the baseline (November 2004) and 6-year follow-up visit (2011-2017) of a population-based cohort study in Singapore. CVD was defined based on the presence of existing (prevalent) or new onset (incident) cases of acute myocardial infarction (AMI) or stroke. The validity of SR-CVD was assessed by comparing it against diagnosed CVD using sensitivity and specificity. The reliability of SR-CVD was evaluated by calculating the percentage of positive agreement between baseline and follow-up visits. The sensitivity and specificity of SR-CVD were 62.7% and 93.8% for prevalent SR-CVD and 50.9% and 98.5% for incident SR-CVD. The negative predictive value (NPV) was 98.1% for both prevalent and incident SR-CVD. The reliability of positive self-reports between the baseline and follow-up was substantial, at 85%. The excellent specificity and NPV of SR-CVD suggest that it could serve as a valuable tool for excluding AMI and stroke. However, its moderate sensitivity suggests that positive SR-CVD reports should prompt further clinical evaluation to prevent potential false positives.

Circulating ketone bodies, genetic predisposition, and incident atrial fibrillation

Abstract Background Ketone bodies (KB) are essential alternative fuel sources for the myocardium. However, the evidence on the level of circulating KB and heart disorders is inconsistent. Whether the total and individual KB are associated with risk of onset atrial fibrillation (AF) in the general population and in individuals with different genetic susceptibilities to AF are still unclear. Purpose To examine the association between circulating KB and AF risk and to further test whether genetic risk could modify the above association. Methods In the UK Biobank, 247,304 participants (mean age 56.5, 45.3% men) with available data on KB and without baseline AF were included. The concentrations of KB, including β-hydroxybutyrate (β-OHB), acetoacetate, and acetone, were measured using nuclear magnetic resonance, and the values of KB were increased by one and then log10-transformed for analyses. The genetic risk of AF was based on the standard polygenic risk score. The definitions of AF were based on the ICD-10 code I48, which was linked to primary care, hospital admission electronic health records and death records. Cox proportional hazard model was used to estimate the hazard ratio (HR) with 95% confidence interval (CI). Results During a median follow-up of 13.8 years, 16,936 cases of onset of AF were recorded. After adjusting for age, sex, race, Townsend index, education, alcohol intake frequency, smoking status, healthy diet, metabolic equivalent, body mass index, systolic blood pressure (SBP), total cholesterol, estimated glomerular filtration rate, cardiovascular diseases, and diabetes, elevated total KB, β-OHB, acetoacetate, and acetone were all with the risk of AF (HR, 95% CI per 10-fold increase: 1.20, 1.13-1.28; 1.13, 1.07-1.19; 1.12, 1.06-1.18; and 1.78, 1.57-2.01, respectively). The highest risk of AF was observed among individuals at high genetic risk to AF and had the highest quartile of total KB (HR 2.91, 95% CI 2.66-3.19). Participants who had low genetic risk were more susceptible to high total KB for incident AF (p for interaction = 0.036). The associations of total KB, β-OHB, and acetone with AF risk were more prominent for men (HR, 95% CI per 10-fold increase: 1.32, 1.22-1.44; 1.22, 1.14-1.31; 2.01, 1.72-2.36) than for women (p for interaction &amp;lt;0.05). The association between total KB and AF risk was strengthened in individuals &amp;lt;60 years, current smokers, and those with SBP&amp;lt;130 mmHg (p for interaction = 0.033, 0.021, and 0.017, respectively). Conclusions Circulating KB concentrations were associated with AF risk, with acetone showing the strongest relationship with AF. Individuals at low genetic risk were more susceptible to the level of total KB for incident AF. Our findings suggest that KB may be a biomarker, particularly for identifying individuals without AF at baseline who are at low genetic risk. The additive value of plasma KB to a risk prediction score warrants further investigation.

Eating disorder debut cases during COVID-19 lockdown in adults. Exploring differences in treatment outcome contrasting with pre-pandemic onset cases.

Despite an increase in eating disorder (ED) cases during the COVID-19 pandemic, there are limited longitudinal studies exploring treatment outcomes. The aims of the present study were: (1) to compare the clinical features of patients with EDs whose onset was during the COVID-19 lockdown (pandemic cohort) against patients with EDs whose onset was prior to the pandemic (pre-pandemic cohort) and, (2) to compare therapy responses between the cohorts. The sample consisted of 115 adult women with an ED. N=37 new ED cases (pandemic cohort) were diagnosed and included in the study during the pandemic (May 2020-May 2021); these patients did not have any previous history of an ED. We also included N=78 ED cases (pre-pandemic cohort) diagnosed prior to the COVID-19 pandemic breakout (prior to March 2020). All ED subtypes were considered in both groups and several clinical variables were assessed. At baseline, pandemic cohort reported lower levels of impulsivity and higher emotional regulation capacities than the pre-pandemic cohort; however, no differences were found in aspects of general psychopathology and ED related severity. Following treatment, the pandemic cohort showed higher rates of good outcome and lower rates of dropouts than the pre-pandemic cohort. Although both cohorts showed similar ED-related symptoms and general psychopathology scores, treatment outcomes were more favourable in the pandemic cohort.

Application of multimodal intraoperative neurophysiological monitoring technology in neurofibromatosis type 1 related peripheral nerve tumor surgery

To summarize application effect and clinical experience of multimodal intraoperative neurophysiological monitoring (IONM) technology in the surgery of neurofibromatosis type 1 (NF1) related peripheral nerve tumors. A retrospective study was conducted on NF1 patients, who admitted between January 2019 and December 2023 and treated with peripheral nerve tumor resection surgery assisted by multimodal IONM technology. There were 49 males and 45 females. The age ranged from 5 to 78 years, with an average of 33.7 years. Tumor morphological classification included 71 cases of nodular type, 13 cases of diffuse type, and 10 cases of mixed type. Target tumors were distributed in craniofacial region (47 cases), neck (11 cases), trunk (12 cases), and limbs (24 cases). Preoperatively, 44 cases had no obvious neurological symptoms, while the remaining patients had neurological symptoms, including 15 cases of visual impairment, 5 cases of hearing impairment, 16 cases of somatic movement disorders, and 31 cases of somatic sensory disorders, of which 7 cases had more than one symptom. IONM plans were selected based on the relevant nerves and adjacent important structures of the target tumor, including visual evoked potential (17 cases), somatosensory evoked potential (44 cases), motor evoked potential (88 cases), and electromyogram (94 cases). All surgeries were successfully completed. Ninety-three patients underwent total/near total resection and 1 patient underwent palliative resection. Pathological examination showed 80 cases of neurofibroma and 14 cases of malignant peripheral nerve sheath tumors. Complications included 2 cases of hematoma and 3 cases of incision infection. All patients were followed up 3-61 months (median, 15 months). During follow-up, no significant changes in neurological symptoms or tumor recurrence were found. Among the patients with preoperative visual impairment, there were 14 cases with no improvement in symptoms and 1 with improvement after surgery. Among the patients with somatic movement disorders, there were 11 cases with no improvement in symptoms, 3 cases with improvement, 2 cases with aggravation, 4 newly onset cases, and 1 case with significant impact on daily life after surgery. Among the patients with somatic sensory disorders, there were 17 cases with no improvement in symptoms, 14 cases with improvement, and 13 newly onset cases. The patients with hearing impairment showed improvement after surgery. The clinical manifestations of NF1 related peripheral nerve tumors are complex. Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.

Clinical Implication of Time of Ischaemic Stroke Among Post-Stroke Survivors from Eastern India: A Circadian Perspective.

The circadian variation in stroke occurrence is a well-documented phenomenon. However, the circadian effect on stroke outcome, particularly on post-stroke cognition, has not yet been fully elucidated. We aim to evaluate the influence of diurnal variation of stroke onset upon post-stroke cognition and development of post-stroke depression. Based on 4-hourly time period of stroke occurrence, 249 recruited cohorts were categorized into 6 groups. Several clinical and cognitive parameters were compared among the groups. Then, the mRNA expression of core clock genes in Peripheral Blood Mononuclear Cells were quantified and correlated with post-stroke outcomes among 24 acute phase cases with day-time or night-time stroke occurrence. Furthermore, the genetic susceptibility towards a higher number of cases in the morning was examined by genotyping CLOCK (rs1801260T/C, rs4580704G/C) and CRY2 (rs2292912C/G) genes variants in cases and 292 controls. In our study, the peak for highest incidence although observed during the early morning from 4 to 8 am, the nocturnal-onset stroke cases showed more severity (12.2 ± 5.67) at the time of admission irrespective of arterial territory involved. The night onset cases were also found to be more susceptible to develop language impairment and post-stroke depression in due course of time. Upon transcript analysis, circadian genes (BMAL1 and CRY1) were found to be downregulated in night-time cases than day-time ones during the acute phase of onset. In addition, those mRNA levels also showed a correlation with raw scores for language and depression. However, the difference in incidence frequency along a day did not reveal any genetic correlation. Therefore, we suggest night-time stroke to be positively associated with higher immediate severity and poor cognitive outcome than day-time injury and propose downregulation of circadian genes during the acute phase could be the underlying molecular mechanism for this.

8100 Late Onset Sheehan Syndrome 23 Years After Post-Partum Hemorrhage: A Rare Case

Abstract Disclosure: I. Dosunmu: None. A. Alvi: None. S. Kaufman: None. A. Malik: None. Introduction: Sheehan syndrome is defined as ischemic necrosis of pituitary gland following massive postpartum hemorrhage. The majority of cases remain undiagnosed for many years after delivery. We present a unique case of late onset of Sheehan syndrome 23 years after the last childbirth which was complicated by hemorrhage. Although the syndrome can present with panhypopituitarism, most patients have partial hormone deficiency which leads to a delay in the diagnosis. Patients can remain asymptomatic for many years until the body is exposed to stressful situations. This is what we believe caused our patient to develop hyponatremia after staying symptom free for 23 years. Case Description: A 46-year-old female with no medical history presented with abdominal pain and dark colored urine. Her initial vital signs were normal. Labs showed sodium of 132 mmol/L, AST of 552 U/L, ALT of 518 U/L, ALP of 196 U/L, GGT of 166 U/L. CT scan of abdomen, liver ultrasound, and liver biopsy were unremarkable. AMA was positive with value of 1.98, consistent with diagnosis of primary biliary cholangitis. On day 2 her blood pressure decreased to 76/42 mmHg and her sodium decreased to 129mmol/L and on day 5 her blood pressure was 88/43mmHg and her sodium decreased to 122mmol/L. TSH was found to be 2.54 uIu/ml. Upon further evaluation by endocrinology, patient appeared to have sluggish speech and appeared edematous particularly in her face. A free T4 was found to be less than 0.07 ng/dl and cortisol 0.5 mcg/dl, and ACTH 22.4 pg/ml, FSH of 4.2 mIU/ml, LH 1.3 mIU/ml. On further questioning, patient confirmed history of complicated childbirth 23 years ago requiring multiple transfusions and a hysterectomy and she reported agalactorrhea after delivery. Brain MRI confirmed empty sella and she was diagnosed with Sheehan syndrome. She was started on levothyroxine and hydrocortisone and ursodiol for PBC. Discussion: Delayed onset Sheehan's syndrome stems from inadequate blood supply or ischemia to the pituitary gland during childbirth. Diagnosis can be challenging due to its gradual onset and vague presenting symptoms. In our patient, the possibility of Sheehan syndrome was suspected after evaluation for hyponatremia revealed central hypothyroidism and secondary adrenal insufficiency. &amp;#x2028;The immediate initiation of hydrocortisone followed by levothyroxine, resulted in the normalization of blood pressure and sodium and an increase in free T4 levels from &amp;lt;0.07 to 0.26 four days after hormone initiation. Early diagnosis and prompt treatment are crucial for the best outcomes. Our patient reported feeling much better and denied any symptoms 6 months after discharge. Conclusion: Delayed onset Sheehan's syndrome is a rare but important condition that can occur months or years after childbirth. Early diagnosis, proper medical management, and hormone replacement therapy are essential for improving the quality of life for affected women. Presentation: 6/2/2024

S5093 A Case of Early Onset Y-90 Radiation-Induced Gastritis

S5093 A Case of Early Onset Y-90 Radiation-Induced Gastritis

Findings from the individualized management of a patient with Acyl-CoA Oxidase-1 (ACOX1) deficiency: A bedside-to-bench-to-bedside strategy

Acyl-CoA Oxidase-1 (ACOX1) deficiency (MIM 264470) is an autosomal recessive disease characterized by impairments in the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, which is the first step in the catalysis of the β-oxidative breakdown of very long chain fatty acids (VLCFA) occuring in peroxisomes. The deleterious accumulation of VLCFA in several organs, including the brain, is a key biochemical feature of this disease which has devastating neurological consequences. ACOX1 deficiency is ultra-rare; as such, few studies have been conducted to determine the leading causes of symptoms or uncover new therapeutics. When confronted with one such case, we decided to bring drug discovery tools to the patient's bedside in an attempt to identify a cure. A skin biopsy was performed on a young patient with ACOX1 deficiency, following which screening technologies and mass spectrometry analysis techniques were applied to design a cellular assay that enabled the direct measurement of the effect of small molecules on the patient's primary fibroblasts. This approach is particularly well adapted to inherited metabolic disorders such as ACOX1 deficiency. Through the evaluation of a proprietary library of repurposable drugs, we found that the anthelmintic drug niclosamide led to a significant reduction in VLCFA in vitro. This drug was subsequently administered to the patient for more than six years. This study outlines the screening and drug selection processes. Additionally, we present our comprehensive clinical and biochemical findings that aided in understanding the patient's natural history and analysis of the progression of the patient's symptoms throughout the treatment period. Although the patient's overall lifespan was extended compared to the average age at death in severe early onset cases of ACOX1 deficiency, we did not observe any definitive evidence of clinical or biochemical improvement during niclosamide treatment. Nonetheless, our study shows a good safety profile of long-term niclosamide administration in a child with a rare neurodegenerative disease, and illustrates the potential of individualized therapeutic strategies in the management of inherited metabolic disorders, which could benefit both patients and the broader scientific and medical communities.

Risk of spontaneous intracerebral hemorrhage associated with NOACs compared with aspirin and warfarin: A long-term single hospital follow-up study

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation. MethodsThis retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants. ResultsWe analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively. ConclusionsThough NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center.

Cushing’s syndrome developing myasthenia gravis with takotsubo cardiomyopathy after adrenalectomy: a case report

BackgroundSeveral cases of autoimmune disease onset after treatment for Cushing’s syndrome have been reported.Case presentationHerein, we report a case of myasthenia gravis crisis in a 51-year-old woman 2 months after adrenalectomy for adrenal Cushing’s syndrome accompanied by takotsubo cardiomyopathy. The resolution of excessive endogenous cortisol after adrenalectomy may have triggered the onset of previously latent myasthenia gravis.ConclusionsObserving the similarities in symptoms between myasthenia gravis and adrenal crisis, which can sometimes be challenging to differentiate, is essential. Moreover, the presence of takotsubo cardiomyopathy as a non-motor manifestation of myasthenic crisis must be noted.

Early warning and predicting of COVID-19 using zero-inflated negative binomial regression model and negative binomial regression model

BackgroundIt is difficult to detect the outbreak of emergency infectious disease based on the exiting surveillance system. Here we investigate the utility of the Baidu Search Index, an indicator of how large of a keyword is in Baidu’s search volume, in the early warning and predicting the epidemic trend of COVID-19.MethodsThe daily number of cases and the Baidu Search Index of 8 keywords (weighted by population) from December 1, 2019 to March 15, 2020 were collected and analyzed with times series and Spearman correlation with different time lag. To predict the daily number of COVID-19 cases using the Baidu Search Index, Zero-inflated negative binomial regression was used in phase 1 and negative binomial regression model was used in phase 2 and phase 3 based on the characteristic of independent variable.ResultsThe Baidu Search Index of all keywords in Wuhan was significantly higher than Hubei (excluded Wuhan) and China (excluded Hubei). Before the causative pathogen was identified, the search volume of “Influenza” and “Pneumonia” in Wuhan increased with the number of new onset cases, their correlation coefficient was 0.69 and 0.59, respectively. After the pathogen was public but before COVID-19 was classified as a notifiable disease, the search volume of “SARS”, “Pneumonia”, “Coronavirus” in all study areas increased with the number of new onset cases with the correlation coefficient was 0.69 ~ 0.89, while “Influenza” changed to negative correlated (rs: -0.56 ~ -0.64). After COVID-19 was closely monitored, the Baidu Search Index of “COVID-19”, “Pneumonia”, “Coronavirus”, “SARS” and “Mask” could predict the epidemic trend with 15 days, 5 days and 6 days lead time, respectively in Wuhan, Hubei (excluded Wuhan) and China (excluded Hubei). The predicted number of cases would increase 1.84 and 4.81 folds, respectively than the actual number of cases in Wuhan and Hubei (excluded Wuhan) from 21 January to 9 February.ConclusionThe Baidu Search Index could be used in the early warning and predicting the epidemic trend of COVID-19, but the search keywords changed in different period. Considering the time lag from onset to diagnosis, especially in the areas with medical resources shortage, internet search data can be a highly effective supplement of the existing surveillance system.