Advanced Stages Of Disease Research Articles

The Recovered Independent Ambulation Rate and Prognostic Factors of Non-ambulatory Patients After Metastatic Spinal Cord Compression Surgery.

Surgery could regain the ability to walk even in non-ambulatory patients with spinal cord compression due to metastatic spine disease. However, many patients cannot reach the stage of independent ambulation because most are at an advanced disease stage. This study investigated the regained independent ambulation rate after surgery and prognostic factors for independent ambulation after metastatic spinal cord compression surgery. In a retrospective cohort study, 38 non-ambulatory patients with spinal metastases at the cervical or thoracic lesions, who underwent surgery, were included. All surgeries were performed using laminectomy and posterior fixation. Recovery rates of independent ambulation and its prognostic factors were examined. Independent ambulation was defined as the use of a walking aid without wheelchair requirement. Factors, including age, tumor type, visceral organ metastasis, past systematic cancer therapy, neurological grade, the time from leg-symptom onset to non-ambulatory stage, and the time from non-ambulatory stage to surgery, were investigated. The regained independent ambulation rate was 18% (7/38). Compared to non-ambulatory patients, those who regained independent ambulation were more likely to have less past systematic therapy (14% [1/7] vs. 74% [23/31], P=0.003) and slow paralysis progression (over seven days from leg-symptom onset to non-ambulatory stage) (86% [6/7] vs. 23% [7/31], P=0.002). Recovery to independent ambulation in non-ambulatory patients with metastatic spinal cord compression was poor, even if surgery was performed. Absence of past systematic therapy and slow paralysis progression were favorable factors for regaining independent ambulation.

Defining and Understanding Diagnostic Delays Among Pancreatic Cancer Patients: A Retrospective Cohort Study

Pancreatic cancer is a lethal cancer of increasing incidence, presenting with several clinically detectable signals allowing for earlier diagnosis. However, there are limited data related to diagnostic process, including prevalence of diagnostic delays and their contributing factors. We aimed to develop a standardized definition of diagnostic delay, evaluate its prevalence, and identify its contributing factors among pancreatic cancer patients. We convened an expert panel who defined diagnostic delay among pancreatic cancer patients. We then conducted a retrospective cohort study among pancreatic adenocarcinoma patients consecutively diagnosed from 2007 to 2019 at a tertiary care Veterans Affairs medical center. We manually reviewed diagnostic delay instances for contributing factors. Secondary analyses, using multivariate logistic regression and Cox proportional hazards models, explored associations between diagnostic delays and cancer outcomes. Diagnostic delay was defined as cancer diagnosis made ≥60 days after first clinical presence of predefined red flag(s). Among 197 pancreatic adenocarcinoma patients, 38.6% experienced a diagnostic delay. Among delay cases, the most common primary contributing factor was related to the patient-provider encounter (44.7% with lack of recognition of objective weight loss). Patients with delays were more likely to be diagnosed at advanced stage disease (adjusted odds ratio, 1.62; 95% confidence interval, 0.79-3.30) and less likely to receive potentially curative treatment (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.84), although these trends did not reach statistical significance. Over one-third of pancreatic cancer patients experienced a diagnostic delay, mostly due to inadequate recognition of red flag findings. Results can inform targeted interventions to reduce preventable diagnostic delays among pancreatic cancer patients.

Stage-Affected Quality of Life in Endometrial Cancer Patients

OBJECTIVE This study aims to compare the aspects of quality of life between early and advanced-stage endometrial cancer patients. METHODS From January to February 2021, women diagnosed with endometrial cancer and treated at Maharaj Nakorn Chiang Mai Hospital were invited to participate. Two qualities of life questionnaires, the European Organization for Research and Treatment of Cancer Quality of Life QLQ-C30 questionnaire (EORTC QLQ-C30) and the CMU Endometrial Cancer Quality of Life (gastrointestinal, urinary, lymphatic, sexual, and hormonal domains) were used. The chi-squared test, the Mann-Whitney U test, and multivariable linear regression were used for statistical analysis. RESULTS A total of 103 participants were divided into two groups: 65 individuals with early-stage disease and 38 with advanced-stage disease. All participants completed the quality-of-life questionnaires. The two groups were comparable in terms of global health status/QoL for EORTC QLQ-C30. However, the early-stage group had significantly higher functional scales and quality-of-life summary scores than the advanced-stage group. As for the CMU endometrial cancer QoL, the advanced-stage group had more negative issues related to the gynecologic and hormonal system compared to the early-stage group. CONCLUSIONS Women with endometrial cancer generally have a good quality of life. Survivors of advanced stages may have a quality of life similar to those in the early stage but with a higher incidence of gastrointestinal, sexual, and hormonal complications. KEYWORDS chemotherapy, endometrial cancer, oncology, quality of life

Pathophysiology and therapeutic options for cirrhotic portal hypertension.

Portal hypertension represents the primary non-neoplastic complication of liver cirrhosis and has life-threatening consequences, such as oesophageal variceal bleeding, ascites, and hepatic encephalopathy. Portal hypertension occurs due to increased resistance of the cirrhotic liver vasculature to portal blood flow and is further aggravated by the hyperdynamic circulatory syndrome. Existing knowledge indicates that the profibrogenic phenotype acquired by sinusoidal cells is the initial factor leading to increased hepatic vascular tone and fibrosis, which cause increased vascular resistance and portal hypertension. Data also suggest that the phenotype of hepatic cells could be further impaired due to the altered mechanical properties of the cirrhotic liver itself, creating a deleterious cycle that worsens portal hypertension in the advanced stages of liver disease. In this Review, we discuss recent discoveries in the pathophysiology and treatment of cirrhotic portal hypertension, a condition with few pharmacological treatment options.

Research Progress in Predicting Hepatocellular Carcinoma with Portal Vein Tumour Thrombus in the Era of Artificial Intelligence.

Hepatocellular Carcinoma (HCC) is a condition associated with significant morbidity and mortality. The presence of Portal Vein Tumour Thrombus (PVTT) typically signifies advanced disease stages and poor prognosis. Artificial intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), has emerged as a promising tool for extracting quantitative data from medical images. AI is increasingly integrated into the imaging omics workflow and has become integral to various medical disciplines. This paper provides a comprehensive review of the mechanisms underlying the formation and progression of PVTT, as well as its impact on clinical management and prognosis. Additionally, it outlines the advancements in AI for predicting the diagnosis of HCC and the development of PVTT. The limitations of existing studies are critically evaluated, and potential future research directions in the realm of imaging for the diagnostic prediction of HCC and PVTT are discussed, with the ultimate goal of enhancing survival outcomes for PVTT patients.

Visual detection of misfolded alpha-synuclein and prions via capillary-based quaking-induced conversion assay (Cap-QuIC)

Neurodegenerative protein misfolding diseases impact tens of millions of people worldwide, contributing to millions of deaths and economic hardships across multiple scales. The prevalence of neurodegenerative disease is predicted to greatly increase over the coming decades, yet effective diagnostics for such diseases are limited. Most diagnoses come from the observation of external symptoms in clinical settings, which typically manifest during relatively advanced stages of disease, thus limiting potential therapeutic applications. While progress is being made on biomarker testing, the underlying methods largely rely on fragile and expensive equipment that limits their point-of-care potential, especially in developing countries. Here we present Capillary-based Quaking Induced Conversion (Cap-QuIC) as a visual diagnostic assay based on simple capillary action for the detection of neurodegenerative disease without necessitating expensive and complex capital equipment. We demonstrate that Cap-QuIC has the potential to be a detection tool for a broad range of misfolded proteins by successfully distinguishing misfolded versus healthy proteins associated with Parkinson’s disease (α-synuclein) and Chronic Wasting Disease (prions). Additionally, we show that Cap-QuIC can accurately classify biological tissue samples from wild white-tailed deer infected with Chronic Wasting Disease. Our findings elucidate the underlying mechanism that enables the Cap-QuIC assay to distinguish misfolded protein, highlighting its potential as a diagnostic technology for neurodegenerative diseases.

Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization.

Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling (P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.

Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1-G93A mice.

Persistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)-G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild-type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age-matched littermates. Specifically, the Na+ and Ca2+ PICs are larger, whereas the lasting SK-mediated (SKL) POC is smaller than WT (Na+ PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age-based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS. KEY POINTS: Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature. Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na+ and Ca2+ PICs but reduced SKL POC vs. wild-type littermates. Na+ PIC is the largest and SKL POC is the smallest current in SOD cells. The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS. Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.

MT1G induces lipid droplet accumulation through modulation of H3K14 trimethylation accelerating clear cell renal cell carcinoma progression

BackgroundLipid droplet formation is a prominent histological feature in clear cell renal cell carcinoma (ccRCC), but the significance and mechanisms underlying lipid droplet accumulation remain unclear.MethodsExpression and clinical significance of MT1G in ccRCC were analyzed by using TCGA data, GEO data and scRNASeq data. MT1G overexpression or knockdown ccRCC cell lines were constructed and in situ ccRCC model, lung metastasis assay, metabolomics and lipid droplets staining were performed to explore the role of MT1G on lipid droplet accumulation in ccRCC.ResultsInitially, we observed low MT1G expression in ccRCC tissues, whereas high MT1G expression correlated with advanced disease stage and poorer prognosis. Elevated MT1G expression promoted ccRCC growth and metastasis both in vitro and in vivo. Mechanistically, MT1G significantly suppressed acylcarnitine levels and downstream tricarboxylic acid (TCA) cycle activity, resulting in increased fatty acid and lipid accumulation without affecting cholesterol metabolism. Notably, MT1G inhibited H3K14 trimethylation (H3K14me3) modification. Under these conditions, MT1G-mediated H3K14me3 was recruited to the CPT1B promoter through direct interaction with specific promoter regions, leading to reduced CPT1B transcription and translation.ConclusionsOur study unveils a novel mechanism of lipid droplet accumulation in ccRCC, where MT1G inhibits CPT1B expression through modulation of H3K14 trimethylation, consequently enhancing lipid droplet accumulation and promoting ccRCC progression.Graphical abstract figure Schematic diagram illustrating MT1G/H3K14me3/CPT1B-mediated lipid droplet accumulation promoted ccRCC progression via FAO inhibition.

Health utility of patients with established rheumatoid arthritis and its influencing factors: a multi-center study in China

To assess the health utility value (HUV) of Rheumatoid Arthritis (RA) patients and its influencing factors in China. A cross-sectional survey was conducted in 8 tertiary hospitals across four capital-cities. The demographic characteristics, patient-reported outcomes including the HUV got by EQ-5D-5L, clinical characteristics, and clinician-reported outcomes of 171 RA patients were collected both from themselves and their physicians. Both the univariate and multivariate analyses were used to assess the potential factors of EQ-5D-5L HUV of the patients. The mean age of the patients was 50.7 years, with female being 64.9% (n = 111). The mean HUV and EQ visual analogue scale score of all patients were 0.586 and 47.3, respectively. The univariate analysis showed that the patients who were female, older, living in rural areas, with lower education level, advanced disease stage, higher the patient's assessment of arthritis pain visual analogue scale (PtAAP-VAS), the patient's global assessment of disease activity visual analogue scale (PtGADA-VAS), and the Physician’s global assessment of disease activity visual analogue scale (PhGADA-VAS) scores had significantly lower EQ-5D-5L HUVs. The multivariate analysis further suggested that older age, female, higher body mass index and higher PtGADA-VAS score were statistically significantly related to lower HUVs. The study provided the HUVs for RA patients with different characteristics and outcomes, which could be used in the economic evaluation of interventions for the RA patients. The identified factors could also assist the health care managing and improving the health-related quality of life on RA patients.

Evolution of the treatment of esophageal cancer: artificial intelligence and the role of sentinel lymph node assessment in esophageal cancer

Sentinel lymph node (SLN) biopsy has revolutionized the staging and prognosis of breast cancer and melanoma. Because of the complicated lymphatic network around the esophagus, the utility of SLN biopsy for esophageal cancer is less clear. The accuracy of SLN mapping in esophageal cancer depends on tumor site, disease stage, use of neoadjuvant therapy, and patient characteristics. SLN biopsy may improve staging and result in less morbidity in patients with early esophageal cancer, compared with radical lymphadenectomy and esophagectomy. A recent study that investigated hybrid tracers in sentinel node navigation surgery (SNNS) demonstrated promising results for the detection of peritumoral SLNs. However, evidence that firmly establishes the concept of the SLN for esophageal cancer is still lacking. Big data analytics and artificial intelligence have been associated with improvements in the detection and prognosis of esophageal cancer. This review considers the roles of the evolving technologies of SLN biopsy and artificial intelligence, which together have the potential to further improve prognoses and outcomes for patients with esophageal cancer. Additional investigation is necessary to establish standardized protocols and to determine the long-term effectiveness of these approaches in settings involving neoadjuvant therapy and advanced-stage disease.

Targeted immunotherapy and nanomedicine for rhabdomyosarcoma: The way of the future.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Histology separates two main subtypes: embryonal RMS (eRMS; 60%-70%) and alveolar RMS (aRMS; 20%-30%). The aggressive aRMS carry one of two characteristic chromosomal translocations that result in the expression of a PAX3::FOXO1 or PAX7::FOXO1 fusion transcription factor; therefore, aRMS are now classified as fusion-positive (FP) RMS. Embryonal RMS have a better prognosis and are clinically indistinguishable from fusion-negative (FN) RMS. Next to histology and molecular characteristics, RMS risk groupings are now available defining low risk tumors with excellent outcomes and advanced stage disease with poor prognosis, with an overall survival of about only 20% despite intensified multimodal treatment. Therefore, development of novel effective targeted strategies to increase survival and to decrease long-term side effects is urgently needed. Recently, immunotherapies and nanomedicine have been emerging for potent and effective tumor treatments with minimal side effects, raising hopes for effective and safe cures for RMS patients. This review aims to describe the most relevant preclinical and clinical studies in immunotherapy and targeted nanomedicine performed so far in RMS and to provide an insight in future developments.

Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.

Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis. Independent analysis of published genomic and transcriptomic sequencing identified that receptor tyrosine kinase (RTK) ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM. To target these unique genetic changes, a zebrafish acral melanoma model was exposed to a panel of narrow and broad spectrum multi-RTK inhibitors, revealing that dual FGFR/VEGFR inhibitors decrease acral-analogous melanocyte proliferation and migration. The potent pan-FGFR/VEGFR inhibitor, Lenvatinib, uniformly induces tumor regression in AM patient-derived xenograft (PDX) tumors but only slows tumor growth in CM models. Unlike other multi-RTK inhibitors, Lenvatinib is not directly cytotoxic to dissociated AM PDX tumor cells and instead disrupts tumor architecture and vascular networks. Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.

Renin-angiotensin system inhibitor prescriptions in Chinese hospitalized chronic kidney disease patients

BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients. AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China. METHODS It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription. RESULTS A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age &lt; 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions. CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.

Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences.

The study aims to evaluate the clinical benefit of CGP in our Comprehensive Cancer Center Methods and patients: CGP was introduced into our routine clinical practice in 2021. An NGS-based large (> 500 genes) gene panel was used for cases where molecular genetic testing was approved by the National Molecular Tumor Board. From 2021 until August 2023 163 cases were tested. The majority of them were ECOG 0-1 patients with advanced-stage diseases, histologically rare cancer, or cancers with unknown primary tumours. Seventy-four cases (74 of 163, 45%) had clinically relevant genetic alterations. In 34 patients, the identified variants represented an indication for an approved therapy (approved by the Hungarian authorities, on-label indication), while in 40 cases the recommended therapy did not have an approved indication in Hungary for certain tumour types, but off-label indication could be recommended. Based on our CGP results, 24 patients (24/163; 14.7%) received targeted therapy. Treatment duration was between 1 and 60 months. In total 14 (14/163; 8.5% of the tested cases) patients had a positive clinical response (objective response or stable disease) and were treated for more than 16 weeks. NGS-based CGP was successfully introduced in our institution and a significant number of patients benefited from comprehensive genetic tests. Our preliminary results can serve as the starting point of Drug Rediscovery Protocol (DRUP) studies.

Intensive Longitudinal Methods Among Adults With Breast or Lung Cancer: Scoping Review.

Intensive longitudinal methods offer a powerful tool for capturing daily experiences of individuals. However, its feasibility, effectiveness, and optimal methodological approaches for studying or monitoring experiences of oncology patients remain uncertain. This scoping review aims to describe to what extent intensive longitudinal methods with daily electronic assessments have been used among patients with breast or lung cancer and with which methodologies, associated outcomes, and influencing factors. We searched the electronic databases (PubMed, Embase, and PsycINFO) up to January 2024 and included studies reporting on the use of these methods among adults with breast or lung cancer. Data were extracted on population characteristics, intensive monitoring methodologies used, study findings, and factors influencing the implementation of these methods in research and clinical practice. We identified 1311 articles and included 52 articles reporting on 41 studies. Study aims and intensive monitoring methodologies varied widely, but most studies focused on measuring physical and psychological symptom constructs, such as pain, anxiety, or depression. Compliance and attrition rates seemed acceptable for most studies, although complete methodological reporting was often lacking. Few studies specifically examined these methods among patients with advanced cancer. Factors influencing implementation were linked to both patient (eg, confidence with intensive monitoring system) and methodology (eg, option to use personal devices). Intensive longitudinal methods with daily electronic assessments hold promise to provide unique insights into the daily lives of patients with cancer. Intensive longitudinal methods may be feasible among people with breast or lung cancer. Our findings encourage further research to determine optimal conditions for intensive monitoring, specifically in more advanced disease stages.

Opinion survey on organ donation

Background: In the field of contemporary medicine, receiving a transplanted organ can be the last hope for many patients suffering from advanced-stage diseases. Despite its benefits, there still persist numerous obstacles that complicate the organ donation process. Presented here are the main findings of a survey that explores the opinions of healthcare personnel and ordinary citizens regarding organ donation. Material and methods: A prospective, open-label, observational, descriptive study was conducted using a non-validated survey adapted from Grupo Ángeles Servicios de Salud. A total of 65 surveys were administered at the Graphic Clinic of Buenos Aires City, and 65 surveys were given to citizens of Buenos Aires City. Results: The gathered information was categorized into four content-based categories: I. Knowledge of the issue; II. Attitudes towards the donation process; III. Personal actions taken; IV. Expectations regarding the organ transplant process. The results are presented in table format, and no statistically significant differences were observed among them. Conclusion: It is not feasible to reach a categorical conclusion regarding whether health personnel show a greater willingness to donate organs compared to citizens in general. This is due, in part, to the equivalence of the results and the size of the sample, obtaining a result that may not be representative of the entire population. It is possible that increasing the number of people who register as organ donors will increase the number of transplants

Dose and Time Effects of Renin-Angiotensin Inhibitors on Patients With Advanced Stages 4 to 5 of Diabetic Kidney Disease.

Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.

Chart review study of real-world clinical outcomes in patients with cutaneous T-cell lymphoma treated with extracorporeal photopheresis in the US in 2017–2019

Background Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients. Methods A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months. Results The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months (N = 22), 75.0% at 9 months (N = 24), and 60.0% at 12 months (N = 15) after ECP initiation. Conclusions Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.

The Protective Role of miR-125b in Hepatocellular Carcinoma: Unraveling Tumor-Suppressive Mechanisms

Abstract: MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene, depending on the context. As a tumor suppressor, miR-125b inhibits HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, a complex network of regulatory mechanisms influences the dysregulation of miR-125b expression in HCC. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.