Tyrosine kinase inhibitors in the treatment of leptomeningeal carcinomatosis.

Leptomeningeal carcinomatosis (LMC) is a devastating complication of advanced cancers, such as lung cancer and breast cancer, which is usually indicative of a poor prognosis. The current treatments for LMC include palliative care, with others aiming to prolong survival and relieve neurological symptoms. Traditional treatments for LMC include radiotherapy, systemic chemotherapy, and intrathecal injection. Furthermore, the application of molecularly targeted agents, such as antiepidermal growth factor receptor (anti-EGFR), antihuman epidermal growth factor receptor 2 (anti-HER2), and anti-PD-1 monoclonal antibody, have prolonged the survival of LMC patients. Targeted therapy with tyrosine kinase inhibitors has also been proven to be an effective treatment. Tyrosine kinases can be overactive or expressed at high levels in some cancer cells; therefore, the use of tyrosine kinase inhibitors may prevent the activation of tumor-related pathways, preventing cancer cell growth. The EGFR family are cell surface receptors directly related to tumor occurrence with tyrosine kinase activity; it is the most widely used target for tyrosine kinase inhibitors in the treatment of LMC. In this review, we introduced the clinical manifestation and diagnostic criteria of LMC, clarified the treatment mechanism of tyrosine kinase inhibitors for LMC with mutations in EGFR, HER2, or anaplastic lymphoma kinase, reviewed the current application of various generation tyrosine kinase inhibitors in patients with LMC, and discussed new clinical trials and the future directions of tyrosine kinase inhibitor therapy.

Bridging therapy improves functional outcomes and reduces 90-day mortality compared with direct endovascular thrombectomy in patients with acute posterior ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: It remains unclear whether bridging therapy can achieve better neurologic outcomes than direct endovascular thrombectomy (EVT) in patients with posterior ischemic stroke. METHODS: We systematically searched PubMed, EMBASE, and Cochrane databases with posterior artery occlusion treated with bridging therapy vs. EVT. Efficacy was assessed based on functional independence at 90 days and successful recanalization, whereas safety was assessed by mortality, rate of symptomatic intracranial hemorrhage (sICH), and occurrence of any hemorrhage. All data were analyzed with Review Manager software v5.3 and the risk of bias was determined using the Methodological Index for Non-randomized Studies. RESULTS: We included 17 studies with a total of 3278 patients (1211 in the bridging therapy group and 2067 in the EVT group). Patients in the bridging group had a better functional outcome at 90 days, as evidenced by a higher proportion with a Modified Rankin Scale (mRS) score of 0-2 compared with the EVT group (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.54-2.19, P < 0.01), while no difference in mRS score of 0-3 (OR = 1.18, 95% CI: 0.96-1.45, P = 0.11). Patients in the bridging therapy group also had lower 90-day mortality rate (OR = 0.75, 95% CI: 0.59-0.95, P = 0.02). There were no significant differences between groups in rates of successful recanalization (OR = 0.96, 95% CI: 0.74-1.25, P = 0.77), sICH (OR = 1.27, 95% CI: 0.86-1.89, P = 0.24), and hemorrhage (OR = 1.22, 95% CI: 0.60-2.50, P = 0.58). CONCLUSIONS: Among patients with posterior ischemic stroke, bridging therapy may be superior to EVT in achieving a good functional outcome and lowering the mortality without increasing the risks of hemorrhage.

Safety and efficacy of bone marrow mononuclear cell therapy for ischemic stroke recovery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cell-based therapy represents a potential treatment for ischemic stroke (IS). Here, we performed a systematic review and meta-analysis to summarize the evidence provided by randomized controlled trials (RCTs) for the transplantation of bone marrow mononuclear cells (BMMNCs) in patients with IS in any phase after stroke. METHODS: We searched several databases for relevant articles up to the 10th of March 2023, including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov. Subgroup analyses were implemented to evaluate the dose and route of BMMNC administration. Statistical data were analyzed by Review Manager version 5.3 software. RESULTS: Six RCTs were included in this article, including 177 patients who were treated by the transplantation of BMMNCs and 166 patients who received medical treatment. The three-month National Institutes of Health Stroke Scale (NIHSS) score indicated a favorable outcome for the BMMNC transplantation group (standardized mean difference (SMD), - 0.34; 95% confidence interval (CI), - 0.57 to - 0.11; P = 0.004). There were no significant differences between the two groups at six months post-transplantation with regards to NIHSS score (SMD 0.00; 95% CI - 0.26 to 0.27; P = 0.97), modified Rankin Scale (risk ratio (RR) 1.10; 95% CI 0.75 to 1.63; P = 0.62), Barthel Index change (SMD 0.68; 95% CI - 0.59 to 1.95; P = 0.29), and infarct volume change (SMD - 0.08; 95% CI - 0.42 to 0.26; P = 0.64). In addition, there was no significant difference between the two groups in terms of safety outcome (RR 1.24; 95% CI 0.80 to 1.91; P = 0.33). CONCLUSION: Our meta-analysis demonstrated that the transplantation of BMMNCs was safe; however, the efficacy of this procedure requires further validation in larger RTCs.

External stenting for saphenous vein grafts in coronary artery bypass grafting: A meta-analysis.

OBJECTIVES: Autologous saphenous vein grafts (SVGs) are the most commonly used bypass conduits in coronary artery bypass grafting (CABG) with multivessel coronary artery disease. Although external support devices for SVGs have shown promising outcomes, the overall efficacy and safety remains controversial. We aimed to evaluate external stenting for SVGs in CABG versus non-stented SVGs. METHODS: MEDLINE, EMBASE, Cochrane Library and clinicaltrails.gov were searched for randomized controlled trials (RCTs) to evaluate external-stented SVGs versus non-stented SVGs in CABG up to 31 August 2022. The risk ratio and mean difference with 95% confidence interval were analysed. The primary efficacy outcomes included intimal hyperplasia area and thickness. The secondary efficacy outcomes were graft failure (≥50% stenosis) and lumen diameter uniformity. RESULTS: We pooled 438 patients from three RCTs. The external stented SVGs group showed significant reductions in intimal hyperplasia area (MD: -0.78, p < 0.001, I2 = 0%) and thickness (MD: -0.06, p < 0.001, I2 = 0%) compared to the non-stented SVGs group. Meanwhile, external support devices improved lumen uniformity with Fitzgibbon I classification (risk ratio (RR):1.1595, p = 0.05, I2 = 0%). SVG failure rates were not increased in the external stented SVGs group during the short follow-up period (RR: 1.14, p = 0.38, I2 = 0%). Furthermore, the incidences of mortality and major cardiac and cerebrovascular events were consistent with previous reports. CONCLUSIONS: External support devices for SVGs significantly reduced the intimal hyperplasia area and thickness, and improved the lumen uniformity, assessed with the Fitzgibbon I classification. Meanwhile, they did not increase the overall SVG failure rate.

Identification of Asymptomatic COVID-19 Patients on Chest CT Images Using Transformer-Based or Convolutional Neural Network-Based Deep Learning Models.

Novel coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world; however, it is difficult for clinicians to make early diagnoses. This study is to evaluate the feasibility of using deep learning (DL) models to identify asymptomatic COVID-19 patients based on chest CT images. In this retrospective study, six DL models (Xception, NASNet, ResNet, EfficientNet, ViT, and Swin), based on convolutional neural networks (CNNs) or transformer architectures, were trained to identify asymptomatic patients with COVID-19 on chest CT images. Data from Yangzhou were randomly split into a training set (n = 2140) and an internal-validation set (n = 360). Data from Suzhou was the external-test set (n = 200). Model performance was assessed by the metrics accuracy, recall, and specificity and was compared with the assessments of two radiologists. A total of 2700 chest CT images were collected in this study. In the validation dataset, the Swin model achieved the highest accuracy of 0.994, followed by the EfficientNet model (0.954). The recall and the precision of the Swin model were 0.989 and 1.000, respectively. In the test dataset, the Swin model was still the best and achieved the highest accuracy (0.980). All the DL models performed remarkably better than the two experts. Last, the time on the test set diagnosis spent by two experts-42 min, 17 s (junior); and 29 min, 43 s (senior)-was significantly higher than those of the DL models (all below 2 min). This study evaluated the feasibility of multiple DL models in distinguishing asymptomatic patients with COVID-19 from healthy subjects on chest CT images. It found that a transformer-based model, the Swin model, performed best.

Association between breastfeeding and periodontitis in Korean women using Korea National Health and Nutrition Examination Survey (KNHANES): a cross-sectional study.

OBJECTIVES: The effect of breastfeeding on periodontal disease in women remains unclear. This cross-sectional study used data from the Korean National Health and Nutrition Examination Survey to explore the association between breastfeeding and periodontitis in Korean women using data from the Korean National Health and Nutrition Examination Survey (KNHANES VII). MATERIALS AND METHODS: Cross-sectional data was analyzed from the KNHANES 2016-2018. The study population included 5,587 parous women aged ≥ 30 years. The outcome variable was the presence or absence of periodontitis. The explanatory variable, period of breastfeeding, was defined as "none", "1-11 months", and "more than 12 months". Confounder variables (socio-educational, personal healthcare practice, and systemic medical characteristics) were adjusted for in the logistic regression analysis. RESULTS: Approximately 60% of the participants breastfed for ≥ 12 months. In all statistical models, the prevalence of periodontitis was approximately 60% greater in women that did not breastfeed compared to women that had breastfed for 12 months or longer. When adjusted for age, statistical significance was only present in the 50-59 years age group (adjusted odds ratio [aOR], 1.678; 95% confidence interval [CIs], 1.046-2.691). CONCLUSION: Our study shows that women that breastfed for a relatively long duration had a lower risk of periodontitis. Therefore, breastfeeding may be beneficial for women's periodontal health. These results are expected to be helpful in oral health education for pregnant women.

Segmented carotid endarterectomy for treatment of Riles type 1A common carotid artery occlusion.

OBJECTIVE: Common carotid artery occlusion (CCAO) is a rare cause of cerebrovascular events. Symptomatic lesions are resistant to medical treatment and revascularization is often required, but there is no consensus on the treatment of CCAO at present. Riles type 1A CCAO is most likely to benefit from revascularization because it has patent outflow tract (internal carotid artery) which was supplied by patent external carotid artery (ECA) from collateral circulation. We described a novel surgical technique improved on the basis of the carotid endarterectomy (CEA) for treatment of Riles type 1A CCAO. METHODS: We rigorously screened ten patients with symptomatic Riles type1A CCAO for surgery from January 2017 to May 2019 and performed a full preoperative assessment of the inadequate collateral circulation compensation. Moreover, we retrospectively reviewed our experience of the segmented CEA in the treatment of them in our single center. RESULTS: Segmented CEA was performed on the left side in four cases and on the right side in six cases. The technical success rate of the procedure was 100%. Primary suture was used in nine cases. Only one patient (right CCAO) who had a history of neck radiotherapy was treated by the patch CEA. The mean temporary blocking time during surgery was 52.8 ± 9.15 min. The mean temporary blocking time for treating the upper segment of the common carotid artery (CCA) was 11.1 ± 2.64 min. In the postoperative period, cerebral perfusion on the ipsilateral site improved in all patients, myocardial infarction occurred in one patient, and recurrent laryngeal nerve damage occurred in another. No ischemic events or re-occlusion or restenosis (> 50%) of the treated CCA occurred during the mean follow-up of 32.6 ± 9.3 months. The preoperative mean modified Rankin Scale (mRS) score was 1.9 (range, 1-3; median, 2). At last follow-up for all patients, the mRS score was 1 (range, 0-3; median, 1). CONCLUSION: Segmented CEA, which utilizes the compensatory effect of collateral circulation, is an effective and safe technique to treat patients suffering from Riles type 1A CCAO with hemodynamic cerebrovascular compromise.

Utility of indocyanine green videoangiography with FLOW 800 analysis in brain tumour resection as a venous protection technique.

BACKGROUND: In regard to central nervous system tumour resection, preserving vital venous structures to avoid devastating consequences such as brain oedema and haemorrhage is important. However, in clinical practice, it is difficult to obtain clear and vivid intraoperative venous visualization and blood flow analyses. METHODS: We retrospectively reviewed patients who underwent brain tumour resection with the application of indocyanine green videoangiography (ICG-VA) integrated with FLOW 800 from February 2019 to December 2020 and present our clinical cases to demonstrate the process of venous preservation. Galen, sylvian and superior cerebral veins were included in these cases. RESULTS: Clear documentation of the veins from different venous groups was obtained via ICG-VA integrated with FLOW 800, which semiquantitatively analysed the flow dynamics. ICG-VA integrated with FLOW 800 enabled us to achieve brain tumour resection without venous injury or obstruction of venous flux. CONCLUSIONS: ICG-VA integrated with FLOW 800 is an available method for venous preservation, although further comparisons between ICG-VA integrated with FLOW 800 and other techniques of intraoperative blood flow monitoring is needed.

Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials.

BACKGROUND: To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of Parkinson's disease (PD). METHODS: The databases of Medline, EMBASE, and the Cochrane Library were searched for eligible randomized controlled trials comparing focused ultrasound surgery (FUS) group vs. sham procedure group in PD. Weighted mean differences and standardized mean differences with corresponding 95% confidence intervals were used to summarize the primary outcome, namely, the effect of MRgFUS to improve limb tremor in PD patients and adverse events, and the secondary outcome, which is the effect of MRgFUS in improving the quality of life, activities of daily living, and non-motor symptoms. RESULTS: The pooled analysis comprised 2 studies. The blinded phase lasted for 4 months in one experiment and up to 3 months in the other. The FUS group showed significant improvement in limb tremor on the treated side (SMD: - 1.20; 95% CI: - 2.06, - 0.34) and the ability to perform daily activities (SMD: - 0.86; 95% CI: - 1.41, - 0.32) compared to the sham group, but there were no significant group differences in other indicators. Of the process-related adverse events, dizziness (OR: 4.68; 95% CI: 1.20, 18.23) was more common in the treatment group, with no group differences in the remaining adverse events. CONCLUSIONS: These findings suggest beneficial effects of MRgFUS in PD patients with no serious side effects. Larger multicenter studies are needed in the future to select the most appropriate target and surgical device setup parameters.

Tranexamic Acid Inhibits Hematoma Expansion in Intracerebral Hemorrhage and Traumatic Brain Injury. Does Blood Pressure Play a Potential Role? A Meta-Analysis from Randmized Controlled Trials.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent, which has shown an effect on reducing blood loss in many diseases. Many studies focus on the effect of TXA on cerebral hemorrhage, however, whether TXA can inhibit hematoma expansion is still controversial. Our meta-analysis performed a quantitative analysis to evaluate the efficacy of TXA for the hematoma expansion in spontaneous and traumatic intracranial hematoma. METHOD: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to May 2020 for randomized controlled trials (RCTs). RESULT: We pooled 3102 patients from 7 RCTs to evaluate the efficacy of TXA for hematoma expansion. Hematoma expansion (HE) rate and hematoma volume (HV) change from baseline were used to analyze. We found that TXA led to a significant reduction in HE rate (P = 0.002) and HV change (P = 0.03) compared with the placebo. Patients with moderate or serious hypertension benefit more from TXA. (HE rate: P = 0.02, HV change: P = 0.04) TXA tends to have a better efficacy on HV change in intracerebral hemorrhage (ICH). (P = 0.06) CONCLUSIONS: TXA showed good efficacy for hematoma expansion in spontaneous and traumatic intracranial hemorrhage. Patients with moderate/severe hypertension and ICH may be more suitable for TXA administration in inhibiting hematoma expansion .

Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials.

BACKGROUND: Galcanezumab is a novel monoclonal antibody that target to calcitonin gene-related peptide (CGRP). It has been tested for the preventive treatment of migraine and episodic cluster headache by multiple randomized clinical trials (RCTs) and have been found to reduce headache frequency. METHODS: We systematically searched PubMed and Embase on Cochrane Central Register of Controlled Trials (CENTRAL) from the earliest date to August 1, 2019. Relative risk (RR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS: Seven studies were pooled with 3889 patients. Subcutaneous injection of Galcanezumab at 120 mg, 240 mg leads to a statistically significant response rate for the treatment of migraine compared with placebo (120 mg: RR = 1.51; 95% CI, 1.33 to 1.70; P < 0.001; 240 mg: RR = 1.58; 95% CI, 1.43 to 1.76; P < 0.001). Among them, 120 mg group has the same treatment efficacy with 240 mg group (50% response: RR = 1.06; 95% CI, 0.92 to 1.22; P = 0.425; 75% response: RR = 1.07; 95% CI, 0.94 to 1.23; P = 0.301; 100% response; RR = 1.06; 95% CI, 0.81 to 1.37; P = 0.682; MHD: RR = - 0.08; 95% CI, - 0.55 to - 0.40; P = 0.748) while related to a lower risk for adverse events for the treatment of migraine (120 mg RR = 1.06; 95% CI, 0.99 to 1.14; P = 0.084; 240 mg: RR = 1.17; 95% CI, 1.09 to 1.25; P < 0.001). 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache measured by at least 50% reduction of cluster headache frequency at week 3 (RR = 1.36; 95% CI, 1.00-1.84; P = 0.048). CONCLUSIONS: Use of galcanezumab is related to a significantly reduced monthly headache frequency compared with placebo for the treatment of migraine and episodic cluster headache, 120 mg has the same treatment efficacy with 240 mg group while related to a lower risk for adverse effects for the treatment of migraine. 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache with no significantly increased adverse events.

[The glymphatic system: concept, function and research progresses].

The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. ß-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

Inequality in dental flossing behavior among Korean adults based on household income levels.

OBJECTIVES: The aim of this study was to estimate the association between household income and dental flossing. METHODS: This cross-sectional study investigated the impact of household income on flossing among 9,391 adults aged 30+ with ≥20 natural teeth, utilizing data from the seventh Korea National Health and Nutrition Examination Survey (2016-2018). Outcome measures included flossing (yes/no), with income categorized into 4 levels: lowest, medium to low, medium to high, and highest. Logistic regression, adjusted for age, gender, brushing frequency, recent dental exams, periodontitis, smoking, and alcohol use, was employed to evaluate the influence of socioeconomic status on oral hygiene practices. RESULTS: In the highest income group, flossing was 62.6% more prevalent than in the lowest income group (adjusted odds ratio [aOR], 1.63; 95% CI, 1.27 to 2.08). The strongest association between income levels and flossing was observed in individuals aged ≥70 years (aOR, 3.64; 95% CI, 1.86 to 7.11), with a decreasing strength of association in the 60s (aOR, 1.72; 95% CI, 1.05 to 2.84) and 50s age groups (aOR, 1.69; 95% CI, 1.07 to 2.68). Higher-income women demonstrated a higher frequency of flossing than their lower-income counterparts (aOR, 1.67; 95% CI, 1.24 to 2.23). Higher-income individuals without periodontitis were more likely to floss (aOR, 1.64; 95% CI, 1.23 to 2.18), and among those with periodontitis, flossing was significantly associated only with the highest income category (aOR, 1.64; 95% CI, 1.10 to 2.44). CONCLUSIONS: The findings of this study indicate a significant correlation between higher household income levels and an increased prevalence of flossing.

Effects of multigrain rice and white rice on periodontitis: an analysis using data from the Korea National Health and Nutrition Examination Survey 2012-2015.

OBJECTIVES: Numerous studies have investigated the efficacy of whole grains; however, research on multigrain remains limited. Grains exhibit combined positive effects against various diseases. The purpose of this study was to examine the impact of multigrain and white rice consumption on periodontitis. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey V-3 and VI, collected between 2012 and 2015, which included 12,450 patients (4,859 male and 7,591 female) aged 19-64 years. The World Health Organization's Community Periodontal Index (CPI) was utilized to assess the presence of periodontitis, with periodontitis defined as a CPI index score of ≥3. Multivariable logistic regression analysis was performed after adjusting for potential confounding variables. RESULTS: The group that consumed only multigrain rice was less likely to have periodontitis than the group that consumed only white rice (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.69 to 0.93). When stratified by sex, the risk of periodontitis demonstrated a 24% decrease in female who consumed only multigrain rice (OR, 0.76; 95% CI, 0.62 to 0.93). A similar result was observed in the age group of 40-64 years (OR, 0.84; 95% CI, 0.71 to 0.99). In the diabetes stratification model, the normal group that consumed only multigrain rice exhibited a 25% decrease in the odds of periodontitis (OR, 0.75; 95% CI, 0.62 to 0.91). CONCLUSIONS: Our findings suggest that the prevalence of periodontitis may vary depending on the type of rice consumed.

The impact of COVID-19 on clinical outcomes in people undergoing neurosurgery: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has created a global crisis unique to the healthcare system around the world. It also had a profound impact on the management of neurosurgical patients. In our research, we investigated the effect of the COVID-19 pandemic on clinical outcomes in people undergoing neurosurgery, particularly vascular and oncological neurosurgery. METHOD: Two investigators independently and systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrail.Gov, and Web of Science to identify relevant studies respecting the criteria for inclusion and exclusion published up to June 30, 2022. The outcomes of our research included mortality rate, length of stay, modified Rankin Score, delay in care, Glasgow outcome scale, and major complications. The risk of bias was assessed using the Methodological Index for Non-randomized Studies (MINORS) checklist. RESULTS: Two investigators independently and systematically searched 1378 results from MEDLINE, EMBASE, Cochrane database, ClinicalTrail.Gov, and Web of Science and extracted the detailed data from 13 studies that met the review's eligibility criteria. Two articles reported on patients with intracerebral hemorrhages, five on patients with subarachnoid hemorrhages, four on patients undergoing surgery for neuro-oncology, and in two studies the patients' conditions were unspecified. A total of 26,831 patients were included in our research. The number who died was significantly increased in the COVID-19 pandemic group (OR 1.52, 95% CI 1.36-1.69, P < 0.001). No significant difference was found between the two groups in terms of length of stay (SMD - 0.88, 95% CI - 0.18-0.02, P = 0.111), but it differed between regions, according to our subgroup analysis. CONCLUSION: Compared to the pre-pandemic group, the number who died was significantly increased in the COVID-19 pandemic group. Meanwhile, the effect of the pandemic on clinical outcomes in people undergoing neurosurgery might differ in different regions, according to our subgroup analysis.

The FDA-approved anti-amyloid-ß monoclonal antibodies for the treatment of Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-ß (anti-Aß) monoclonal antibodies (mabs) for the treatment of AD. METHOD: PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included Aß, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model. RESULT: Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-Aß mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-Aß mabs increased cerebrospinal fluid (CSF) Aß1-42 (P = 0.002) and plasma Aß42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-Aß mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-Aß mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001). CONCLUSION: FDA-approved anti-Aß mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.

Long-term survival of patients with intracranial metastases from thyroid cancer presenting with seizures: a case report and literature review.

Background: Thyroid cancer has low incidence and mortality. While metastatic cancer is the most common type of intracranial cancer, patients with intracranial metastases from thyroid cancer very rarely present with seizures. Here, we describe a case study and review the neurological symptoms and histopathology of intracranial metastases from thyroid cancer. Case Description: A 38-year-old woman was diagnosed with intracranial metastases from papillary thyroid cancer, with the chief symptom being generalized seizures. The bilateral frontal masses were completely resected in 2 operations, after which the patient was treated with whole-brain radiotherapy and tyrosine kinase inhibitors (TKIs). It has now been over 13 years since thyroid cancer resection and 51 months since she was diagnosed with intracranial metastases from papillary thyroid cancer. The long-term survival might be due to the effective and prompt treatment. Through literature review, we found the incidence of intracranial metastases from different subtypes of thyroid cancer to be inconsistent with epidemiological findings in thyroid cancer. Conclusions: Intracranial metastases of thyroid cancer should be considered when the patient has a history of thyroid cancer with seizures. A combination of surgery, radiation therapy, and TKI drugs may prolong survival.

Early versus late tracheostomy in stroke-related patients: A systematic review and meta-analysis.

BACKGROUND: Tracheostomy is an operative intervention for patients who require ventilator assistance while in the intensive care unit (ICU). This study aimed to compare efficacy and safety between early tracheostomy (ET) and late tracheostomy (LT) in stroke patients. METHODS: Embase, PubMed, and the Cochrane Library were searched for available studies. Stroke-related patients were categorized into ET and LT groups using seven days as the cutoff timepoint. The primary efficacy outcome was mortality; secondary efficacy outcomes were modified Rankin Scores (mRS) obtained at follow up, as well as durations of hospital stay, ICU stay, and ventilator use. Safety outcomes were total complication and ventilator associated pneumonia (VAP) incidence. RESULTS: Nine studies with 3,789 patients were included in the current analysis. No statistical difference in mortality was observed. ET was associated with shorter hospital stay (MD -5.72, 95% CI -9.76 to -1.67), shorter ICU stay (MD -4.77, 95% CI -6.82 to -2.72), and shorter ventilator duration (MD -4.65, 95% CI -8.39 to -0.90); however, no statistically significant difference was found in follow-up mRS scores. Examination of safety measures found the ET group exhibited a lower rate of VAP compared with LT (OR 0.80, 95 % CI 0.68 to 0.93), while no statistical difference was found in total complications. CONCLUSION: Our meta-analysis concluded that ET was associated with shorter hospital stay, less time on a ventilator, and lower incidence of VAP. Future studies are warranted to investigate the functional outcomes and the occurrence of complications of ET in stroke patients.

Different doses of dual orexin receptor antagonists in primary insomnia: a Bayesian network analysis.

Background: Systematic comparisons of the doses of the Food and Drug Administration (FDA)-approved dual orexin receptor antagonists (DORAs) for people with insomnia are limited. Methods: PubMed, Embase, Cochrane Library, and Clinicaltrials. gov were systematically searched to identify relevant studies published before 31 October 2022. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Results: We pooled 7257 participants from 9 randomized controlled trials (RCTs). Moderate to high certainty evidence demonstrated suvorexant (20 and 40 mg) and daridorexant (10 and 50 mg) as the most effective in latency to persistent sleep (LPS) reduction. Lemborexant at 5 and 10 mg was the most effective in subjective sleep onset time (sTSO) reduction. For wake time after sleep onset (WASO), all drugs except daridorexant 5 mg were more effective than placebo. Lemborexant 5 mg was among the best in subjective WASO (sWASO) (moderate to high certainty) and had the highest surface under the curve ranking area (SUCRA) values for sWASO (100%). For total sleep time (TST), suvorexant and daridorexant, except the respective minimum doses, were more effective than placebo, while suvorexant 40 mg and lemborexant 10 mg may have been the most effective for subjective TST (sTST) (low to very low certainty). Suvorexant 40 mg (RR 1.09), suvorexant 80 mg (RR 1.65), and daridorexant 25 mg (RR 1.16) showed a higher safety risk than placebo. Conclusion: Suvorexant 20 mg, lemborexant 5 mg, lemborexant 10 mg, and daridorexant 50 mg represent suitable approaches for insomnia. Clinical Trial Registration: clinicaltrials.gov, PROSPERO (CRD42022362655).

Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: a Bayesian network analysis.

Background: A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG. Methods: PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86). Conclusion: While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings. Systematic review registration: https://inplasy.com/?s=202370112, identifier 202370112.