Evaluating the Efficacy of ChatGPT as a Patient Education Tool in Prostate Cancer: Multimetric Assessment.

BACKGROUND: Artificial intelligence (AI) chatbots, such as ChatGPT, have made significant progress. These chatbots, particularly popular among health care professionals and patients, are transforming patient education and disease experience with personalized information. Accurate, timely patient education is crucial for informed decision-making, especially regarding prostate-specific antigen screening and treatment options. However, the accuracy and reliability of AI chatbots' medical information must be rigorously evaluated. Studies testing ChatGPT's knowledge of prostate cancer are emerging, but there is a need for ongoing evaluation to ensure the quality and safety of information provided to patients. OBJECTIVE: This study aims to evaluate the quality, accuracy, and readability of ChatGPT-4's responses to common prostate cancer questions posed by patients. METHODS: Overall, 8 questions were formulated with an inductive approach based on information topics in peer-reviewed literature and Google Trends data. Adapted versions of the Patient Education Materials Assessment Tool for AI (PEMAT-AI), Global Quality Score, and DISCERN-AI tools were used by 4 independent reviewers to assess the quality of the AI responses. The 8 AI outputs were judged by 7 expert urologists, using an assessment framework developed to assess accuracy, safety, appropriateness, actionability, and effectiveness. The AI responses' readability was assessed using established algorithms (Flesch Reading Ease score, Gunning Fog Index, Flesch-Kincaid Grade Level, The Coleman-Liau Index, and Simple Measure of Gobbledygook [SMOG] Index). A brief tool (Reference Assessment AI [REF-AI]) was developed to analyze the references provided by AI outputs, assessing for reference hallucination, relevance, and quality of references. RESULTS: The PEMAT-AI understandability score was very good (mean 79.44%, SD 10.44%), the DISCERN-AI rating was scored as "good" quality (mean 13.88, SD 0.93), and the Global Quality Score was high (mean 4.46/5, SD 0.50). Natural Language Assessment Tool for AI had pooled mean accuracy of 3.96 (SD 0.91), safety of 4.32 (SD 0.86), appropriateness of 4.45 (SD 0.81), actionability of 4.05 (SD 1.15), and effectiveness of 4.09 (SD 0.98). The readability algorithm consensus was "difficult to read" (Flesch Reading Ease score mean 45.97, SD 8.69; Gunning Fog Index mean 14.55, SD 4.79), averaging an 11th-grade reading level, equivalent to 15- to 17-year-olds (Flesch-Kincaid Grade Level mean 12.12, SD 4.34; The Coleman-Liau Index mean 12.75, SD 1.98; SMOG Index mean 11.06, SD 3.20). REF-AI identified 2 reference hallucinations, while the majority (28/30, 93%) of references appropriately supplemented the text. Most references (26/30, 86%) were from reputable government organizations, while a handful were direct citations from scientific literature. CONCLUSIONS: Our analysis found that ChatGPT-4 provides generally good responses to common prostate cancer queries, making it a potentially valuable tool for patient education in prostate cancer care. Objective quality assessment tools indicated that the natural language processing outputs were generally reliable and appropriate, but there is room for improvement.

T Cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination With Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy (INT) targeting up to 34 patient-specific tumor neoantigens to induce T cell responses and potentiate anti-tumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T cell responses to neoantigens from the first-in-human phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1mg mRNA-4157 + 200mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event (AE); there were no grade 4/5 AEs or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo, and strengthened pre-existing, T cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA INT approach in oncology.

Exploring the versatility of miRNA-128: a comprehensive review on its role as a biomarker and therapeutic target in clinical pathways.

MicroRNAs (miRNAs/ miRs) are short, noncoding RNAs, usually consisting of 18 to 24 nucleotides, that control gene expression after the process of transcription and have crucial roles in several clinical processes. This article seeks to provide an in-depth review and evaluation of the many activities of miR-128, accentuating its potential as a versatile biomarker and target for therapy; The circulating miR-128 has garnered interest because of its substantial influence on gene regulation and its simplicity in extraction. Several miRNAs, such as miR-128, have been extracted from circulating blood cells, cerebrospinal fluid, and plasma/serum. The miR-128 molecule can specifically target a diverse range of genes, enabling it to have intricate physiological impacts by concurrently regulating many interrelated pathways. It has a vital function in several biological processes, such as modulating the immune system, regulating brain plasticity, organizing the cytoskeleton, and inducing neuronal death. In addition, miR-128 modulates genes associated with cell proliferation, the cell cycle, apoptosis, plasma LDL levels, and gene expression regulation in cardiac development. The dysregulation of miR-128 expression and activity is associated with the development of immunological responses, changes in neural plasticity, programmed cell death, cholesterol metabolism, and heightened vulnerability to autoimmune illnesses, neuroimmune disorders, cancer, and cardiac problems; The paper highlights the importance of studying the consequences of miR-128 dysregulation in these specific locations. By examining the implications of miRNA-128 dysregulation in these areas, the article underscores its significance in diagnosis and treatment, providing a foundation for research and clinical applications.

Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study.

BACKGROUND: Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study. METHODS: This analysis included adult patients (aged ≥18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group performance status score of 0-2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment (version 9.0, Dec 15, 2021). Pirtobrutinib 200 mg was administered orally once a day in 28-day cycles. The primary endpoint of phase 1 of the BRUIN trial as a whole, which has been previously reported, was to establish the recommended phase 2 dose for pirtobrutinib monotherapy and the phase 2 primary endpoint was overall response rate. Safety and activity were measured in all patients who received at least one dose of pirtobrutinib monotherapy. This BRUIN phase 1/2 trial was registered with ClinicalTrials.gov and is closed to enrolment (NCT03740529). FINDINGS: Between Dec 26, 2019, and July 22, 2022, 82 patients were enrolled, of whom five were enrolled during phase 1 and 77 during phase 2. All but one patient received a starting dose of 200 mg pirtobrutinib once a day as the recommended phase 2 dose. The remaining patient received 150 mg pirtobrutinib once a day, which was not escalated to 200 mg. The median age of patients was 67 years (IQR 59-72). 55 (67%) of 82 patients were male and 27 (33%) were female. Most patients were White (65 [79%] of 82). 74 (90%) of 82 patients received at least one previous Richter transformation-directed therapy. Most patients (61 [74%] of 82) had received previous covalent BTK inhibitor therapy for chronic lymphocytic leukaemia or Richter transformation. The overall response rate was 50·0% (95% CI 38·7-61·3). 11 (13%) of 82 patients had a complete response and 30 (37%) of 82 patients had a partial response. Eight patients with ongoing response electively discontinued pirtobrutinib to undergo stem-cell transplantation. The most common grade 3 or worse adverse event was neutropenia (n=19). There were no treatment-related deaths. INTERPRETATION: Pirtobrutinib shows promising safety and activity among patients with Richter transformation, most of whom received previous Richter transformation-directed therapy, including covalent BTK inhibitors. These data suggest that further investigation is warranted of pirtobrutinib as a treatment option for patients with relapsed or refractory Richter transformation after treatment with a covalent BTK inhibitor. FUNDING: Loxo Oncology.

A systematic review of the patient reported outcomes that affect patients with muscle invasive bladder cancer after radical cystectomy and urinary diversion.

Objectives: To determine the functional domains and symptom scales that affect patients most following radical cystectomy (RC) and urinary diversion (UD), and if a single instrument (or combination) adequately captures these bothersome symptoms. It is unclear whether current patient reported outcome (PRO) instruments that have been used to assess quality of life in patients following RC and UD adequately cover the most bothersome symptoms affecting patients. Materials and methods: A systematic search of MEDLINE, EMBASE, PubMed, Cinahl and Cochrane was conducted from January 2000 to May 2023 for original articles of patients who had RC and UD since 2000 for muscle invasive bladder cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) process was followed. Extracted data included the PRO measures used, domains reported and scores in the first 12 months post-surgery (short-term) and after 12 months (long-term). A conservative threshold of <70 for functional domains and >30 for symptom domains was used to determine which PRO domains were potentially concerning to patients in each study. Quality assessment was performed using the QUALSYST appraisal tool. Results: Thirty-five studies met the inclusion criteria, including a total of eight unique PRO instruments. The main findings indicated that physical function was the most concerning PRO for patients with both neobladder (NB) and ileal conduit (IC) in the short and long term. Additionally, bowel, urinary and sexual bother were concerning symptoms for patients with NB in the long-term, but only in the short-term for those with IC. Conclusions: The main issues are adequately addressed using the combination of EORTC QLQ-C30 and QLQ-BLM30 instruments.

Fixed-Duration Pirtobrutinib plus Venetoclax with or without Rituximab in Relapsed/Refractory CLL: Phase 1b BRUIN Trial.

Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial (NCT03740529). Prior covalent BTKi therapy was allowed, but not prior venetoclax. Patients were assigned to receive PV (n=15) or PVR (n=10) for 25 cycles. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4), and 17 (68%) patients had received prior covalent BTKi. At the data-cutoff date (May 5, 2023), median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% CI:68.1-99.8%) for PV and 100% (95% CI:69.2-100.0%) for PVR, with 10 complete responses (PV:7; PVR:3). After 12 cycles of treatment, 85.7% (95% CI:57.2-98.2%) of PV and 90.0% (95% CI:55.5-99.7%) of PVR patients achieved undetectable minimal residual disease assessed in peripheral blood by clonoSEQ® assay at a sensitivity of <1x10-4. Progression-free survival at 18 months was 92.9% (95% CI: 59.1-99.0) for PV patients and 80.0% (95% CI: 40.9-94.6) for PVR patients. No DLTs were observed in either treatment combination during the 5-week assessment period. The most common grade ≥3 adverse events for all patients included neutropenia (52%) and anemia (16%). Adverse events led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi.

The endophytic fungus Serendipita indica affects auxin distribution in Arabidopsis thaliana roots through alteration of auxin transport and conjugation to promote plant growth.

Plants share their habitats with a multitude of different microbes. This close vicinity promoted the evolution of interorganismic interactions between plants and many different microorganisms that provide mutual growth benefits both to the plant and the microbial partner. The symbiosis of Arabidopsis thaliana with the beneficial root colonizing endophyte Serendipita indica represents a well-studied system. Colonization of Arabidopsis roots with S. indica promotes plant growth and stress tolerance of the host plant. However, until now, the molecular mechanism by which S. indica reprograms plant growth remains largely unknown. This study used comprehensive transcriptomics, metabolomics, reverse genetics, and life cell imaging to reveal the intricacies of auxin-related processes that affect root growth in the symbiosis between A. thaliana and S. indica. Our experiments revealed the sustained stimulation of auxin signalling in fungus infected Arabidopsis roots and disclosed the essential role of tightly controlled auxin conjugation in the plant-fungus interaction. It particularly highlighted the importance of two GRETCHEN HAGEN 3 (GH3) genes, GH3.5 and GH3.17, for the fungus infection-triggered stimulation of biomass production, thus broadening our knowledge about the function of GH3s in plants. Furthermore, we provide evidence for the transcriptional alteration of the PIN2 auxin transporter gene in roots of Arabidopsis seedlings infected with S. indica and demonstrate that this transcriptional adjustment affects auxin signalling in roots, which results in increased plant growth.

Efficacy and safety of the Ayurvedic herbal preparation Maharishi Amrit Kalash: a systematic review of randomized controlled trials.

Background: Maharishi Amrit Kalash (MAK) 4 and 5 are Ayurvedic herbal nutritional supplements that are believed to have beneficial effects on overall health and wellbeing. This study aimed to systematically review all available randomized controlled trials (RCTs) investigating the clinical effects and safety of MAK. Methods: We included RCTs on therapy, health promotion, and prevention for patients and healthy volunteers of all ages. We systematically searched MEDLINE (via PubMed), EMBASE (via Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), DHARA, Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Google Scholar from inception through 7 May 2023, with no time or language restrictions. The risk of bias was assessed using the Cochrane Risk of Bias Tool version 1. The protocol was registered with PROSPERO before conducting the review (CRD42023421655). Results: Three RCTs with 418 study participants were included. Two studies were on breast cancer patients and one on healthy adults. The two studies on cancer evaluated the efficacy of MAK in reducing the side effects of chemotherapy in women with breast cancer. The study on healthy adults evaluated whether MAK has an effect on an age-related alertness task as an indicator of cognitive aging. Both studies on breast cancer patients found beneficial effects on performance status, anorexia, vomiting, and body weight. One study reported positive effects regarding stomatitis. Regarding visual alertness, results showed that individuals who received MAK improved in performance. None of the three included studies reported adverse events. The risk of bias was mixed. Due to the small number and heterogeneity of the RCTs, no meta-analysis could be performed. Conclusion: There is evidence that MAK may have supportive effects in chemotherapeutic treatments for breast cancer patients and for healthy individuals regarding visual discrimination. However, it is difficult to verify treatment effects due to the small number of RCTs and the mixed risk of bias. Furthermore, none of the included studies recorded adverse events. Therefore, further high-quality studies are warranted to confirm the potential health benefits of MAK and to determine its optimal dosage and duration of use. Systematic review registration: PROSPERO, CRD42023421655.

Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors.

BACKGROUND: Preclinical studies have demonstrated that VT1021, a first-in-class therapeutic agent, inhibits tumor growth via stimulation of thrombospondin-1 (TSP-1) and reprograms the tumor microenvironment. We recently reported data from the dose escalation part of a phase I study of VT1021 in solid tumors. Here, we report findings from the dose expansion phase of the same study. METHODS: We analyzed the safety and tolerability, clinical response, and biomarker profile of VT1021 in the expansion portion of the phase I study (NCT03364400). Safety/tolerability is determined by adverse events related to the treatment. Clinical response is determined by RECIST v1.1 and iRECIST. Biomarkers are measured by multiplexed ion beam imaging and enzyme-linked immunoassay (ELISA). RESULTS: First, we report the safety and tolerability data as the primary outcome of this study. Adverse events (AE) suspected to be related to the study treatment (RTEAEs) are mostly grade 1-2. There are no grade 4 or 5 adverse events. VT1021 is safe and well tolerated in patients with solid tumors in this study. We report clinical responses as a secondary efficacy outcome. VT1021 demonstrates promising single-agent clinical activity in recurrent GBM (rGBM) in this study. Among 22 patients with rGBM, the overall disease control rate (DCR) is 45% (95% confidence interval, 0.24-0.67). Finally, we report the exploratory outcomes of this study. We show the clinical confirmation of TSP-1 induction and TME remodeling by VT1021. Our biomarker analysis identifies several plasmatic cytokines as potential biomarkers for future clinical studies. CONCLUSIONS: VT1021 is safe and well-tolerated in patients with solid tumors in a phase I expansion study. VT1021 has advanced to a phase II/III clinical study in glioblastoma (NCT03970447).

The network of cells that surround a tumor, the tumor microenvironment, can help cancers to grow. Therapies targeting the tumor microenvironment may help to stop tumor growth. One such therapy is VT1021. In animal models, VT1021 treatment stops tumor cells from growing by changing the tumor microenvironment. Here, we have tested VT1021 in a clinical trial and found that VT1021 treatment is safe and well tolerated in patients with cancer. We also see signs of efficacy in some patients and observe evidence that VT1021 modifies the tumor microenvironment, which may help to block tumor growth. Finally, we identified several markers from the blood that may help to predict which patients will best benefit from VT1021 treatment. With further testing in clinical trials, VT1021 may be a useful therapy for patients with cancer.

Long-Term Outcomes of Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion in Robot-Assisted Radical Cystectomy (RARC): Multicenter Results from the Asian RARC Consortium.

PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.

Identification and characterisation of functional Kir6.1-containing ATP-sensitive potassium channels in the cardiac ventricular sarcolemmal membrane.

BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.

Genetic Diversity and Population Structure of Maize (Zea mays L.) Inbred Lines in Association with Phenotypic and Grain Qualitative Traits Using SSR Genotyping.

Maize (Zea mays L.) is an important cereal and is affected by climate change. Therefore, the production of climate-smart maize is urgently needed by preserving diverse genetic backgrounds through the exploration of their genetic diversity. To achieve this, 96 maize inbred lines were used to screen for phenotypic yield-associated traits and grain quality parameters. These traits were studied across two different environments (Anand and Godhra) and polymorphic simple sequence repeat (SSR) markers were employed to investigate the genetic diversity, population structure, and trait-linked association. Genotype-environment interaction (GEI) reveals that most of the phenotypic traits were governed by the genotype itself across the environments, except for plant and ear height, which largely interact with the environment. The genotypic correlation was found to be positive and significant among protein, lysine and tryptophan content. Similarly, yield-attributing traits like ear girth, kernel rows ear-1, kernels row-1 and number of kernels ear-1 were strongly correlated to each other. Pair-wise genetic distance ranged from 0.0983 (1820194/T1 and 1820192/4-20) to 0.7377 (IGI-1101 and 1820168/T1). The SSRs can discriminate the maize population into three distinct groups and shortlisted two genotypes (IGI-1101 and 1820168/T1) as highly diverse lines. Out of the studied 136 SSRs, 61 were polymorphic to amplify a total of 131 alleles (2-3 per loci) with 0.46 average gene diversity. The Polymorphism Information Content (PIC) ranged from 0.24 (umc1578) to 0.58 (umc2252). Similarly, population structure analysis revealed three distinct groups with 19.79% admixture among the genotypes. Genome-wide scanning through a mixed linear model identifies the stable association of the markers umc2038, umc2050 and umc2296 with protein, umc2296 and umc2252 with tryptophan, and umc1535 and umc1303 with total soluble sugar. The obtained maize lines and SSRs can be utilized in future maize breeding programs in relation to other trait characterizations, developments, and subsequent molecular breeding performances for trait introgression into elite genotypes.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Objective: Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Design: Retrospective cohort study. Methods: From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. Results: A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Conclusions: Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.

Metabolite Profiling, Biological and Molecular Analyses Validate the Nutraceutical Potential of Green Seaweed Acrosiphoniaorientalis for Human Health.

Seaweeds have proven to be nutrient-dense and are rich in antioxidants, like phenolics, flavonoids, and other essential metabolites that help to provide their medicinal benefits. Non-targeted metabolite profiling of the tropical green seaweed Acrosiphonia orientalis showed the presence of numerous groups of contents, including sugars, essential amino acids, and fatty acids. Targeted metabolite profiling using HPLC identified 17 amino acids. The extract exhibited a very low half-maximal effective concentration (EC50) dosage for HeLa and Huh-7 cell lines, indicating a high likelihood of anticancer properties. A significant positive correlation was found between biological activities, such as antioxidation, scavenging, and reducing power with the phenolic and flavonoid contents. The extract revealed augmentation of proliferation in selected cervical cells, as it upregulated p53 1.3-fold, and downregulated important cancerous genes such as Cas-3 and DNMT 12- and 8-fold, respectively. An approximate 55-fold downregulation was observed in selected hepatic cell lines. Microarray analysis of hepatic cells indicated 0.27% and 0.07% upregulation of coding and non-coding genes, respectively, and 0.41% and 0.13% downregulation of coding and non-coding genes, respectively. As a consequence, it can be said that A. orientalis has possible medicinal use, such as anticancer activity, and therefore may be an intriguing food component that has potential as a regular dietary supplement.

Ventriculo-arterial uncoupling with an impella assisted HVAD: The p-D LVAD.

This paper presents the novel use of a temporary percutaneous ventricular assist device (pVAD) in a 51-year-old man with an implanted durable left ventricular assist device (d-LVAD). The pre-existing left ventricular assist device was unable to successfully unload the left ventricle, and the addition of the temporary pVAD achieved successful unloading as well as a decrease in pulmonary artery pressures without compromising the function of the right ventricle allowing safe UNOS listing for orthotopic heart transplantation.

Prostate Cancer Survivorship Essentials for men with prostate cancer on androgen deprivation therapy: protocol for a randomised controlled trial of a tele-based nurse-led survivorship care intervention (PCEssentials Hormone Therapy Study).

INTRODUCTION: Androgen deprivation therapy (ADT) is commonly used to treat men with locally advanced or metastatic prostate cancer. Men receiving ADT experience numerous side effects and frequently report unmet supportive care needs. An essential part of quality cancer care is survivorship care. To date, an optimal effective approach to survivorship care for men with prostate cancer on ADT has not been described. This protocol describes a randomised trial of tele-based nurse-led survivorship that addresses this knowledge gap: (1) determine the effectiveness of a nurse-led survivorship care intervention (PCEssentials), relative to usual care, for improving health-related quality of life (HR-QoL) in men with prostate cancer undergoing ADT and (2) evaluate PCEssentials implementation strategies and outcomes, including cost-effectiveness, compared with usual care. METHODS AND ANALYSIS: This is an effectiveness-implementation hybrid (type 1) trial with participants randomised to one of two arms: (1) minimally enhanced usual care and (2) nurse-led prostate cancer survivorship essentials (PCEssentials) delivered over four tele-based sessions, with a booster session 5 months after session 1. Eligible participants are Australian men with prostate cancer commencing ADT and expected to be on ADT for a minimum of 12 months. Participants are followed up at 3, 6 and 12 months postrecruitment. Primary outcomes are HR-QoL and self-efficacy. Secondary outcomes are psychological distress, insomnia, fatigue and physical activity. A concurrent process evaluation with participants and study stakeholders will be undertaken to determine effectiveness of delivery of PCEssentials. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Metro South Health HREC (HREC/2021/QMS/79429). All participants are required to provide written informed consent. Outcomes of this trial will be published in peer-reviewed journals. The findings will be presented at conferences and meetings, local hospital departments, participating organisations/clinical services, and university seminars, and communicated at community and consumer-led forums. TRIAL REGISTRATION NUMBER: ACTRN12622000025730.

Ezabenlimab (BI 754091), an anti-PD-1 antibody, in patients with advanced solid tumours.

BACKGROUND: Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics and antitumour activity of ezabenlimab at the recommended Phase II dose in patients with selected advanced solid tumours. STUDY DESIGN: Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States. Study 1381.4 (NCT03433898) was conducted in Japan. Study 1381.3 (NCT03780725) was conducted in the Netherlands. The primary endpoints were: number of patients experiencing dose-limiting toxicities (DLTs) in the first cycle (dose escalation parts), number of patients with DLTs during the entire treatment period and objective response (dose expansion part of Study 1381.1). RESULTS: Overall, 117 patients received ezabenlimab intravenously every 3 weeks (80 mg, n = 3; 240 mg, n = 111; 400 mg, n = 3). No DLTs were observed and the MTD was not reached. Fifty-eight patients (52.3%) had grade ≥ 3 adverse events, most commonly anaemia (10.8%) and fatigue (2.7%). In 111 assessed patients treated with ezabenlimab 240 mg, disease control rate was 56.8% and objective response rate was 16.2%. Three patients had complete response; at data cut-off (November 2021) one remained in response and was still receiving ongoing treatment (duration of response [DoR]: 906 days). Partial responses occurred across several tumour types; DoR ranged from 67 to 757 days. CONCLUSIONS: Ezabenlimab was well tolerated and associated with durable antitumour activity in multiple solid tumours, comparable to other immune checkpoint inhibitors in similar patient populations and treatment settings.