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Nature Medicine Jun 2024Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies...
Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.
PubMed: 38942992
DOI: 10.1038/s41591-024-03075-7 -
International Journal of Behavioral... Jun 2024Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but...
BACKGROUND
Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but uptake is low among adolescents, particularly in resource-limited settings. We assessed awareness and acceptability of PrEP and PEP among Kenyan adolescents.
METHOD
Focus group discussions were conducted with 120 adolescent boys and girls ages 15 to 19 in Kisumu. Data were analyzed using the Framework Approach.
RESULTS
Adolescent participants often had not heard of or could not differentiate between PrEP and PEP. They also confused these HIV prevention tools with emergency contraceptives. Taking a daily pill to prevent HIV was perceived as analogous to taking a pill to treat HIV. Boys were aware of and willing to consider using PrEP and PEP due to their dislike for using condoms. Adolescents identified insufficient information, cost, and uncomfortableness speaking with healthcare workers about their HIV prevention needs due to sexuality stigma as barriers to using PrEP and PEP.
CONCLUSION
Low awareness and poor understanding of PrEP and PEP among adolescents reveal the need for increased education and sensitization about these HIV prevention options. Expanding access to sexual and reproductive health services that are tailored to the needs of adolescents and staffed with non-judgmental providers could help reduce sexuality stigma as a barrier to accessing care. New HIV prevention approaches such as long-acting injectables or implants, on-demand regimens, and multipurpose prevention technologies may encourage increased uptake of PrEP and PEP by adolescents.
PubMed: 38942977
DOI: 10.1007/s12529-024-10290-6 -
Acta Diabetologica Jun 2024The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy...
The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy balance. Any form of weight loss dramatically affects the natural history of T2D, favoring prevention, treatment, and even remission in the case of significant weight loss. However, weight regain, which is often accompanied by the recurrence or worsening of obesity complications such as T2D, is an inevitable biological phenomenon that is an integral part of the pathophysiology of obesity. This can occur not only after weight loss, but also during obesity treatment if it is not effective enough to counteract the physiological responses aimed at restoring adiposity to its pre-weight-loss equilibrium state. Over the past few years, many controlled and randomized studies have suggested a superior efficacy of bariatric surgery compared to conventional therapy in terms of weight loss, glycemic control, and rates of T2D remission. Recently, the therapeutic armamentarium in the field of diabetology has been enriched with new antihyperglycemic drugs with considerable efficacy in reducing body weight, which could play a pathogenetic role in the remission of T2D, not through the classical incretin effect, but by improving adipose tissue functions. All these concepts are discussed in this position statement, which aims to deepen the pathogenetic links between obesity and T2D, shift the paradigm from a "simple" interaction between insulin resistance and insulin deficiency, and evaluate the efficacy of different therapeutic interventions to improve T2D management and induce diabetes remission whenever still possible.
PubMed: 38942960
DOI: 10.1007/s00592-024-02317-x -
Surgical Endoscopy Jun 2024As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and...
BACKGROUND
As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery.
METHODS
Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology.
RESULT
Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery.
CONCLUSIONS
MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.
PubMed: 38942944
DOI: 10.1007/s00464-024-10977-7 -
Scientific Reports Jun 2024Viscum album L. (VA) is a unique plant with regard to its biological content. It is rich in many different metabolites with high potential in various spheres of human...
Viscum album L. (VA) is a unique plant with regard to its biological content. It is rich in many different metabolites with high potential in various spheres of human activity. We conducted a pilot study with 5 VA aqueous extracts of different host-tree species for pre-sowing treatment of Cucurbita maxima 'Hokkaido orange' seeds. We set the following objectives consisting of hypotheses (1) H01 is based on different effects of tested VA extracts depending on host trees and time of pre-treatment; (2) H02 focuses on the allopathic properties of the tested extracts affecting the plant growth and development by dose-response relationship; (3) A01 considers highly biologically active compounds of VA extracts also containing allelochemicals that can be used to regulate plant growth processes and create eco-friendly and resilient cities. The analysis of the stimulatory allelopathy index for 7 parameters demonstrates the direct effect of VA extracts in 62.3% of cases. The variability of the broad spectrum of effects of VA extracts of different host trees on the ontogenesis of C. maxima plants shows the presence of potential allelochemicals, resulting from the vital products of the host-parasite relationship. These effects are not fully explained by total polyphenol content and antioxidant activity as in previous studies of other mistletoe species. The authors consider this work a pilot study that expands the areas of application of VA extracts and knowledge about potential sources of allelochemicals.
Topics: Cucurbita; Plant Extracts; Viscum album; Allelopathy; Pilot Projects; Pheromones; Seeds
PubMed: 38942921
DOI: 10.1038/s41598-024-65918-0 -
Scientific Reports Jun 2024A comprehensive emergency medical service (EMS) system significantly enhances a city's capacity to prevent and mitigate disasters. Using Huangshi as a case study, this...
A comprehensive emergency medical service (EMS) system significantly enhances a city's capacity to prevent and mitigate disasters. Using Huangshi as a case study, this research evaluated the service radium coverage rate of the current EMS system by examining its transport capacity, population density, and prevalence rate, finding it to be only 61.49% with an inefficient spatial layout. To address this, we proposed transforming urban brownfields into EMS parks. By selecting the most suitable brownfields based on capacity and service radius, we increased the coverage rate to 90.21%. We introduced a new "consultation-referral" model, where existing EMS facilities serve as pre-diagnosis and triage centers, and the urban brownfield EMS parks function as isolation and centralized treatment centers. GIS network analysis confirmed the feasibility, showing all transit times to be under 30 min. The methodology outlined in this study-comprising "demand assessment, supply optimization, and feasibility verification"-not only strengthens the city's EMS system but also facilitates the renewal of urban brownfields. This approach can serve as a valuable reference for enhancing EMS systems in other cities.
PubMed: 38942906
DOI: 10.1038/s41598-024-66080-3 -
Scientific Reports Jun 2024Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic...
Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.
Topics: Humans; Crohn Disease; Ustekinumab; Male; Female; Adult; Treatment Outcome; Middle Aged; Prospective Studies; Follow-Up Studies; Remission Induction; Hungary
PubMed: 38942890
DOI: 10.1038/s41598-024-65987-1 -
American Journal of Medical Genetics.... Jun 2024The ability to make informed decisions about reproductive health is a cornerstone principle of the practice of prenatal medical genetics. Unfortunately, these...
The ability to make informed decisions about reproductive health is a cornerstone principle of the practice of prenatal medical genetics. Unfortunately, these reproductive health decisions have become entangled in the current, contentious political climate. This debate reached an inflection point in 2022 with Dobbs v. Jackson when the Supreme Court of the United States (SCOTUS) overturned the national right to abortion previously established in Roe v. Wade. This decision prompted a reassessment of the opinions of medical students on reproductive health and abortion. Our study focused on a medical school in Alabama, a conservative state that enacted a restrictive abortion ban following the Dobbs ruling. Two surveys, conducted in 2015 and 2022, explored students' viewpoints on reproductive health topics, including abortion. The comparison revealed a significant shift toward more pro-choice perspectives among medical students. Notably, religious affiliation did not consistently align with opinions, as many Christian students supported pro-choice views. Our results suggest that medical students' reproductive health opinions at our institution have shifted to a more pro-choice position over the last decade.
PubMed: 38942743
DOI: 10.1002/ajmg.a.63787 -
Journal of Cardiothoracic and Vascular... Mar 2024To investigate the incidence and risk factors of acute kidney injury (AKI) stage 3 in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO)...
OBJECTIVE
To investigate the incidence and risk factors of acute kidney injury (AKI) stage 3 in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support.
DESIGN
A retrospective case-control study.
SETTING
Single center, Fuwai Hospital.
PARTICIPANTS
Adult VA-ECMO patients age ≥18 years and older treated between January 2020 and December 2022 were included.
INTERVENTIONS
The patients were grouped by whether they developed AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 or <3. Multivariate logistic regression was performed t"o evaluate risk factors of AKI stage 3.
MEASUREMENTS AND MAIN RESULTS
Among enrolled patients, 40 (53.3%) developed AKI stage 3. The in-hospital mortality of AKI stage 3 patients was significantly higher than that of AKI stage <3 patients (67.5% vs 34.3%; p = 0.004). Multivariate logistic regression analysis revealed that concomitant hypertension (odds ratio [OR], 0.250; 95% confidence interval [CI], 0.063, 0.987), p = 0.048), pre-ECMO hemoglobin (OR, 0.969; 95% CI, 0.947-0.992; p = 0.009), pre-ECMO lactate (OR, 1.173; 95% CI, 1.028-1.339; p = 0.018), and pre-ECMO creatinine (OR, 1.014; 95% CI, 1.003-1.025; p = 0.011) were independent risk factors for AKI stage 3.
CONCLUSIONS
This study found a high incidence (53.3%) of AKI stage 3 in adult patients with VA-ECMO support and an association with increased in-hospital mortality. Concomitant hypertension, low pre-ECMO hemoglobin, and elevated pre-ECMO lactate and pre-ECMO creatinine were independent risk factors for AKI stage 3 in patients receiving VA-ECMO. It is imperative to identify and adjust these risk factors to enhance outcomes for those supported by VA-ECMO.
PubMed: 38942685
DOI: 10.1053/j.jvca.2024.03.038 -
Ophthalmology. Retina Jun 2024To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME).
OBJECTIVE
To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME).
DESIGN
Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula.
METHODS
Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein.
MAIN OUTCOME MEASURES
The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set.
RESULTS
Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups.
CONCLUSIONS
This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.
PubMed: 38942386
DOI: 10.1016/j.oret.2024.06.013