High-risk Patients Research Articles

Cerebral oximetry in high-risk surgical patients: where are we?

This review aims to summarize the latest evidence on the role of near-infrared spectroscopy (NIRS) in monitoring cerebral oxygenation in high-risk surgical patients, including both cardiac and noncardiac surgeries, and to present a new algorithm for its application. NIRS effectively measures brain oxygen saturation noninvasively, proving valuable in cardiac surgeries to reduce neurological complications, though its impact on nonneurological outcomes is less clear. In noncardiac surgeries, NIRS can help prevent complications like postoperative cognitive dysfunction, particularly in high-risk and major surgeries. Studies highlight the variability of cerebral oxygenation impacts based on surgical positions, with mixed results in positions like the beach chair and sitting positions. A structured algorithm for managing cerebral desaturation has been proposed to optimize outcomes by addressing multiple factors contributing to blood oxygen content and delivery. Despite its limitations, including spatial resolution and interindividual variability, NIRS is a useful tool for intraoperative cerebral monitoring. Further studies are needed to confirm its broader applicability in noncardiac surgeries, but current evidence supports its role in reducing postoperative complications especially in cardiac surgeries.

Comparative Performance of 68Ga-PSMA-11 PET/CT and Conventional Imaging in the Primary Staging of High-Risk Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT's impact on patient management. Sixty castration-sensitive high-risk (ISUP 4-5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22-17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Similarities and differences between European guidelines for the management of postmenopausal osteoporosis

SummaryWe conducted a review of 10 national guidelines from five EU countries to identify similarities or differences in recommendations for the management of patients with osteoporosis. We found general alignment of key recommendations; however, there are notable differences, largely attributed to country-specific approaches to risk assessment and reimbursement conditions.IntroductionThe classification of fracture risk is critical for informing treatment decisions for post-menopausal osteoporosis. The aim of this review was to summarise 10 national guidelines from five European countries, with a focus on identifying similarities or differences in recommendations for the management of patients with osteoporosis.MethodsWe summarised the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease-International Osteoporosis Foundation guidelines and reviewed guidelines from France, Germany, Italy, Spain and the UK.ResultsThe approach to risk assessment differed across the guidelines. In France, and Spain, risk assessment was based on DXA scans and presence of prior fractures, whereas UK, German and Italian guidelines recommended use of a validated risk tool. These differences led to distinct definitions of very high and high-risk patients. Guidelines aligned in recommending antiresorptive and anabolic agents as pharmacologic options for the management of osteoporosis, with sequential treatment recommended. There was agreement that patients at high or very high risk of fracture or with severe osteoporosis should receive anabolic agents first, followed by antiresorptive drugs. Variations were identified in recommendations for follow up of patients on anti-osteoporosis therapies. Reimbursement conditions in each country were a key difference identified.ConclusionsCriteria for risk assessment of fractures differ across European guidelines which may impact treatment and access to anabolic agents. Harmonisation across EU guidelines may help identify patients eligible for treatment and impact treatment uptake. However, country-specific reimbursement and prescribing processes may present a challenge to achieving a consistent approach across Europe.

Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD – PILOT trial

BackgroundAnthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10–15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatmentMethodsThe EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.ResultsDuring the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04–0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.ConclusionEmpagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group.

Disrupted self, therapy, and the limits of conversational AI

ABSTRACT Conversational agents (CA) are thought to be promising for psychotherapy because they give the impression of being able to engage in conversations with human users. However, given the high risk for therapy patients who are already in a vulnerable situation, there is a need to investigate the extent to which CA are able to contribute to therapy goals and to discuss CA’s limitations, especially in complex cases. In this paper, we understand psychotherapy as a way of dealing with existential situations and position CAs in the context of the therapeutic experience of patients. This experience is determined by the patient’s unique personal context and specific therapy goals. We suggest that psychotherapy is a fundamentally dialogical activity, because it crucially involves work on the self and one’s self-narrative. This brings us to our central question: is it possible for CAs to engage in a productive therapeutic dialogue, given their limitations as epistemic agents? We will discuss several of those limitations, show how these undermine the possibility of engaging in a therapeutic dialogue, and illustrate those limitations through discussions of the cases of grief and abuse.

Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death

BackgroundNeuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective.Materials and MethodsThe Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors.ResultUsing scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB.ConclusionThe results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.

WT1 Expression Is Associated with Poor Overall Survival after Azacytidine and DLI in a Cohort of Adult AML and MDS Patients.

Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine-donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.

Construction and validation of nomogram to predict surgical site infection after hysterectomy: a retrospective study

This study aimed to develop a predictive tool for surgical site infections (SSI) following hysterectomy and propose strategies for their prevention and control. We conducted a retrospective analysis at a tertiary maternity and child specialist hospital in Zhejiang Province, focusing on patients who underwent hysterectomy between January 2018 and December 2023 for gynecological malignancies or benign reproductive system diseases resistant to medical treatment. Risk factors associated with surgical site infections (SSI) following hysterectomy were identified using LASSO regression analysis on data from 2018 to 2022 as the training set. Independent risk factors were then used to develop a nomogram. The model was validated using data from 2023 as the validation set. Model performance was assessed using the area under the receiver operating characteristic curve (ROC), while calibration curves were employed to gauge model accuracy. Furthermore, clinical utility was evaluated through clinical decision curve analysis (DCA) and clinical impact curve analysis (CIC), providing insights into the practical application of the nomogram. Multivariate analysis identified six independent risk factors associated with SSI development after hysterectomy: BMI ≥ 24 kg/m2 (OR: 2.58; 95% CI 1.14–6.19; P < 0.05), hypoproteinaemia diagnosis (OR: 4.99; 95% CI 1.95–13.02; P < 0.05), postoperative antibiotic use for ≥ 3 days (OR: 49.53; 95% CI 9.73–91.01; P < 0.05), history of previous abdominal surgery (OR: 7.46; 95% CI 2.93–20.01; P < 0.05), hospital stay ≥ 10 days (OR: 9.67; 95% CI 2.06–76.46; P < 0.05), and malignant pathological type (OR: 4.62; 95% CI 1.78–12.76; P < 0.05). A nomogram model was constructed using these variables. ROC and calibration curves demonstrated good model calibration and discrimination in both training and validation sets. Analysis with DCA and CIC confirmed the clinical utility of the nomogram. Personalized nomogram mapping for SSI after hysterectomy enables early identification of high-risk patients, facilitating timely interventions to reduce SSI incidence post-surgery.

Risk factors for regional lymph node metastasis in rectal neuroendocrine tumors: a population-based study.

The identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis. Patient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model. Univariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction. The novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

Medially Based “Abdominal Rotation Advancement Flap”: A Promising Technique for Mastectomy Defect Reconstruction in “High-Risk Patients” Awaiting Adjuvant Radiotherapy

Abstract Background Extensive postmastectomy defects and soft-tissue defects often require some additional flap cover of reconstruction after excision. The reconstruction aim in this group should be a diligent and easy closure with a quality skin cover, early recovery, and brief stay in hospital so that the patients can receive early postoperative radiotherapy/chemotherapy. Medially based abdominal transposition flap is a type C fasciocutaneous flap based on medial perforating vessels. We present our experience in significant postmastectomy defects, especially in high-risk morbid patients. Materials and Methods This is a retrospective study conducted by the department of plastic surgery, from an analysis of the breast cancer database maintained by our hospital from 2019 to 2023. A total of 826 breast cancer patients underwent surgery, of which 547 were locally advanced breast cancer (LABC) patients and 138 (32.5%) LABC patients needed flap cover for mastectomy defect. Medially based abdominal transposition flap was used in 56 of 138 (40.5%) LABC patients for defect closure, and 42 of the 56 patients were stage IIIB patients. Upfront surgery was primarily done in 20 patients and 36 patients underwent surgery after neoadjuvant chemotherapy. This analysis aimed to assess the operative duration, postoperative morbidity, hospital stay, and time taken to start adjuvant treatment by analyzing the medical records of patients who underwent this procedure. Results Fifty-six patients with breast cancer underwent surgical intervention, whereby 8 patients presented with tip and edge necrosis, and 3 patients were infected. The mean duration of operation was 58.852 minutes, and the average length of hospital stay was 5.39 days. It took 24.57 days for the patients to stabilize sufficiently for adjuvant therapy. The average age of the patients in the study was 48.73 years. Conclusion Our clinical experience has demonstrated that the medial abdominal transposition fasciocutaneous (MATF) flap represents a straightforward, reliable, and cost-effective method for managing extensive postmastectomy soft-tissue defects in a subset of patients with LABC. This group typically consists of high-risk and comorbid patients. The procedure holds considerable promise for developing countries with limited infrastructure and expertise, owing to its ease of execution and short learning curve. By its simplicity and affordability, the MATF flap offers a viable and sustainable solution for treating LABC-associated soft-tissue defects.

Construction of a cuproptosis‑related lncRNA signature to predict biochemical recurrence of prostate cancer.

Biochemical recurrence (BCR) is common in prostate cancer (PCa), and patients with BCR usually have a poor prognosis. Cuproptosis is a unique type of cell death, and copper homeostasis is crucial to the occurrence and development of malignancies. The present study aimed to explore the prognostic value of cuproptosis-related long non-coding RNAs (lncRNAs; CRLs) in PCa and to develop a predictive signature for forecasting BCR in patients with PCa. Using The Cancer Genome Atlas database, transcriptomic, mutation and clinical data were collected from patients with PCa. A total of 121 CRLs were identified using Pearson's correlation coefficient. Subsequently, a 6-CRL signature consisting of AC087276.2, CNNM3-DT, AC090198.1, AC138207.5, METTL14-DT and LINC01515 was created to predict the BCR of patients with PCa through Cox and least absolute shrinkage and selection operator regression analyses. Kaplan-Meier curve analysis demonstrated that high-risk patients had a low BCR-free survival rate. In addition, there was a substantial difference between the high- and low-risk groups in the immune microenvironment, immune therapy, drug sensitivity and tumor mutational burden. A nomogram integrating the Gleason score, 6-CRL signature and clinical T-stage was established and evaluated. Finally, the expression of signature lncRNAs in PCa cells was verified through reverse transcription-quantitative PCR. In conclusion, the 6-CRL signature may be a potential tool for making predictions regarding BCR in patients with PCa, and the prognostic nomogram may be considered a practical tool for clinical decision-making.

Mutation Spectrum Comparison between Benign Breast Lesion Cohort, Unselected Cancer Cohort and High-Risk Breast Cancer Cohort.

Mutation study for high-risk breast and ovarian cancer (HBOC) has been extensively studied in patients of different ethnicities. Here we compared the germline mutation rate and mutation spectrum of patients (n = 4341) with benign breast diseases or breast cancers, with and without other risk factors. Three cohorts of Chinese patients were recruited. The first cohort, high-risk cohort (HR, n = 3935) included high-risk breast cancer patients fulfilling high-risk HBOC criteria and who are recruited at our genetics clinic. The second cohort, unselected cancer cohort (CC, n = 307) was from general recruitment of patients with breast cancer at breast surgery clinics. The third cohort, benign breast lesion cohort (NC, n = 99) comprised 99 patients with benign breast diseases such as fibroadenoma, fibroadenomatoid hyperplasia, and intraductal papilloma. Thirty HBOC related genes were sequenced on the above-mentioned patient cohorts. The germline mutation rates of HR, CC, and NC cohort were 11.9%, 6.5%, and 8.1%, respectively. In the CC cohort, 29.3% (90/307) of patients fulfilled the National Comprehensive Cancer Network (NCCN) high-risk genetic test criteria 2022 v.2. The mutation rate for this group of patients was 11.1%, similar to that of the HR cohort, while the mutation rate for those not fulfilling testing criteria was 4.6%, like that of the NC cohort. High penetrance genes (BRCA1/2, CDH1, PALB2, PTEN, and TP53) mutations were only found in the HR (10.6%) and CC (3.3%) cohorts but were not found in the NC cohort. ATM, BRIP1, RAD51C, and RAD51D mutations were identified in all cohorts. RAD51C and RAD51D mutations showed conflicting penetrance. An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients.

Development and preliminary validation of a diagnostic prediction model to optimise outpatient management of patients with urolithiasis using urinary stones and intervention quality of life (USIQoL) measure.

Patients with urinary calculi undergo resource-intensive follow-up. Application of a PROM, Urinary Stones and Intervention Quality of Life (USIQoL), can potentially optimise current practices if it matches the outcomes of traditional follow-up. Our objective was to develop, and conduct, a preliminary validation of the USIQoL based prediction model to aid triage. We performed a two phase prospective cohort study. The 1st phase included development of the USIQoL-based decision model using multicentre data. The 2nd phase involved prospective single-blind external validation for the outpatient application. The aim was to evaluate correlations between the USIQoL scores and key predictors; clinical outcomes and global health ratings (EuroQoL EQ-5D). We used statistical analysis to validate USIQoL cut-off scores to aid triage and the decision to intervene. Of 503 patients invited, 91% (n = 455, Development [305] and Validation [150]; M = 308, F = 147) participated. The relationship between USIQoL domain scores and clinical outcomes was consistently significant (estimated odds: PPH 1.24, p < 0.001, 95% CI 1.13-1.36; PSH 1.22, p < 0.001, 95% CI 1.12-1.33). The ROC values for the model were ≥ 0.75. The optimum domain cut-off scores were derived with rising scores implying increased need to intervene. The model demonstrated satisfactory sensitivity (0.81-0.89) and specificity (0.36-0.47). The study demonstrates satisfactory correlation between the USIQoL and clinical outcomes making this model a valid aid for triage and optimising outpatient management with the cut-off scores able to identify high risk patients who need active treatment.

Risk factors for inadequate bowel preparation in colonoscopy: a comprehensive systematic review and meta-analysis.

Inadequate bowel preparation (IBP) prior to colonoscopy remains a common problem. This meta-analysis aimed to assess the risk factors associated with IBP. We searched multiple databases for studies that assessed risk factors for IBP after adjustment and reported the data as adjusted odds ratios (OR) with 95% confidence intervals. Meta-analyses were conducted using a random-effects model, and pooled adjusted ORs for risk factors reported in ≥3 studies were constructed. 154 studies with 258,257 participants were included. We analyzed 48 unique risk factors. Sociodemographic predictors of IBP were Medicaid insurance, obesity, current tobacco use, age≥65, Black race, low education level, male gender, and unmarried status. Comorbidity-related predictors of IBP were any psychiatric disease, cirrhosis, ASA class≥3, poor functional status, constipation, diabetes, prior abdominopelvic surgery, and hematochezia. Medication-related predictors of IBP were tricyclic antidepressants (TCA), antidepressants, opioid, non-TCA antidepressants, and calcium channel blockers. Preparation/procedure-related predictors of IBP were brown liquid rectal effluent, any incomplete bowel preparation (BP) intake, lack of split-dose BP, increased BP-to-defecation interval, any non-adherence to dietary instructions, increased BP-to-colonoscopy interval, any BP intolerance, prior IBP, and inpatient status. While afternoon colonoscopy was a predictor of IBP, subgroup analysis of prospective studies revealed no significant association. Our meta-analysis focused on adjusted risk factors to provide precise estimates of the most important risk factors for IBP. Our findings could help develop a validated prediction model to identify high-risk patients for IBP, improve colonoscopy outcomes, reduce the need for repeat colonoscopies, and reduce associated healthcare costs.

Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study

BackgroundMicrocirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA−I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock.MethodsThe present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA−I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA−I interval was analyzed.ResultsA total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6–16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9–40), of whom 18 died during ICU stay. The GA−I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA−I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA−I at 0.30–2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355–47.503].ConclusionGA−I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA−I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA−I may be beneficial for clinicians to identify high-risk patients.

Vascular diseases: Clinical-surgical intervention in abdominal aortic aneurysms

Introduction: Abdominal aortic aneurysms (AAAs) are dangerous dilations of the aorta that, if left untreated, can lead to rupture and sudden death. The management of AAAs has evolved with the development of techniques such as endovascular repair (EVAR) and open surgical repair. This study systematically reviews the efficacy, benefits, and limitations of each approach to determine the most appropriate intervention for different patient profiles. Methods: A systematic review was performed in the PubMed, Scopus, and Cochrane Library databases, from 2006 to 2024. Studies comparing EVAR and open surgical repair regarding mortality, complications, length of hospital stay, and quality of life were included. Methodological quality was assessed, and data were analyzed through narrative synthesis and meta-analysis when applicable. Results: Twenty-five studies with 15,432 patients were included. EVAR demonstrated lower perioperative mortality (3.2% vs. 7.8%) and fewer immediate complications compared to open repair, in addition to shorter hospital stay (3.8 days vs. 7.2 days) and better short-term quality of life. However, EVAR presented a higher need for long-term reinterventions (5.9% vs. 2.4%). Open repair showed greater durability with a lower rate of late complications. Conclusion: EVAR is advantageous for high-risk patients or those with comorbidities due to its immediate benefits. However, the higher need for reinterventions limits its long-term effectiveness. Open repair remains preferred for young patients or those with suitable anatomies due to its durability. The choice between the two techniques should be personalized, considering the patient profile and aneurysm characteristics. Future studies should focus on improving the durability of endovascular devices and reducing EVAR complications.

Clinical practice guideline supported administration of monoclonal antibody therapy for high-risk patients with COVID-19: Experience of a quaternary care centre

Background: Immunocompromised patients remain at risk of progression to severe COVID-19 disease. Methods: We describe clinical COVID-19-related outcomes after administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) following institutional clinical practice guidelines (CPGs) in 205 high-risk patients between November 2021 and April 2022 at a Canadian quaternary care centre. Results: Median patient age was 59 years; 102 (50%) were female. Eighty-two (40%) were transplant recipients, 47 (23%) patients had hematologic malignancies, 25 (12%) had solid organ malignancies, and 51 (25%) had another indication. Forty-eight (23%) had received fewer than two doses of anti-SARS-CoV-2 vaccines. The majority (80%) had mild disease at presentation with 14% moderate and 6% severe. Median time from symptom onset to mAb administration was 3 days (IQR 2.0-5.5 days). Of those who received mAb as outpatients, 90 (93%) had favourable clinical outcomes (no COVID-19-related hospitalizations or death within 3 months). Of those who received mAb as inpatients, 93 (86%) had favourable outcomes (discharged without COVID-19-related re-admission or death), 4% were re-admitted, and 10% died. In logistic regression analysis, only disease severity at time of mAb administration was associated with unfavourable outcomes. Fewer than two vaccine doses was not associated with unfavourable outcomes, suggesting potential benefit among the under-vaccinated. There was a significant difference in adherence to CPGs between administration of mAb in outpatients versus inpatients (adherent for 85% versus 58%, p&lt;0.001), where non-adherence occurred in cases of severe disease. Conclusion: CPG-supported mAb administration for management of COVID-19 in high-risk patients was associated with favourable clinical outcomes and may be a useful model to guide future therapies.

Clinical features of pneumocystis pneumonia in non-human immunodeficiency virus-infected patients: A systemic review and meta-analysis

Objectives: Pneumocystis pneumonia (PCP) is an opportunistic disease that causes potentially fatal pneumonia in immunocompromised individuals. The clinical features of PCP without HIV remain incompletely understood. Methods: This study aimed to identify the clinical features of PCP without HIV in a systematic review following a meta-analysis. Results: 65 articles that included 10,133 PCP patients without HIV infection were enrolled. PCP occurred most commonly at age 59.2 years (95%CI: 57.7, 60.7) in a gender ratio of approximately 3 to 2 (males to females). Dyspnea, fever, cough, and sputum were nonspecific clinical findings in 73% (95%CI: 69, 79), 73% (95%CI: 65, 81), 56% (95%CI: 48%, 64%), and 32% (96%CI: 16, 48) of patients, respectively. Viral, bacterial, and fungal co-infection were observed in 28% (95%CI: 13, 44), 19% (95%CI: 13, 25), and 11% (95%CI: 6, 16) of patients, respectively. Laboratory data showed a trend of elevated WBC, LDH, CRP, β-D glucan, and KL-6. Ground glass opacity (GGO) was found in 87% (95%CI: 83, 91) of patients. In-hospital mortality was 41% (95%CI: 35, 46). Conclusions: PCP is a life-threatening disease in immune-compromised patients. Despite being a nonspecific clinical finding, GGO might offer a clue to diagnosing PCP in high-risk patients.

Reduced Intensity transplantation vs chemotherapy in CR1. A prospective, pseudorandomized study in 50-70 year old AML patients.

The aim of this prospective, international multicenter, pseudorandomized study comparing RICT HCT to standard-of-care chemotherapy in intermediate- or high-risk AML patients 50-70 years using the donor versus no-donor concept. Part 1 included only patients with potential family donors (RD) at the date of HLA-typing of the first potential sibling or CR-date, if later. Part 2 allowed the inclusion of patients without a possible sibling donor using the start of an unrelated donor (URD) search as inclusion date. 360 patients were registered and 309 analyzed. The median follow-up was 47 months (1-168). There was no difference in overall survival (OS) between the RD (n = 124) and the Control (n = 77) groups (p = 0.50, 3-year OS RD: 0.41(95% CI; 0.32-0.50); Controls: 0.49 (95% CI; 0.37-0.59)). The main cause of death was relapse (67% RD; 88% Controls). In Part 2, the 3-year OS was 0.60 (95% CI 0.50-0.70) for URD-HCT (n = 86) and 0.37 (95% CI 0.13-0.62) for Controls (n = 20), respectively (p = 0.10). When analyzing transplanted patients (Part 2), the OS at 3-years was higher for URD-HCT than RD-HCT (0.67 (0.55-0.76) vs. 0.42 (0.26-0.57; p = 0.005). This study doesn't support elderly HLA-identical siblings as donors for older AML patients undergoing a RICT allogeneic HCT in first CR.

Reducing financial toxicity in bladder cancer care.

Financial toxicity is a significant concern for many individuals with bladder cancer, which is, overall, the most expensive malignancy, per patient. Financial toxicity, defined as the harmful effects of treatment costs on an individual's quality of life, is associated with worse outcomes and decreased quality of life. Awareness of the objective and subjective factors that contribute to financial toxicity, and ways to mitigate their effects on patients, is essential to reduce the burden of bladder cancer care. This commentary aims to discuss the elements contributing to financial toxicity amongst bladder cancer patients, identify at-risk populations, and review current and potential strategies for mitigating financial burden. Bladder cancer is becoming more expensive as the use of novel therapies increases. Early data suggest how some of these novel treatments or changes in treatment delivery may impact costs. Potential innovative strategies for cost reduction include blue light cystoscopy, intravesical gemcitabine-docetaxel rather than BCG for high-risk nonmuscle-invasive patients, home BCG therapy, and surveillance guideline optimization. However, there is still much work to be done on the potential impacts of these treatment on financial toxicity. While there is a paucity of data on treatment changes to reduce financial toxicity, and cost data can be hard to access, clinicians can still reduce the financial burden of cancer care. Awareness, financial toxicity screening, cost communication, and/or early referral to financial navigators or other similar resources have the potential to reduce financial burden. Despite mounting evidence, these tools/techniques are largely underutilized. Many individuals with bladder cancer face significant financial toxicity, with the potential for this to worsen in the setting of rising treatment costs. Novel diagnostic and treatment modifications may reduce financial toxicity. However, awareness, screening, cost discussions, and utilization of financial navigators are tools/techniques that are currently available and should be used to reduce financial burden.