Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Association of Multimodal Pain Control with Patient-Reported Outcomes in Children Undergoing Surgery

IntroductionOur aim was to describe practices in multimodal pain management at US children's hospitals and evaluate the association between non-opioid pain management strategies and pediatric patient-reported outcomes (PROs).MethodsData were collected as part of the 18-hospital ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) clinical trial. Non-opioid pain management strategies included use of preoperative and postoperative non-opioid analgesics, regional anesthetic blocks, and a biobehavioral intervention. PROs included perioperative nervousness, pain-related functional disability, health-related quality of life (HRQoL). Associations were analyzed using multinomial logistic regression models.ResultsAmong 186 patients, 62 (33%) received preoperative analgesics, 186 (100%) postoperative analgesics, 81 (44%) regional anesthetic block, and 135 (73%) used a biobehavioral intervention. Patients were less likely to report worsened as compared to stable nervousness following regional anesthetic block (relative risk ratio [RRR]:0.31, 95% confidence interval [CI]:0.11–0.85), use of a biobehavioral technique (RRR:0.26, 95% CI:0.10–0.70), and both in combination (RRR:0.08, 95% CI:0.02–0.34). There were no associations of non-opioid pain control modalities with pain-related functional disability or HRQoL.ConclusionUse of postoperative non-opioid analgesics have been largely adopted, while preoperative non-opioid analgesics and regional anesthetic blocks are used less frequently. Regional anesthetic blocks and biobehavioral interventions may mitigate postoperative nervousness in children.Level of evidenceIII.     

The Optimal Primary Treatment for Pediatric Perianal Abscess and Anal Fistula: A Systemic Review and Meta-Analysis

BackgroundPerianal abscesses and anal fistulas are common. The principle of intention-to-treat has not been considered in previous systemic reviews. Thus, the comparison between primary and post-recurrence management was confused, and the recommendation of primary treatment is obscure. The current study aims to identify the optimal initial treatment for pediatric patients.MethodsUsing PRISMA guidelines, studies were identified from MEDLINE, EMBASE, PubMed, Cochrane Library, and Google Scholar without any language or study design restriction. The inclusion criteria include original articles or articles with original data, studies of management for a perianal abscess with or without anal fistula, and patient age of <18 years. Patients with local malignancy, Crohn's disease, or other underlying predisposing conditions were excluded. Studies without analyzing recurrence, case series of <5, and irrelevant articles were excluded in the screening stage. Of the 124 screened articles, 14 articles had no full texts or detailed information. Articles written in a language other than English or Mandarin were translated by Google Translation first and confirmed with native speakers. After the eligibility process, studies that compared identified primary managements were then included in the qualitative synthesis.ResultsThirty-one studies involving 2507 pediatric patients met the inclusion criteria. The study design consisted of two prospective case series of 47 patients and retrospective cohort studies. No randomized control trials were identified. Meta-analyses for recurrence after initial management were performed with a random-effects model. Conservative treatment and drainage revealed no difference (Odds ratio [OR], 1.222; 95% Confidential interval [CI]: 0.615–2.427, p = 0.567). Conservative management had a higher risk of recurrence than surgery without statistical significance (OR 0.278, 95% CI: 0.109–0.707, p = 0.007). Compared with incision/drainage, surgery can prevent recurrence remarkably (OR 4.360, 95% CI: 1.761–10.792, p = 0.001). Subgroup analysis of different approaches within conservative treatment and operation was not performed for lacking information.ConclusionStrong recommendations cannot be made due to the lack of prospective or randomized controlled studies. However, the current study based on real primary management supports initial surgical intervention for pediatric patients with perianal abscesses and anal fistula to prevent recurrence.Level of evidenceType of study: Systemic review; Evidence level: Level II.     

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation

ObjectiveThe use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation.MethodsThe AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement.ResultsThe expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively.ConclusionsAchieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.     

国外动物智能军事应用情报研究

目的：阐述动物智能在军事学的应用及意义。方法：以学术论文、新闻、报纸、智库报告等作为信息源，综合研究国外动物智能军事应用实例及内在关联，描述动物智能在未来战场应用场景。结果：动物智能军事应用主要是动物特殊能力的军事应用和动物智能的仿生武器应用。结论：动物部队、仿生作战部队和动物战术是未来战争不可忽视的重要组成部分，动物智能的隐匿、灵活、多变等特点正逐渐被广泛应用于战场。     

Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Utility of Differential White Cell Count and Cell Population Data for Ruling Out COVID-19 Infection in Patients With Community-Acquired Pneumonia

IntroductionThe main aim of this study was to assess the utility of differential white cell count and cell population data (CPD) for the detection of COVID-19 in patients admitted for community-acquired pneumonia (CAP) of different etiologies.MethodsThis was a multicenter, observational, prospective study of adults aged ≥18 years admitted to three teaching hospitals in Spain from November 2019 to November 2021 with a diagnosis of CAP. At baseline, a Sysmex XN-20 analyzer was used to obtain detailed information related to the activation status and functional activity of white cells.ResultsThe sample was split into derivation and validation cohorts of 1065 and 717 patients, respectively. In the derivation cohort, COVID-19 was confirmed in 791 patients and ruled out in 274 patients, with mean ages of 62.13 (14.37) and 65.42 (16.62) years, respectively (p < 0.001). There were significant differences in all CPD parameters except MO-Y. The multivariate prediction model showed that lower NE-X, NE-WY, LY-Z, LY-WY, MO-WX, MO-WY, and MO-Z values and neutrophil-to-lymphocyte ratio were related to COVID-19 etiology with an AUC of 0.819 (0.790, 0.846). No significant differences were found comparing this model to another including biomarkers (p = 0.18).ConclusionsAbnormalities in white blood cell morphology based on a few cell population data values as well as NLR were able to accurately identify COVID-19 etiology. Moreover, systemic inflammation biomarkers currently used were unable to improve the predictive ability. We conclude that new peripheral blood biomarkers can help determine the etiology of CAP fast and inexpensively.     

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.