Treatment Of High-risk Patients Research Articles

Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Atherothrombosis Intervention in High-Risk Patients Using Serelaxin), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

The Evolving Role of Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.

The advent of targeted therapies such as monoclonal antibodies, adoptive T-cell therapies, and antibody-drug conjugates (ADCs) dramatically changed the treatment landscape of diffuse large B-cell lymphoma (DLBCL) over the last two decades. Rituximab was the first one approved. Chimeric antigen receptor T-cells are currently approved as second-line treatment in patients with DLBCL refractory to first-line chemo-immunotherapy. Polatuzumab, a CD79b-targeting ADC, is approved as first-line treatment in high-risk patients in combination with chemo-immunotherapy. Bispecific antibodies (BsAbs) are a novel category of drugs that are also changing the treatment paradigm of patients with DLBCL. They are engineered to bind to two different targets at the same time. To date, two BsAbs (glofitamab and epcoritamab) are approved as monotherapy in third-line treatment in DLBCL. Combination strategies with chemotherapy, immunotherapy, and ADCs are currently under investigation with encouraging results in first-line or subsequent lines of treatment. In the following review, we focus on the structure of BsAbs, the mechanism of action, clinical efficacy, and the mechanisms of resistance to BsAbs.

The predictive value of the MASCC score in patients with febrile neutropenia.

e23059 Background: Febrile neutropenia (FN) is a life-threatening complication in patients receiving cytotoxic chemotherapy. Guidelines classify FN as a one-time oral temperature of greater than 38.3°C or sustained temperature greater than 38°C for ≥ 1 hour with an absolute neutrophil count (ANC) of less than 500 cells/μL or an ANC expected to decrease to less than 500 cells/μL within a 48-hour period. This condition has a high rate of hospitalization and mortality. Currently, the Multinational Association of Supportive Care in Cancer (MASCC) risk score is used to classify patients as high or low risk. The current study outlines the predictive role of MASCC scoring in risk stratifying patients with FN at our institution. Methods: This is a single-center, retrospective observational study. IRB approval was obtained for this study. Electronic medical record data was reviewed to record mortality, length of stay (LOS), and antimicrobial use as primary outcomes with age at time of admission, sex, race, type of malignancy, any confirmed infection diagnosis, MASCC risk score, and subspecialist consultation as predictors of outcomes. Results: 220 records of possible FN episodes were screened, 160 were excluded leaving a total of 60 patients for review. The median age was 72.5 with 28 males and 32 females. Overall mortality rate was 10%.33 patients (55%) did not have an identifiable source of infection. Among the 27 patients with confirmed infection, 7 were associated with COVID-19, 12 had gram negative rod (GNR) sepsis and 8 were other bacterial infections. Patients with GNR sepsis had the highest mortality risk in which 4 of the 12 (33%) died. LOS was also significantly longer in patients with GNR sepsis. Lower MASCC scores were associated with identification of GNR sepsis. Of the patients with MASCC score of < 24, significantly more patients 7/20 (35%) developed GNR sepsis compared to 5/40 (12.5%) of those with MASCC score of 24 or greater (p = .004). Patients with GNR sepsis received a mean 5.7 days of broad spectrum antibiotics compared to 3 days in those without, (p < 0.001). Those with no identified infection had significantly lower LOS (4.5 days) compared to the groups with GNR sepsis (11.1 days) or other bacterial infections (10.1 days). Conclusions: Febrile neutropenia is a complication of cytotoxic chemotherapy that warrants special attention due to high mortality rates. We found lower MASCC scores were associated with GNR sepsis and that in the setting of FN these patients had higher mortality rates and longer LOS. This highlights the importance of risk stratification with MASCC index scoring as early recognition and treatment of high risk patients could lead to improved patient outcomes.

Variables that predict hospital stay and the outcome of Fournier gangrene at King Abdulaziz University Hospital: a retrospective study

BackgroundThe aggressive nature of Fournier gangrene and the associated health issues can result in a more complex clinical course and potentially a longer hospital stay. This study aimed to assess factors that affect the length of hospital stay (LHS) and its relation to the outcome of Fournier gangrene patients.MethodsA retrospective study was performed at King Abdulaziz University Hospital (KAUH), Saudi Arabia, on patients diagnosed with Fournier gangrene between 2017 and 2023. Data about length of hospital stay (LHS), age, BMI, clinical and surgical data and outcome was obtained.ResultsThe mean age of the studied patients was 59.23 ± 11.19 years, the mean body mass index (BMI) was 26.69 ± 7.99 kg/m2, and the mean duration of symptoms was 10.27 ± 9.16 days. The most common presenting symptoms were swelling or induration (64%), 88% had comorbidities with diabetes mellitus (DM) (84%), and 76% had uncontrolled DM. of patients, 24% had a poly-microbial infection, with E. coli being the most common (52%). The mean length of hospital stay (LHS) was 54.56 ± 54.57 days, and 24% of patients had an LHS of more than 50 days. Longer LHS (> 50 days) was associated with patients who did not receive a compatible initial antibiotic, whereas shorter LHS was associated with patients who received Impenem or a combination of vancomycin and meropenem as alternative antibiotics following incompatibility. Reconstruction patients had significantly longer LHS and a higher mean temperature. However, none of the studied variables were found to be predictors of long LHS in the multivariate regression analysis.ConclusionKnowledge of the values that predict LHS allows for patient-centered treatment and may be useful in predicting more radical treatments or the need for additional treatment in high-risk patients. Future multicenter prospective studies with larger sample sizes are needed to assess the needed variables and predictors of long LHS.

Identification of metabolic components of carotid plaque in high-risk patients utilizing liquid chromatography-tandem mass spectrometry.

Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.

Abstract PO4-02-05: Elevated tumor to aorta ratio of Hounsfield units and late recurrence in patients with estrogen receptor positive breast cancer

Abstract Background) More than half of the recurrent disease in breast cancer will happen more than 5 years after initial diagnosis in breast cancer, especially in patients with ER positive disease. Higher proportions of late recurrence lead to escalated treatment and/or or extended treatment for high risk patients. However, it is unclear what characteristics make whom as high risk patients. This study aimed to assess initial tumor vascularity as a prognostic marker for late recurrence. Methods) Female patients with estrogen receptor positive breast cancer who were diagnosed breast cancer between 2003 and 2018 and disease-free at 5 years after primary breast cancer at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics were collected. Hounsfield units(HU) on contrast-enhanced computed tomography(CT) was used as a marker indicating tumor vascularity. Tumor to aortic arch ratio(TAR) of HU on contrast enhanced CT was applied to enhance objectivity of measurement. Patients were categorized according to the cut-off values retrieved from the receiver operating characteristic curve. Kaplan-Meier curves were generated to compare recurrence-free survival (RFS) and overall survival (OS). Hazard ratio(HR) with confidence interval(CI) was derived with Cox’s proportional hazard model to analyze univariate and multivariate risk factors. Results) The final cohort included 451 patients with a mean age of 56.21 ± 11.2 (22-83) years. Two third of patients had estrogen receptor positive disease and a quarter of patients had HER2 overexpressed disease. Initial TAR was 0.345 ± 0.108 (range, 0.062 - 1.114). Patients with recurrence free survival(RFS)-related events had significantly higher TAR than patients who did not(0.39 ± 0.097 vs. 0.34 ± 0.108, p=0.012). Patients with overall survival(OS)-related events also had higher TAR than patients who did not(0.408 ± 0.096 vs. 0.342 ± 0.107, p=0.002). Cutoff value of 0.408 was driven from area under the receiver operating characteristic curve. Patients with TAR higher than 0.408 showed significantly worse RFS(p=0.001) and OS(p< 0.001) than patients who had TAR equal or lower than 0.408. Hazard ratio(HR) of TAR in late recurrence was 6.17 (CI, 4.89 – 9.23, p=0.003), suggesting it is an independent factor. Other independent factors were age (HR, 1.502; CI, 10.14 – 10.91; p=0.006), tumor size (HR, 1.268; CI, 1.071 – 1.502; p=0.006), and metastatic nodal disease (HR, 2.770; CI, 1.176 – 6.526; p=0.020). Conclusion) TAR of primary tumor was significantly related with patients RFS and OS. Patients with high TAR larger than 0.408 showed worse RFS and OS than patients who did not. According to the Cox proportional hazard model, TAR was an independent factor along with age, tumor size, and metastatic nodal disease, suggesting late recurrence may rather be influenced by clinical factor Citation Format: Airi Han, Hyang Suk Choi, Seok Hahn, In-jeoung Cho, Seung Taek Lim, Jong-In Lee. Elevated tumor to aorta ratio of Hounsfield units and late recurrence in patients with estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-05.

The Association Between Mental Disorders and Postoperative Outcomes of Scoliosis Surgery: A Systematic Review and Meta-analysis.

Mental disorders may adversely impact postoperative recovery in scoliosis surgery. However, study findings have been inconsistent and a systematic synthesis is lacking. We searched PubMed, Embase, PsycINFO, and Cochrane Library for studies examining associations between preoperative mental disorders, assessed by various scales, such as the Patient Health Questionnaire (PHQ), the Modified Somatic Perception Questionnaire (MSPQ), and the State-Trait Anxiety Inventory (STAI), and postoperative outcomes, such as pain, disability, quality of life, and satisfaction, in scoliosis surgery. Random-effects meta-analyses pooled standardized mean differences (SMDs) in postoperative outcomes between patients with and without mental disorders. Twelve observational studies were included for the systematic review, and 5 studies were included in the meta-analysis. The meta-analysis demonstrated significantly worse postoperative outcomes in patients with mental disorders compared to those without (SMD -1.96, 95% confidence interval [CI] -3.08 to -0.84, P < 0.001). Significant heterogeneity was present (I2 = 76%). Review of included studies found mental disorders linked to higher preoperative pain/disability and lower quality of life/satisfaction, as well as worse postoperative scores on these outcomes. Moderating factors identified included mental disorder severity, treatment specifics, and patient demographics. Preoperative mental disorders, especially depression and anxiety, are associated with significantly worse postoperative pain, disability, quality of life, and satisfaction in scoliosis surgery. This association may be mediated by psychological factors, such as catastrophizing, self-criticism, and kinesiophobia, and biological factors, such as inflammation, neuroendocrine changes, and central sensitization. Routine psychological screening and interventions for high-risk patients may improve postoperative outcomes but not necessarily surgical effectiveness. Further research is warranted to confirm these findings and elucidate optimal treatment approaches.

Percutaneous Tricuspid Valve Repair: The Triclip.

Tricuspid regurgitation is an often overlooked, but severe cardiac valvular disease associated with significant morbidity and poor quality of life. Tricuspid valve surgery is the only treatment that prevents progression of the disease but is often complicated or made impossible by perioperative risk factors. Due to the high-risk nature, tricuspid valve surgery is typically only done for severe tricuspid regurgitation at the time of left heart surgery, leaving many patients untreated. Medical therapy is limited primarily to diuretic agents, which are often unsuccessful in alleviating symptoms. Treatment of tricuspid regurgitation with transcatheter edge-to-edge repair has emerged after the success of this technique in mitral valve pathologies. This percutaneous procedure parallels surgical principles previously used for valve repair but eliminates the need for cardiac surgery, thus having the potential to serve as an alternative treatment in high-risk patients. The TriClip (Abbott Labs) device is an example of this therapy and the subject of this review.

403 Epithelial hypoxia maintains colonization resistance against Candida albicans

OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

Analysis of Risk Prediction Models to Identify Patients at High Risk of Urinary Incontinence

Introduction: Urinary incontinence (UI) is a common health problem and is often undiagnosed in hospital patients. UI can cause complications such as urinary tract infections, dermatitis, and decreased quality of life. This study aims to apply a risk prediction model to identify patients at high risk of experiencing UI at Tengku Peukan General Hospital, Southwest Aceh, Indonesia.&#x0D; Methods: This study used a prospective cohort design. Data was collected from 100 patients hospitalized at Tengku Peukan General Hospital, Southwest Aceh. A risk prediction model was developed using logistic regression. Model performance is measured by AUC-ROC values and accuracy.&#x0D; Results: The risk prediction model developed had an AUC-ROC value of 0.85 (95% CI: 0.78-0.92) and an accuracy of 82%. The most significant risk factors for UI are age, gender, history of UI, and use of diuretic medications.&#x0D; Conclusion: This risk prediction model can help nurses and doctors identify patients who are at high risk of experiencing UI at Tengku Peukan General Hospital, Southwest Aceh. Early intervention in high-risk patients can help prevent UI complications and improve the patient's quality of life.

Possibilities of Transfistula Ultrasound in Predicting Intraoperative Bleeding in Patients with Infected Pancreatic Necrosis

Introduction. Assessing the risk of intraoperative bleeding is of great importance in the treatment of patients with infected pancreatic necrosis.The aim of the study — determine the role of transfistula ultrasound in assessing the risk of intraoperative bleeding in patients with infected pancreatic necrosis.Materials and methods. From 2015 to 2019, 193 people with infected pancreatic necrosis were treated at Regional Clinical Hospital No. 2 (Krasnodar). At stage 1, drains of various diameters were installed in all patients; at stage 2, necrotic tissue was removed using transfistula videoscopic necrosequestrectomy in 48 patients (24.9 %). Before performing instrumental necrosequestrectomy, a developed diagnostic method was used — transfistula ultrasound scanning — to determine the relationship between the location of foci of necrosis in the pancreas and blood vessels in 22 patients (11.4 %; group 1); the method was not used in 26 people (13.5 %; group 2).Results. The number of accesses created into the omental bursa was as follows: 141 patients (73.1 %) had 3 accesses, 52 people (26.9 %) had 2 accesses; into the retroperitoneal space: 102 patients (52.8 %) had 2 accesses, 51 people (26.4 %) had 1 access. Transfistula videoscopic necrosequestrectomy was performed 35 and 37 times in groups 1 and 2, respectively (p &gt; 0.05). Transfistula ultrasound scanning to assess the risk of intraoperative bleeding was used 33 times in patients in group 1. In group 1, intraoperative bleeding was observed in 5 patients (23.8 %), in group 2 — in 7 patients (26.9 %) (p &gt; 0.05). The volume of blood loss was (436.0±83.6) and (887.0±41.8) ml in groups 1 and 2, respectively (p &lt; 0.05). There were no cases of death due to intraoperative bleeding in either group.Discussion. Transfistula ultrasound scanning makes it possible to stratify patients: into a high-risk group (with intimate adjacency of necrosis to vessels), medium (at a distance of up to 15 mm) and low-risk (with a distant location). In this regard, interventions in high-risk patients were carried out in the X-ray operating room to allow for endovascular hemostasis, which made it possible to reduce the volume of blood loss, as well as to create a supply of transfusion media in advance to replenish the volume of blood volume.Conclusion. The developed method of direct transfistula ultrasound scanning makes it possible to assess the risk of intraoperative bleeding in patients with infected pancreatic necrosis to achieve timely hemostasis and compensate for acute blood loss.

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial

The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. gov/study/NCT02270242.

Development and external validation of a novel model for predicting new clinically important atrial fibrillation after thoracoscopic anatomical lung cancer surgery: a multicenter retrospective cohort study.

New clinically important postoperative atrial fibrillation (POAF) is the most common arrhythmia after thoracoscopic anatomical lung cancer surgery and is associated with increased morbidity and mortality. The full spectrum of predictors remains unclear, and effective assessment tools are lacking. This study aimed to develop and externally validate a novel model for predicting new clinically important POAF. This retrospective study included 14074 consecutive patients who received thoracoscopic anatomical lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital. Based on the split date of 1 January 2018, we selected 8717 participants for the training cohort and 5357 participants for the testing cohort. For external validation, we pooled 2941 consecutive patients who received this surgical treatment from July 2016 to July 2021 in Shanghai Ruijin Hospital. Independent predictors were used to develop a model and internally validated using a bootstrap-resampling approach. The area under the receiver operating characteristic curves (AUROCs) and Brier score were performed to assess the model discrimination and calibration. The decision curve analysis (DCA) was used to evaluate clinical validity and net benefit. New clinically important POAF was defined as a new-onset of POAF that causes symptoms or requires treatment. Multivariate analysis suggested that age, hypertension, preoperative treatment, clinical tumor stage, intraoperative arrhythmia and transfusion, and operative time were independent predictors of new clinically important POAF. These seven candidate predictors were used to develop a nomogram, which showed a concordance statistic (C-statistic) value of 0.740 and good calibration (Brier score; 0.025). Internal validation revealed similarly good discrimination (C-statistic, 0.736; 95% CI: 0.705-0.768) and calibration. The decision curve analysis showed positive net benefits with the threshold risk range of 0-100%. C-statistic value and Brier score were 0.717 and 0.028 in the testing cohort, and 0.768 and 0.012 in the external validation cohort, respectively. This study identified seven predictors of new clinically important POAF, among which preoperative treatment, intraoperative arrhythmia, and operative time were rarely reported. The established and externally validated model has good performance and clinical usefulness, which may promote the application of prevention and treatment in high-risk patients, and reduce the development and related adverse outcomes of this event.

Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.

The neutrophil to apolipoprotein A1 ratio has emerged as a possible prognostic biomarker in different medical conditions. Nonetheless, the predictive potential of neutrophil to apolipoprotein A1 ratio in determining the 3-month prognosis of acute ischaemic stroke patients who undergo intravenous thrombolysis has yet to be fully acknowledged. In this study, 196 acute ischaemic stroke patients with recombinant tissue plasminogen activator and 133 healthy controls were included. Meanwhile, we incorporated a total of 386 non-thrombolytic acute ischaemic stroke patients. The acute ischaemic stroke patients with recombinant tissue plasminogen activator were divided into four groups based on quartiles of neutrophil to apolipoprotein A1 ratio. The association between neutrophil to apolipoprotein A1 ratio and the 3-month prognosis was evaluated through univariate and multivariate regression analyses. Additionally, subgroup analyses were conducted to investigate the predictive value of neutrophil to apolipoprotein A1 ratio in different patient populations. Adverse outcomes were defined as a modified Rankin Scale score of 3-6. The study findings revealed a significant association between elevated neutrophil to apolipoprotein A1 ratio levels and poor prognosis in acute ischaemic stroke patients. In the highest quartile of neutrophil to apolipoprotein A1 ratio levels (Q4), after controlling for age, gender, admission National Institutes of Health Stroke Scale score, blood urea nitrogen and stroke subtypes, the odds ratio for adverse outcomes at 3 months was 13.314 (95% confidence interval: 2.878-61.596, P = 0.001). An elevated neutrophil to apolipoprotein A1 ratio value was found to be associated with a poor prognosis in acute ischaemic stroke patients, regardless of whether they received recombinant tissue plasminogen activator treatment or not. The new model, which incorporating neutrophil to apolipoprotein A1 ratio into the conventional model, demonstrated a statistically significant improvement in discriminatory power and risk reclassification for 3-month poor outcomes in acute ischaemic stroke patients treated with recombinant tissue plasminogen activator. The new model exhibited a categorical net reclassification index (P = 0.035) of 12.9% and an integrated discrimination improvement (P = 0.013) of 5.2%. Subgroup analyses indicated that the predictive value of neutrophil to apolipoprotein A1 ratio differed across stroke subtypes. Neutrophil to apolipoprotein A1 ratio is a potential biomarker for predicting the prognosis of acute ischaemic stroke patients. The clinical implications of our findings are significant, as early identification and intervention in high-risk patients can improve their outcomes. However, further studies are required to validate our results and elucidate the underlying mechanisms of the association between neutrophil to apolipoprotein A1 ratio and poor prognosis in acute ischaemic stroke patients.

Disease trajectory research in critical illness: applications, examples, and prospects

Trajectories refer to the motion paths followed by objects in space. Disease trajectories, which depict the evolution of disease processes over time, are significantly important for assessing diseases, formulating treatment strategies, and predicting prognosis. Critical illness is one of the leading causes of death. With advances in critical care medicine, there is increasing focus on the occurrence and development of critical illnesses. Understanding the development trajectory of critical illness is helpful to promote the early identification, intervention, and treatment of high-risk patients, avoid prolongation of the course of disease, reduce the risk of multiple organ failure, and provide important reference for the development of targeted prevention and intervention strategies, thereby reducing the incidence and mortality of critical illness. In recent years, various trajectory modeling methods have been applied to the study of critical illness. These include, but are not limited to, latent growth curve modeling (LGCM), growth mixture modeling (GMM), group-based trajectory modeling (GBTM), latent transition analysis (LTA), and latent class analysis (LCA). The aim of this article is to review the definition of disease trajectories, the methods used in trajectory modeling, and their applications and future prospects in critical illness research.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study

Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. This was a single-center retrospective cohort study. This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

Integrating bulk and single-cell RNA sequencing data reveals epithelial-mesenchymal transition molecular subtype and signature to predict prognosis, immunotherapy efficacy, and drug candidates in low-grade gliomas.

Objective: Epithelial-mesenchymal transition (EMT) is a tightly regulated and dynamic process occurring in both embryonic development and tumor progression. Our study aimed to comprehensively explore the molecular subtypes, immune landscape, and prognostic signature based on EMT-related genes in low-grade gliomas (LGG) in order to facilitate treatment decision-making and drug discovery. Methods: We curated EMT-related genes and performed molecular subtyping with consensus clustering algorithm to determine EMT expression patterns in LGG. The infiltration level of diverse immune cell subsets was evaluated by implementing the single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms. The distinctions in clinical characteristics, mutation landscape, and immune tumor microenvironment (TME) among the subtypes were subjected to further investigation. Gene Set Variation Analysis (GSVA) was performed to explore the biological pathways that were involved in subtypes. The chemo drug sensitivity and immunotherapy of subtypes were estimated through GDSC database and NTP algorithm. To detect EMT subtype-related prognostic gene modules, the analysis of weighted gene co-expression network (WGCNA) was performed. The LASSO algorithm was utilized to construct a prognostic risk model, and its efficacy was verified through an independent CGGA dataset. Finally, the expression of the hub genes from the prognostic model was evaluated through the single-cell dataset and in-vitro experiment. Results: The TCGA-LGG dataset revealed the creation of two molecular subtypes that presented different prognoses, clinical implications, TME, mutation landscapes, chemotherapy, and immunotherapy. A three-gene signature (SLC39A1, CTSA and CLIC1) based on EMT expression pattern were established through WGCNA analysis. Low-risk patients showed a positive outlook, increased immune cell presence, and higher expression of immune checkpoint proteins. In addition, several promising drugs, including birinapant, fluvastatin, clofarabine, dasatinib, tanespimycin, TAK-733, GDC-0152, AZD8330, trametinib and ingenol-mebutate had great potential to the treatment of high risk patients. Finally, CTSA and CLIC1 were highly expressed in monocyte cell through single-cell RNA sequencing analysis. Conclusion: Our research revealed non-negligible role of EMT in the TME diversity and complexity of LGG. A prognostic signature may contribute to the personalized treatment and prognostic determination.

Risk factors associated to incisional hernia in stoma site after stoma closure: A systematic review and meta-analysis.

This study aims to identify which risk factors are associated with the appearance of an incisional hernia in a stoma site after its closure. This in the sake of identifying which patients would benefit from a preventative intervention and thus start implementing a cost-effective protocol for prophylactic mesh placement in high-risk patients. A systematic review of PubMed, Cochrane library, and ScienceDirect was performed according to PRISMA guidelines. Studies reporting incidence, risk factors, and follow-up time for appearance of incisional hernia after stoma site closure were included. A fixed-effects and random effects models were used to calculate odds ratios' estimates and standardized mean values with their respective grouped 95% confidence interval. This to evaluate the association between possible risk factors and the appearance of incisional hernia after stoma site closure. Seventeen studies totaling 2899 patients were included. Incidence proportion between included studies was of 16.76% (CI95% 12.82; 21.62). Out of the evaluated factors higher BMI (p = 0.0001), presence of parastomal hernia (p = 0.0023), colostomy (p = 0,001), and end stoma (p = 0.0405) were associated with the appearance of incisional hernia in stoma site after stoma closure, while malignant disease (p = 0.0084) and rectum anterior resection (p = 0.0011) were found to be protective factors. Prophylactic mesh placement should be considered as an effective preventative intervention in high-risk patients (obese patients, patients with parastomal hernia, colostomy, and end stoma patients) with the goal of reducing incisional hernia rates in stoma site after closure while remaining cost-effective.

Obstructive sleep apnea is associated with the long-term prognosis of patients in acute coronary syndromes with prior myocardial infarction: Insights from OSA-ACS study

ObjectiveThe prognostic significance of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS) according to prior myocardial infarction (MI) remains unclear. We aimed to investigate the association between OSA and long-term cardiovascular outcomes in ACS patients with or without prior MI. MethodsWe prospectively recruited eligible 2160 ACS patients with portable sleep monitoring in Beijing Anzhen Hospital between June 2015 and January 2020. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/hour. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. ResultsAmong 1927 patients enrolled, 1014 (52.6%) had OSA and 316 (16.4%) had prior MI. During 2.9 (1.5, 3.6) years of follow-up, multivariate analysis showed that OSA was associated with 1.7 times the risk of MACCE in patients with prior MI (50 events [28.2%] vs 24 events [17.3%]; adjusted HR = 1.74, 95%CI 1.04–2.90, P = 0.034), but not in patients without prior MI group (177 events [21.1%] vs 138 events [17.8%]; adjusted HR = 1.19, 95%CI 0.94–1.51, P = 0.15). There was no significant interaction between prior MI and OSA for MACCE (interaction P = 0.14). ConclusionsOSA was independently associated with an increased risk of MACCE among ACS patients, particularly among ACS patients with prior MI. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS characterized by prior MI are warranted.

Remote Expert DVT Triaging of Novice-User Compression Sonography with AI-Guidance

Compression ultrasonography of the leg is established for triaging proximal lower extremity deep vein thrombosis (DVT). AutoDVT, a machine-learning software, provides a tool for nonspecialists in acquiring compression sequences to be reviewed by an expert for patient triage. The purpose of this study was to test image acquisition and remote triaging in a clinical setting. Patients with a suspected DVT were recruited at 2 centers in Germany and Greece. Enrolled patients underwent an artificial intelligence-guided two-point compression examination by a nonspecialist using a handheld ultrasound device prior to a standard scan. Images collected by the software were uploaded for blind review by 5 qualified physicians. All reviewers rated the quality of all sequences on the American College of Emergency Physicians (ACEP) image quality scale (score 1-5, ≥ 3 defined as adequate imaging quality) and for an ACEP score ≥3, chose "Compressible", "Incompressible", or "Other". Sensitivity and specificity were calculated for adequate quality scans with an assessment as "Compressible" or "Incompressible". We define this group as diagnostic quality. To simulate a triaging clinical algorithm, a post hoc analysis was performed merging the "incomplete", the "low quality", and the "Incompressible" into a high-risk group for proximal DVT. Seventy-three patients (average age 64.2years, 44% females) were eligible for inclusion and scanned by 3 nonultrasound-qualified healthcare professionals. Three patients were excluded from further analysis due to incomplete scans. Sixty two of 70 (88.57%) of the completed scans were judged to be of adequate image quality with an average ACEP score of 3.35. Forty seven of 62 adequate AutoDVT scans were assessed as diagnostic quality, of which 8 were interpreted as positive for proximal DVT by the reviewers resulting in a sensitivity of 100% and specificity of 95.12%. When simulating a triaging algorithm, 34/73 (46.58%) of patients would be triaged as high risk and 8 would be confirmed as positive for proximal DVT (6 in the diagnostic and 2 in the low-quality cohort). Of 39/73 patients triaged as low risk, all were negative for proximal DVT in standard duplex; thus, this triaging algorithm could potentially save 53.42% of standard duplex scans. Machine learning software was able to aid nonexperts in acquiring valid ultrasound images of venous compressions and allowed remote triaging. This strategy allows faster diagnosis and treatment of high-risk patients and can spare the need for multiple unnecessary duplex scans, the vast majority being negative.