Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.

BACKGROUND AND AIM: The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies. METHODS: The study included 15 489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database. RESULTS: A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies. CONCLUSIONS: The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

Recognition and characterising non-motor profile in early onset Parkinson's disease (EOPD).

Early onset Parkinson's disease (EOPD) has been recently defined as a clinical entity with subjects presenting with Parkinson's disease (PD) between the ages of 21-50 and replaces the term Young Onset PD (YOPD). Presentations in this age group are somewhat different to the typical Late Onset sporadic PD (LOPD) and genetic basis may play an important role. The presentations are however, to be differentiated from other causes of juvenile onset or early onset parkinsonism, which are often driven by rare genetic, brain metal deposition, or metabolic progressive disorders with a levolevodopa unresponsive or poorly responsive phenotype. Specific genetic mutations can also underpin EOPD and include nonmotor symptoms of EOPD, which have not been studied extensively. However, some real-life comparator studies with LOPD suggest a nonmotor profile in EOPD dominated by neuropsychiatric symptoms (anxiety), pain, sexual dysfunction, and a higher risk of impulse control disorders and segregation to the recently described noradrenergic and Park-sleep nonmotor endophenotypes may occur. Awareness of the phenotypic variants and nonmotor expression will pave the way for future precision and personalised medicine.

The impact of different lifestyle factors on disability in multiple sclerosis at older ages: a monocentric retrospective study.

Background: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system affecting approximately 2.8 million people worldwide. In addition to genetic and environmental factors, various lifestyle factors contribute to disease development and progression. Objectives: We performed a monocentric retrospective study and investigated the effect of lifestyle factors such as obesity, smoking, alcohol consumption, physical activity, and dietary habits on the degree of disability in a cohort of people with MS (pwMS) with an average onset of disease after the age of 55. Design: This late-onset MS (LOMS) study group (n = 47) was characterized by a mean age of 60.9 years and a mean duration of disease of 5.0 years. The LOMS study group was compared with two control groups. The study participants in the "old control group" (Cold) were on average as old and in the "young control group" (Cyoung) as long suffering from MS as the pwMS in the LOMS group. Methods: Data from medical documentation and a questionnaire were analyzed using descriptive frequency analyses and testing for correlation between different variables also by generalized estimating equations. The Expanded Disabilty Status Scale (EDSS) score and the progression index were used as a measure of disability. Results: We found a significant association between smoking history and the current EDSS score in the Cyoung group, but not in the two older study groups. For physical activity, there was a significant negative correlation with EDSS score in the study group and the Cold group, alcoholic beverage consumption correlated with decreased EDSS in the Cold group. The intake of meat negatively correlated with the progression index in the LOMS group. Conclusion: In summary, different life-style factors correlated with disability depending on patient age and disease duration. These life-style factors may be considered in the future counseling of pwMS at older ages.

Prediction model for early diagnosis of late-onset sepsis in preterm newborns.

AIM: Late-onset neonatal sepsis has a high mortality rate in premature infants. To date, no single test in the evaluation of neonatal sepsis has been demonstrated to be both sensitive and specific enough to assist in timely decision making. The aim of our study is to develop a predictive model that can be applied to all premature babies, using clinical and laboratory findings in premature babies, to recognize late-onset neonatal sepsis. STUDY DESIGN: 65 premature patients diagnosed with culture-proven late-onset neonatal sepsis and hospitalized in Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital neonatal intensive care unit between January 2018 and December 2020, and 65 premature newborns of similar age and gender who did not have sepsis were included in the study retrospectively. RESULTS: In our study, feeding difficulties, worsening in clinical appearance and fever were found to be significant among clinical findings, while thrombocytopenia and high C-reactive protein among laboratory findings are the strongest data supporting late-onset neonatal sepsis. In multiple regression analysis, thrombocytopenia, mean platelet volume, C-reactive protein, lymphocyte count and feeding difficulties had the highest odds ratio (p < 0.05). By converting these data into a scoring system, a nomogram was created that can be easily used by all clinicians. CONCLUSION: In our study, we developed a scoring system that can be easily applied to all premature patients by evaluating the clinical and laboratory findings in late-onset neonatal sepsis. We think that it will help in recognizing late-onset neonatal sepsis and strengthening the treatment decision. Predicting the individual probability of sepsis in preterm newborns may provide benefits for uninfected newborns to be exposed to less antibiotics, not to be separated from mother and baby, and to reduce healthcare system expenditures. The nomogram can be used to assess the likelihood of sepsis and guide treatment decision.

Role of Inflammatory Markers and Doppler Parameters in Late-Onset Fetal Growth Restriction: A Machine-Learning Approach.

OBJECTIVES: This study evaluates the association of novel inflammatory markers and Doppler parameters in late-onset FGR (fetal growth restriction), utilizing a machine-learning approach to enhance predictive accuracy. MATERIALS AND METHODS: A retrospective case-control study was conducted at the Department of Perinatology, Ministry of Health Etlik City Hospital, Ankara, from 2023 to 2024. The study included 240 patients between 32 and 37 weeks of gestation, divided equally between patients diagnosed with late-onset FGR and a control group. We focused on novel inflammatory markers-systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and neutrophil-percentage-to-albumin ratio (NPAR)-and their correlation with Doppler parameters of umbilical and uterine arteries. Machine-learning algorithms were employed to analyze the data collected, including demographic, neonatal, and clinical parameters, to develop a predictive model for FGR. RESULTS: The machine-learning model, specifically the Random Forest algorithm, effectively integrated the inflammatory markers with Doppler parameters to predict FGR. NPAR showed a significant correlation with FGR presence, providing a robust tool in the predictive model (Accuracy 77%, area under the curve [AUC] 0.851). In contrast, SII and SIRI, while useful, did not achieve the same level of predictive accuracy (Accuracy 75% AUC 0.818 and Accuracy 73% AUC 0.793, respectively). The model highlighted the potential of combining ultrasound measurements with inflammatory markers to improve diagnostic accuracy for late-onset FGR. CONCLUSIONS: This study illustrates the efficacy of integrating machines with traditional diagnostic methods to enhance the prediction of late-onset FGR. Further research with a larger cohort is recommended to validate these findings and refine the predictive model, which could lead to improved clinical outcomes for affected pregnancies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06372938.

The aging brain and late onset drug-refractory epilepsies.

While late-onset epilepsies are characterized by a good pharmacoresponsiveness, a relevant subgroup of this patient population suffers from drug-refractory epilepsy with its impact on overall quality of life and a high risk of seizure-related injuries. Particular attention should be paid to accurate diagnosis and thorough exclusion of pseudoresistance. Challenges include the likelihood of multimorbidities and polypharmacotherapy in an elderly patient population. Network, cellular, molecular, and metabolic alterations associated with aging and age-related disorders have the potential to affect the intrinsic severity of late-onset epilepsies, neural network function, and the pharmacodynamics and pharmacokinetics of antiseizure medications (ASMs). Whereas age-related changes in pharmacokinetics tend to favor responsiveness to low doses, respective changes in network excitability and pharmacodynamics of ASMs are more likely to contribute to drug resistance. There are particular gaps in our knowledge of the mechanisms of drug resistance and the impact of influencing factors in this patient population. Therefore, experimental and clinical research needs to be intensified to advance our understanding of drug-resistant epilepsy in patients with late-onset epilepsies and to develop multivariate prediction algorithms. In this context, the heterogeneity of an elderly patient population should be taken into account, considering differences in etiology, comorbidities, co-medications, frailty, activity and environmental factors.

Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks' gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and ß-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

Systemic Lupus Erythematosus in a Nonagenarian Woman: A Case Report.

In this case report, we present an elderly Hispanic woman with systemic lupus erythematosus (SLE) exhibiting a unique presentation characterized by a substantial unilateral pleural effusion, cardiac effusion, nephrotic-range proteinuria, and arthritis. The patient demonstrated improvement after receiving intravenous corticosteroids, followed by oral corticosteroids and a low dose of azathioprine. This case underscores the atypical presentation of SLE in the elderly, involving major organ systems, and highlights the patient's stability after three years of low immunosuppressive treatment.

Significance of early diagnosis and treatment of adult late-onset Pompe disease on the effectiveness of enzyme replacement therapy in improving muscle strength and respiratory function: a case report.

BACKGROUND: Pompe disease, a rare autosomal recessive disorder, is caused by mutations in the acid α-glucosidase gene. Pompe disease is a congenital metabolic disorder that affects all organs, particularly the striated muscle and nerve cells. Diagnosis is typically confirmed through enzyme assays that reveal reduced acid α-glucosidase activity. Enzyme replacement therapy utilizing human α-glucosidase is an available treatment option. Timely diagnosis and treatment in the early stages of the disease significantly impact the effectiveness of enzyme replacement therapy in enhancing patient condition. Here, we present a case of a patient with Pompe disease diagnosed 20 years after the onset of clinical symptoms. CASE PRESENTATION: A 38-year-old Iranian Baloch woman referred to our rheumatology clinic with progressive muscle weakness presents with a complex medical history. On mechanical ventilation for 12 years, she has endured fatigue and limb weakness since the age of 16, exacerbated following an abortion at 19. Despite undergoing corticosteroid and azathioprine therapies, the suspected diagnosis of inflammatory myopathy did not yield improvement. Hospitalization at 23 due to respiratory failure post-pregnancy led to her continued reliance on a ventilator. A dried blood spot test indicated reduced GAA enzyme activity, confirming a diagnosis of Pompe disease through genetic testing. Treatment with myozyme for 2 years demonstrated limited efficacy, as the patient experienced improved breathing but no significant overall improvement in limb-girdle muscular weakness. This case underscores the challenges and complexities involved in diagnosing and managing rare neuromuscular disorders like Pompe disease. CONCLUSION: Early intervention with enzyme replacement therapy plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients. It is important to note that treatment during advanced stages of the disease may not yield substantial benefits. Nevertheless, enzyme instability and denaturation due to temperature and neutral pH levels, along with limited delivery to disease-relevant tissues, can pose challenges in treatment. However, timely diagnosis of Pompe disease is paramount for its effective management and improved outcomes.

Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report.

BACKGROUND: Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life. CASE PRESENTATION: In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene. CONCLUSION: This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.

The association between APOE gene polymorphisms and the risk, characteristics, and prognosis of epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Epilepsy is one of the most common neurological diseases. Current evidence suggests that the apolipoprotein E (APOE) gene may be related to epilepsy. The purpose was to explore whether the APOE gene is associated with the risk, characteristics, and prognosis of epilepsy. METHODS: The study was a systematic review and meta-analysis. We searched WANFANG, VIP, CNKI, Embase, CENTRAL, and Medline for relevant studies published in English and Chinese inception up to December 27, 2023. Studies containing both APOE genotypes or at least one type of APOE allele and epilepsy were included. RESULTS: A total of 46 studies were included. Fourteen studies reported APOE genotypes and epilepsy risk (2539 patients and 2847 controls). The meta-analyses showed that the APOE 4 was higher in epilepsy (OR [95 % CI] = 1.32 [1.07, 1.62], I2 = 30 %), the APOE 2 was lower in epilepsy (OR [95 % CI] = 0.73 [0.62, 0.87], I2 = 0 %), and the APOE 3 didn't differ between epilepsy and controls (OR [95 % CI] = 1.01 [0.86, 1.19], I2 = 29 %). Our findings highlight that the risk of epilepsy is different depending on the subtype, with the APOE gene being more associated with temporal lobe epilepsy, drug-refractory epilepsy, and late-onset epilepsy. Patients with the ɛ4 allele have an earlier onset, worse cognition, and are more likely to have a history of febrile convulsion. No association between the ɛ4 allele and psychiatric symptoms and seizure-free after surgery. INTERPRETATION: These findings will help inform the provision of epilepsy services, including clinical management an important option for epilepsy patients with cognitive impairment, temporal lobe epilepsy, late-onset epilepsy, and drug-refractory epilepsy. However, whether APOE gene testing should be used as a routine test in people with epilepsy remains to be determined.

Late-onset chylothorax after lung cancer surgery: clinical characteristics, management, and prevention.

BACKGROUND: The clinical characteristics and management of late-onset chylothorax after lung cancer surgery remained unknown. Here we aimed to provide evidence on the management of late-onset chylothorax by analysis of several cases with the largest sample size. METHODS: We retrospectively collected clinical data of patients who developed late-onset chylothorax after lung cancer surgery and were re-admitted by a single surgeon in our center from 2016 to 2022. The clinical characteristics and management for these patients were analysed. The role of Hem-o-lok clipping after lymphadenectomy in preventing late-onset chylothorax was further explored by comparing the surgical outcomes between treated group and control group. RESULT: A total of six patients who were re-admitted for late-onset chylothorax after lung cancer surgery were included for analysis. The mean age of them was 60.7 years old. The symptom of late-onset chylothorax was mainly dyspnea and cough and the diagnosis was all made by Sudan III staining between postoperative day 17 to 42. All patients were firstly treated with thoracocentesis and low-fat diet with intravenous nutrition. Four patients were successfully managed with low-fat diet and thoracocentesis, while the other two patients were further managed with pleurodesis with 50% glucose fluid solution. We found a significantly decreased risk of late-onset chylothorax in the treated group with improved procedure of applying Hem-o-lok clipping after lymphadenectomy than in the control group (0% versus 2.6%, P < 0.01). CONCLUSION: Late-onset chylothorax after lung cancer surgery was a rare and negligible complication, which may usually be managed by non-surgical methods. Hem-o-lok clipping during lymphadenectomy seemed to be an effective method to prevent late-onset chylothorax after lung cancer surgery.

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Late-onset sepsis (LOS) is commonly seen in neonates who are hospitalized for extended periods, particularly in very low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI). Currently, the management of LOS in preterm infants faces dual challenges of delayed diagnosis and treatment, as well as antibiotic overtreatment. To address these issues, the Hunan Neonatal Medical Quality Control Center and the Neonatology Group of Perinatal Medical Committee of Hunan Medical Association organized a group of neonatal experts from Hunan Province to formulate recommendations based on published literature and statistical data from the Hunan Neonatal Medical Quality Control Center, as well as real-world practices in most neonatal intensive care units in Hunan Province. The group of neonatal experts proposed 15 recommendations for the diagnosis and antibiotic treatment of LOS in hospitalized preterm infants in the neonatal intensive care unit.

Associations of KRAS Mutations and Clinical Characteristics of Colorectal Cancer Patients in Indonesia.

BACKGROUND: Colorectal cancer (CRC) remains a major burden worldwide, ranking third and second in incidence and mortality respectively. Detection of biomarkers including KRAS mutations can help predict prognosis and response to therapy in CRC, thus this study evaluated the frequency of KRAS mutations among Indonesian patients and their associations with clinicopathologic characteristics. METHODS: Fifty-three CRC samples were collected from January to September 2022 in the Department of Surgery, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. KRAS mutations were analyzed using PCR followed by Sanger sequencing. Associations between KRAS mutations were evaluated using binary logistic regression analysis. RESULT: KRAS mutations were detected in 52.8% of patients (n=28), of which 3.6% were p.Gly12Ser (n=1), 32.1% were p.Gly12Asp (n=9), 7.1% were p.Gly13Asp (n=2), 3.6% were p.Gln61His (n=1), 3.6% were p.Asp126His (n=1), and 3.6% were p.Lys169Glu (n=1). The p.Asp73= polymorphism was detected in 57.1% of the samples (n=16). KRAS mutation status did not differ significantly between the groups based on the age of onset, sex, tumor location, tumor histology, stage, and family history. CONCLUSION: KRAS mutations are present in high frequency in this cohort of CRC patients in a tertiary hospital in West Java, Indonesia. However, KRAS mutation status is not associated with the age of onset, sex, tumor location, tumor histology, stage, and family history.

Identification of the mutations in BTD gene in Iranian patients with biotinidase deficiency and evaluating their genotype-phenotype correlations.

BACKGROUND: Biotinidase (BTD, encoded by the BTD gene) deficiency is an autosomal recessive neurometabolic disease caused by abnormal BTD activity in the biotin cycle. The clinical symptoms of patients, which are mainly neurocutaneous, range from mild to severe based on the enzyme activity level. This study aimed to identify BTD gene mutations in suspected BTD deficiency patients for the first time in the southwest of Iran and evaluate their genotype-phenotype correlations. METHODS: 11 clinically and biochemically suspected patients from nine unrelated families and their available family members were subjected to Sanger sequencing. Segregation analysis was performed for novel mutation. The effect of each mutation on protein stability and hydropathicity, as well as the pathogenicity prediction of all detected mutations were assessed using various in silico analysis tools. RESULTS: Six mutations including a novel and five previously reported mutations were identified in patients with different ethnicities. Three out of five known mutations were reported for the first time in Iran. Various common clinical manifestations and a rarely reported coexistence of celiac disease in biotinidase deficiency patients were observed. The novel missense variant c.787G > A (p.Glu263Lys) was detected in exon 4 of the BTD gene, within the biotinidase-like domain of the BTD protein. This variation was found in two cousins of a family, both developed the same initial clinical presentation. In silico analyses revealed that this missense substitution decreased protein stability and increased protein hydrophilicity. Additionally, the known frameshift mutation c.1264delG (p.val422serfster59), was the most frequent allele in the studied population. We also predicted and visualized the effects of the novel and frameshift mutations on protein structure. CONCLUSION: Our findings expanded the mutational spectrum of the BTD gene and provided valuable data on genotype-phenotype correlations, which helps in genetic counseling. Furthermore, the necessity of performing molecular analysis along with enzymatic analysis was highlighted by this study.

Psychiatry and sensation: the epigenetic links.

A complex interaction among sensory, social and epigenetic determinants in psychiatric conditions was described across all age strata. The high prevalence of mental disorders in individuals with sensory deficits might be attributed to the interaction among social isolation, cognitive functioning and sensory processing. The epigenetic implications of such interactions were examined: environmental and social factors can affect gene expression and impact the pathogenesis of psychiatric disorders also through sensory processing. This article discussed the role of social determinants, in other words, social isolation, loneliness and chronic stress, in promoting psychiatric disorders and, in a vicious circle, sensory deficits (vision, hearing, olfaction and somatosensation). We emphasized the importance of integrating social, sensory and epigenetic factors to target different treatments for psychiatric conditions.

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Complications of Long COVID: Unraveling a Case of Very-Late-Onset Myasthenia Gravis.

Myasthenia gravis (MG) is defined as an autoimmune neuromuscular disorder where autoantibodies disrupt synaptic transmission at the neuromuscular junction by targeting the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), or other proteins related to the AChR complex. This disruption leads to characteristic muscle weakness and rapid fatigability. Clinically, MG is classified based on the age of onset into three distinct categories: early-onset MG (younger than 50 years), late-onset MG (between 50 and 64 years), and very-late-onset MG (65 years and older). We present a rare case of an 81-year-old man who presented with dysarthria, shortness of breath, diplopia, and oropharyngeal dysphagia to both solids and liquids for approximately seven days and was noted to be more progressive in the last 48 hours prior to his presentation to the emergency room. Upon arrival at the emergency room, he complained of shortness of breath and diplopia. Of note, approximately four months prior to this admission, he was diagnosed with COVID-19 pneumonia and was treated appropriately with remdesivir and corticosteroids. He had an uneventful COVID-19 pneumonia hospitalization and was discharged home. Given the progressive nature of his symptomatology, particularly dyspnea, he was transferred to the ICU for further evaluation and treatment. Laboratory results were positive for AChR binding, blocking, and modulating antibodies, confirming the diagnosis of MG. The patient received treatment consisting of pyridostigmine, a pulse dose of methylprednisolone, and intravenous immunoglobulin (IVIG) therapy. This case is unique and highlights a case of a very late onset of MG and the manifestation of new-onset MG four months following COVID-19. Additionally, this patient had a very delayed onset of MG symptoms, as he presented four months after his infection with COVID-19, compared to the average onset of reported cases of post-COVID MG being four to eight weeks post-infection with COVID-19. This uniquely delayed onset, occurring beyond a three-month window post-COVID-19 infection, aligns with the criteria established by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) for a diagnosis of "Post-COVID Condition," also known as "Long COVID." This case illustrates the intricate link between post-viral states and autoimmune responses, particularly in geriatric patients. The pathophysiology linking COVID-19 to MG primarily involves immune dysregulation triggered by the viral infection, which may disrupt immune tolerance and lead to clinical autoimmunity. This case stresses the need for vigilance in diagnosis and managing neurological complications in the context of viral respiratory illnesses, particularly in vulnerable populations.

The combination of 18F-fluorodeoxyglucose and 18F 9-fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography for distinguishing between early-onset and late-onset idiopathic Parkinson disease and analyzing influencing factors.

Background: The classification of Parkinson disease by age of onset has proven to be a valuable method for subtyping, given its practical application in clinical settings. However, the interactions between the metabolic brain changes, dopaminergic dysfunction, and clinical manifestations in patients with early-onset (early-iPD) and late-onset (late-iPD) idiopathic Parkinson disease have not been adequately evaluated. Therefore, this study aimed to investigate the difference in cerebral metabolism and presynaptic dopaminergic function between patients with early-iPD and those with late-onset disease using 18F-fluorodeoxyglucose (18F-FDG) and [18F] 9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) positron emission tomography (PET). Furthermore, the goal was to further explore the correlation between imaging measurements and clinical manifestations in the early and late idiopathic patients with Parkinson disease. Methods: This cross-sectional study included 80 patients with idiopathic Parkinson disease and 29 healthy control participants who underwent 18F-FDG and18F-FP-DTBZ PET imaging at Xuanwu Hospital, Capital Medical University from August 2022 to August 2023. The patients were categorized into early-iPD (n=27) and late-iPD (n=53) groups based on an age threshold of 50 years. The mean standardized uptake value of 18F-FDG and the standardized uptake value ratio (SUVR) of 18F-FP-DTBZ were compared between the early-iPD and late-iPD groups using unpaired Student t-tests. Furthermore, pairwise correlations among cerebral metabolism, dopaminergic function, and corresponding clinical ratings in all patients were conducted using Pearson correlation analysis. Results: Patients with late-iPD exhibited a significant metabolic decrease in the frontal, parietal, and temporal cortex, along with the globus pallidus, putamen, thalamus, and cerebellum, compared to those with early-iPD in 18F-FDG PET imaging (all P values <0.05). Furthermore, the 18F-FP-DTBZ binding potential was significantly lower in the contralateral caudate and anterior putamen of patients with late-iPD compared to those with early-iPD (contralateral caudate: 3.16±1.2 vs. 2.63±0.7, P=0.020; contralateral anterior putamen: 2.49±1.2 vs. 2.05±0.7, P=0.040). Further analysis of the correlations between imaging clinical features revealed that glucose metabolism increases and dopaminergic function decreases with higher motor ratings. Conclusions: 18F-FDG and 18F-FP-DTBZ PET offer an objective molecular imaging basis for distinguishing between early-onset and late-onset idiopathic with Parkinson disease. Additionally, correlation analysis between imaging and clinical data represents a new approach for exploring the potential applications in future studies involving patients with early-iPD and late-iPD.

Racial/ethnic differences in the association of incident stroke with late onset epilepsy: The Northern Manhattan Study.

OBJECTIVE: Little is known about the incidence of late onset epilepsy (LOE) across different racial/ethnic groups in the USA, particularly in the Hispanic population. Stroke, a strong predictor of LOE, is more common in non-Hispanic Blacks (NHBs) and Hispanics than in non-Hispanic Whites (NHWs). We assessed the incidence of LOE across racial/ethnic groups and examined whether the associations of stroke with LOE risk differ by race/ethnicity. METHODS: The Northern Manhattan Study is a population-based longitudinal study of older adults enrolled between 1993 and 2001. Participants free of history of stroke or epilepsy at baseline (n = 3419) were followed prospectively for incidence of LOE. We estimated LOE incidence per 1000 person-years in each racial/ethnic group. We used Cox proportional hazards regression to assess the association of race/ethnicity with LOE and multiplicative interactions of race/ethnicity with incident stroke in relation to LOE, adjusting for demographics and comorbid diagnoses. RESULTS: During 51 176 person-years of follow-up, 183 individuals developed LOE. Incidence of LOE was significantly higher in NHBs (6.2 per 1000 person-years) than in NHWs (3.3 per 1000 person-years, p = .004). There was no significant difference in LOE incidence between NHWs (3.3 per 1000 person-years) and Hispanics (2.6 per 1000 person-years, p = .875). However, following incident stroke, the risk of LOE differed across racial/ethnic groups. Incident stroke was associated with 2.55 times the risk of LOE among NHWs (95% confidence interval [CI] = .88-7.35), 8.53 times the risk of LOE among Hispanics (95% CI = 5.36-13.57, p = .04 for stronger association than that in NHWs), and 6.46 times the risk of LOE among NHBs (95% CI = 3.79-11.01, p = .12 for stronger association than that in NHWs). SIGNIFICANCE: We found a stronger association of incident stroke with LOE risk in Hispanics and NHBs than in NHWs, offering some insight into the racial/ethnic disparities of LOE incidence.