Outcome prioritization and preferences among older adults with cancer starting chemotherapy in a randomized clinical trial.

INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.

Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.

PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.

Glycan-directed SARS-CoV-2 inhibition by leek extract and lectins with insights into the mode-of-action of Concanavalin A.

Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies. Given the high genetic plasticity of SARS-CoV-2 and the rapid emergence of immune escape variants, targeting the glycan shield by carbohydrate-binding agents emerges as a promising strategy. However, the potential of carbohydrate-targeting reagents as viral inhibitors remains underexplored. Here, we tested seven plant-derived carbohydrate-binding proteins, called lectins, and one crude plant extract for their antiviral activity against SARS-CoV-2 in two types of human lung cells: A549 cells ectopically expressing the ACE2 receptor and Calu-3 cells. We identified three lectins and an Allium porrum (leek) extract inhibiting SARS-CoV-2 infection in both cell systems with selectivity indices (SI) ranging between >2 and >299. Amongst these, the lectin Concanavalin A (Con A) exerted the most potent and broad activity against a panel of SARS-CoV-2 variants. We used multiplex super-resolution microscopy to address lectin interactions with SARS-CoV-2 and its host cells. Notably, we discovered that Con A not only binds to SARS-CoV-2 virions and their host cells, but also causes SARS-CoV-2 aggregation. Thus, Con A exerts a dual mode-of-action comprising both, antiviral and virucidal, mechanisms. These results establish Con A and other plant lectins as candidates for COVID-19 prevention and basis for further drug development.

Effect of chemotherapy on hippocampal volume and shape in older long-term breast cancer survivors.

Purpose: The objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5-15 years prior. Methods: This study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C-), and healthy controls (HC). The participants were recruited 5-15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests. Results: At TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = -0.585, p = 0.007). Conclusion: The observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

Magnolia officinalis Rehder & E. Wilson ameliorates white adipogenesis by upregulating AMPK and SIRT1 in vitro and in vivo.

Although there is an established link between Magnolia Cortex (MO) and lipid metabolism in previous research, its exploration within the context of obesity has been limited. Therefore, the present study investigated the therapeutic effects of MO on obesity and its mechanism of action in vitro and in vivo. Our chromatography analysis revealed that Honokiol and Magnolol are contained in MO extract. In vitro experiments showed that lipid droplets, adipogenic, and lipogenic genes were notably diminished by increasing sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK) protein expression in MO-treated 3T3-L1 adipocytes. In vivo experiments exhibited that MO administration significantly recovered the adipogenesis, lipogenesis, and fatty acid oxidation genes by increasing the SIRT1 and AMPK expression in white adipose tissue. Furthermore, hepatic steatosis by HFD feeding was ameliorated in MO-administered obese mice. We conclude that MO could be important manager for treating obesity through AMPK and SIRT1 regulation.

Evolution of SARS-CoV-2 in the Rhine-Neckar/Heidelberg Region 01/2021 - 07/2023.

In January 2021, the monitoring of circulating variants of SARS-CoV-2 was initiated in Germany under the Corona Surveillance Act, which was discontinued after July 2023. This initiative aimed to enhance pandemic containment, as specific amino acid changes, particularly in the spike protein, were associated with increased transmission and reduced vaccine efficacy. Our group conducted whole genome sequencing using the ARTIC protocol (currently V4) on Illumina's NextSeq 500 platform (and, starting in May 2023, on the MiSeq DX platform) for SARS-CoV-2 positive specimen from patients at Heidelberg University Hospital, associated hospitals, and the public health office in the Rhine-Neckar/Heidelberg region. In total, we sequenced 26,795 SARS-CoV-2-positive samples between January 2021 and July 2023. Valid sequences, meeting the requirements for upload to the German electronic sequencing data hub (DESH) operated by the Robert Koch Institute (RKI), were determined for 24,852 samples, and the lineage/clade could be identified for 25,912 samples. The year 2021 witnessed significant dynamics in the circulating variants in the Rhine-Neckar/Heidelberg region, including A.27.RN, followed by the emergence of B.1.1.7 (Alpha), subsequently displaced by B.1.617.2 (Delta), and the initial occurrences of B.1.1.529 (Omicron). By January 2022, B.1.1.529 had superseded B.1.617.2, dominating with over 90%. The years 2022 and 2023 were then characterized by the dominance of B.1.1.529 and its sublineages, particularly BA.5 and BA.2, and more recently, the emergence of recombinant variants like XBB.1.5. Since the global dominance of B.1.617.2, the identified variant distribution in our local study, apart from a time delay in the spread of new variants, can be considered largely representative of the global distribution. om a time delay in the spread of new variants, can be considered largely representative of the global distribution.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

Cell-Penetrating Peptide-Bismuth Bicycles.

Cell-penetrating peptides (CPPs) play a significant role in the delivery of cargos into human cells. We report the first CPPs based on peptide-bismuth bicycles, which can be readily obtained from commercially available peptide precursors, making them accessible for a wide range of applications. These CPPs enter human cells as demonstrated by live-cell confocal microscopy using fluorescently labelled peptides. We report efficient sequences that demonstrate increased cellular uptake compared to conventional CPPs like the TAT peptide (derived from the transactivating transcriptional activator of human immunodeficiency virus 1) or octaarginine (R8 ), despite requiring only three positive charges. Bicyclization triggered by the presence of bismuth(III) increases cellular uptake by more than one order of magnitude. Through the analysis of cell lysates using inductive coupled plasma mass spectrometry (ICP-MS), we have introduced an alternative approach to examine the cellular uptake of CPPs. This has allowed us to confirm the presence of bismuth in cells after exposure to our CPPs. Mechanistic studies indicated an energy-dependent endocytic cellular uptake sensitive to inhibition by rottlerin, most likely involving macropinocytosis.

Live-virus serum neutralization after bivalent SARS-CoV-2 mRNA vaccination in hemodialysis patients.

The development of bivalent booster vaccines addresses the ongoing evolution of the emerging B.1.1.529 (omicron) variant subtypes that are known to escape vaccine-induced neutralizing antibody response. Little is known about the immunogenicity and reactogenicity of bivalent mRNA vaccines in hemodialysis patients with impaired vaccine response. In this prospective, observational cohort study, we analyzed SARS-CoV-2 anti-S1 IgG, surrogate neutralizing antibodies (SNA), and live-virus neutralization against the SARS-CoV-2 wildtype and the BA.5 variant in 42 hemodialysis patients with and without prior SARS-CoV-2 infection before and after an additional fifth bivalent vaccine dose. Anti-S1 IgG and SNA were significantly higher in hemodialysis patients with prior infection than in patients without infection (p < 0.001 and p < 0.01, respectively). In patients without prior infection, both antibody levels increased, and live-virus neutralizing antibodies against the wildtype and the BA.5 variant were correspondingly significantly higher after bivalent booster vaccination (p < 0.001 for both). Conversely, in patients with prior infection, anti-S1 IgG and SNA did not alter significantly, and bivalent booster vaccination did not induce additional humoral immune response against the SARS-CoV-2 wildtype and the BA.5 variant. Thus, bivalent mRNA vaccines might increase humoral responses in hemodialysis patients without prior infection. Larger clinical trials are needed to help guide vaccination strategies in these immunocompromised individuals.

Brain white matter microstructural changes in chemotherapy-treated older long-term breast cancer survivors.

PURPOSE: To assess white matter microstructural changes in older long-term breast cancer survivors 5-15 years post-chemotherapy treatment. METHODS: Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C-) and age- and sex-matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract-based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. RESULTS: There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family-wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. CONCLUSIONS: Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.

In Silico Analysis of Pyeongwi-San Involved in Inflammatory Bowel Disease Treatment Using Network Pharmacology, Molecular Docking, and Molecular Dynamics.

BACKGOUND: Pyeongwi-san (PWS) is a widely used formula for treating digestive disorders in Korea and China. Inflammatory bowel disease (IBD) is characterized by progressive inflammation of the gastrointestinal tract. Emerging evidence supports the protective effect of PWS against IBD, but specific mechanisms are still elusive. METHODS: Active compounds of PWS were screened from the medicinal materials and chemical compounds in Northeast Asian traditional medicine (TM-MC) in the consideration of drug-likeness and oral bioavailability. Target candidates of active compounds were predicted using the ChEMBL database. IBD-related targets were obtained from the GeneCards and DisGeNET databases. The network of composition-targets-disease was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Molecular docking was used to simulate the binding affinity of active compounds on target proteins and molecular dynamics was used to validate the molecular docking result. RESULTS: A total of 26 core target proteins of PWS were related to IBD. Enrichment analysis suggested that PWS is highly associated with tumor necrosis factor signaling pathway, apoptosis, and the collapse of tight junctions. Moreover, molecular docking and molecular dynamics simulation proposed ß-eudesmol and (3R,6R,7S)-1,10-bisaboladien-3-ol to ameliorate IBD through the binding to TNF and MMP9, respectively. CONCLUSION: Present in silico analysis revealed potential pathways and insight of PWS to regulate IBD. These results imply that the therapeutic effect of PWS might be achieved via an inhibitory effect.

BA.1/BA.5 Immunogenicity, Reactogenicity, and Disease Activity after COVID-19 Vaccination in Patients with ANCA-Associated Vasculitis: A Prospective Observational Cohort Study.

Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective studies that have focused exclusively on AAV patients are lacking. In addition, there are safety concerns regarding the use of highly immunogenic mRNA vaccines in autoimmune diseases, and further studies investigating reactogenicity are urgently needed. In this prospective observational cohort study, we performed a detailed characterization of neutralizing antibody responses against omicron subtypes and provided a longitudinal assessment of vaccine reactogenicity and AAV disease activity. Different vaccine doses were generally well tolerated and no AAV relapses occurred during follow-up. AAV patients had significantly lower anti-S1 IgG and surrogate-neutralizing antibodies after first, second, and third vaccine doses as compared to healthy controls, respectively. Live-virus neutralization assays against omicron subtypes BA.1 and BA.5 revealed that previous SARS-CoV-2 vaccines result in an inadequate neutralizing immune response in immunocompromised AAV patients. These data demonstrate that new vaccination strategies including adapted mRNA vaccines against epitopes of emerging variants are needed to help protect highly vulnerable individuals such as AAV patients.

Enhanced SARS-CoV-2 entry via UPR-dependent AMPK-related kinase NUAK2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remodels the endoplasmic reticulum (ER) to form replication organelles, leading to ER stress and unfolded protein response (UPR). However, the role of specific UPR pathways in infection remains unclear. Here, we found that SARS-CoV-2 infection causes marginal activation of signaling sensor IRE1α leading to its phosphorylation, clustering in the form of dense ER-membrane rearrangements with embedded membrane openings, and XBP1 splicing. By investigating the factors regulated by IRE1α-XBP1 during SARS-CoV-2 infection, we identified stress-activated kinase NUAK2 as a novel host-dependency factor for SARS-CoV-2, HCoV-229E, and MERS-CoV entry. Reducing NUAK2 abundance or kinase activity impaired SARS-CoV-2 particle binding and internalization by decreasing cell surface levels of viral receptors and viral trafficking likely by modulating the actin cytoskeleton. IRE1α-dependent NUAK2 levels were elevated in SARS-CoV-2-infected and bystander non-infected cells, promoting viral spread by maintaining ACE2 cell surface levels and facilitating virion binding to bystander cells.

Anti-obesity effect of Lythri herba water extracts in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Lythrum salicaria L., also called purple loosestrife, has traditionally been used as a medicinal plant to treat internal dysfunction, such as gastrointestinal disorders or hemorrhages. It contains numerous phytochemical compounds, including orientin, and has been reported to have anti-diarrheal, anti-inflammatory, antioxidant, and antimicrobial properties. AIM OF THE STUDY: The effects of Lythrum salicaria L. on obesity have not been explored. Therefore, we investigated the anti-obesity effects of Lythri Herba, the aerial part of this plant, in vitro and in vivo. MATERIALS AND METHODS: Using distilled water, Lythri Herba water extracts (LHWE) were prepared by extracting Lythri Herba at 100°Ï¹. The contents of orientin in LHWE were identified using High Performance Liquid Chromatography (HPLC) analysis. To evaluate the anti-obesity effect of LHWE, 3T3-L1 adipocytes and a high-fat diet (HFD)-fed mice were used. Oil-red O staining was performed to examine the anti-adipogenic effects of LHWE in vitro. The histological changes in epididymal white adipose tissue (epiWAT) by LHWE were examined using hematoxylin and eosin staining. Serum leptin levels were measured by enzyme-linked immunosorbent assay. Specific quantification kits measured total cholesterol and triglyceride levels in the serum. The relative fold induction of protein and mRNA was determined using western blot and Quantitative real-time Polymerase Chain Reaction analysis, respectively. RESULTS: HPLC analysis demonstrated the presence of orientin in LHWE. LHWE treatment markedly reduced lipid accumulation in differentiated 3T3-L1 adipocytes. LHWE administration also conferred resistance to HFD-induced weight gain in mice and reduced epiWAT mass. Mechanistically, LHWE significantly decreased lipogenesis by downregulating lipoprotein lipase (LPL), glucose-6-phosphate dehydrogenase, ATP-citrate lyase, fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding transcription factor 1, and carbohydrate response element binding protein expression and increased the expression of genes involved in fatty acid oxidation (FAO), peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1 in 3T3-L1 adipocytes and epiWAT. Furthermore, LHWE significantly up-regulated the phosphorylation of AMP-activated protein kinase in 3T3-L1 adipocytes and epiWAT. CONCLUSION: LHWE decreases white adipogenesis in vitro and HFD-induced weight gain in vivo, which is associated with reduced lipogenesis and enhanced FAO.

Electroacupuncture at GB34 modulates neurogenesis and BDNF-ERK signaling in a mouse model of Parkinson's disease.

Background and aim: It has been reported that acupuncture at GB34 can enhance neurogenesis in the subventricular zone (SVZ) of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the signaling pathway that plays a critical role in neurogenesis needs to be established. Herein, we investigated the neurogenesis-promoting pathway mediated by acupuncture, focusing on extracellular signal-regulated kinase (ERK) signaling. Experimental procedure: Male 10-week-old C57BL/6 mice were intraperitoneally injected with 30 mg/kg MPTP once daily for 5 days. Subsequently, mice were intraperitoneally injected with 50 mg/kg bromodeoxyuridine (BrdU), and electroacupuncture (EA) was performed at GB34 and BL60 for 3 weeks. The survival of dopaminergic neurons in the nigrostriatal pathway, cell proliferation in the SVZ, and expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated ERK (pERK) were evaluated. Results and conclusion: MPTP induced dopaminergic neuronal death in the nigrostriatal pathway, and reduced the number of BrdU-positive and BrdU/doublecortin double-positive cells in the SVZ; these parameters were restored by EA. Moreover, EA prevented MPTP-induced reduction in striatal expression of BDNF and pERK. These results indicate that EA could prevent dopaminergic neuronal death in the nigrostriatal pathway and restore neurogenesis in the SVZ, which may be attributed to the activation of the BDNF-ERK pathway.

A Case Report on Ground-Level Alternobaric Vertigo Due to Eustachian Tube Dysfunction With the Assistance of Conversational Generative Pre-trained Transformer (ChatGPT).

Alternatenobaric vertigo (ABV) develops when the middle ear pressure (MEP) is not equal at the same height in the sea or the air. This is possible when the altitude changes. Eustachian tube dysfunction (ETD) is a common cause of ABV. In this case report, we discuss a patient who experienced repeated bouts of ground-level alternobaric vertigo (GLABV) due to ETD. We also discuss how Conversational Generative Pre-trained Transformer (ChatGPT) might be used in the creation of this case report. A 41-year-old male patient complained of vertigo at ground level on several occasions. His medical history included chronic sinusitis, nasal congestion, and laryngopharyngeal reflux (LPR). During the physical exam, his tympanic membranes were dull and moved less. Tympanometry showed that he had an asymmetric type A and that both of his middle ears had negative pressure. The results of the audiometry test were normal, and the laryngoscopy revealed LPR. The patient was found to have GLABV because of ETD, and different treatment options, such as Eustachian tube catheterization (ETC), were thought about. This case study demonstrates how ChatGPT can be used to assist with medical documentation and the treatment of GLABV caused by ETD. Even though ChatGPT did not provide specific diagnostic or treatment recommendations for the patient's condition, it did assist the doctor in determining what was wrong and how to treat it while writing the case report. It also aided the doctor in writing the case report by allowing them to discuss it. The use of artificial intelligence (AI) tools such as ChatGPT has the potential to improve the accuracy and speed of medical documentation, thereby streamlining clinical workflows and improving patient care. Nonetheless, it is critical to consider the ethical implications of using AI in clinical practice This case study emphasizes the importance of understanding that ETD is a common cause of GLABV and how ChatGPT can aid in the diagnosis and treatment of this condition. More research is needed to fully understand how long-term AI interventions in medicine work and how reliable they are.

Evaluation of pharmacokinetic interactions between lobeglitazone, empagliflozin, and metformin in healthy subjects.

Concomitant administration of lobeglitazone, empagliflozin, and metformin is expected to enhance blood glucose-lowering effects and improve medication compliance in patients with diabetes mellitus. In this study, we investigated the pharmacokinetic (PK) interactions and safety of lobeglitazone and co-administered empagliflozin and metformin, which are approved agents used in clinical settings. Two randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover clinical trials (parts 1 and 2) were conducted independently. In part 1, lobeglitazone monotherapy or lobeglitazone, empagliflozin, and metformin triple therapy was administered for 5 days. In part 2, empagliflozin and metformin dual therapy or the abovementioned triple therapy were administered for 5 days. Serial blood samples were collected up to 24 hours after the last dose in each period for PK evaluation. The primary PK parameters (AUCtau,ss, Cmax,ss) of treatment regimens in each study part were calculated and compared. For lobeglitazone, the geometric mean ratios (GMRs) with 90% confidence intervals (CI) for triple therapy over monotherapy were 1.08 (1.03-1.14) for Cmax,ss and 0.98 (0.90-1.07) for AUCtau,ss. For empagliflozin, the GMRs and 90% CIs for triple therapy over dual therapy were 0.87 (0.78-0.97) for Cmax,ss and 0.97 (0.93-1.00) for AUCtau,ss. For metformin, the GMRs and 90% CIs for triple therapy over dual therapy were 1.06 (0.95-1.17) for Cmax,ss and 1.04 (0.97-1.12) for AUCtau,ss. All reported adverse events were mild. The triple therapy consisting of lobeglitazone, empagliflozin, and metformin did not show any clinically relevant drug interactions in relation to the PKs and safety of each drug substance. Trial Registration: ClinicalTrials.gov Identifier: NCT04334213.

Altered gyrification in chemotherapy-treated older long-term breast cancer survivors.

Purpose: The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long-term breast cancer survivors 5 to 15 years after chemotherapy treatment. Methods: Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C-) 5-15 years prior and age & sex-matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI. Results: The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C+ group, 12 participants for the C- group, and 13 participants for the HC group. The C+ group had increased gyrification in 6 local gyrus regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in 2 local gyrus regions from TP1 to TP2 (p < 0.05, Bonferroni corrected). The C- and HC groups showed decreased gyrification only (p < 0.05, Bonferroni corrected). In C+ group, changes in right paracentral gyrification and crystalized composite scores were negatively correlated (R = -0.76, p = 0.01). Conclusions: Altered gyrification could be the neural correlate of cognitive changes in older chemotherapy-treated long-term breast cancer survivors.

Delta Neutrophil Index as a New Early Mortality Predictor after Liver Transplantation.

BACKGROUND: Patients with liver disease display numerous defects of the immune system, so infection is a frequent complication of both acute and chronic liver disease. These infections are independently associated with poor outcomes after liver transplantation. Our objective was to evaluate the delta neutrophil index (DNI), a new inflammation marker, as a predictor of survival after liver transplantation (LT). METHODS: This observational study retrospectively evaluated the records of 712 patients who underwent LT from January 2010 to February 2018. DNI was evaluated at pre-transplantation and 1, 7, 14, and 30 days after operation. Statistical analysis was performed using the T-test or chi-square test, and logistic regression analysis. RESULTS: The mean MELD score was 16.7 ± 9.4 (0-48). There were 125 mortality cases (17.8%) after liver transplantation. Mean DNI was 1.61 at pre-transplantation, 3.94 one day after operation, 2.67 seven days after operation, 1.61 fourteen days after operation, and 1.64 thirty days after operation, respectively. In multivariate analysis, DNI seven and fourteen days after operation was revealed as an independent prognostic factor for mortality after liver transplantation (p = 0.040 and p < 0.0001). CONCLUSIONS: The DNI is a simple and reliable predictor of patient mortality after liver transplantation.