Cardiovascular adverse events in patients with hepatocellular carcinoma receiving vascular endothelial growth factor inhibitors.

BACKGROUND: Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti-angiogenics, are first-line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off-target adverse effects compared with bevacizumab (anti-angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed. OBJECTIVE: To compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab. METHODS: This cohort study included adult patients with hepatocellular carcinoma who received first-line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE). RESULTS: The study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow-up of 5 months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58-1.24; p = 0.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub-distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02-2.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68-1.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087-15.83; p = 0.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83-4.87; p = 0.124), and tobacco use (SHR: 2.85; 95% CI: 0.90-8.97; p = 0.074). CONCLUSIONS: Cardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first-line VEGF inhibitors.

Shared genetics of psychiatric disorders and type 2 diabetes:a large-scale genome-wide cross-trait analysis.

BACKGROUND: Individuals with psychiatric disorders have elevated rates of type 2 diabetes comorbidity. Although little is known about the shared genetics and causality of this association. Thus, we aimed to investigate shared genetics and causal link between different type 2 diabetes and psychiatric disorders. METHODS: We conducted a large-scale genome-wide cross-trait association study(GWAS) to investigate genetic overlap between type 2 diabetes and anorexia nervosa, attention deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. By post-GWAS functional analysis, we identify variants genes expression in various tissues. Enrichment pathways, potential protein interaction and mendelian randomization also provided to research the relationship between type 2 diabetes and psychiatric disorders. RESULTS: We discovered that type 2 diabetes and psychiatric disorders had a significant correlation. We identified 138 related loci, 32 were novel loci. Post-GWAS analysis revealed that 86 differentially expressed genes were located in different brain regions and peripheral blood in type 2 diabetes and related psychiatric disorders. MAPK signaling pathway plays an important role in neural development and insulin signaling. In addition, there is a causal relationship between T2D and mental disorders. In PPI analysis, the central genes of the DEG PPI network were FTO and TCF7L2. CONCLUSION: This large-scale genome-wide cross-trait analysis identified shared genetics andpotential causal links between type 2 diabetes and related psychiatric disorders, suggesting potential new biological functions in common among them.

Optimization of Opioid Discharge Prescriptions Following Thyroid and Parathyroid Surgery.

OBJECTIVE: To evaluate the impact of a quality improvement bundle on opioid discharge prescribing following thyroidectomy and parathyroidectomy. METHODS: This before-and-after study included patients undergoing thyroidectomy or parathyroidectomy at an academic medical center. The quality improvement bundle included a patient education flyer, electronic health record order sets with multimodal analgesia regimens, and provider education. The preimplementation cohort included patients treated from January 2018 to December 2019. The postimplementation cohort included patients treated from June 2021 to August 2021. The primary outcome was the proportion of patients who received new opioid discharge prescriptions. RESULTS: A total of 160 patients were included in the preimplementation cohort, and the first 80 patients treated after bundle implementation were included in the postimplementation cohort. Patients receiving new opioid discharge prescriptions decreased from 80% (128/160) in the preimplementation cohort to 35% (28/80) in the postimplementation cohort with an unadjusted absolute reduction of 45% (95% CI, 33%-57%; P < .001; number needed to treat = 3) and an adjusted odds ratio (OR) of 0.08 (95% CI, 0.04-0.19; P < .001). The bundle was associated with reductions in opioid discharge prescriptions that exceeded 112.5 oral morphine milligram equivalents (33% pre- vs 10% postimplementation; adjusted OR, 0.20; P = .001) or 5 days of therapy (17% pre- vs 6% postimplementation; adjusted OR, 0.34; P = .049). DISCUSSION: Implementation of a pain management quality improvement bundle reduced opioid discharge prescribing following thyroidectomy and parathyroidectomy. IMPLICATIONS FOR PRACTICE: Unnecessary opioid prescriptions generate unused opioids in patients' homes that can lead to opioid misuse. We believe that this bundle reduced the risk for opioid misuse in our community. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT04955444) before implementation.

Obsessive-Compulsive Disorder and Metabolic Disorders: Overview and Future Perspective.

ABSTRACT: Obsessive-compulsive disorder (OCD) has a bidirectional relationship with metabolic disorders. The purposes of this review are to decipher the links between OCD and metabolic disorders and to explore the etiological mechanism of OCD in metabolism, which may aid in early identification of and tailored interventions for OCD and metabolic disorders.

Wound characteristics and infiltration with immune globulin for rabies postexposure prophylaxis in the emergency department.

OBJECTIVE: This study described characteristics of wounds caused by animal exposures and evaluated patient factors and wound factors associated with wound infiltration of human rabies immune globulin (HRIG). MATERIALS AND METHODS: This retrospective cohort study evaluated wound characteristics among patients who had visible wounds and received HRIG or rabies vaccine for rabies postexposure prophylaxis (PEP) at 15 emergency departments from May 2016 to June 2018. RESULTS: Of 110 included patients (9 children, 82 adults, and 19 older adults), 21% (n = 23) had ≥2 wounds, and 10% (n = 11) had infected wounds. Twenty-eight (25%) patients had severe wounds, defined as receiving sutures (n = 20) or reaching subcutaneous tissue or bone (n = 20). Wounds were present on upper extremities for 42% (n = 46) of patients, lower extremities for 35% (n = 38), head/face for 3% (n = 3), and in multiple locations for 21% (n = 23). Wounds were < 3 cm in length for 64% (n = 70) of patients. Puncture wounds were present in 60% (n = 66) of patients, abrasions in 45% (n = 49), and lacerations in 38% (n = 42). Among 108 wounds from 82 patients with documented HRIG administration sites, 57% (n = 62) of wounds received HRIG infiltration. Infiltration occurred less frequently for wounds on the face/head/torso (adjusted odds ratio [aOR] = 0.07, 95% confidence interval [CI] = 0.01 to 0.49), wounds on hands/fingers (aOR = 0.20, 95% CI = 0.06 to 0.65), and abrasion-only wounds (aOR = 0.26, 95% CI = 0.08 to 0.80) after adjusting for age. CONCLUSIONS: Upon presentation for rabies PEP, most patients did not have severe wounds and did not require emergency services or complex wound management. Wounds on the face, head, torso, hands, or fingers and abrasions were less likely to receive HRIG infiltration.

Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.

AIMS: Epidemiological studies demonstrate an association between classes of obesity and psychiatric disorders, although little is known about shared genetics and causality of association. Thus, we aimed to investigate shared genetics and causal link between different classes of obesity and psychiatric disorders. METHODS: We used genome-wide association study (GWAS) summary data range from 9725 to 500,199 sample sizes of European descent, conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between the classes of obesity and anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. We conducted transcriptome-wide association study analysis (TWAS) to identified variants regulated gene expression in those related disorders. Finally, pathway enrichment analysis to identified major pathways. RESULTS: In the combined analysis, we replicated 211 previously reported loci and discovered 58 novel independent loci that were associated with all three classes of obesity and related psychiatric disorders. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, circulatory, adipose, digestive, respiratory, and nervous systems, such as DCC, NEGR1, INO80E. Mendelian randomization analyses suggested that there may be a two-way or one-way causal relationship between obesity and psychiatric disorders. CONCLUSION: This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between classes of obesity and psychiatric disorders (attention deficit hyperactivity disorder, autism spectrum disorder, anorexia nervosa, major depressive disorder, schizophrenia, and obsessive-compulsive disorder). Such shared genetics suggests potential new biological functions in common among them.

Functional Connectivity within the Frontal-Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. RESULTS: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. CONCLUSIONS: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal-striatal network, which distinguishes OCD from washing OCD.

Implementation of Clinical Decision Support on Emergency Department Delivery of Human Rabies Immune Globulin.

Importance: Fatal human rabies infections can be prevented through appropriate rabies postexposure prophylaxis (PEP). Errors in patient selection and administration of human rabies immune globulin in the emergency department (ED) setting were identified in a previous study of rabies PEP administration. Objective: To test the a priori hypothesis that implementation of a rabies PEP bundle in the ED would improve full adherence to 6 human rabies immune globulin quality indicators compared with preimplementation controls. Design, Setting, and Participants: This quality improvement study was conducted in 15 EDs in a US multihospital health system. Patients who received human rabies immune globulin or rabies vaccine in the ED from January 2015 to June 2018 were included in the preimplementation control group and from December 2019 to November 2020 were included in the postimplementation intervention group. Data were analyzed in January 2021. Exposure: The PEP bundle was implemented in December 2019 and consisted of electronic health record enhancements, including clinical decision support, ED staff education, and patient education. Main Outcomes and Measures: Full adherence to 6 human rabies immune globulin quality indicators: patient selection, dose, timing, infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock. Results: The study included 324 patients; 254 patients were in preimplementation group (mean [SD] age, 39 [21] years; 135 [53%] women) and 70 in the postimplementation group (mean [SD] age, 38 [19] years; 33 [47%] women). Most patients presented to EDs embedded in a community hospital (231 patients [71%]). Full adherence increased from 37% in the preimplementation group to 61% postimplementation (absolute increase, 24%; 95% CI, 11% to 37%; P < .001). Adherence improved for quality indicators for infiltration into wounds (137 of 254 patients [54%] to 50 of 70 patients [71%]; P = .009), administration distant from rabies vaccine site (180 of 254 [71%] to 58 of 70 [83%]; P = .04), and administration that avoids the buttock (168 of 254 [66%] to 58 of 70 [83%]; P = .007). No instances of sciatic nerve injury or compartment syndrome were observed. Conclusions and Relevance: In this quality improvement study, implementation of a rabies PEP bundle was associated with improved patient selection and delivery of human rabies immune globulin in EDs across a multihospital health system. Although the bundle included ED staff education and patient discharge education, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research should evaluate implementation of this clinical decision support at other health systems.

Scientometric Analysis of The Relationship between a Built Environment and Cardiovascular Disease.

The prevention and treatment of cardiovascular disease (CVD) are necessary to improve patient quality of life and to reduce the burden of medical and other social problems. Reducing the impact of CVD through environmental intervention was hailed as the most economical approach and research into such interventions is becoming key. The purpose of this article is to summarize the research topics and developments in the field of the built environment and CVD between 2000 and 2021 using scientometric analysis. In total, 1304 records retrieved from the Web of Science core database were analyzed using CiteSpace software, and the results were displayed using knowledge mapping. The number of publications and conferences relating to the built environment and CVD showed an upward trend over the study period, with the United States taking the lead. Physical activity and the food environment were used as mediators and entry points to map the relationship between the built environment and CVD. Walkability, residence characteristics, the food environment, and greenness were key research topics. Research shifted over the period to incorporate quantitative analyses of subjective feelings while focusing on decreasing sedentary behavior. Understanding the variability in the built environment is critical to improving the generalizability of the findings presented in the individual studies. Inter-disciplinary and multi-disciplinary research is conducive to innovation and ensuring the integration of real environmental elements. This study provides an overview and valuable guidance for researchers relating to how the built environment impacts CVD.

Avoidable emergency department visits for rabies vaccination.

BACKGROUND: Administering subsequent doses of rabies vaccine is not a medical emergency and does not require access to emergency department (ED) services. This study reviewed ED visits for rabies postexposure prophylaxis (PEP) to identify avoidable ED visits for subsequent rabies vaccination. METHODS: This retrospective study included patients who received human rabies immune globulin (HRIG) or rabies vaccine at 15 EDs of a multi-hospital health system from 2016 to 2018. All ED visits were classified as initial or non-initial healthcare visits after animal exposure. Emergency department visits for non-initial healthcare were classified as necessary (HRIG administration, worsening symptoms, other emergent conditions, or vaccination during a natural disaster) or avoidable (rabies vaccination only). RESULTS: This study included 145 patients with 203 ED visits (113 initial and 90 non-initial healthcare visits). Avoidable ED visits were identified for 19% (28 of 145) of patients and 66% (59 of 90) of ED visits for non-initial healthcare. Contributing factors for avoidable ED visits were suboptimal ED discharge instructions to return to the ED for vaccination (n = 20 visits) and patients' inability to coordinate outpatient follow-up (n = 17 visits). Patients with previous avoidable ED visits had a 73% probability for unnecessarily returning to the ED for vaccination. The average number of avoidable ED visits observed per patient was 0.41 (95% CI = 0.25 to 0.56). Since the Centers for Disease Control and Prevention reports that 30,000 to 60,000 Americans initiates rabies PEP each year, we estimate that 7500 to 33,600 avoidable ED visits occur for rabies vaccination in the US each year. CONCLUSIONS: One of 5 patients who received rabies PEP in the ED had avoidable ED visits for subsequent rabies vaccination. This study highlights systemic lack of coordination following ED discharge and barriers to accessing rabies vaccine.

Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma.

Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity. We aim to improve treatments for MM by (1) using nanoparticle delivery to enhance efficacy and reduce toxicity; (2) targeting the tumor-associated endothelium for specific delivery of the cargo to the tumor area, and (3) synchronizing the delivery of chemotherapy (bortezomib; BTZ) and BMME-disrupting agents (ROCK inhibitor) to overcome BMME-induced drug resistance. We find that targeting the BMME with P-selectin glycoprotein ligand-1 (PSGL-1)-targeted BTZ and ROCK inhibitor-loaded liposomes is more effective than free drugs, non-targeted liposomes, and single-agent controls and reduces severe BTZ-associated side effects. These results support the use of PSGL-1-targeted multi-drug and even non-targeted liposomal BTZ formulations for the enhancement of patient outcome in MM.

Luminescence of Eu (III) complex under near-infrared light excitation for curcumin detection.

An intrinsic Eu(III) luminescence phenomenon of Eu(III) complex was found under near-infrared light (NIRL) excitation of xenon lamp, and the maximum excitation wavelength is about twice the excitation wavelength of its Stokes fluorescence. The NIRL excitation fluorescence was mainly originated from second order diffracted light (SODL) excitation. The Eu(III) complex was consist of Eu(III), Gd(III), 2-trifluoroacetylacetone (TTA) and cetyltrimethylammonium bromide (CTAB). Curcumin (Cur) could notably quench the luminescence intensity of the Eu(III) complex. Based on this, a sensitive method for Cur detection was developed. Under optimum conditions, the decrease extent in the fluorescence intensity at 611 nm exhibited a good linear relationship with the Cur concentration in the range of 2.0 × 10-9 mol/L - 6.0 × 10-8 mol/L under 746 nm excitation, the limit of detection (LOD, S/N = 3) was 5.2 × 10-10 mol/L. While, the linear relationship and the LOD of Stokes fluorescence method (λex/λem = 360/611 nm) were found to be 1.0 × 10-8 mol/L - 6.0 × 10-8 mol/L and 2.6 × 10-9 mol/L, respectively. The former method is superior to the latter one in Cur detection. Both two methods were successfully applied to determine Cur in real samples. The luminescence mechanism of Eu(III) complex under the NIRL excitation and the quenching mechanism of Cur on the Eu(III) fluorescence was also investigated.

Silver nanoflowers-enhanced Tb(III)/La(III) co-luminescence for the sensitive detection of dopamine.

A sensitive fluorescent analytical method for the detection of dopamine (DA) was developed based on surface-enhanced Tb(III)/La(III) co-luminescence using silver nanoflowers (AgNFs). Anisotropic AgNFs show strong surface-enhanced fluorescence effect owing to the abundant sharp tips. Tb(III)/La(III)-DA complexes mainly bind to the sharp tips of AgNFs and thus shorten the distance between the complexes. The shortened distance gives rise to obvious surface-enhanced Tb(III)/La(III) co-luminescence effect. In this work, AgNFs offer many superior properties, such as enhanced intrinsic green fluorescence of Tb(III) (λex/λem = 310/546 nm), increased fluorescence lifetime, and improved energy transfer efficiency. Under the optimum conditions, the fluorescence intensity is linearly correlated with the concentration of DA in the range of 0.80-10 nM (R2 = 0.9970), and the detection limit is 0.34 nM (S/N = 3). The fluorescent nanoprobe was successfully applied to the determination of DA in human serum samples with recoveries ranging from 99.1 to 102.6%. Graphical abstract.

A specific fluorescent nanoprobe for dopamine based on the synergistic action of citrate and gold nanoparticles on Tb(III) luminescence.

A nanoprobe was developed for the fluorometric determination of the neurotransmitter dopamine (DA). It is based on the synergistic enhancement action of citrate and gold nanoparticles (AuNPs) on the luminescence of Tb(III). AuNPs serve as substrates of surface enhanced fluorescence (SEF). Citrate, in turn, acts as a spacer for the SEF effect, a co-ligand of Tb(III) complex, and a recognizing component for DA. The synergistic action of citrate and AuNPs significantly increases the intrinsic green fluorescence of Tb(III) (best measured at excitation/emission peaks of 300/547 nm). Under the optimum conditions, the fluorescence intensity increases linearly in the 3.0 to 200 nM DA concentration ranging (with an R2 value of 0.9959), and the limit of detection (at S/N = 3) is 0.84 nM. The nanoprobe shows good selectivity for DA among other interfering neurotransmitters, some amino acids and ions. The method was applied to the detection of DA in human serum samples where it gave recoveries ranging from 100.5 to 102.9%. Graphical abstract Schematic of a Tb(III) composite fluorescent nanoprobe for the sensitive determination of dopamine (DA). Citrate and gold nanoparticles (AuNPs) synergistically enhance the fluorescence of Tb(III)-DA.