Challenges and Perspectives of Neurological Disorders.

Neurological disorders pose significant challenges to healthcare systems worldwide [...].

Drugs to Treat Neuroinflammation in Neurodegenerative Disorders.

Neuroinflammation is associated with disorders of the nervous system, and it is induced in response to many factors, including pathogen infection, brain injury, toxic substances, and autoimmune diseases. Astrocytes and microglia have critical roles in neuroinflammation. Microglia are innate immune cells in the central nervous system (CNS), which are activated in reaction to neuroinflammation-inducing factors. Astrocytes can have pro- or anti-inflammatory responses, which depend on the type of stimuli presented by the inflamed milieu. Microglia respond and propagate peripheral inflammatory signals within the CNS that cause low-grade inflammation in the brain. The resulting alteration in neuronal activities leads to physiological and behavioral impairment. Consequently, activation, synthesis, and discharge of various pro-inflammatory cytokines and growth factors occur. These events lead to many neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis discussed in this study. After understanding neuroinflammation mechanisms and the involvement of neurotransmitters, this study covers various drugs used to treat and manage these neurodegenerative illnesses. The study can be helpful in discovering new drug molecules for treating neurodegenerative disorders.

Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies.

Previous epidemiological studies have raised the concern that the use of proton pump inhibitors (PPIs) is associated with an increased risk of kidney diseases. To date, no comprehensive meta-analysis has been conducted to assess the association between PPIs and the risk of chronic kidney disease (CKD). Therefore, we conducted a systematic review and meta-analysis to address the association between PPIs and CKD. The primary search was conducted in the most popular databases, such as PubMed, Scopus, and Web of Science. All observational studies evaluated the risk of CKD among PPI users, and non-users were considered for inclusion. Two reviewers conducted data extraction and assessed the risk of bias. Random-effect models were used to calculate pooled effect sizes. A total of 6,829,905 participants from 10 observational studies were included. Compared with non-PPI use, PPI use was significantly associated with an increased risk of CKD (RR 1.72, 95% CI: 1.02-2.87, p = 0.03). This updated meta-analysis showed that PPI was significantly associated with an increased risk of CKD. Association was observed in the same among moderate-quality studies. Until further randomized control trials (RCTs) and biological studies confirm these results, PPI therapy should not stop patients with gastroesophageal reflux disease (GERD). However, caution should be used when prescribing to patients with high-risk kidney disease.

Impact of gut-brain interaction in emerging neurological disorders.

The central nervous system (CNS) is a reservoir of immune privilege. Specialized immune glial cells are responsible for maintenance and defense against foreign invaders. The blood-brain barrier (BBB) prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery. When the double-edged neuroinflammatory response is overloaded, it no longer has the protective function of promoting neuroregeneration. Notably, microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology, causing microbiome-gut-brain axis dysregulation from the bottom-up. When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability, peripheral immune cells are recruited to the brain. This results in amplification of neuroinflammatory circuits in the brain, which eventually leads to specific neurological disorders. Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders, which can lead to potential protective effects in the CNS. Accordingly, this study investigated the mutual effects of microbiota and the gut-brain axis, which may provide targeting strategies for future disease treatment.

Salmonella Group D1 Subdural Empyema Mimicking Subdural Hematoma: A Case Report.

Subdural empyema is caused by various pathogens. The most typical clinical presentation may include fever, headache, seizures, and altered consciousness. However, Salmonella infections are relatively rare. Representative features of Salmonella infection include fever and gastrointestinal symptoms such as diarrhea, vomiting, and abdominal cramping pain. Extra-gastrointestinal invasion of Salmonella in the central nervous system is unusual. We present the case of an afebrile 58-year-old male who presented with a headache and a progressive dull response for a week. He had a closed head injury approximately 1 week before this visit. A tentative diagnosis led to a subdural hematoma (SDH), and he underwent urgent burr hole surgery. Intraoperative findings showed a large amount of brown-yellow pus in the subdural space instead of the pathognomonic bloody serosanguinous or thick motor oil, which is typical of SDH. The intraoperative culture yielded Salmonella group D1. After initial brain surgery and 52 days of effective intravenous administration of a third-generation cephalosporin (Ceftriaxone 2000 mg per day), the patient recovered fully without neurological deficits. His consciousness and mentality remained normal without focal weakness of the limbs for over 5 years of follow-up. This is a unique case with an atypical initial presentation that leads to a final unexpected diagnosis. Ongoing treatment strategies include a combination of surgical drainage for disease confirmation and appropriate medical antibiotics.

Association between systemic rheumatic diseases and dementia risk: A meta-analysis.

Background and aims: Epidemiological studies have been conducted on the relationship between systemic rheumatic diseases (SRDs) and dementia. Therefore, we focused on determining the extent of alliances bounded by SRDs, along with the risk of dementia. Materials and methods: Two independent reviewers assessed all studies retrieved from the PubMed, EMBASE, Scopus, and Web of Science databases between January 1, 2000 and November 30, 2021. Only observational studies that estimated the possibility of dementia in participants with SRD were considered. The random-effects model was applied to forecast pooled risk ratios (RRs) and 95% confidence intervals (CI). Heterogeneity among the studies was evaluated using the Q and I2 statistics. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Funnel plots were used to calculate the risk of bias. Results: Seventeen observational studies with 17,717,473 participants were recruited. Our findings showed that among the participants with SRDs, those with osteoarthritis, systemic lupus erythematosus, and Sjogren's syndrome were highly related to an elevated risk of dementia (pooled RR: 1.31; 95% CI: 1.15-1.49, p<0.001; pooled RR: 1.43; 95% CI: 1.19-1.73, p<0.001; and pooled RR: 1.26; 95% CI: 1.14-1.39, p<0.001, respectively). However, participants with rheumatoid arthritis (RA) were not associated with an increased risk of dementia (pooled RR: 0.98; 95% CI: 0.90-1.07, p<0.001). Conclusion: This systematic review and meta-analysis demonstrated an increased dementia risk among SRDs participants, except for RA.

Homogeneous Chronic Subdural Hematoma with Diverse Recurrent Possibilities.

Background: Evidence suggests that hyperdense (HD) chronic subdural hematomas (CSDHs) have a higher recurrence than hypodense (LD) chronic subdural hematomas. The value of mean hematoma density (MHD) has been proven to be associated with postoperative recurrence. The MHD levels in homogeneous CSDHs likely underestimate the risk of recurrence in HD homogeneous subtypes. Methods: This study investigated 42 consecutive CSDH cases between July 2010 and July 2014. The area of the hematoma was quantified to determine the MHD level using computer-based image analysis of preoperative brain CT scans. Results: In terms of the MHD distribution of the four types of CSDHs (homogeneous, laminar, separated, and trabecular), wide 95% CI (11.80-16.88) and high standard deviation (4.59) can be found in homogeneous types, reflecting a high variability in the MHD levels between cases (from low to high density). The categorization of homogeneous types into LD and HD (type five) displayed a minor standard deviation in the MHD levels for LD and HD subtypes (1.15, and 0.88, respectively). MHD values demonstrated concentrated distributions among the respective five types, compared to the four-type setting. Conclusions: In the current research, we provide a consideration that if LD and HD hematomas are separated from homogeneous CSDHs, the variability of the MHD quantification can potentially be reduced, thereby avoiding the possibility of undetected high-risk groups.

mHealth Research for Weight Loss, Physical Activity, and Sedentary Behavior: Bibliometric Analysis.

BACKGROUND: Research into mobile health (mHealth) technologies on weight loss, physical activity, and sedentary behavior has increased substantially over the last decade; however, no research has been published showing the research trend in this field. OBJECTIVE: The purpose of this study was to provide a dynamic and longitudinal bibliometric analysis of recent trends of mHealth research for weight loss, physical activity, and sedentary behavior. METHODS: A comprehensive search was conducted through Web of Science to retrieve all existing relevant documents published in English between January 1, 2010, and November 1, 2021. We developed appropriate research questions; based on the proven bibliometric approaches, a search strategy was formulated to screen the title for eligibility. Finally, we conducted bibliometric analyses to explore the growth rate of publications; publication patterns; and the most productive authors, institutions, and countries, and visualized the trends in the field using a keyword co-occurrence network. RESULTS: The initial search identified 8739 articles, of which 1035 were included in the analyses. Our findings show an exponential growth trend in the number of annual publications of mHealth technology research in these fields. JMIR mHealth and uHealth (n=214, 20.67%), Journal of Medical Internet Research (n=71, 6.86%), and BMC Public Health (n=36, 3.47%) were the top 3 journals, publishing higher numbers of articles. The United States remained the leading contributor in these areas (n=405, 39.13%), followed by Australia (n=154, 14.87%) and England (n=125, 12.07%). Among the universities, the University of Sydney (n=36, 3.47%) contributed the most mHealth technology research in these areas; however, Deakin University (n=25, 2.41%) and the National University of Singapore (n=23, 2.22%) were in the second and third positions, respectively. CONCLUSIONS: Although the number of papers published on mobile technologies for weight loss, physical activity, and sedentary behavior was initially low, there has been an overall increase in these areas in recent years. The findings of the study indicate that mobile apps and technologies have substantial potential to reduce weight, increase physical activity, and change sedentary behavior. Indeed, this study provides a useful overview of the publication trends and valuable guidance on future research directions and perspectives in this rapidly developing field.

Combination of Acupoints for Alzheimer's Disease: An Association Rule Analysis.

Background: Alzheimer's disease (AD) is an ongoing neurological degeneration characterized by amnesia and a decline in cognitive abilities. Hippocampal neurogenesis is the leading cause of AD. Mild cognitive impairment (MCI), a prodromal state of AD, is mainly due to the degradation of neuropsychiatric manifestations. Previous systematic reviews demonstrated that treatment with acupuncture with Chinese herbs is tolerable and effective in improving cognitive function in patients with AD. Our investigation aimed to discover the main acupoint combination for AD management based on a preceding systematic review and meta-analysis of randomized control trials (RCTs). Materials and Methods: Our investigation was executed using association rule analysis, which is a common data mining technique accessible within R. Our study elucidated acupoint locations as binary data from 15 of the included studies using the Apriori algorithm. Results: Thirty-two acupoints were selected from 15 RCTs. The 10 most frequent acupoints were selected. We inspected 503 association rules using the interpreted acupuncture data. The obtained results showed that {SP6, BI10} ≥ {HT7} and {HT7, BI10} ≥ {SP6} were the most associated rules in 15 RCTs. Conclusion: The combination of acupoints ({SP6, BI10} ≥ {HT7} and {HT7, BI10} ≥ {SP6}) can be acknowledged as a core combination for future acupuncture regimens of AD.

Nationwide Prevalence and Outcomes of Long-Term Nasogastric Tube Placement in Adults.

Tube feeding (TF) is commonly used for patients with severe swallowing disturbance, and patients with chronic dysphagia are often provided with a long-term nasogastric tube (NGT). However, nationwide epidemiological data on long-term NGT placement are limited. The present study identified the prevalence and outcomes of patients with long-term NGT placement in Taiwan. Data were obtained from the Longitudinal Health Insurance Database. Patients with NGT placement for more than 3 months between 2000 and 2012 were enrolled in this cohort study. An NGT cohort of 2754 patients was compared with 11,016 controls matched for age, sex, residential area, and comorbidities. The prevalence rate of long-term NGT reached 0.063% in 2005 and then remained stable at 0.05-0.06%. The major causes of NGT placement were stroke (44%), cancer (16%), head injury (14%), and dementia (12%). Men (63%) were more likely to have long-term NGT placement than women (37%). The adjusted hazard ratios were 28.1 (95% CI = 26.0, 30.3) for acute and chronic respiratory infections; 26.8 (95% CI = 24.1, 29.8) for pneumonia, 8.84 (95% CI = 7.87, 9.93) for diseases of the esophagus, stomach, and duodenum; and 7.5 (95% CI = 14.7, 20.8) for mortality. Patients with NGT placement for more than 6 months had a higher odds ratio (1.58, 95% CI = 1.13, 2.20) of pneumonia than those with NGT placement for less than 6 months. Only 13% and 0.62% of the patients underwent rehabilitation therapy and percutaneous endoscopic gastrostomy, respectively. Long-term NGT use was associated with a higher risk of comorbidities and mortality. Stroke was the main illness contributing to long-term NGT use. Further interventions are necessary to improve the negative effects of long-term TF.

Anti-Inflammatory CDGSH Iron-Sulfur Domain 2: A Biomarker of Central Nervous System Insult in Cellular, Animal Models and Patients.

Spinal cord injury (SCI) promotes brain inflammation; conversely, brain injury promotes spinal neuron loss. There is a need to identify molecular biomarkers and therapeutic targets for central nervous system (CNS) injury. CDGSH iron-sulfur structural domain 2 (CISD2), an NF-κB antagonist, is downregulated after injury in vivo and in vitro. We aimed to examine the diagnostic value of CISD2 in patients with CNS insult. Plasma and cerebrospinal fluid (CSF) CISD2 levels were decreased in 13 patients with CNS insult and were negatively correlated with plasma IL6 levels (associated with disease severity; r = −0.7062; p < 0.01). SCI-induced inflammatory mediators delivered through CSF promoted mouse brain inflammation at 1 h post-SCI. Anti-CISD2 antibody treatment exacerbated SCI-induced inflammation in mouse spine and brain. Lipopolysaccharide-stimulated siCISD2-transfected EOC microglial cells exhibited proinflammatory phenotypes (enhanced M1 polarization, decreased M2 polarization, and increased intranuclear NF-κB p65 translocation). Plasma and CSF CISD2 levels were increased in three patients with CNS insult post-therapeutic hypothermia. CISD2 levels were negatively correlated with plasma and CSF levels of inflammatory mediators. CISD2 inhibition and potentiation experiments in cells, animals, and humans revealed CISD2 as a biomarker for CNS insult and upregulation of CISD2 anti-inflammatory properties as a potential therapeutic strategy for CNS insult.

Posterior Reversible Encephalopathy Syndrome after Lenvatinib Therapy in a Patient with Olfactory Neuroblastoma.

Posterior reversible encephalopathy syndrome (PRES) is a rare but severe neurological syndrome that may stem from the use of some medications. Although its mechanism is not well-known, hypertension and endothelial dysfunction have been mentioned in previous literature as being related. Lenvatinib serves as a neoplastic agent that inhibits the tyrosine kinase of vascular endothelial growth factor receptors (VEGFR). VEGFR inhibitors result in endothelial dysfunction and consequent hypertension by nitric oxide pathway suppression and endothelin (ET)-1 stimulation. We hypothesized that VEGFR inhibitors would cause PRES. Herein, we report the case of a 40-year-old man with olfactory neuroblastoma who developed PRES while undergoing treatment with lenvatinib, 7 months after initiation. The symptoms included loss of consciousness and seizures. Fortunately, the symptoms and presence of PRES in imaging resolved, 7 days and 1 month, respectively, after cessation of lenvatinib.

A Deep Learning Model to Predict Knee Osteoarthritis Based on Nonimage Longitudinal Medical Record.

PURPOSE: To develop deep learning model (Deep-KOA) that can predict the risk of knee osteoarthritis (KOA) within the next year by using the previous three years nonimage-based electronic medical record (EMR) data. PATIENTS AND METHODS: We randomly selected information of two million patients from the Taiwan National Health Insurance Research Database (NHIRD) from January 1, 1999 to December 31, 2013. During the study period, 132,594 patients were diagnosed with KOA, while 1,068,464 patients without KOA were chosen randomly as control. We constructed a feature matrix by using the three-year history of sequential diagnoses, drug prescriptions, age, and sex. Deep learning methods of convolutional neural network (CNN) and artificial neural network (ANN) were used together to develop a risk prediction model. We used the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and precision to evaluate the performance of Deep-KOA. Then, we explored the important features using stepwise feature selection. RESULTS: This study included 132,594 KOA patients, 83,111 females (62.68%), 49,483 males (37.32%), mean age 64.2 years, and 1,068,464 non-KOA patients, 545,902 females (51.09%), 522,562 males (48.91%), mean age 51.00 years. The Deep-KOA achieved an overall AUROC, sensitivity, specificity, and precision of 0.97, 0.89, 0.93, and 0.80 respectively. The discriminative analysis of Deep-KOA showed important features from several diseases such as disorders of the eye and adnexa, acute respiratory infection, other metabolic and immunity disorders, and diseases of the musculoskeletal and connective tissue. Age and sex were not found as the most discriminative features, with AUROC of 0.9593 (-0.76% loss) and 0.9644 (-0.25% loss) respectively. Whereas medications including antacid, cough suppressant, and expectorants were identified as discriminative features. CONCLUSION: Deep-KOA was developed to predict the risk of KOA within one year earlier, which may provide clues for clinical decision support systems to target patients with high risk of KOA to get precision prevention program.

Anemia and the Risk of Cognitive Impairment: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment is one of the most common, burdensome, and costly disorders in the elderly worldwide. The magnitude of the association between anemia and overall cognitive impairment (OCI) has not been established. OBJECTIVE: We aimed to update and expand previous evidence of the association between anemia and the risk of OCI. METHODS: We conducted an updated systematic review and meta-analysis. We searched electronic databases, including EMBASE, PubMed, and Web of Science for published observational studies and clinical trials between 1 January 1990 and 1 June 2020. We excluded articles that were in the form of a review, letter to editors, short reports, and studies with less than 50 participants. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We estimated summary risk ratios (RRs) with random effects. RESULTS: A total of 20 studies, involving 6558 OCI patients were included. Anemia was significantly associated with an increased risk of OCI (adjusted RR (aRR) 1.39 (95% CI, 1.25-1.55; p < 0.001)). In subgroup analysis, anemia was also associated with an increased risk of all-cause dementia (adjusted RR (aRR), 1.39 (95% CI, 1.23-1.56; p < 0.001)), Alzheimer's disease [aRR, 1.59 (95% CI, 1.18-2.13; p = 0.002)], and mild cognitive impairment (aRR, 1.36 (95% CI, 1.04-1.78; p = 0.02)). CONCLUSION: This updated meta-analysis shows that patients with anemia appear to have a nearly 1.39-fold risk of developing OCI than those without anemia. The magnitude of this risk underscores the importance of improving anemia patients' health outcomes, particularly in elderly patients.

Lumbar Extradural Pseudogout Mass Manifesting as Radiculopathy: A Case Report.

BACKGROUND: Calcium pyrophosphate dihydrate (CPPD) disease, also known as pyrophosphate arthropathy or pseudogout, is defined as CPPD deposition within the articular cartilage. It was first described in 1962. The representative locations where CPPD disease occurs include the most common knee joint, followed by the wrist joint. Joint swelling and pain are the most common clinical presentations, and the typical differential diagnosis is degenerative arthritis. Microscopically, the specimen demonstrates numerous positively birefringent rhomboid shaped crystals when examined under polarized light. CASE REPORT: We present a 70-year-old female with right painful sciatica accompanied by coexisting affected limb soreness and clumsiness. Her final diagnosis was unusual lumbar extradural tumoral pseudogout that was worth noticing. Tumoral CPPD deposition was excised after laminectomy. Subsequently, her symptoms were abated postoperatively without a need for more analgesics. Her neurological function was properly recovered. CONCLUSION: This is a rare report to proffer pseudogout in an unfamiliar lumbar extradural location, which is an unexpected diagnosis. Making a precise tentative diagnosis for the ongoing disease entity might be difficult for the clinicians because the clinical manifestations of this pathology are similar to those of other common degenerative lumbar spinal diseases.