St. Claraspital

Healthcare across Europe was affected by COVID-19 pandemic lockdowns. How different national healthcare systems coped with this impact remains unclear. Healthcare in Switzerland differs significantly from that in Scotland, for example, in terms of centralization. The aim of this study was to assess the impact of the COVID-19 pandemic on the diagnosis and surgical treatment of colorectal cancer (CRC) in contrasting healthcare systems. This retrospective cohort study was conducted in south-east Scotland and in the extended north-west of Switzerland from January 1st, 2019 to February 28th, 2023. All patients diagnosed with CRC were included. The primary outcomes were the time from CRC diagnosis to treatment and the UICC stage at diagnosis, assessed prior to, during, and following the period of lockdown. The lockdown in Scotland lasted from March 2020 to October 2020 and in Switzerland from March 2020 to April 2020. A total of 6745 patients were included (4127 from Scotland and 2618 from Switzerland). Median time from diagnosis to treatment remained unaltered during the lockdown period in both countries. However, after the lockdown, the median time from diagnosis to treatment increased from 59 to 76days in Scotland. The median number of patients who were diagnosed per annual quarter declined from 177 (IQR: 171-190) to 152 (IQR: 150-154), and the median number of who received treatment from declined from 256 (IQR: 253-259) to 203 (IQR: 186-218) during lockdown in Scotland. In multivariable logistic regression, the odds of being diagnosed with UICC stage IV increased by 42% for patients diagnosed during lockdown (95%-CI: 12%-81%). In Switzerland, the time from diagnosis to treatment increased slightly after the pandemic. However, the other effects described above were not observed in Switzerland. This descriptive study demonstrated that the impact of the pandemic on colorectal cancer care was less pronounced in Switzerland, but considerable in Scotland. Because separate subgroup analyses were conducted, direct comparisons cannot be made between Scotland and Switzerland. This trial is registered on clinicaltrials.gov as part of the EvaCol study (NCT04550156).

Integrative oncology (IO) combines conventional cancer medicine with evidence-based complementary procedures, thereby placing special demands on the concept of evidence, research methodology, and the evaluation of care quality. This article highlights key theoretical, methodological, and practical principles. The classic concept of evidence is examined in detail through the three pillars of evidence-based medicine. Complementary research designs such as mixed methods, pragmatic studies, whole-systems approaches, and preference-based designs, are discussed as they offer new perspectives for generating valid and patient-centered evidence. In addition, regulation and practice-oriented quality criteria are presented as well as the current consensus process within the newly founded "Swiss Network for Integrative Oncology" (SNIO), which defines common standards, training structures, and research strategies. These efforts lay the foundation for the ongoing development of the field - toward an IO that is safe, effective, and truly patient-centered.

The application of patient-derived organoids (PDOs) in prostate cancer (PCa) research has been hampered by poor take rates and benign overgrowth. We highlight the limitations of existing culture conditions and identify extracellular matrix composition as a determinant of organoid outcome. Single-cell RNA sequencing reveals that Matrigel-free PDOs exhibit cellular heterogeneity, preserve patient-specific PCa cells with active androgen receptor signaling, and enrich in intermediate cells. In contrast, Matrigel fails to maintain primary PCa cells and produces in vitro basal-like features divergent from patient samples. Furthermore, we redefine cell-type signatures, identify biomarkers discriminating tumor versus other cell types, and show that expression of laminin-binding integrins is a hallmark of Matrigel-derived organoids. Finally, integrating previously published datasets with our data, we generate a prostate PDO single-cell atlas (PPScA), which captures a spectrum of cellular identities while revealing pathways altered in vitro. Our study provides methodological improvements for short-term culture and cellular biology insights.

<bold>Background:</bold> Pulmonary embolism (PE) is a major health burden. Its acute management has been extensively studied permitting in the past decades progress on mortality. Recent studies showed that number of patients complains of long-term symptoms after a PE. Up to half of patients report dyspnea months after acute PE. The term post-PE syndrome was proposed as definition for all the manifestations after PE that cannot be associated to other causes. These symptomatic patients seem to have a higher morbidity and therefore to consume more healthcare resources. <bold>Objectives:</bold> The aim of this study is to analyses which are the preexisting conditions associated with a dyspnea after PE. <bold>Methods:</bold> This study is a post-hoc analysis on a large cohort of PE patients (n=508) followed with a dyspnea-based algorithm (INPUT study). We analyzed which baseline characteristics of these patients were significantly associated with a NYHA functional class ≥ II after an acute PE. <bold>Results:</bold> 19% of the patients in the cohort presented new dyspnea during the two years following an acute PE. Multivariate and univariate analysis showed that higher BMI (OR 1.08), female sex (OR 2.48) and CETPH were significantly associated with dyspnea. Age, smoking status, anticoagulation type, active cancer, cause of PE were not significantly associated with dyspnea. <bold>Conclusions:</bold> Dyspnea is a frequent complain after a PE. Pre-existing characteristics such BMI and female sex may play a role in its development. The comorbidities probably also play a relevant role in the development of a dyspnea after a PE. Further studies are needed to assess and help patient with persisting respiratory symptoms after PE.

The bone marrow (BM) is altered in obesity to promote myeloid cell generation, but the mechanisms driving these changes remain unclear. Here, we show that obesogenic stimuli promote adipose tissue macrophages to recruit neutrophils from the BM in mice. Recruitment of BM neutrophils activates hematopoietic stem cells, which produce myeloid cells that accumulate in the circulation and drive inflammation. This recruitment is not resolved by weight loss, leading to sustained myelopoiesis in previously obese mice. Inhibiting neutrophil recruitment out of the BM in obese mice or during weight loss reduces BM myelopoiesis and adipose tissue inflammation, and improves glucose tolerance. In humans with obesity, plasma neutrophil chemokines are increased, correlate with increased insulin resistance, but do not decrease with weight loss. Our results demonstrate that neutrophil recruitment is a key mediator of myelopoiesis during obesity, and targeting this pathway is a potential strategy to improve inflammation during obesity and weight loss.