First-in-human clinical studies

BACKGROUND: The "translational roadblock" between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution. METHODS: To verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study...

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) are monogenic in some cases, however, there are still no clear guidelines on genetic testing in the clinical practice of SRNS in children. METHODS: Three hundred thirty-two children were diagnosed with SRNS, and all children underwent genetic testing, including gene panels and/or whole-exome/genome sequencing (WES/WGS), during treatment. We analysed the relationship between clinical manifestation and genotype, and compared different genetic testing methods' detection rates and prices...

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included...

OBJECTIVE: This systematic review aims to outline the use of population and disease registries for clinical trial pre-screening. MATERIALS AND METHODS: The search was conducted in the time period of January 2014 to December 2022 in three databases: MEDLINE, Embase, and Web of Science Core Collection. References were screened using the Rayyan software, firstly based on titles and abstracts only, and secondly through full text review. Quality of the included studies was assessed using the List of Included Studies and quality Assurance in Review tool, enabling inclusion of publications of only moderate to high quality...

BACKGROUND: The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD. METHODS: To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched...

BACKGROUND: Communication skills (CS) represent a core competency in radiology residency training. However, no structured curriculum exists to train radiology residents in CS in China. The aim of this study was to evaluate the status and prevalence of doctor-patient communication training among radiology residents in nine Chinese accredited radiology residency training programs and to determine whether there is a perceived need for a formalized curriculum in this field. METHODS: We administered a cross-sectional online survey to radiology residents involved in CS training at nine standard residency training programs in China...

BACKGROUND: The precise influence of plate position on clinical outcomes in the context of volar fixed-angle plating for distal radius fractures is not fully understood. This article aims to investigate the influence of plate position on clinical results, and functional outcomes in patients treated with volar fixed plating for distal radius fractures. METHODS: A total of 58 patients with 64 distal radius fractures were included in the study. Patient demographics, fracture characteristics, surgical details, and radiographic data were collected...

INTRODUCTION: Childbirth may be associated with psychological, social, and emotional effects and provide the background for women's health or illness throughout their life. This research aimed at comparing the impact of non-pharmacological pain relief and pharmacological analgesia with remifentanil on childbirth fear and postpartum depression. MATERIALS AND METHOD: This randomized clinical trial with two parallel arms was conducted on 66 women with term pregnancy referred to Taleghani Hospital in Tabriz for vaginal delivery during September 2022 to September 2023...

BACKGROUND: Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease...

BACKGROUND: The National Institute for Health and Care Excellence guidelines state that psychosocial interventions should be the first line of treatment for people with dementia who are experiencing distress behaviours, such as agitation and depression. However, little is known about the characteristics and outcomes of psychosocial interventions or the facilitators and barriers to implementation on inpatient mental health dementia wards which provide care for people with dementia who are often experiencing high levels of distress...

BACKGROUND: This study aimed to determine the median effective dose (ED50) and 95% effective dose (ED95) of nicardipine for treating pituitrin-induced hypertension during laparoscopic myomectomy, providing guidance for the management of intraoperative blood pressure in such patients. METHODS: Among the initial 40 participants assessed, 24 underwent elective laparoscopic myomectomy. A sequential up-and-down method was employed to ascertain the ED50 of nicardipine based on its antihypertensive efficacy...

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study...

While there is data assessing the test performance of artificial intelligence (AI) chatbots, including the Generative Pre-trained Transformer 4.0 (GPT 4) chatbot (ChatGPT 4.0), there is scarce data on its diagnostic accuracy of clinical cases. We assessed the large language model (LLM), ChatGPT 4.0, on its ability to answer questions from the United States Medical Licensing Exam (USMLE) Step 2, as well as its ability to generate a differential diagnosis based on corresponding clinical vignettes from published case reports...

Chronic myeloid leukemia (CML) is a neoplastic disease of genetic origin resulting from clonal proliferation of hematopoietic stem cells (HSCs). The reciprocal translocation t(9;22)(q34;q11) is the main chromosomal abnormality involved in this pathology, usually detected by conventional cytogenetics. This article aims to investigate the epidemiological, cytogenetic, therapeutic, and clinical characteristics of Moroccan patients with CML. This research represents the first large-scale study of CML patients in Morocco and was carried out at Institut Pasteur of Morocco...

OBJECTIVE: To prospectively evaluate a deep learning-based denoising reconstruction (DLR) for improved resolution and image quality in musculoskeletal (MSK) magnetic resonance imaging (MRI). METHODS: Images from 137 contrast-weighted sequences in 40 MSK patients were evaluated. Each sequence was performed twice, first with the routine parameters and reconstructed with a routine reconstruction filter (REF), then with higher resolution and reconstructed with DLR, and with three conventional reconstruction filters (NL2, GA43, GA53)...

OBJECTIVE: The incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants significantly reduce CR-POPF. A new biodegradable sealant patch was able to reduce POPF and to achieve bleeding control in a preclinical porcine DP model. The aim of this first-in-human study was to assess the safety and performance of the sealant patch. METHODS: In this multicenter, single-arm study, 40 patients undergoing distal pancreatectomy were prospectively enrolled from 8 centers...

INTRODUCTION: To increase the likelihood of research responding to societal needs, intermediary structures such as Science Shops are being created. Science Shops respond to research needs identified and prioritized through participatory processes involving civil society. However, these are not mainstream structures, and most research needs addressed by the scientific community are not defined by a diversity of stakeholders (including citizens) but are mostly prioritized by researchers and funders...

INTRODUCTION: Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial. When given at low doses, the anthracycline epirubicin promotes tissue damage control and lessens the severity of sepsis independently of the host-pathogen load by conferring disease tolerance to infection...

OBJECTIVE: The 2022 Australian winter was the first time that COVID-19, influenza and respiratory syncytial virus (RSV) were circulating in the population together, after two winters of physical distancing, quarantine and borders closed to international travellers. We developed a novel surveillance system to estimate the incidence of COVID-19, influenza and RSV in three regions of Queensland, Australia. DESIGN: We implemented a longitudinal testing-based sentinel surveillance programme...

Clinical relevance of miRNAs as biomarkers is growing due to their stability and detection in biofluids. In this, diagnosis at asymptomatic stages of Alzheimer's disease (AD) remains a challenge since it can only be made at autopsy according to Braak NFT staging. Achieving the objective of detecting AD at early stages would allow possible therapies to be addressed before the onset of cognitive impairment. Many studies have determined that the expression pattern of some miRNAs is dysregulated in AD patients, but to date, none has been correlated with downregulated expression of cellular prion protein (PrPC ) during disease progression...