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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Jiaolong capsule protects SD rats against 2,4,6-trinitrobenzene sulfonic acid induced colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiaolong capsule (JLC) was approved for the therapy of gastrointestinal diseases by the State Food and Drug Administration (SFDA) of China. It has a satisfactory curative effect in the treatment of patients with inflammatory bowel disease, however, the mechanism remains to be elucidated. AIM OF THE STUDY: In current study, the effects and possible mechanisms of JLC on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated. MATERIALS AND METHODS: Sulfasalazine and JLC were administrated orally and initialized 6 h after TNBS enema, once a day for seven consecutive days. The effect of JLC on intestinal microbial populations and LPS/TLR-4/NF-κB pathway was observed and assessed. Thirty female SD rats were distributed into six groups randomly and equally, namely, control, TNBS, TNBS + sulfasalazine (625 mg/kg), and TNBS + three different doses of JLC (25, 50, and 100 mg/kg) groups. RESULTS: The effect of JLC on restoring normal structures of colorectum and repairing colonic damage were superior to that of sulfasalazine. JLC showed a positive effect in re-balancing intestinal bacteria population of colitis, and suppressed the activation of LPS/TLR-4/NF-κB pathway. CONCLUSION: The results suggest that JLC demonstrated a beneficial effect on treating colitis in a rat model. The possible mechanisms may be through the regulatory effect of intestinal commensal bacteria and down-regulation of LPS/TLR-4/NF-κB pathway.

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.

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.

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

ABSTRACT 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.

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.

Morbid obesity is adversely associated with perioperative outcomes in patients undergoing robot-assisted laparoscopic radical prostatectomy.

INTRODUCTION: Robot-assisted laparoscopic radical prostatectomy (RALRP) may be more challenging in obese individuals. This study aimed to evaluate whether obesity had an adverse effect on perioperative outcomes following RALRP. METHODS: Hospitalized patients who underwent RALRP from 2008-2014 were identified using the National Inpatient Sample database. We grouped RALRP patients into non-obese, obesity class I-II, and obesity class III (morbid obesity). Rates of blood transfusion, intraoperative and postoperative complications, in-hospital mortality, prolonged length of stay, and total costs were compared among the three groups by univariate regression, multivariate regression, and propensity score weighting analysis. RESULTS: Of 53 301 patients identified, 48 725 were non-obese, 3572 were diagnosed with obesity class I-II, and 1004 were diagnosed with morbid obesity. Compared to non-obesity (7.62%), overall postoperative complications were commonly observed in obesity class I-II (10.55%) and morbid obesity (17.11%). Multivariable analyses suggested that morbid obesity was associated with increased overall postoperative (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.65-2.42), cardiac (OR 1.63, 95% CI 1.03-2.58), respiratory (OR 4.03, 95% CI 3.04-5.36), genitourinary (OR 1.77, 95% CI 1.08-2.90), miscellaneous medical (OR 1.94, 95% CI 1.58-2.39) complications, prolonged hospitalization (OR 1.86, 95% CI 1.57-2.21), and 12% higher total cost. Propensity score weighting analysis yielded similar results. Adequate covariate balance was achieved for all variables after weighting. CONCLUSIONS: Morbid obesity is adversely associated with perioperative outcomes in RALRP. Close management is required in patients undergoing RALRP with morbid obesity for potential worse prognosis.

Ear and labyrinth toxicities induced by immune checkpoint inhibitors: a disproportionality analysis from 2014 to 2019.

Aim: We aimed to systematically characterize ear and labyrinth toxicities after immune checkpoint inhibitors (ICIs) initiation. Materials & methods: Data were extracted from the US FDA Adverse Event Reporting System database. Disproportionality analysis including information component and reporting odds ratio (ROR) was performed to access potential signals. Results: In FDA Adverse Event Reporting System database, 284 records for ICIs-associated ear/labyrinth adverse events (AEs) were involved. In general, there was no significant association between total ICIs use and total ear and labyrinth AEs (ROR025: 0.576). However, in ICIs monotherapy and polytherapy groups, signals were detected in several specific ear and labyrinth AEs. Conclusion: Total ear and labyrinth toxicities were not significantly reported with ICI immunotherapy, while class-specific ear toxicities were detected in some strategies.

Prior bariatric surgery is associated with lower complications, in-hospital mortality, and healthcare utilization after elective spine fusion surgery.

BACKGROUND: Grade 3 obesity could potentially increase postoperative complications after spinal fusion surgery. However, the relationship between prior bariatric surgery (BS) and postoperative complications after spinal fusion surgery is not well-established. SETTING: Inpatient hospital admissions from the Nationwide Inpatient Sample. METHODS: Patients with a primary procedure of spinal fusion surgery discharged between 2006 and 2014 were identified. In-hospital outcomes included postoperative complications, mortality, cost, and length of stay were compared between patients with prior BS and grade 3 obesity. RESULTS: A total of 3,132,192 patients who underwent elective spinal fusion surgery were identified. There were 33,936 (1.1%) patients with a diagnosis of prior BS. The prevalence of prior BS increased significantly from .1% in 2006 to 1.5% in 2014. Compared with patients with grade 3 obesity, patients with prior BS were younger, more likely to be female, had less co-morbidities, and higher proportion of cervical surgery. Multivariable analysis indicated that patients with prior BS had lower risk of overall complications (odds ratio [OR]: .44; 95% confidence interval [CI]: .38-.49), neurologic (OR: .55; 95%CI: .35-.84), respiratory (OR: .30; 95%CI: .23-.37), cardiac (OR: .38; 95%CI: .24-.60), gastrointestinal (OR: .61; 95%CI: .44-.84), urinary and renal (OR: .34; 95%CI: .26-.44), venous thromboembolism (OR: .35; 95%CI: .19-.63), wound-related complications (OR: .67; 95%CI: .53-.85), and in-hospital mortality (OR: .12; 95%CI: .02-.88). Prior BS was also related to 13% shorter length of stay and 2% lower cost. CONCLUSIONS: Among patients undergoing spinal fusion surgery, prior BS is associated with lower complications, in-hospital mortality, and healthcare utilization. BS might mitigate risk of worse outcomes associated with grade 3 obesity after spine fusion surgery.