London Cancer

In Germany, the German Cancer Society (Deutsche Krebsgesellschaft [DKG]) accredits hospitals to ensure high-quality cancer treatment through adherence to clinical guidelines and a multidisciplinary approach. Evidence suggests certified hospitals (CHs) achieve better clinical outcomes and prognoses than non-certified hospitals (NCHs). However, additional services required for certification incur substantial, unreimbursed costs, necessitating a focused cost-effectiveness evaluation. This retrospective cohort study utilized anonymized administrative routine healthcare data from Allgemeine Ortskrankenkasse, Germany's largest statutory health insurance. The study sample comprised 143,720 incident breast cancer (BC) patients treated between 2009 and 2017 across both CHs and NCHs. A health system perspective was used in this cost-effectiveness analysis. Direct medical costs (inpatient, outpatient, medication, and certification) were compared between CHs and NCHs. Life-years gained (LYG) were calculated from 5-year restricted mean survival time. The incremental cost-effectiveness ratio (ICER), quantified as cost per LYG, served as the primary outcome measure, reported in 2024 euro. Treatment in CHs significantly improved breast cancer survival, yielding 201 LYG per 1000 patients (95% confidence interval: 185-216). Accounting for €1.5 M in certification-related costs and marginal direct medical costs, the total incremental cost was €1.81 M per 1000 patients. This resulted in an ICER of €9036 per LYG. Despite the financial investment required for DKG certification, BC treatment in CHs provided significant survival benefits at a reasonable incremental cost, reinforcing the clinical and economic value. These findings offer critical insights for hospital authorities and healthcare policymakers, supporting the continued investment in certification.

Abstract Background The contribution of cytotoxic T cells to the pathogenesis and treatment outcomes of ulcerative colitis (UC) remains poorly understood. Methods We integrated in vitro functional assays, multiparameter flow cytometry, bulk transcriptomics, single-cell RNA sequencing (scRNAseq), and single-cell spatial transcriptomics analyses to characterise cytotoxic T-cell responses in UC and evaluate their association with clinical and endoscopic outcomes. Results In vitro stimulation of lamina propria mononuclear cells (LPMCs) from UC patients with agonistic anti-CD3 antibodies upregulated cytotoxic gene programs, including GZMB, indicating enhanced T-cell cytotoxicity. Bulk transcriptomics analysis using the TaMMA resource1 confirmed upregulation of these cytotoxic genes in the UC colonic mucosa compared to non-IBD controls and Crohn’s disease. Multiparameter flow cytometry of 42 UC patients and 22 controls showed increased GZMB+ LPMCs in UC. Surprisingly, CD4+ T cells were a major source of GZMB in UC patients and were significantly more abundant than in controls. These GZMB+ CD4+ T cells exhibited a “hyper-inflammatory” polyfunctional phenotype, co-expressing IFN-γ, IL-13, IL-17, IL-22, and TNFα, with cells producing ≥3 pro-inflammatory cytokines significantly increased in UC compared to controls (p = 0.004). Analysis of UC scRNAseq data2 confirmed that GZMB+ CD4+ T cells co-expressed cytotoxic genes (GZMA, PRF1) and pro-inflammatory mediators (IFNG, IL26, OSM) compared to GZMB- CD4+ T cells. A cytotoxic CD4+ T-cell gene signature derived from these data was strongly enriched in UC compared to controls in a large independent cohort (n = 525)3, increasing with endoscopic disease severity and stratifying UC patients by degree of cytotoxic enrichment (Figure 1). Independent single-cell spatial transcriptomics analysis further validated enrichment of this cytotoxic CD4+ T-cell signature in UC versus non-IBD colonic tissues. This signature was also detected in multiple murine models of colitis, with strongest upregulation observed in T-cell transfer colitis. Notably, higher cytotoxic CD4+ T-cell signature enrichment predicted poor response to ustekinumab at week 8 in the UNIFI trial4 (n = 384) for mucosal healing (OR 0.11, p-value = 0.042), even after adjusting for CRP, faecal calprotectin, Total Mayo Score, disease duration, and prior anti-TNF failure. Similarly, the signature was upregulated (p-value = 0.013) in baseline biopsies from UC patients who failed to achieve mucosal healing to infliximab compared with responders in an independent cohort. Conclusion Pro-inflammatory cytotoxic GZMB+ CD4+ T cells are increased in the colonic mucosa of UC patients, correlate with endoscopic disease severity, and predict resistance to biologic therapies.

The vast advancement in pharmaceutical analysis technology, and the evolutionary rise in molecular Biology following the milestone coding of the human genome and the splendid utilisation of computational chemistry and bioinformatics, have called for urgent employment of knowledge, tools and skills to optimise therapies and clinical management. Oral iron chelators have long been in the market but nevertheless require a quality booster to parallel the overall upgrade in all life aspects let alone clinical advances, drugs, and therapeutics. The implementation for such development lies in the hands of medicinal chemists and experts in drug design and discovery. Using bioinformatic approaches, this study aims to predict an ideal structural configuration capable of producing a more effective compound than the long-used oral iron chelator, Deferiprone. In pursuit of such an aspiration, a range of fluorinated hydroxypyridinones (the backbone structure for Deferiprone) have been investigated. Fluorination of drugs in general, has recently been shown to bring about many desired features such as metabolic stability. ADMET lab 2.0 along with few other software that are used in molecular docking; have been brought into play to unfold an ideal, more potent fluorinated hydroxypyridinone than Deferiprone particularly with regards to the toxicity profile.

Cardio-oncology remains a speciality dominated by cardiologists despite the importance of doctors from other specialties, such as oncology and haematology, for managing the cardiovascular health of patients living with cancer. A major reason for this is a distinct lack of cardio-oncology training opportunities for the noncardiology trainee. This is because of several factors, including a lack of awareness of cardio-oncology as a specialty. We propose a cardio-oncology training programme that involves early exposure to cardio-oncology as a specialty and provides the noncardiologist with a good understanding of cardiological investigations and treatment in the context of cancer treatment. Future work should elucidate additional barriers to cardio-oncology training as well as identifying programmes that have integrated cross-disciplinary cardio-oncology content to inform future curriculum development. Future work should also focus on establishing pilot cardio-oncology training programmes for the noncardiologist.