Dynamic Behavior of Impacting Droplet on the Edges of Different Wettability Surface.

The dynamic behavior of impacting droplet shearing by the surface edge with different wettabilities is complicated and has great significance for engineering application. The morphological evolution of droplet with various Weber numbers (We) and wettability impacting on the edge of square substrate is investigated by high-speed photography. Moreover, the effects of the contact angle (α) and Weber numbers (We) on the shear breaking process of droplets are obtained. There are three types morphological evolution of impacting droplet are observed experimentally, including unbroken, tensile breakup, and shear breakup. Contact angle and Weber number have been proved to be the significant factors affecting the type of droplet morphological evolution. Meanwhile, the critical Weber number of different types are obtained quantitatively. Moreover, as α increases, the critical Weber numbers for breakup increase. In the shear breakup process, the mass ratio between the droplets remaining on the substrate and the initial droplets is maintained at 50%. Particularly, a reliable prediction model for the spreading of droplet impacting the side wall is proposed and compared with the experimental data. Overall, this study provides new direction and guidance for exploring droplet breakup kinetics.

Braden score can independently predict 90-day mortality in critically ill patients with dementia.

BACKGROUND: Dementia is a significant cause of death in the older population and is becoming an important public health issue as the population ages and the prevalence of dementia increases. The Braden score is one of the most commonly used clinical tools to assess the risk of skin pressure injury in patients, and some studies have reported that it may reflect the state of frailty of patients. The present study attempted to explore the association between Braden score and 90-day mortality, pressure injury, and aspiration pneumonia in older patients with dementia in the intensive care unit (ICU). METHODS: The study involved extracting crucial data from the Medical Information Market for Intensive Care IV (MIMIC-IV) database using Structured Query Language, with a license certificate obtained after completing the necessary training and examination available on the MIMIC-IV website. A retrospective analysis was performed on older patients with dementia, aged 65 or older, who were first admitted to the ICU. Ninth and tenth revision International Classification of Diseases codes were used to identify patients with dementia. The primary outcome was 90-day mortality. Cox proportional hazards models were used to determine the association between Braden score and death, and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Propensity score matching and E-value assessments were employed for sensitivity analysis. RESULTS: A total of 2892 patients with a median age of approximately 85 years (interquartile range 78.74-89.59) were included, of whom 1625 were female (56.2%). Patients had a median Braden score of 14 (interquartile range 12-15) at ICU admission. Braden score at ICU admission was inversely associated with 90-day mortality risk after adjustment for demographics, severity of illness, treatment and medications, delirium, and sepsis (adjusted HR: 0.92, 95% CI: 0.87-0.98, p = 0.006). Patients were divided into two groups with a cut-off value of 15: high-risk group and low-risk group. Compared to the low-risk group (Braden score >15), the risk of 90-day mortality was significantly increased in the high-risk group (Braden score ≤15) (adjusted HR: 1.52, 95% CI: 1.10-2.09, p = 0.011, E-value: 2.01), the risk of pressure injury (adjusted OR: 2.62, 95% CI: 2.02-3.43, E-value: 2.62) and aspiration pneumonia (adjusted OR: 2.55, 95% CI: 1.84-3.61, E-value: 2.57) was also significantly higher. CONCLUSIONS: The Braden score may be a quick and simple screening tool to identify the risk of adverse outcomes in critically ill older adults with dementia.

Assessing the Risk of Delirium and Death in Sepsis Using the Braden Score: A Retrospective Study.

AIMS AND OBJECTIVES: To provide a viable tool for the early clinical identification of high-risk populations in patients with sepsis. BACKGROUND: Sepsis-associated delirium (SAD) has the potential to significantly impact the short- and long-term prognosis of patients. However, accurately predicting and effectively managing SAD remains a significant challenge. METHODS: This study employed a retrospective analysis of adult sepsis patients admitted to the intensive care unit (ICU) for the first time. Patients were divided into two groups based on their initial Braden score upon admission to the ICU: a high-risk group (≤ 15 points) and a low-risk group (> 15 points). The relationship between Braden score and delirium was assessed using logistic regression and restricted cubic splines, while restricted mean survival time was employed to analyse the relationship between Braden scores and patients' 90- and 180-day mortality. RESULTS: Of the 28,312 patients included in the study, those in the high-risk group exhibited a significantly elevated risk of delirium (44.8% vs. 29.7%) and higher 90-day (28.7% vs. 19.4%) and 180-day (33.2% vs. 24.1%) mortality rates (all p < 0.001). After adjusting for confounding variables, logistic regression demonstrated that the risk of delirium was 1.54 times higher in the high-risk group (95% CI = 1.45-1.64, p < 0.001). Following propensity score matching, the difference in survival was statistically significant at both time points, with the high-risk group having a reduced survival rate of 7.50 days (95% CI = -8.24, -6.75; p < 0.001) and 15.74 days (95% CI = -17.40, -14.08; p < 0.001) at 90 days and 180 days, respectively. CONCLUSIONS: The Braden score is a simple and effective tool for the early identification of patients at increased risk of adverse outcomes in sepsis. DESIGN: Retrospective study. RELEVANCE TO CLINICAL PRACTICE: The Braden score can be employed by clinical nurses for the purpose of early identification of poor prognostic risk in patients with sepsis. REPORTING METHOD: This study was conducted according to the Strengthening Research in Observational Studies in Epidemiology (STROBE) guidelines. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in the sample of the study.

Braden score predicts 30-day mortality risk in patients with ischaemic stroke in the ICU: A retrospective analysis based on the MIMIC-IV database.

BACKGROUND: Ischaemic stroke remains a significant global health challenge, associated with high mortality rates. While the Braden Scale is traditionally employed to assess pressure ulcer risk, its potential to predict mortality among the intensive care unit (ICU) patients with ischaemic stroke has not been thoroughly investigated. AIM/S: This study evaluates the predictive value of the Braden Scale for 30-day mortality among patients with ischaemic stroke admitted to ICU. STUDY DESIGN: We conducted a retrospective analysis of 4710 adult patients with ischaemic stroke from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The association between the Braden Scale scores and 30-day mortality was assessed using receiver operating characteristic (ROC) curve analysis, Cox regression models and Kaplan-Meier survival estimates. RESULTS: Patients with Braden Scale scores ≤ 15.5 showed significantly higher 30-day mortality rates (p-value < 0.001; hazard ratio (HR): 2.08, 95% confidence interval (CI): 1.71-2.53). The area under the ROC curve (AUC) was 0.71, demonstrating good predictive performance. Multivariate analysis confirmed the Braden Scale as an independent predictor of mortality, after adjusting for age, gender and comorbidities. CONCLUSIONS: The Braden Scale effectively identifies high-risk ischaemic stroke patients in ICU settings, endorsing its integration into routine assessments to facilitate early intervention strategies. RELEVANCE TO CLINICAL PRACTICE: Integrating the Braden Scale into routine ICU evaluations can enhance mortality risk stratification and improve patient care tailoring.

Elderly patients with dysphagia in the intensive care unit: Association between malnutrition and delirium.

BACKGROUND: Dysphagia, as a geriatric syndrome, is prevalent in the intensive care unit (ICU). Malnutrition resulting from swallowing disorders is likely to correlate with adverse ICU outcomes, including delirium, thereby escalating the costs of care and hospitalization. However, malnutrition has not received the attention it deserves in ICU clinical nursing practice. As two preventable and correctable conditions-malnutrition and delirium-the advantages of early identification and intervention are substantial. Exploring the relationship between malnutrition and delirium, starting from the high-risk group of elderly patients with swallowing difficulties in the ICU, will aid us in managing patients promptly and effectively. AIM: To investigate the relationship between malnutrition and the incidence of delirium in elderly patients with dysphagia in the ICU. SUDY DESIGN: This is a retrospective study. Data for this study were obtained from the Medical Information Mart for Intensive Care-IV. All 2273 patients included were dysphagia older patients over 65 years of age admitted to the ICU, and logistic regression was used to explore the relationship between malnutrition and delirium. We also used propensity score matching (PSM) for sensitivity analysis. RESULTS: Among the included patients with swallowing difficulties, 13% individuals (297/2273) exhibited malnutrition, with a delirium incidence rate of 55.9% (166/297). In the non-malnutrition group (1976/2273), the delirium incidence rate is 35.6% (704/1976). After adjusting for 31 covariates, multifactorial logistic regression showed that malnutrition was significantly positively associated with the incidence of delirium in elderly dysphagic patients in the ICU (adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.47-2.62). The results remained stable after analysis by PSM. CONCLUSION: Malnutrition was significantly positively associated with the incidence of delirium in elderly dysphagic patients in the ICU. Malnutrition should be given adequate attention in the ICU. RELEVANCE TO CLINICAL PRACTICE: ICU nurses should pay particular attention to malnutrition, especially among the high-prevalence group of patients with dysphagia. Early identification and nutritional intervention for these patients may help reduce the costs of care and health care expenditures.

Proteomic Landscape of Exosomes Reveals the Functional Contributions of CD151 in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Patients with TNBC have poor overall survival because of limited molecular therapeutic targets. Recently, exosomes have been recognized as key mediators in cancer progression, but the molecular components and function of TNBC-derived exosomes remain unknown. The main goal of this study was to reveal the proteomic landscape of serum exosomes derived from ten patients with TNBC and 17 healthy donors to identify potential therapeutic targets. Using a tandem mass tag-based quantitative proteomics approach, we characterized the proteomes of individual patient-derived serum exosomes, identified exosomal protein signatures specific to patients with TNBC, and filtered out differentially expressed proteins. Most importantly, we found that the tetraspanin CD151 expression levels in TNBC-derived serum exosomes were significantly higher than those exosomes from healthy subjects, and we validated our findings with samples from 16 additional donors. Furthermore, utilizing quantitative proteomics approach to reveal the proteomes of CD151-deleted exosomes and cells, we found that exosomal CD151 facilitated secretion of ribosomal proteins via exosomes while inhibiting exosome secretion of complement proteins. Moreover, we proved that CD151-deleted exosomes significantly decreased the migration and invasion of TNBC cells. This is the first comparative study of the proteomes of TNBC patient-derived and CD151-deleted exosomes. Our findings indicate that profiling of TNBC-derived exosomal proteins is a useful tool to extend our understanding of TNBC, and exosomal CD151 may be a potential therapeutic target for TNBC.

Gastrointestinal Disease and COVID-19: A Review of Current Evidence.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented and catastrophic impact on humanity and continues to progress. In addition to typical respiratory symptoms such as fever, cough, and dyspnea, a large percentage of COVID-19 patients experience gastrointestinal (GI) complaints, with the most common symptoms being diarrhea, nausea, vomiting, and abdominal discomfort. SUMMARY: We comprehensively summarize the latest knowledge of the adverse effects of COVID-19 and therapeutic drugs on the GI system, as well as related disease pathogenesis, and then provide a discussion focusing on the management and vaccination of patients who have inflammatory bowel disease (IBD) and GI cancer. The virus can affect the digestive system via binding to ACE2 receptors and subsequent gut microbiome dysbiosis. Through a variety of molecular pathways and mechanisms, numerous drugs for the treatment of COVID-19 could interfere with GI function and lead to multiple clinical manifestations, which may further intensify the risk and severity of GI symptoms of COVID-19 infection, such as nausea, vomiting, gastroparesis, and gastric ulcers. KEY MESSAGES: We should monitor GI manifestations closely while managing COVID-19 patients and take timely measures to reduce the incidence of SARS-CoV-2 infections in GI cancer patients. IBD patients should receive vaccination timely, but corticosteroid use should be minimized when they are vaccinated. Simultaneously, for persons with IBD who have known or suspected COVID-19, immunosuppressive agents, especially thiopurines, should be avoided/minimized if possible.

IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase that may play a part in chemoresistance in ovarian cancer. However, its role in cisplatin (DDP) resistance is unclear. Here, the expression level of IDO1 in tumors in platinum-resistant (n = 22) and -sensitive (n = 46) ovarian cancer patients was determined, and then how IDO1 modulated DDP resistance was explored in vitro and in vivo. The IDO1 expression level in platinum-resistant patients was higher than that in -sensitive patients, and a higher IDO1 level was correlated with poor prognosis in type II cancer patients. Up-regulating IDO1 decreased DDP-induced apoptosis in SKOV3 cells via inhibiting the ROS/p53 cell-death pathway, thereby attenuating cytotoxicity of DDP. Silencing IDO1 enhanced p53-dependent apoptosis by increasing ROS accumulation, thereby enhancing DDP against SKOV3 cells. Down-knocking IDO1 augmented the action of DDP in vivo. These data demonstrated that silencing IDO1 enhanced the efficacy of DDP by intensifying p53-dependent apoptosis, and that targeting IDO1 can be a strategy to modulate DDP-based chemotherapy for epithelial ovarian cancer.

Ultrasound Enhances ZD2767P-Carboxypeptidase G2 against Chemoresistant Ovarian Cancer Cells by Altering the Intracellular Pharmacokinetics of ZD2767D.

Prodrug-carboxypeptidase G2 (e.g., ZD2767P+CPG2) can realize a targeted treatment where the specific advantage is a lack of CPG2 analogues in humans, but it is limited by low efficacy. Here ultrasound was employed to enhance ZD2767P+CPG2 (i.e., ZD2767P+CPG2+US) against chemoresistant human ovarian cancer cells. The release dynamics of ZD2767D (activated drug) by CPG2 were investigated. The in vitro efficacy was explored in SKOV3 and SKOV3/DDP (cisplatin-resistant subline) cells; spectrophotometry was established to quantify ZD2767P and ZD2767D, and then intracellular pharmacokinetics were evaluated. The in vivo efficacy was validated in both subcutaneous and orthotopic tumors. With insonation, the ZD2767D concentration was increased during an early period. Insonation synergized ZD2767P+CPG2 to enhance cell death and apoptosis, and efficacies in SKOV3 and SKOV3/DDP cells were similar. Intracellular pharmacokinetics of ZD2767D were nonproportional, and insonation increased the peak level, area under the level vs time curve, and mean residence time. In subcutaneous xenografts, ZD2767P+CPG2 and ZD2767P+CPG2+US resulted in volume-inhibitory rates of 20.4% and 26.5% in SKOV3 tumors and 36.8% and 81.6% in SKOV3/DDP tumors, respectively. In the orthotopic tumor model, the survival time in group ZD2767P+CPG2 or ZD2767P+CPG2+US was prolonged compared with group control, in SKOV3 (33.0 ± 3.5 or 39.2 ± 1.8 vs 25.0 ± 1.6 days, p < 0.0001) and SKOV3/DDP (16.2 ± 4.8 or 22.3 ± 7.3 vs 8.7 ± 3.9 days, p = 0.0015) tumors. These data indicated that ZD2767P+CPG2+US was effective against resistant ovarian cancer cells.

The Perioperative Hyperchloremia Is Associated With Postoperative Acute Kidney Injury in Patients With off-Pump Coronary Artery Bypass Grafting: A Retrospective Study.

BACKGROUND: The relationship between perioperative hyperchloremia and postoperative acute kidney injury (AKI) is not well established. Our study aimed to evaluate the association between perioperative hyperchloremia and acute kidney injury in patients undergoing off-pump coronary artery bypass grafting (CABG). METHODS: Patients with coronary disease who underwent off-pump CABG between April 2017 and December 2019 were enrolled in this retrospective study. The patients with perioperative hyperchloremia were matched 1:1 to patients without perioperative hyperchloremia. The primary outcome was the postoperative acute kidney injury rate. The secondary outcomes included intensive care unit (ICU)-free days, postoperative hospitalization days, wound infection rate, and in-hospital mortality. Propensity score matching and univariate and multivariate logistic regression analyses were used in this study. RESULTS: A total of 321 patients who underwent off-pump CABG were included in the analysis. Propensity score matching selected 83 pairs for the final comparison. The results showed that the postoperative AKI rate was significantly different between the hyperchloremia and no hyperchloremia groups (56.6% versus 15.7%; P < .001). The number of ICU-free days, postoperative hospitalization days, wound infection rate, and in-hospital mortality were similar between the two groups. In the multivariable, logistic regression analysis, hyperchloremia was independently associated with the development of postoperative AKI (odds ratio [OR] = 1.814, 95% confidence interval [CI]: 1.072-3.070, P = .026). CONCLUSIONS: Perioperative hyperchloremia is associated with an increase in the postoperative AKI rate among patients undergoing off-pump CABG.

[Militarine alleviates white matter damage and cognitive impairment in rats with chronic cerebral hypoperfusion].

Chronic cerebral hypoperfusion is a model for white matter lesions (WMLs) and cognitive impairment. In this study, we used the model in testing the protective effect of (-)-(2R)-1-[（4-ß-D-glucopyranosyloxy)benzyl]-4-[4-(ß-D-glucopyranosyloxy)benzyl]-2-isobutyl malate (militarine) on the white matter damaged. The model was established by bilateral common carotid ligation. Militarine (10 and 20 mg·kg(-1)·d(-1)) or saline was intragastrically administered daily for 30 days following the operation. Militarine (20 mg·kg-1·d-1)-treated rats exhibited significantly shorter escape latency, latency of the first time crossing and more numbers of platform crossings in Morris water maze task. Luxol fast blue (LFB) staining and Western blot analysis indicated that militarine promoted rehabilitation of white matter and increased levels of myelin basic protein (MBP) in the rats. Immunohistochemical staining for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) revealed that militarine (20 mg·kg(-1)·d(-1)) markedly suppressed loss of CNPase-positive oligodendrocytes in the rat model. In conclusion, militarine can improve WMLs and cognitive impairment in the rat chronic hypoperfusion model.

Clinical Trials of High-Intensity Focused Ultrasound for Cancer: Concerns Arising from Low Post-Hoc Power.

Prospective controlled trials of high-intensity focused ultrasound for cancers were evaluated. Post-hoc power was <0.80 in 30/47 trials and in 22/39 trials with positive results, indicating low quality in most trials. Unscientific endpoints, small sample sizes, and high dropout rates led to low post-hoc power that caused inter-trial heterogeneity and overestimated the therapeutic effect. The objective response rate was not a substitute for survival time for estimating the sample size and assessing the efficacy. The present data can interpret a paradox: HIFU is considered to have slighter cytotoxicity to non-cancer tissues and no radiation but is frequently combined with chemotherapy and/or radiotherapy in practice.

Toward Genetic Testing of Rivaroxaban? Insights from a Systematic Review on the Role of Genetic Polymorphism in Rivaroxaban Therapy.

BACKGROUND: Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis. RESULTS: A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (Cmin/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results. CONCLUSIONS: Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42022347907.

Intracellular Pharmacokinetics of Activated Drugs in a Prodrug-Enzyme-Ultrasound System: Evaluations on ZD2767P+CPG2+US.

Intracellular pharmacokinetics (PK) of activated drugs is a window to understanding the pharmacodynamics of prodrug-enzyme-ultrasound therapy. Herein PK of ZD2767D (i.e., activated drug) in the ZD2767P+CPG2+US system on A549, A549/DDP, SKOV3, and SKOV3/DDP cells were evaluated (A549/DDP and SKOV3/DDP were cisplatin-resistant sublines). The noncompartment model under extravascular input mode was deemed appropriate for evaluating drug level vs time curves; Cmax, AUClast, MRTlast, Vz, and Cl can reflect the PK feature, but t1/2, AUCinf, and MRTinf were irrational; higher accumulation and slower elimination characterized the PK mechanism of ZD2767P+CPG2+US; enhanced permeability and retention effect can be assessed with Cmax, AUClast, MRTlast, and tlast; ultrasound equivalently modulated Cmax and AUClast in sensitive and resistant cells. The experimental design and dose proportionality were discussed.

Phenotypes of patients with systemic sclerosis in the Chinese Han population: a cluster analysis.

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is commonly subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. This subclassification may not reflect the full range of clinical phenotypic variation. This study aimed to investigate clinical features and aggregation of patients with SSc in Chinese based on SSc manifestations and organ involvements, in order to achieve precise treatment of SSc early prevention of complications. METHODS: In total 287 SSc patients were included in this study. A cluster analysis was applied according to 13 clinical and serologic variables to determine subgroups of patients. Survival rates between obtained clusters and risk factors affecting prognosis were also compared. RESULT: In this study, six clusters were observed: cluster 1 (n = 66) represented the skin type, with all patients showing skin thickening. In cluster 2 (n = 56), most patients had vascular and articular involvement. Cluster 3 (n = 14) individuals mostly had cardiac and pulmonary involvement. In cluster 4 (n = 52), the gastrointestinal type, 50 patients presented with stomach symptoms and 28 patients presented with esophageal symptoms. In cluster 5 (n = 50), patients barely had any major organ involvement. Cluster 6 (n = 49) included 46% of all patients presenting with renal crisis. CONCLUSION: The results of our cluster analysis study implied that limiting SSc patient subgroups to those based only on skin involvement might not capture the full heterogeneity of the disease. Organ damage and antibody profiles should be considered when identifying homogeneous patient groups with a specific prognosis. Key Points • Provides a new method of categorizing SSc patients. • Can better explain disease progression and guide subsequent treatment.

Therapeutic drug monitoring guidelines in oncology: what do we know and how to move forward? Insights from a systematic review.

Background: Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited. Objective: We aimed to provide a comprehensive understanding of TDM guidelines for antineoplastic drugs and to promote the development of individualized drug therapy in oncology. Design: This study type is a systematic review. Data sources and methods: This study was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Databases including PubMed, Embase, the official websites of TDM-related associations and Chinese databases were comprehensively searched up to March 2023. Two investigators independently screened the literature and extracted data. The methodological and reporting quality was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT), respectively. Recommendations and quality evaluation results were presented by visual plots. This study was registered in PROSPERO (No. CRD42022325661). Results: A total of eight studies were included, with publication years ranging from 2014 to 2022. From the perspective of guideline development, two guidelines were developed using evidence-based methods. Among the included guidelines, four guidelines were for cytotoxic antineoplastic drugs, three for small molecule kinase inhibitors, and one for antineoplastic biosimilars. Currently available guidelines and clinical practice provided recommendations of individualized medication in oncology based on TDM, as well as influencing factors. With regard to methodological quality based on AGREE II, the average overall quality score was 55.21%. As for the reporting quality by RIGHT evaluation, the average reporting rate was 53.57%. Conclusion: From the perspective of current guidelines, TDM in oncology is now being expanded from cytotoxic antineoplastic drugs to newer targeted treatments. Whereas, the types of antineoplastic drugs involved are still small, and there is still room for quality improvement. Furthermore, the reflected gaps warrant future studies into the exposure-response relationships and population pharmacokinetics models.

Association between modified frailty index and postoperative delirium in patients after cardiac surgery: A cohort study of 2080 older adults.

AIM: To evaluate the association between frailty and postoperative delirium (POD) in elderly cardiac surgery patients. METHODS: A retrospective study was conducted of older patients admitted to the intensive care unit after cardiac surgery at a tertiary academic medical center in Boston from 2008 to 2019. Frailty was measured using the Modified Frailty Index (MFI), which categorized patients into frail (MFI ≥3) and non-frail (MFI = 0-2) groups. Delirium was identified using the confusion assessment method for the intensive care unit and nursing notes. Logistic regression models were used to examine the association between frailty and POD, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 2080 patients included (median age approximately 74 years, 30.9% female), 614 were frail and 1466 were non-frail. The incidence of delirium was significantly higher in the frail group (29.2% vs. 16.4%, p < 0.05). After adjustment for age, sex, race, marital status, Acute Physiology Score III (APSIII), sequential organ failure assessment (SOFA), albumin, creatinine, hemoglobin, white blood cell count, type of surgery, alcohol use, smoking, cerebrovascular disease, use of benzodiazepines, and mechanical ventilation, multivariate logistic regression indicated a significantly increased risk of delirium in frail patients (adjusted OR: 1.61, 95% CI: 1.23-2.10, p < 0.001, E-value: 1.85). CONCLUSIONS: Frailty is an independent risk factor for POD in older patients after cardiac surgery. Further research should focus on frailty assessment and tailored interventions to improve outcomes.

Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes.

BACKGROUND/OBJECTIVES: Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in "adiponectin paradox", we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation. METHODS: This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α. RESULTS: This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036-0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (Poverall < 0.001 and Pnon-linear < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03-0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5-49.2, P = 0.02). CONCLUSIONS: In patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.

Modified frailty index effectively predicts adverse outcomes in sepsis patients in the intensive care unit.

BACKGROUND: Frailty and sepsis have a significant impact on patient prognosis. However, research into the relationship between frailty and sepsis in the general adult population remains inadequate. This paper aims to investigate the association between frailty and adverse outcomes in this population. METHOD: This retrospective analysis investigated sepsis patients who were initially admitted to the intensive care unit (ICU). The Modified Frailty Index (MFI) was derived by tracking patients' International Classification of Diseases (ICD) codes during their hospitalization. Patients were classified into two groups based on their MFI scores: a frail group (MFI ≥ 3) and a non-frail group (MFI = 0-2). The key outcomes were mortality rates at 90 and 180 days, with secondary outcomes including the incidence of delirium and pressure injury. RESULT: Of the 21,338 patients who were recruited for this study (median age about 68 years, 41.8 % female), 5,507 were classified as frail and 15,831 were classified as non-frail. Frail patients were significantly more likely to have delirium (48.9 % vs. 36.1 %, p < 0.001) and pressure injury (60.5 % vs. 51.4 %, p < 0.001). After controlling for confounding variables, the multifactorial Cox proportional hazard regression analyses revealed a significantly elevated mortality rate at 90 days (adjusted HR: 1.58, 95 % CI: 1.24-2.02, p < 0.001) and 180 days (adjusted HR: 1.47, 95 % CI: 1.18, 1.83, p < 0.001) in the frail group compared to their non-frail counterparts. CONCLUSIONS: Frailty independently predisposes adult sepsis patients in the ICU to adverse outcomes. Future investigations should concentrate on evaluating frailty and developing targeted interventions to improve patient prognosis. IMPLICATION FOR CLINICAL PRACTICE: The MFI provides a simple clinical assessment tool that can be integrated into electronic medical records for immediate calculation. This simplifies the assessment process and plays a key role in predicting patient outcomes.