Generating the Evidence Base for Convalescent Plasma Use for a New Infectious Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept across the world in the waning months of 2019 and emerged as the cause of the coronavirus disease 19 (COVID-19) pandemic in early 2020. The use of convalescent plasma (CP) for prior respiratory pandemics provided a strong biological rationale for the rapid deployment of COVID-19 convalescent plasma (CCP) in early 2020 when no validated treatments or prior immunity existed. CCP is an antiviral agent, with its activity against SARS-CoV-2 stemming from specific antibodies elicited by the virus. Early efforts to investigate the efficacy of CCP in randomized clinical trials (RCTs) that targeted hospitalized patients with COVID-19 did not demonstrate the overall efficacy of CCP despite signals of benefit in certain subgroups, such as those treated earlier in disease. In contrast, studies adhering to the principles of antibody therapy in their study design, choice of patient population, and product qualification, i.e., those that administered high levels of specific antibody during the viral phase of disease in immunocompromised or very early in immunocompetent individuals, demonstrated benefits. In this chapter, we leverage the knowledge gained from clinical studies of CCP for COVID-19 to propose a framework for future studies of CP for a new infectious disease. This framework includes obtaining high-quality CP and designing clinical studies that adhere to the principles of antibody therapy to generate a robust evidence base for using CP.

Epidemiology of heart failure in diabetes: a disease in disguise.

Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.

The bronchoalveolar lavage dilution conundrum: an updated view on a long-standing problem.

Bronchoalveolar lavage (BAL) is used by researchers to study molecular interactions within healthy and diseased human lungs. However, the utility of BAL fluid measurements may be limited by difficulties accounting for dilution of the epithelial lining fluid (ELF) sampled and inconsistent collection techniques. The use of endogenous markers to estimate ELF dilution has been proposed as a potential method to normalize acellular molecule measurements in BAL fluid, but these markers are also imperfect and prone to inaccuracy. The focus of this report is to review factors that affect the interpretation of acellular molecule measurements in lung ELF and present original data comparing the performance of several BAL dilution markers during health and in a human endobronchial endotoxin challenge model of acute inflammation. Our findings suggest that incomplete ELF and lavage fluid mixing, flux of markers across the alveolar barrier, and lung inflammation are all possible factors that can affect marker performance. Accounting for these factors, we show that commonly used markers including urea, total protein, albumin, and immunoglobulin M are likely unreliable BAL dilution markers. In contrast, surfactant protein D appears to be less affected by these factors and may be a more accurate and biologically plausible marker to improve the reproducibility of acellular BAL component measurements across individuals during health and inflammatory states.NEW & NOTEWORTHY In this report, mathematical prediction models and real-world measurements are used to compare the performance of molecular markers of dilution in bronchoalveolar lavage fluid samples. Effects of acute inflammation within individual subjects are highlighted. These findings inform recommendations for normalizing measurements across bronchoalveolar lavage samples and highlight the need for additional markers to improve the rigor of translational studies utilizing bronchoalveolar lavage measurements.

Probable antibody-mediated rejection in kidney transplantation is a rare and challenging phenotype to define: Findings from a single-center study.

The Banff 2022 consensus introduced probable antibody-mediated rejection (AMR), characterized by mild AMR histologic features and human leukocyte antigen (HLA) donor-specific antibody (DSA) positivity. In a single-center observational cohort study of 1891 kidney transplant recipients transplanted between 2004 and 2021, 566 kidney biopsies were performed in 178 individual HLA-DSA-positive transplants. Evaluated at time of the first HLA-DSA-positive biopsy of each transplant (N = 178), 84 of the 178 (47.2%) of first biopsies were scored as no AMR, 22 of the 178 (12.4%) as probable AMR, and 72 of the 178 (40.4%) as AMR. The majority (77.3%) of probable AMR cases were first diagnosed in indication biopsies. Probable AMR was associated with lower estimated glomerular filtration rate (mL/min/1.73m2) than no AMR (20.2 [8.3-32.3] vs 40.1 [25.4-53.3]; P = .001). The one-year risk of (repeat) AMR was similar for probable AMR and AMR (subdistribution hazard ratio (sHR), 0.99; 0.42-2.31; P = .97) and higher than after no AMR (sHR, 3.05; 1.07-8.73; P = .04). Probable AMR had a higher five-year risk of transplant glomerulopathy vs no AMR (sHR, 4.29; 0.92-19.98; P = 06), similar to AMR (sHR, 1.74; 0.43-7.04; P = .44). No significant differences in five-year risk of graft failure emerged between probable AMR and AMR (sHR, 1.14; 0.36-3.58; P = .82) or no AMR (sHR, 2.46; 0.78-7.74; P = .12). Probable AMR is a rare phenotype, however, sharing significant similarities with AMR in this single-center study. Future studies are needed to validate reproducible diagnostic criteria and associated clinical outcomes to allow for defining best management of this potentially relevant phenotype.

Development of an improved Scientific Registry of Transplant Recipients deceased donor heart yield model using donor critical care data from the Donor Management Goal Registry cohort.

Organ procurement organizations (OPOs) face increasing regulatory scrutiny, and the performance of predictive models used to assess OPO performance is critical. We sought to determine whether adding deceased donor physiological and critical care data to the existing Scientific Registry of Transplant Recipients (SRTR) heart yield model would improve the model's performance. Donor data and heart transplanted (yes/no), the outcome of interest, were obtained from the United Network for Organ Sharing Donor Management Goal (DMG) Registry for 19 141 donors after brain death, from 25 OPOs. The data were split into training and testing portions. Multivariable LASSO regression was used to develop a statistical model incorporating DMG data elements with the existing components of the SRTR model. The DMG + SRTR and SRTR models were applied to the test data to compare the predictive performance of the models. The sensitivity (84%-86%) and specificity (84%-86%) were higher for the DMG + SRTR model compared to the SRTR model (71%-75% and 76%-77%, respectively). For the DMG + SRTR model, the C-statistic was 0.92 to 0.93 compared to 0.80 to 0.81 for the SRTR model. DMG data elements improve the predictive performance of the heart yield model. The addition of DMG data elements to the Organ Procurement and Transplantation Network data collection requirements should be considered.

Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation.

Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely.

Increased risk of haematological malignancy in adults over age 60 with thrombocytopenia compared with matched controls: Time for an upfront bone marrow evaluation?

International societies have conflicting recommendations on whether bone marrow aspirate/biopsy (BMB) is needed during workup for isolated thrombocytopenia. Our objective was to determine if thrombocytopenia in patients aged ≥60 years is associated with an increased incidence of haematological malignancy. We performed a retrospective population-based cohort study in patients aged ≥60 years between January 1, 2009 to December 31, 2019. Exposed patients had specialist consultation for thrombocytopenia, with platelet count <100 × 109/L, but normal haemoglobin and white blood cell count. Unexposed patients were those who never had specialist consultation for thrombocytopenia and whose platelets were ≥100 × 109/L. The primary outcome was the diagnosis of haematological malignancy using a competing risk of death model. During 4.0 years (IQR 2.2-6.7) of follow-up, 378/4930 exposed (19.1/1000PY, 95% CI 17.1-21.0), and 204/17556 unexposed patients (2.5/1000PY, 95% CI 2.2-2.8) were diagnosed with haematological malignancy (HR 15.5 (95% CI 11.3-21.4, p < 0.0001) in year 1, and 5.3 (95% CI 4.4-6.6, p < 0.0001) in years 2+). This finding persisted in analyses stratified by sex, age, severity, or duration of thrombocytopenia, and treatment with corticosteroids within 2 weeks of consultation. This study found a strong association between isolated thrombocytopenia and haematological malignancy in patients ≥60 years, supporting consideration of diagnostic testing including BMB during outpatient specialist consultation.

Real-world outcomes following third or subsequent lines of therapy: A Danish population-based study on 189 patients with relapsed/refractory large B-cell lymphomas.

Outcome data of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) beyond the second line are scarce outside of clinical trials. Novel therapies in the R/R setting have been approved based on single-arm trials, but results need to be contextualized by real-world outcomes. Medical records from 3753 Danish adults diagnosed with DLBCL were reviewed. Patients previously treated with rituximab and anthracycline-based chemotherapy who received the third or later line (3 L+) of treatment after 1 January 2015, were included. Only 189 patients with a median age of 71 years were eligible. The median time since the last line of therapy was 6 months. Patients were treated with either best supportive care (22%), platinum-based salvage therapy (13%), low-intensity chemotherapy (22%), in clinical trial (14%) or various combination treatments (32%). The 2-year OS-/PFS estimates were 25% and 12% for all patients and 49% and 17% for those treated with platinum-based salvage therapy. Age ≥70, CNS involvement, elevated LDH and ECOG ≥2 predicted poor outcomes, and patients with 0-1 of these risk factors had a 2-year OS estimate of 65%. Only a very small fraction of DLBCL patients received third-line treatment and were eligible for inclusion. Outcomes were generally poor, but better in intensively treated, fit young patients with limited disease.

Progression-free survival is a weakly predictive surrogate end-point for overall survival in follicular lymphoma: A systematic review and meta-analysis.

Although progression-free survival (PFS) is a commonly used surrogate end-point for clinical trials of follicular lymphoma (FL), no analyses have evaluated the strength of surrogacy for PFS with overall survival (OS). A systematic review was performed and 20 studies (total participants, 10 724) met final inclusion criteria. PFS was weakly associated with OS (correlation coefficient; 0.383, p < 0.001). The coefficient of determination was 0.15 (95% CI: 0.002-0.35) suggesting 15% of OS variance could be explained by changes in PFS. This challenges the role for PFS as a surrogate end-point for clinical trials and drug approvals.

Philadelphia-like B-cell acute lymphoblastic Leukaemia: Disease features and outcomes in the era of immunotherapy.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL.

Lost in the plot: missing visual elements in Kaplan-Meier plots of phase III oncology trials.

Missing visual elements (MVE) in Kaplan-Meier (KM) curves can misrepresent data, preclude curve reconstruction, and hamper transparency. This study evaluated KM plots of phase III oncology trials. MVE were defined as an incomplete y-axis range or missing number at risk table in a KM curve. Surrogate endpoint KM curves were additionally evaluated for complete interpretability, defined by (1) reporting the number of censored patients and (2) correspondence of the disease assessment interval with the number at risk interval. Among 641 trials enrolling 518 235 patients, 116 trials (18%) had MVE in KM curves. Industry sponsorship, larger trials, and more recently published trials were correlated with lower odds of MVE. Only 3% of trials (15 of 574) published surrogate endpoint KM plots with complete interpretability. Improvements in the quality of KM curves of phase III oncology trials, particularly for surrogate endpoints, are needed for greater interpretability, reproducibility, and transparency in oncology research.

Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action.

BACKGROUND: Lung cancer remains a critical public health issue, presenting multifaceted challenges in prevention, diagnosis, and treatment. This article aims to review the current landscape of lung cancer research and management, delineate the persistent challenges, and outline pragmatic solutions. MATERIALS AND METHODS: Global experts from academia, regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the National Cancer Institute (NCI), professional societies, the pharmaceutical and biotech industries, and patient advocacy groups were gathered by the New York Lung Cancer Foundation to review the state of the art in lung cancer and to formulate calls to action. RESULTS: Improving lung cancer management and research involves promoting tobacco cessation, identifying individuals at risk who could benefit from early detection programs, and addressing treatment-related toxicities. Efforts should focus on conducting well-designed trials to determine the optimal treatment sequence. Research into innovative biomarkers and therapies is crucial for more personalized treatment. Ensuring access to appropriate care for all patients, whether enrolled in clinical trials or not, must remain a priority. CONCLUSIONS: Lung cancer is a major health burden worldwide, and its treatment has become increasingly complex over the past two decades. Improvement in lung cancer management and research requires unified messaging and global collaboration, expanded education, and greater access to screening, biomarker testing, treatment, as well as increased representativeness, participation, and diversity in clinical trials.

Recent clinical researches and technological development in TIL therapy.

Tumor-infiltrating lymphocyte (TIL) therapy represents a groundbreaking advancement in the solid cancer treatment, offering new hope to patients and their families with high response rates and long overall survival. TIL therapy involves extracting immune cells from a patient's tumor tissue, expanding them ex vivo, and infusing them back into the patient to target and eliminate cancer cells. This revolutionary approach harnesses the power of the immune system to combat cancers, ushering in a new era of T cell-based therapies along with CAR-T and TCR-therapies. In this comprehensive review, we aim to elucidate the remarkable potential of TIL therapy by delving into recent advancements in basic and clinical researches. We highlight on the evolving landscape of TIL therapy as a prominent immunotherapeutic strategy, its multifaceted applications, and the promising outcomes. Additionally, we explore the future horizons of TIL therapy, next-generation TILs, and combination therapy, to overcome the limitations and improve clinical efficacy of TIL therapy.

Artificial intelligence in clinical research of cancers.

Several factors, including advances in computational algorithms, the availability of high-performance computing hardware, and the assembly of large community-based databases, have led to the extensive application of Artificial Intelligence (AI) in the biomedical domain for nearly 20 years. AI algorithms have attained expert-level performance in cancer research. However, only a few AI-based applications have been approved for use in the real world. Whether AI will eventually be capable of replacing medical experts has been a hot topic. In this article, we first summarize the cancer research status using AI in the past two decades, including the consensus on the procedure of AI based on an ideal paradigm and current efforts of the expertise and domain knowledge. Next, the available data of AI process in the biomedical domain are surveyed. Then, we review the methods and applications of AI in cancer clinical research categorized by the data types including radiographic imaging, cancer genome, medical records, drug information and biomedical literatures. At last, we discuss challenges in moving AI from theoretical research to real-world cancer research applications and the perspectives toward the future realization of AI participating cancer treatment.

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy, as well as the current status of nanomedicine formulations of CBD, and discusses the potential and challenges of CBD in glioma therapy in the future.

Correlation between oxygenation status of extra-synovial tissue of wrist and disease activity in rheumatoid arthritis: a photoacoustic imaging study.

OBJECTIVES: Rheumatoid arthritis (RA) is characterized by hypoxia in the synovial tissue. While photoacoustic imaging (PA) offers a method to evaluate tissue oxygenation in RA patients, studies exploring the link between extra-synovial tissue of wrist oxygenation and disease activity remain scarce. We aimed to assess synovial oxygenation in RA patients using a multimodal photoacoustic-ultrasound (PA/US) imaging system and establish its correlation with disease activity. METHODS: A retrospective study was conducted on 111 patients with RA and 72 healthy controls from 2022 to 2023. Dual-wavelength PA imaging quantified oxygen saturation (So2) levels in the synovial membrane and peri-wrist region. Oxygenation states were categorised as hyperoxia, intermediate oxygenation, and hypoxia based on So2 values. The association between oxygenation levels and the clinical disease activity index was evaluated using a one-way analysis of variance, complemented by the Kruskal-Wallis test with Bonferroni adjustment. RESULTS: Of the patients with RA, 39 exhibited hyperoxia, 24 had intermediate oxygenation, and 48 had hypoxia in the wrist extra-synovial tissue. All of the control participants exhibited the hyperoxia status. Oxygenation levels in patients with RA correlated with clinical metrics. Patients with intermediate oxygenation had a lower disease activity index compared with those with hypoxia and hyperoxia. CONCLUSION: A significant correlation exists between wrist extra-synovial tissue oxygenation and disease activity in patients with RA.

Correlation between Lactate Dehydrogenase to Albumin Ratio and the Prognosis of Patients with Cardiac Arrest.

Background: Cardiac arrest (CA) is a common event in the intensive care unit (ICU), which seriously threatens the prognosis of patients. Therefore, it is crucial to determine a simple and effective clinical indicator to judge the prognosis of patients after a CA for later treatments. The purpose of this study was to investigate the relationship between the lactate dehydrogenase to albumin ratio (LAR) and the prognosis of patients after a CA. Methods: The clinical data of participants was obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0; 2008 to 2019). According to the 30-day prognosis, patients were divided into a survivors group (n = 216) and a non-survivors group (n = 304). The optimal LAR threshold was determined using restricted cubic spline (RCS), which divided patients into a high LAR group ( ≥ 15.50, n = 257) and a low LAR group ( < 15.50, n = 263). The ICU hospitalization and 30-day accumulative survival curves of the two groups were plotted following the Kaplan-Meier survival analysis. Multivariate Cox regression was used to analyze the relationship between the LAR and the prognosis of CA patients. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive efficacy of the LAR on 30-day all-cause mortality, and sensitivity analysis was used to check the reliability of the findings. Results: A total of 520 patients with CA were enrolled and the 30-day mortality was 58.46%. The LAR in the non-survivors group was higher than in the survivors group. The RCS showed a linear trend relationship between the LAR and the mortality risk in patients during their ICU stay and 30 days; moreover, as the LAR increased, so did the risk of mortality. The Kaplan-Meier survival curve showed that compared with the low LAR group, the cumulative survival rates of ICU hospitalization and 30 days were lower in the high LAR group among CA patients (p < 0.001). Multivariate Cox regression analysis showed that an elevated LAR ( ≥ 15.50) was an independent risk factor for mortality during ICU stay and 30 days (p < 0.005). ROC analysis suggested that the LAR was superior to the sequential organ failure assessment (SOFA) score in predicting the 30-day all-cause mortality in CA patients (area under the curve (AUC) = 0.676, 95% confidence interval [CI]: 0.629-0.723). To verify the reliability of our findings, we performed sensitivity analyses and found that the findings were reliable. Conclusions: An elevated LAR might be a predictor of mortality in patients following a CA during ICU hospitalization and 30 days, thereby it can be used to provide a reference for the clinical management of these patients.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

A systematic review of ethnic minority participation in randomised controlled trials of systemic therapies for gynecological cancers.

OBJECTIVE: Randomised controlled trials (RCTs) must include ethnic minority patients to produce generalisable findings and ensure health equity as cancer incidence rises globally. This systematic review examines participation of ethnic minorities in RCTs of licensed systemic anti-cancer therapies (SACT) for gynecological cancers, defining the research population and distribution of research sites to identify disparities in participation on the global scale. METHODS: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Phase II and III RCTs of licensed therapies for gynecological cancers published 01/11/2012-01/11/2022 that reported patient race/ethnicity were included. Extracted data included race/ethnicity and research site location. RCT populations were aggregated and participation of groups compared. Global distribution of research sites was described. RESULTS: 26 RCTs met inclusion criteria of 351 publications included in full-text screening, representing 17,041 patients. 79.8% were "Caucasian", 9.1% "East Asian", 3.7% "Black/African American" and 6.1% "Other, Unknown, Not Reported". "Caucasian" patients participated at higher rates than all other groups. Of 5,478 research sites, 80.1% were located in North America, 13.0% in Europe, 3.4% in East Asia, 1.3% in the Middle East, 1.3% in South America and 0.8% in Australasia. CONCLUSIONS: Ethnic minorities formed smaller proportions of RCT cohorts compared to the general population. The majority of sites were located in North America and Europe, with few in other regions, limiting enrollment of South Asian, South-East Asian and African patients in particular. Efforts to recruit more ethnic minority patients should be made in North America and Europe. More sites in underserved regions would promote equitable access to RCTs and ensure findings are generalisable to diverse groups. This review assessed the global population enrolled in contemporary RCTs for novel therapies now routinely given for gynecological cancers, adding novel understanding of the global distribution of research sites.

Modeling the Adoption of 5760 Clinical Studies Into Practice Across 5 Surgical Specialties.

INTRODUCTION: No studies exist that explore the factors that influence the process of synthesizing new knowledge into perioperative standards of care and the operating room. We sought to model the adoption of clinical research into surgical practice and identify modifiable factors influencing the latency of this translation. METHODS: We created a data set comprised of all UpToDate articles between 2011 and 2020, sampled at 3-mo intervals, to explore how research is incorporated at the point-of-care (POC)-studying 5760 new references from 204 journals across five surgical specialties, compared to all uncited articles published during the same interval. UpToDate authors serve as specialty curators of the vast surgical literature, with an audience of more than a million clinicians in over 180 countries across 3200 institutions. Unlike society guidelines, UpToDate also provides the necessary granularity to quantify the time in bringing research to the bedside. Our main outcomes are citation rates and time-to-citation, split by specialty, journal, article type, and topics. We also model the influence of impact factor, geography, and funding and, finally, propose new impact indices to help with prioritizing surgical literature. RESULTS: We highlight variation in adoption of clinical research by specialty. We show, despite representing a lower quality of evidence, surgical case reports are one of the most cited article types. Furthermore, most clinical trials (94%-100%) in surgical journals are never incorporated into POC reference lists. While few, pragmatic trials were the most likely to be cited of any article type in any surgical specialty (40%). Journal impact factor did not correlate with time-to-citation or proportion of articles cited in three of five surgical specialties, suggesting differences in how specialties synthesize/value research from specialty journals. Our two metrics, the Clinical Relevancy and Immediacy Indices, were defined to capture this impact/relevance to surgical practice. Of the five surgical subspecialties, gynecology references were >5-fold more likely to get cited, had a larger fraction of higher quality evidence incorporated, and demonstrated more success with POC adoption of practice guidelines. We also quantified the cost of translating research to surgical practice per specialty and generated maps that highlight institutions successful in translating research to the POC. The higher expenditure of National Institutes of Health funding in gynecology may reflect the cost of higher quality research per citation. CONCLUSIONS: Understanding translational latency is the first step to exposing blocks that slow the adoption of research into everyday surgical practice and to understanding why increasing research funding has not yielded comparative gains in surgical outcomes. Our approach reveals new methods to monitoring the efficiency of research investments and evaluating the efficacy of policies influencing the translation of research to surgical practice.