Background
Postoperative relapse rate after gastrectomy and perioperative chemotherapy remain high in patients with advanced gastric cancer due to the spread of disseminated tumour cells in the ...peritoneal cavity. Perioperative administration of catumaxomab could potentially eliminate residual tumour cells after intended curative resection of the primary tumour.
Methods
This open-label, phase II study investigated the safety and efficacy of catumaxomab following neoadjuvant chemotherapy and subsequent surgery in patients with resectable (T2–4, N+, M0) gastric adenocarcinoma. Patients received catumaxomab intra- (single 10 μg dose) and postoperatively (10, 20, 50 and 150 μg on days 7, 10, 13 and 16, respectively). The primary endpoint was the postoperative complication rate (maximum rate defined as <62 %) within 30 days after surgery in patients who received at least the first catumaxomab dose.
Results
Of 64 patients treated with neoadjuvant chemotherapy, 58 underwent surgery and 54 received at least the first catumaxomab dose. Postoperative complications were reported in 18 of 54 evaluable patients (complication rate 33 %; 95 % confidence interval: 21–48 %); thus, the primary endpoint was met. The most frequent complications were pulmonary infection (17 %) and anastomosis insufficiency requiring surgery (11 %). The most common catumaxomab-related adverse events were pyrexia (67 %), leucocytosis (19 %), abdominal pain (17 %) and chills (17 %). The 4-year disease-free and overall survival rates were 38 and 50 %.
Conclusion
Intra- and postoperative administration of catumaxomab as part of a multimodal treatment approach was feasible and tolerable in patients with advanced gastric cancer and should be further investigated in a randomised trial.
Induction of postnatal vasculogenesis, the mobilization of bone marrow-derived endothelial progenitor cells and incorporation of these cells into sites of blood vessel formation, is a well-known ...feature of angiogenic cytokines such as vascular endothelial growth factor. We hypothesized that the angiogenic neuropeptide secretoneurin induces this kind of neovascularization.
Secretoneurin induced mobilization of endothelial progenitor cells to sites of vasculogenesis in vivo in the cornea neovascularization assay. Progenitor cells were incorporated into vascular structures or were located adjacent to them. Systemic injection of secretoneurin led to increase of circulating stem cells and endothelial progenitor cells. In vitro secretoneurin induced migration, exerted antiapoptotic effects, and increased the number of these cells. Furthermore, secretoneurin stimulated the mitogen-activated protein kinase system, as shown by phosphorylation of extracellular signal-regulated kinase, and activated the protein kinase B/Akt pathway. Activation of mitogen-activated protein kinase was necessary for increase of cell number and migration, whereas Akt seemed to play a role in migration of endothelial progenitor cells.
These data show that the angiogenic neuropeptide secretoneurin stimulates postnatal vasculogenesis by mobilization, migration, and incorporation of endothelial progenitor cells.
Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if ...iron dysmetabolism is mechanistically linked to COVID-19 pathobiology.
We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing.
We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia.
Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19.
ClinicalTrials.gov number: NCT04416100.
Summary
There is an unmet need for the treatment of patients with HER2-positive gastroesophageal tumors whose disease progressed on a first-line trastuzumab-based regimen. Several prospective trials ...took a targeted approach and evaluated various HER2-targeted agents as second-line therapy. However, these trials failed to demonstrate a survival benefit and were negative in primary endpoints. Recently, the antibody–drug conjugate trastuzumab deruxtecan has shown promise as a second-line treatment in patients with HER2-positive metastatic gastroesophageal tumors, with a remarkable overall response rate and a relevant prolongation of prognostic outcome. Several clinical trials will introduce more targeted therapy approaches with novel structures, which will hopefully further extend patients’ survival. This mini-review briefly summarizes the past practice of second-line treatment of HER2-positive gastroesophageal tumor patients, describes current knowledge based on recently published studies, and provides a short overview on the novel anti-HER2 compounds that are currently being clinically investigated and could yield positive results in the near future.
Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation ...(AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective analysis of 259 hospitalized patients with COVID-19, we found that, upon admission, 24.7% were anemic, with the majority suffering from AI (68.8%). Anemia was associated with a significantly higher in-hospital mortality (OR 3.729 (95%CI 1.739-7.995),
= 0.001) but not an increased frequency of intensive care unit (ICU) admission or need for mechanical ventilation. FID was present in 80.0% of patients upon admission, linked to more advanced inflammation and associated with significantly longer hospital stay. Notably, a ferritin/transferrin ratio > 10 predicted a five-fold higher risk of ICU admission and an eight-fold higher risk of the need for mechanical ventilation. Anemia and alterations of iron homeostasis are highly prevalent in hospitalized COVID-19 patients. Iron metabolism biomarkers and hemoglobin can contribute to risk stratification of patients, as initial anemia is associated with increased mortality, whereas alterations of iron homeostasis with a higher ferritin/transferrin ratio reflect more advanced inflammation and predicts subsequent insufficient pulmonary oxygenation with the need for ICU admission and mechanical ventilation.
PDF
