Dynamic Bayesian network for predicting physiological changes, organ dysfunctions and mortality risk in critical trauma patients.

BACKGROUND: Critical trauma patients are particularly prone to increased mortality risk; hence, an accurate prediction of their conditions enables early identification of patients' mortality status. Thus, we aimed to develop and validate a real-time prediction model for physiological changes, organ dysfunctions and mortality risk in critical trauma patients. METHODS: We used Dynamic Bayesian Networks (DBNs) to model complicated relationships of physiological variables across time slices, accessing data of trauma patients from the Medical Information Mart for Intensive Care database (MIMIC-III) (n = 2915) and validated with patients' data from ICU admissions at the Changhai Hospital (ICU-CH) (n = 1909). The DBN model's evaluation included the predictive ability of physiological changes, organ dysfunctions and mortality risk. RESULTS: Our DBN model included two static variables (age and sex) and 18 dynamic physiological variables. The differences in ratios between the real values and the 24- and 48-h predicted values of most physiological variables were within 5% in the two datasets. The accuracy of our DBN model for predicting renal, hepatic, cardiovascular and hematologic dysfunctions was more than 0.8.The calculated area under the curve (AUC) from receiver operating characteristic curves and 95% confidence interval for predicting the 24- and 48-h mortality risk were 0.977 (0.967-0.988) and 0.958 (0.945-0.971) in the MIMIC-III and 0.967 (0.947-0.987) and 0.946 (0.925-0.967) in ICU-CH. CONCLUSIONS: A DBN is a promising method for predicting medical temporal data such as trauma patients' mortality risk, demonstrated by high AUC scores and validation by a real-life ICU scenario; thus, our DBN prediction model can be used as a real-time tool to predict physiological changes, organ dysfunctions and mortality risk during ICU admissions.

Discharge Against Medical Advice in Acute Ischemic Stroke: the Risk of 30-Day Unplanned Readmission.

BACKGROUND: Discharge against medical advice may be associated with more readmissions. OBJECTIVE: To evaluate DAMA in patients with acute ischemic stroke (AIS) and identify the relationship between DAMA and 30-day unplanned readmissions. DESIGN: A retrospective cohort study. PARTICIPANTS: The National Readmission Database was used to identify inpatients with a primary diagnosis of AIS who were either discharged home or DAMA between 2010 and 2017 in the USA. MEASURES: Demographic features, hospital type, comorbidities, stroke risk factors, severity indices, and treatments were compared between patients discharged routinely and DAMA. Multivariable logistic regression was used to evaluate predictors of DAMA, and a double robust inverse probability of treatment weighting method was used to assess the association between DAMA and 30-day unplanned readmissions. KEY RESULTS: Overall, 1,335,484 patients with AIS were included, of whom 2.09% (n = 27,892) were DAMA. The prevalence of DAMA in AIS patients increased from 1.65 in 2010 to 2.57% in 2017. The rates of 30-day unplanned readmissions for DAMA and non-DAMA patients were 16.81% and 7.78%, respectively. Patients with drug abuse, alcohol abuse, smoking, prior stroke, psychoses, and intravenous thrombolysis had greater odds of DAMA. DAMA was associated with all-cause readmissions (OR, 2.04; 95% CI, 2.01-2.07) and remained a strong predictor for transient ischemic attack/stroke-specific and cardiac-specific causes of readmissions. CONCLUSIONS: Although the DAMA rate is low in AIS patients, DAMA is a risk factor for all-cause and recurrent stroke-specific readmissions. Future studies are needed to address issues around compliance and engagement with health care to reduce DAMA.

Temporary Trend, Characteristics and Clinical Outcomes of Acute Pancreatitis Patients Infected with Human Immunodeficiency Virus.

BACKGROUND: Compared to general population, human immunodeficiency virus (HIV) infection may increase frequency of acute pancreatitis (AP); however, evidence regarding effects of HIV infection on AP-related outcomes is limited and controversial. AIMS: We aim to investigate the temporary trend, characteristics and clinical outcomes of AP infected with HIV. METHODS: We reviewed data from the 2003-2014 National Inpatient Sample to identify patients with a primary diagnosis of AP. The primary outcomes (in-hospital mortality, acute respiratory failure, acute kidney injury, and prolonged length of stay [LOS]) and secondary outcomes (gastrointestinal hemorrhage, sepsis and total cost) were compared between patients with and without HIV infection using univariate, multivariable and propensity score matching analyses. RESULTS: Of 594,106 patients diagnosed with AP, 6775 (1.14%) had HIV infection. Patients with HIV were more likely to be younger, black, male, less likely to be gallstone-related and had lower rate of interventions. Multivariable analyses based on multiple imputation revealed that HIV infection was associated with higher risk of mortality (odds ratio [OR]: 1.74; 95% confidence interval [CI] 1.34-2.25), acute kidney injury (OR: 1.13; 95% CI 1.19-1.44), prolonged LOS (OR: 1.26; 95% CI 1.15-1.37) and 6% higher cost. There were no differences in sepsis, gastrointestinal bleeding, and respiratory failure between groups. CONCLUSIONS: HIV infection is associated with adverse outcomes including increased mortality, acute kidney injury and more healthcare utilization in AP patients. More assertive management strategies like early intravenous fluid resuscitation in HIV patients hospitalized with AP to prevent acute kidney injury may be helpful to improve clinical outcomes.

Atrial fibrillation in hospitalized patients with end-stage liver disease: temporal trends in prevalence and outcomes.

BACKGROUND & AIMS: End-stage liver disease (ESLD) happens due to the development and progression of chronic liver disease. This study aims to investigate the temporal trend, patient characteristics and outcomes of atrial fibrillation (AF) in hospitalized ESLD patients across the United States. METHODS: Nationwide Inpatient Sample from 2003 to 2014 was utilized to retrospectively study the weighted prevalence of AF in hospitalized ESLD patients. Multivariable regression models were used to assess the association between AF with clinical factors, in-hospital mortality, length of stay (LOS) and cost. RESULTS: 639 345 hospitalizations associated with ESLD were identified, of which 47 710 (7.48%) were diagnosed with AF. The prevalence of AF increased from 5.73% in 2003 to 9.75% in 2014 in ESLD and varied by age, race, income, insurance type and hospital characteristics. Factors associated with AF included advancing age, male, white race, high income and urban teaching hospital. AF presence was associated with significant higher in-hospital mortality (odds ratio, 1.40; 95% confidence interval, 1.35-1.45), 21% longer LOS and 22% higher cost. In addition, a significant decreasing trend in in-hospital mortality was observed (from 16.70% to 10.63% in patients with AF and from 10.74% to 7.50% in patients without AF). CONCLUSIONS: The prevalence of AF in hospitalized ESLD patients has continued to increase from 2003 through 2014. AF is associated with poor prognosis and higher health resource utilization. Innovative anticoagulation strategies through improved collaboration between cardiologists and hepatologists are required for better management of hospitalized ESLD patients comorbid with AF.

Prevalence and Impact of Aphasia among Patients Admitted with Acute Ischemic Stroke.

OBJECTIVE: Aphasia is one of the most severe symptoms in stroke patients, affecting one-third of acute stroke patients. We aimed to investigate the prevalence and outcomes of aphasia in patients with acute ischemic stroke (AIS). METHODS: We computed the weighted prevalence of aphasia in AIS patients using the 2003 to 2014 National Inpatient Sample databases. Crude regression model, multivariable regression model, and propensity score matching were used to evaluate the impact of aphasia on the clinical outcomes in AIS patients. We performed the Subpopulation Treatment Effect Pattern Plot (STEPP) analyses in propensity score matching cohort to visually display the effect of interaction between aphasia and age on the clinical outcomes. RESULTS: A total of 16.93% of 4,339,156 AIS patients identified were with aphasia. The proportion of patients with comorbid aphasia increased from 13.34% in 2003 to 21.94% in 2014 (P < .0001). The results of both multivariable regression model and propensity score matching analyses indicated aphasia in AIS as a risk factor for in-hospital deaths. Aphasia was linked to prolonged length of stay (0.66 day, P < .0001) and high hospitalization cost ($971.35, P < .0001). In the STEPP analyses, in-hospital mortality rate increased with age, and the rate was higher in patients with aphasia, but the ratios decreased with an increase in age. CONCLUSIONS: Prevalence of comorbid aphasia with AIS is increasing, and it has a significant impact on clinical outcomes. Additionally, aphasia shows a greater impact on survival and medical burden among young patients with AIS.

Comparison and trend of perioperative outcomes between robot-assisted radical prostatectomy and open radical prostatectomy: nationwide inpatient sample 2009-2014.

PURPOSE: To make a further evaluation of perioperative outcomes between the robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we conducted a comparison and trend analysis by using the Nationwide Inpatient Sample (NIS) from 2009 to 2014. MATERIALS AND METHODS: Adult prostate cancer patients with radical prostatectomy were abstracted from the NIS. RARP and ORP were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The perioperative outcomes included blood transfusion, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Propensity score matching method and multivariable logistic regression model were performed to adjust for the pre-defined covariates. The annual percent change (APC) was used to detect the change trend of rates for outcomes. RESULTS: A total of 77.054 patients were included in our study. According to the results of propensity score matching analyses, RARP outperformed ORP in blood transfusion (1.96% vs. 9.40%), intraoperative complication (0.73% vs. 1.25%), overall postoperative complications (8.87% vs. 11.97%), and pLOS (13.39% vs. 36.70%). We also found that there was a significant decreasing tendency of incidence in blood transfusion (APC=-9.81), intraoperative complication (APC=-12.84), and miscellaneous surgical complications (APC=-14.09) for the RARP group. The results of multivariable analyses were almost consistent with those of propensity score matching analyses. CONCLUSIONS: The RARP approach has lower incidence rates of perioperative complications than the ORP approach, and there is a potential decreasing tendency of complication incidence rates for the RARP.

Socioeconomic Status and the Risk of Stroke Recurrence in Chinese Patients.

BACKGROUND: The association between socioeconomic status (SES) and the risk of stroke recurrence has been rarely studied, especially in a developing country. OBJECTIVE: This study aimed to evaluate the association between SES and the risk of stroke recurrence in Chinese stroke patients. METHODS: Patients with first-ever ischemic stroke registered in the Nanjing Stroke Registry Program from 2013 to 2015 were enrolled and followed in this study. Information about SES, measured by disposable income and educational level, was collected at baseline. The primary endpoint was defined as fatal or nonfatal recurrent stroke after 7 days of the index stroke. The association between SES and the risk of stroke recurrence was analyzed with multivariate Cox regression model. RESULTS: A total of 2,294 patients with first-ever stroke were included in the study. During a mean follow-up of 2.8 ± 1.2 years, 298 (13.0%) patients had stroke recurrence. After adjusting for potential confounding factors, compared with patients with a monthly family income of USD ≥1,539, those with an income of USD 769-1,538, USD 462-768, and USD 1-461 had an adjusted hazard ratio (HR) of 1.87 (95% CI 1.11-3.17), 2.40 (95% CI 1.43-4.03), and 2.79 (95% CI 1.65-4.69) for recurrence, respectively. Compared with those with an educational level of ≥13 years, patients with an educational level of 7-12 years and 0-6 years had adjusted HRs of 1.21 (95% CI 0.79-1.86) and 1.73 (95% CI 1.11-2.70), respectively. CONCLUSIONS: Chinese stroke patients with lower SES bear higher recurrent risk. These results are suggestive for secondary stroke prevention in Chinese patients.

Detection of cluster adverse drug events in the spontaneous reporting system of China using a disproportionality filter algorithm.

WHAT IS KNOWN AND OBJECTIVE: Cluster adverse drug events (CADEs) are multiple ADEs with similar clinical manifestations involving the same drug, manufactured by the same company, that occur within a short time period. The disproportionality filter algorithm (DFA) is a promising tool for the identification of historical clusters related to ADEs. The Chinese spontaneous adverse drug reaction reporting system (SRS) may serve as an important database for the detection of CADEs. The objective of this study was to evaluate the usefulness of DFA as an approach to identify CADEs using SRS. METHODS: Suspected adverse drug reaction (ADR) reports collected by the Chinese SRS in 2014-2015 were examined to identify potential CADEs. The reports were divided into 48 15-day subsets. Disproportionate excess reporting of ADEs for drugs from specific companies may be a signal for CADEs. The clusters were categorized as 'confirmed', 'potential', 'unlikely', 'indecisive' or 'information-loss' ADEs when evaluated by report units. Furthermore, early warning information in 2014-2015 from the Chinese early warning system (EWS) classified as 'concern', 'monitoring', 'ignorance' or 'rest' was compared with DFA to explore the applicability of the novel algorithm in Chinese SRS. RESULTS AND DISCUSSION: In total, 2294 CADEs, comprising of 380 confirmed, 1753 potential, 15 unlikely and 59 indecisive clusters, were generated; 87 clusters were missing additional information. There were 263 'significant' clusters with DFA, but only 26 'significant' clusters in EWS. The sensitivity of DFA was 88.5%, but the specificity and positive predictive value were low. WHAT IS NEW AND CONCLUSION: Spontaneous adverse drug reaction reporting system in China may be a potential database for the identification of CADEs engaging the DFA. This could supplement the EWS of CADEs in China. The DFA may be of value in detecting CADEs with high sensitivity, although expert screening is required given the low specificity and positive predictive value.

Alteration in temporal-cerebellar effective connectivity can effectively distinguish stable and progressive mild cognitive impairment.

Background: Stable mild cognitive impairment (sMCI) and progressive mild cognitive impairment (pMCI) represent two distinct subtypes of mild cognitive impairment (MCI). Early and effective diagnosis and accurate differentiation between sMCI and pMCI are crucial for administering targeted early intervention and preventing cognitive decline. This study investigated the intrinsic dysconnectivity patterns in sMCI and pMCI based on degree centrality (DC) and effective connectivity (EC) analyses, with the goal of uncovering shared and distinct neuroimaging mechanisms between subtypes. Methods: Resting-state functional magnetic resonance imaging combined with DC analysis was used to explore the functional connectivity density in 42 patients with sMCI, 31 patients with pMCI, and 82 healthy control (HC) participants. Granger causality analysis was used to assess changes in EC based on the significant clusters found in DC. Furthermore, correlation analysis was conducted to examine the associations between altered DC/EC values and cognitive function. Receiver operating characteristic curve analysis was performed to determine the accuracy of abnormal DC and EC values in distinguishing sMCI from pMCI. Results: Compared with the HC group, both pMCI and sMCI groups exhibited increased DC in the left inferior temporal gyrus (ITG), left posterior cerebellum lobe (CPL), and right cerebellum anterior lobe (CAL), along with decreased DC in the left medial frontal gyrus. Moreover, the sMCI group displayed reduced EC from the right CAL to bilateral CPL, left superior temporal gyrus, and bilateral caudate compared with HC. pMCI demonstrated elevated EC from the right CAL to left ITG, which was linked to episodic memory and executive function. Notably, the EC from the right CAL to the right ITG effectively distinguished sMCI from pMCI, with sensitivity, specificity, and accuracy of 0.5806, 0.9512, and 0.828, respectively. Conclusion: This study uncovered shared and distinct alterations in DC and EC between sMCI and pMCI, highlighting their involvement in cognitive function. Of particular significance are the unidirectional EC disruptions from the cerebellum to the temporal lobe, which serve as a discriminating factor between sMCI and pMCI and provide a new perspective for understanding the temporal-cerebellum. These findings offer novel insights into the neural circuit mechanisms involving the temporal-cerebellum connection in MCI.

Directed Functional Connectivity Changes of Triple Networks for Stable and Progressive Mild Cognitive Impairment.

Mild cognitive impairment includes two distinct subtypes, namely progressive mild cognitive impairment and stable mild cognitive impairment. While alterations in extensive functional connectivity have been observed in both subtypes, limited attention has been given to directed functional connectivity. A triple network, composed of the central executive network, default mode network, and salience network, is considered to be the core cognitive network. We evaluated the alterations in directed functional connectivity within and between the triple network in progressive and stable mild cognitive impairment groups and investigated its role in predicting disease conversion. Resting-state functional magnetic resonance imaging was used to analyze directed functional connectivity within the triple networks. A correlation analysis was performed to investigate potential associations between altered directed functional connectivity within the triple networks and the neurocognitive performance of the participants. Our study revealed significant differences in directed functional connectivity within and between the triple network in the progressive and stable mild cognitive impairment groups. Altered directed functional connectivity within the triple network was involved in episodic memory and executive function. Thus, the directed functional connectivity of the triple network may be used as an imaging marker of mild cognitive impairment.

Shared and Specific Changes of Cortico-Striatal Functional Connectivity in Stable Mild Cognitive Impairment and Progressive Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI), the prodromal stage of Alzheimer's disease, has two distinct subtypes: stable MCI (sMCI) and progressive MCI (pMCI). Early identification of the two subtypes has important clinical significance. Objective: We aimed to compare the cortico-striatal functional connectivity (FC) differences between the two subtypes of MCI and enhance the accuracy of differential diagnosis between sMCI and pMCI. Methods: We collected resting-state fMRI data from 31 pMCI patients, 41 sMCI patients, and 81 healthy controls. We chose six pairs of seed regions, including the ventral striatum inferior, ventral striatum superior, dorsal-caudal putamen, dorsal-rostral putamen, dorsal caudate, and ventral-rostral putamen and analyzed the differences in cortico-striatal FC among the three groups, additionally, the relationship between the altered FC within the MCI subtypes and cognitive function was examined. Results: Compared to sMCI, the pMCI patients exhibited decreased FC between the left dorsal-rostral putamen and right middle temporal gyrus, the right dorsal caudate and right inferior temporal gyrus, and the left dorsal-rostral putamen and left superior frontal gyrus. Additionally, the altered FC between the right inferior temporal gyrus and right putamen was significantly associated with episodic memory and executive function. Conclusions: Our study revealed common and distinct cortico-striatal FC changes in sMCIs and pMCI across different seeds; these changes were associated with cognitive function. These findings can help us understand the underlying pathophysiological mechanisms of MCI and distinguish pMCI and sMCI in the early stage potentially.

Ocular toxicities in chimeric antigen receptor T-cell therapy: a real-world study leveraging FAERS database.

Aim: The purpose of this study was to comprehensively explore the ocular toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. Materials & methods: Data were assembled from the US FDA's Adverse Event Reporting System (FAERS) database from 2017 to 2023. Information component and reporting odds ratio methods were used for signal detection in total/categorized CAR T-cell therapy. Results: A total of 17 positive signals (preferred term) were detected, yet none of them were documented in the product information. Some adverse events were with death outcomes and overlapped a lot with cytokine-release syndrome. Conclusion: The ocular adverse events associated with CAR-T cell therapy are noteworthy, and it is imperative to maintain increased alertness and institute early intervention strategies.

CAR-T-cell therapy is a highly effective treatment for blood cancers that has gained significant attention as a promising therapy in recent years. However, a complete analysis of its side effects on eyes has not been determined. In this study, we examined eye-related adverse events with five US Food and Drug Administration (FDA)-approved CAR T-cell therapies by using data from the FDA. We found that certain eye issues such as dilated pupils, impaired pupillary light reflex and eye surface bleeding deserve attention. Surprisingly, these problems were not mentioned in the product information. Since some adverse events can have severe outcomes, it is important to be vigilant and take early action.

Repetitive transcranial magnetic stimulation regulates effective connectivity patterns of brain networks in the spectrum of preclinical Alzheimer's disease.

Objectives: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer's disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function. Methods: This study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed. Results: Cross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged. Conclusion: This study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum. Clinical Trial Registration: http://www.chictr.org.cn, ChiCTR2000034533.

Enhanced toxicity of 2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) by nanopolystyrene particles towards HeLa cells.

2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) has been widely used as an additive in a variety of plastics due to its extremely low toxicity. However, we showed in the study that once mixed with nanopolystyrene particles (NPs), the nontoxic V6 could exhibit significant toxicity to HeLa cells. The enhanced toxicity was much higher than the toxicity of NPs alone and was related to the size of NPs. The mixture of V6 and small polystyrene NPs (10 nm and 15 nm in radius) showed obvious toxicity to HeLa cells. The toxicity increased with the concentrations of both V6 and NPs. On the contrary, the mixture of V6 and larger NPs (25 nm, 50 nm, 100 nm, and 500 nm in radius) showed almost no toxicity even at extremely high concentrations (NPs: 100 mg/L; V6: 50 mg/L). The small NPs could enter the cells and accumulated in cytoplasm. However, the larger NPs did not distribute inside the cells. NPs efficiently adsorbed V6 on the surface. The mechanism of the enhanced toxicity was attributed to the increased intracellular reactive oxygen species (ROS) production and the regulation of gene expression concerning apoptosis and ROS scavenging. Our study not only showed that a safe chemical V6 could be turned to be toxic by NPs, but also pointed out a potential risk caused by the joint toxicity of 'safe' chemicals and plastic particles with small size.

Correlation between cellular uptake and cytotoxicity of polystyrene micro/nanoplastics in HeLa cells: A size-dependent matter.

The cytotoxicity of micro/nanoplastics (MNPs) is known to be strongly influenced by particle size, but the mechanism is not clear so far. We reported the ability of polystyrene MNPs to be internalized by HeLa cells could be a reason for the size dependent cytotoxicity of MNPs. We found that small MNPs (10 nm and 15 nm in radius) could be efficiently internalized by HeLa cells, MNPs of 25 nm in radius could be slightly internalized by the cells, and larger MNPs could not enter the cells at all. We showed that only MNPs, which could be internalized by cells, had a toxic effect on cell activity in a dose-dependent manner. In contrast, MNPs, which could not be internalized by cells, showed no cytotoxicity even if at extremely high concentrations. We attributed the correlation between the size-dependent uptake of MNPs and the size-dependent cytotoxicity of MNPs to the enhanced reactive oxygen species (ROS) level and abnormal gene expression. Our study pointed out that cellular uptake is one of the most fundamental mechanisms for the cytotoxicity of MNPs.

Correction: Correlation between cellular uptake and cytotoxicity of polystyrene micro/nanoplastics in HeLa cells: A size-dependent matter.

[This corrects the article DOI: 10.1371/journal.pone.0289473.].

Aberrant spontaneous static and dynamic amplitude of low-frequency fluctuations in cerebral small vessel disease with or without mild cognitive impairment.

BACKGROUND: Cerebral small vessel disease (CSVD) is considered an age-related degenerative neurological disorder and the most common risk factor for vascular cognitive impairment (VCI). The amplitude of fluctuation of low frequency (ALFF) can detect altered intrinsic brain activity in CSVD. This study explored the static and dynamic ALFFs in the early stage of CSVD with (CSVD-M) or without (CSVD-W) mild cognitive impairment (MCI) in these patients and how these changes contribute to cognitive deterioration. METHODS: Thirty consecutive CSVD cases and 18 healthy controls (HC) were included in this study. All the participants underwent a 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequence to obtain structural T1-weighted images. Simultaneous multislice imaging 5(SMS5) was used for resting-state functional MRI (rs-fMRI), and Data Processing and Analysis of Brain Imaging software helped determine static ALFF (sALFF). The dynamic ALFF (dALFF) was calculated using the sliding window method of DynamicBC software. Analysis of Covariance (ANCOVA) and two-sample t-test were used to evaluate the sALFF and temporal variability of dALFF among the three groups. The subjects were rated on a broad standard neuropsychological scale. Partial correlation analysis was used to evaluate the correlation between sALFF and dALFF variability and cognition (Bonferroni correction, statistical threshold set at p < .05). RESULTS: Compared with HCs, the CSVD-M group indicated decreased sALFF values in the bilateral cerebellum posterior lobe (CPL) and the left inferior Parietal Lobule (IPL), with increased sALFF values in the right SFG. For dALFF analysis, the CSVD-W group had significant dALFF variability in the right fusiform gyrus compared with HC. Moreover, the postcentral gyrus (PoCG) was significantly high in the CSVD-W group. While in the CSVD-M group, the bilateral paracentral lobules (PL) revealed significantly elevated dALFF variability and low dALFF variability in the left CPL and right IPL compared with HCs. The CSVD-M group had high dALFF variability in the bilateral PL but low dALFF variability in the left middle temporal gyrus (MTG) and right PoCG compared with the CSVD-W group. The partial correlation analysis indicated that dALFF variability in the left MTG was positively associated with EM (r = 0.713, p = .002) in CSVD-W and CSVD-M groups. In the groups with CSVD-M and HC, altered dALFF variability in the bilateral PL was negatively correlated with EM (r = -0.560, p = .002). CONCLUSION: There were significant changes in sALFF and dALFF variability in CSVD patients. Abnormal spontaneous static and dynamic ALFFs may provide new insights into cognitive dysfunction in CSVD with MCI and may be valuable biomarkers for early diagnosis.

Size-dependent enhancement on conjugative transfer of antibiotic resistance genes by micro/nanoplastics.

Recently micro/nanoplastics (MNPs) have raised intensive concerns due to their possible enhancement effect on the dissemination of antibiotic genes. Unfortunately, data is still lacking to verify the effect. In the study, the influence of polystyrene MNPs on the conjugative gene transfer was studied by using E. coli DH5ɑ with RP4 plasmid as the donor bacteria and E. coli K12 MG1655 as the recipient bacteria. We found that influence of MNPs on gene transfer was size-dependent. Small MNPs (10 nm in radius) caused an increase and then a decrease in gene transfer efficiency with their concentration increasing. Moderate-sized MNPs (50 nm in radius) caused an increase in gene transfer efficiency. Large MNPs (500 nm in radius) had almost no influence on gene transfer. The gene transfer could be further enhanced by optimizing mating time and mating ratio. Scavenging reactive oxygen species (ROS) production did not affect the cell membrane permeability, indicating that the increase in cell membrane permeability was not related to ROS production. The mechanism of the enhanced gene transfer efficiency was attributed to a combined effect of the increased ROS production and the increased cell membrane permeability, which ultimately regulated the expression of corresponding genes.

Trends and Utilization of Inpatient Palliative Care Among Patients With Metastatic Bladder Cancer.

OBJECTIVE: To explore the trends and utilization of palliative care (PC) service among inpatients with metastatic bladder cancer (MBC). METHODS: A retrospective, cross-sectional analysis was performed using data from the 2003 to 2014 National Inpatient Sample. Palliative care was identified through International Classification of Diseases, Ninth Revision code V66.7. Demographics, comorbidities, hospital characteristics, tumor-related, and treatment-related factors were compared between patients with and without PC. Multivariable logistic regression was used to explore predictors of PC use. RESULTS: Among 131 852 patients with MBC, 13 224 (10.03%) received PC. Rate of PC increased from 2.49% in 2003 to 28.39% in 2014 (P < .0001). Similarly, rate of PC in decedents increased from 7.02% in 2003 to 54.86% in 2014 (P < .0001). Patients receiving PC were older, tendered to be white, had more comorbidities, and higher all-patient refined diagnosis-related group mortality risk. Predictors of PC included age (odds ratio [OR]: 1.02; 95% CI: 1.01-1.02; P < .0001), Medicaid (OR: 1.87; 95%.CI: 1.54-2.26; P < .0001), and private (OR: 1.61; 95% CI: 1.40-1.84; P < .0001) insurance, hospitals in the West (OR: 1.33; 95% CI: 1.10-1.61; P = .0032), and Mid-west (OR: 1.46; 95% CI: 1.22-1.75; P = .0032), major (OR: 1.32; 95% CI: 1.11-1.49; P < .0001), and extreme (OR: 2.37; 95% CI: 2.04-2.76; P < .0001) mortality risk. Chemotherapy and mechanical ventilation were related with lower odds of PC use. Palliative care predictors in the decedents were similar to those in overall patients with bladder cancer. CONCLUSIONS: Palliative care encounter in MBC shows an increasing trend. However, it still remains very low. Disparities in PC use covered age, insurance, and hospital characteristics among metastatic bladder cancer in the United States.

Atrial fibrillation in critically ill patients who received prolonged mechanical ventilation: a nationwide inpatient report.

BACKGROUND/AIMS: To evaluate temporal trends of atrial fibrillation (AF) prevalence in critically ill patients who received prolonged mechanical ventilation (MV) in the United States. METHODS: We used the 2008 to 2014 National Inpatient Sample to compute the weighted prevalence of AF among hospitalized adult patients on prolonged MV. We used multivariable-adjusted models to evaluate the association of AF with clinical factors, in-hospital mortality, hospitalization cost, and length of stay (LOS). RESULTS: We identified 2,578,165 patients who received prolonged MV (21.27% of AF patients). The prevalence of AF increased from 14.63% in 2008 to 24.43% in 2014 (p for trend < 0.0001). Amongst different phenotypes of critically ill patients, the prevalence of AF increased in patients with severe sepsis, asthma exacerbation, congestive heart failure exacerbation, acute stroke, and cardiac arrest. Older age, male sex, white race, medicare access, higher income, urban teaching hospital setting, and Western region were associated with a higher prevalence of AF. AF in critical illness was a risk factor for in-hospital death (odds ratio, 1.13; 95% confidence interval, 1.11 to 1.15), but in-hospital mortality in critically ill patients with AF decreased from 11.6% to 8.3%. AF was linked to prolonged LOS (2%, p < 0.0001) and high hospitalization cost (4%, p < 0.0001). LOS (-1%, p < 0.0001) and hospitalization cost (-4%, p < 0.0001) decreased yearly. CONCLUSION: The prevalence of comorbid AF is increasing, particularly in older patients. AF may lead to poorer prognosis, and high-quality intensive care is imperative for this population.