High-risk Patients Research Articles

The Relationship between D’Amico and ISUP Risk Classifications and 68Ga-PSMA PET/CT SUVmax Values in Newly Diagnosed Prostate Cancers

Introduction: This study aimed to evaluate the relationship between pathological and clinical risk classifications in newly diagnosed prostate cancer patients, and 68Ga-PSMA PET/CT data and serum Prostate Specific Antigen (PSA) values. Method: A total of 203 patients who were diagnosed with prostate cancer between 2019 and 2023, who had not yet received treatment and who underwent 68Ga-PSMA PET/CT for staging purposes were included in this study. Results: There was a substantial correlation between D’Amico risk classification, Gleason score, ISUP classification, and the presence or absence of metastasis (p < 0.0001). The median SUVmax value of the prostate gland and the D’Amico risk classification were statistically significantly correlated. (p < 0.0001). There was a statistically significant correlation between the ISUP classification and the PSA value and prostate gland SUVmax value (p < 0.0001). There was a significant correlation between the median SUVmax values of the prostate gland at the time of diagnosis and the patients with and without metastases (p < 0.0001). According to the data obtained from ROC analysis, patients with prostate gland SUVmax values of 8.75 and above were found to have a high probability of metastasis with a sensitivity of 78.9% and a specificity of 59.05%. Conclusion: Our study showed that 68Ga-PSMA PET/CT is a highly effective method for staging newly diagnosed high-risk prostate cancer. The probability of metastasis was found to be dramatically increased in Gleason 8 and above. According to D’Amico risk classification, metastasis was detected in at least half of high-risk patients. Since the sensitivity of metastasis was 78.9% in patients with prostate gland SUVmax value above 8.75, we think that these patients should be carefully reported in terms of metastasis.

International prevalence of transthyretin amyloid cardiomyopathy in high-risk patients with heart failure and preserved or mildly reduced ejection fraction

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF). Methods This epidemiology study assessed the international prevalence of ATTR-CM among patients aged ≥60 years with a history of HF, left ventricular ejection fraction (LVEF) >40%, an end-diastolic interventricular septum thickness (IVST) ≥12 mm, but without diagnosed amyloidosis, history of LVEF ≤40%, cardiomyopathy of known cause, severe valvular, or coronary heart disease. ATTR-CM was determined using cardiac scintigraphy alongside exclusionary testing for light chain amyloidosis. The study was terminated early due to slow recruitment, without safety concerns. Results Overall, 56/315 (18%; 95% CI: 13.7–22.5) patients with evaluable scintigraphy had ATTR-CM, with a numerically higher prevalence in: Europe (24%) vs. other regions (9% Asia; 5% North America); at specialist vs non-specialist centres (26% vs. 11%); in males vs. females (24% vs. 10%); and in older vs. younger patients (e.g. >40% among those ≥85 years). Other risk markers (p<.05) included a history of carpal tunnel syndrome, higher N-terminal pro B-type natriuretic peptide concentration, and higher end-diastolic IVST. Conclusions ATTR-CM was diagnosed in 18% (95% CI: 13.7–22.5) of evaluable patients with HF, LVEF >40%, and risk markers for ATTR-CM, but no previous diagnosis of amyloidosis. Recruitment bias may have contributed to regional variability. NCT04424914

AxonFinder: Automated segmentation of tumor innervating neuronal fibers.

Neurosignaling is increasingly recognized as a critical factor in cancer progression, where neuronal innervation of primary tumors contributes to the disease's advancement. This study focuses on segmenting individual axons within the prostate tumor microenvironment, which have been challenging to detect and analyze due to their irregular morphologies. We present a novel deep learning-based approach for the automated segmentation of axons, AxonFinder, leveraging a U-Net model with a ResNet-101 encoder, based on a multiplexed imaging approach. Utilizing a dataset of whole-slide images from low-, intermediate-, and high-risk prostate cancer patients, we manually annotated axons to train our model, achieving significant accuracy in detecting axonal structures that were previously hard to segment. Our analysis includes a comprehensive assessment of axon density and morphological features across different CAPRA-S prostate cancer risk categories, providing insights into the correlation between tumor innervation and cancer progression. Our paper suggests the potential utility of neuronal markers in the prognostic assessment of prostate cancer in aiding the pathologist's assessment of tumor sections and advancing our understanding of neurosignaling in the tumor microenvironment.

Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts.

Surveillance recommendations for gastric cancer (GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter community-based cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015-2017 and followed-up until 2021. Cumulative incidence rates (CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixed-effects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic (atrophic gastritis/intestinal metaplasia) and neoplastic lesions (low-grade/high-grade dysplasia), respectively (Ptrend<0.001). Four predictors, including male, ⩾60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients (⩾3 risk factors) with non-neoplastic lesions showed higher GC risks (adjusted HR=7.73, 95%CI: 4.29-13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions (aHR=3.07, 95%CI: 1.67-5.64) and high-risk patients with mild lesions (aHR=7.29, 95%CI: 3.58-14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3-5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance

BackgroundThe plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer.MethodsWe measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing.ResultsCirculating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers.ConclusionThese findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

Clinical and microbiological characteristics and follow-up of invasive Listeria monocytogenes infection among hospitalized patients: real-world experience of 16 years from Hungary

PurposeInvasive Listeria monocytogenes infection is rare, but can lead to life-threatening complications among high-risk patients. Our aim was to assess characteristics and follow-up of adults hospitalized with invasive L. monocytogenes infection.MethodsA retrospective observational cohort study was conducted at a national referral center between 2004 and 2019. Patients with proven invasive listeriosis, defined by the European Centre for Disease Prevention and Control criteria, were included. Data collection and follow-up were performed using the hospital electronic system, up until the last documented visit. The primary outcome was in-hospital all-cause mortality, secondary outcomes included residual neurological symptoms, brain abscess occurrence, and requirement for intensive care unit (ICU) admission.ResultsAltogether, 63 cases were identified (57.1% male, median age 58.8 ± 21.7 years), and 28/63 developed a complicated disease course (44.4%). At diagnosis, 38/63 (60.3%) presented with sepsis, 54/63 (85.7%) had central nervous system involvement, while 9/63 (14.3%) presented with isolated bacteremia. Frequent clinical symptoms included fever (53/63, 84.1%), altered mental state (49/63, 77.8%), with immunocompromised conditions apparent in 56/63 (88.9%). L. monocytogenes was isolated from blood (37/54, 68.5%) and cerebrospinal fluid (48/55, 87.3%), showing in vitro full susceptibility to ampicillin and meropenem (100% each), gentamicin (86.0%) and trimethoprim/sulfamethoxazole (97.7%). In-hospital all-cause mortality was 17/63 (27.0%), and ICU admission was required in 28/63 (44.4%). At discharge, residual neurological deficits (11/46, 23.9%) and brain abscess formation (6/46, 13.0%) were common.ConclusionAmong hospitalized adult patients with comorbidities, invasive L. monocytogenes infections are associated with high mortality and neurological complications during follow-up.

Chronic pain and psychological well-being in soldiers wounded during Russo-Ukrainian war

Background: Chronic pain is highly prevalent among Ukrainian soldiers with gunshot and mine-explosive injuries. Our study examines the impact of acute stress reaction (ASR) and posttraumatic stress disorder (PTSD) on chronic pain development and its effect on soldiers' quality of life post-treatment. Methods: In this retrospective study, we analyzed data from 1,166 wounded soldiers diagnosed with PTSD following ASR. We assessed pain intensity, anxiety/depression, quality of life, and PTSD presence at hospital discharge, one and three months later. Results: We identified significant predictors of chronic pain in wounded soldiers, emphasizing the role of psychological factors and the quality of life. High levels of anxiety and depression, PTSD symptoms, and low quality of life scores were strongly associated with chronic pain, even after adjusting for injury type and initial pain intensity. The presence of an ASR, high Hospital Anxiety and Depression Scale scores (HADS), and low scores on the Chaban Quality of Life Questionnaire (CQLS) were identified as predictors of chronic pain, with a notably high risk (95.6%) for patients meeting these criteria. Our findings suggest a significant association between the risk of chronic pain and ASR, with quality of life scores at discharge, one month, and three months post-treatment, indicating a high predictive accuracy. Moreover, ineffective pain treatment correlated with ineffective PTSD treatment. Conclusion: Soldiers' diminished psychological well-being post-gunshot and mine-explosive injuries significantly increase chronic pain risk. Addressing anxiety, depression, and PTSD symptoms, alongside improving quality of life, could reduce the likelihood of chronic pain and other negative health outcomes in soldiers with combat injuries.

Construction of a prognostic risk model based on pyroptosis-related genes and comprehensive analysis of key genes and tumor immune microenvironment for colon cancer.

Pyroptosis-related genes have great potential for prognosis, an accurate prognostic model based on pyroptosis genes has not been seen in Colorectal adenocarcinoma (COAD). Furthermore, understanding the mechanisms of gene expression characteristics and the Tumor Immune Microenvironment associated with the prognosis of COAD is still largely unknown. Constructing a prognostic model based on pyroptosis-related genes, and revealing prognosis-related mechanisms associated with the gene expression characteristics and tumor microenvironment. 59 pyroptosis-related genes were collected. The gene expression data and clinical data of COAD were downloaded from The Cancer Genome Atlas. External validation datasets were downloaded from the Gene Expression Omnibus database. 10 characteristic genes with prognostic values were obtained using univariate and LASSO Cox. 10-gene Riskscore prognostic model was constructed. Both gene set enrichment analysis and network propagation methods were used to find pathways and key genes leading to different prognostic risks. The area under the ROC curves were used to evaluate the performance of the model to distinguish between high-risk and low-risk patients, the results were 0.718, 0.672, and 0.669 for 1-, 3-, and 5-year survival times. A nomogram based on Riskscore and clinical characteristics showed the probability of survival at 1, 3, and 5 years, and the calibration curves showed good agreement between the predicted and actual observations, its C-index is 0.793. The decision curves showed that the net benefit of the nomogram was significantly superior to that of the other single variables. Four key pathways leading to different prognostic risks were obtained. Six key genes with prognostic value, significant expression differences (P < .05) and significant survival differences (P < .05) between high/low risk groups were obtained from the gene set of all 4 key pathways. This study constructed a prognostic model for COAD using 10 pyroptosis-related genes with prognostic value. This study also revealed significant differences in specific pathways and the tumor immune microenvironment (TME) between the high-risk group and the low-risk group, highlighted the roles of ALDH5A1 and Wnt signaling in promoting COAD and the suppressive effects of the IL-4/IL-13 pathway and RORC on COAD. The study will be helpful for precision therapy.

Bladder drainage methods for acute urinary retention due to benign prostatic hyperplasia: patient-preference analysis

Introduction. Currently, the classical management of acute urinary retention creates a certain discomfort for the patient and leads to explore alternative method of management, such as intermittent catheterization, including focusing on the patient opinions.Objective. To assess the preference of high-risk patients for acute urinary retention relative to bladder drainage in the occurrence of acute urinary retention.Materials &amp; methods. A survey was conducted among 200 ambulatory male patients. All the participants were tested to assess their mental status and ability to perform self-intermittent catheterization before filling out the questionnaire. The questionnaire included questions about the preferred method of bladder drainage for acute urinary retention, as well as factors influencing the patient's choice of self-intermittent catheterization in case of non-recovery. After completing the questionnaire, all the patients were shown a video on self-catheterization and asked to re-take the questionnaire after watching it. This allowed evaluating the impact of the training video on patients' preferences and their confidence in performing self-catheterization.Results. Among the 200 patients, 151 (75.5 %) preferred intermittent catheterization, while 40 (25.5 %) chose an indwelling urinary catheter. Additionally, 152 (76 %) patients opted for intermittent catheterization until the planned surgery, and 48 (24 %) selected a suprapubic catheter. The main factors influencing the patient choice of intermittent catheterization were: the desire to restore bladder function faster (on the first or second day) in 96 (63.2 %) patients; unwillingness to stay in the hospital in 56 (36.8 %); the desire to return to work in 22 (14.5 %); avoiding the use of a suprapubic catheter in 51 (33.5 %). After watching the video, there was a statistically significant change in patients' assessments of their ability to perform self-intermittent catheterization (p &lt; 0.001).Conclusion. The patient's choice of the intermittent catheterization is significantly influenced by the patient self-confidence in the ability to practice self-intermittent catheterization and the demonstration of the video tutorial. Due to the high efficiency and safety of intermittent catheterization, this method should be introduced into clinical practice based on the proposed algorithm.

The preoperative scoring system combining neutrophil/lymphocyte ratio and CA19-9 predicts the long-term prognosis of intrahepatic cholangiocarcinoma patients undergoing curative liver resection

BackgroundThis study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR).MethodsIn this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence.ResultsThe results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion.ConclusionsThe predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.

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.