A retrospective analysis of postpartum red blood cell transfusions at a tertiary care obstetric centre.

BACKGROUND AND OBJECTIVES: Postpartum anaemia is a prevalent health problem. We aimed to determine the compliance rate for red blood cell (RBC) transfusion indication among postpartum women in a single tertiary care centre in Quebec, Canada. MATERIALS AND METHODS: Retrospective cohort study including all women ≥6 h postpartum who received ≥1 RBC transfusion during their delivery hospitalization between January 2005 and February 2022. We determined our centre's compliance rate by indication as compared to current society guidelines, all published after 2015 (Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis [NATA], Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG]). We then explored predictors of guideline non-compliance and described transfusion practices in our centre. RESULTS: A total of 171 women were included. Our centre's compliance rate was 79.5% (95% confidence interval [CI] 72.7-84.8). Predictors of guideline non-compliance were maternal medical comorbidity or abnormal placentation, both limited by large CIs (odds ratio [OR] 2.26, CI 1.02-4.94, p = 0.04; OR 4.00, CI 1.31-12.06, p = 0.01, respectively). Postpartum haemorrhage was diagnosed among 68% of the cohort, mostly due to uterine atony (73.3%). Mean baseline and nadir haemoglobin were 111 g/L (±18) and 62 g/L (±7.7), respectively. Multiple unit initial transfusion was found in a majority of patients (63.7%). Iron therapy was administered to 51.5% of women in-hospital and 81.9% received an oral iron prescription at discharge. There were no differences in primary or secondary outcomes subsequent to relevant guideline publication. CONCLUSION: Our centre's compliance rate for RBC transfusion indication meets current practice guidelines. Areas for improvement include single-unit initial transfusion protocols and adjuvant iron treatment. Antenatal optimization of haemoglobin and ferritin stores may limit postpartum transfusions.

Combination treatments to enhance peptide receptor radionuclide therapy of neuroendocrine tumours.

The incidence of neuroendocrine tumours (NETs) is increasing, but curative therapeutic options are limited because diagnosis is often delayed until the tumour has metastasized. Peptide receptor radionuclide therapy (PRRT) is among the most effective therapeutic options for metastatic NETs because of targeted delivery of radioactivity to the tumour via the somatostatin receptor (SSTR) and relatively low systemic toxicity. However, current PRRT regimes result in palliation rather than cure, and higher doses of PRRT that might achieve remission would also be too toxic to the patients. Therefore, there is a need to improve PRRT of NETs by combining it with other agents to achieve maximum benefits from the internal radiation therapy, while sparing non-target organs from radiation toxicity. Here we review various current and potential combination strategies to improve 177Lu-octreotate-based PRRT of NET, some of which could also apply to other radionuclide therapies. These strategies include co-administered drugs that improve delivery of the radiopharmaceutical via increased tumour perfusion or through increased SSTR density at tumour surface. Other combinations are aimed at enhancing the biological effects of the radiation-induced DNA damage in tumour cells or generating additional DNA damage burden to effectively increase the cytotoxicity of PRRT. We also propose an algorithm for stratifying NET patients to receive or not combination therapies with PRRT. Considering that PRRT and many of these combination agents are already used for treating patients with NET and other cancers, the proposed strategies to improve the efficacy of PRRT could be rapidly translated into the clinic.

Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells.

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3-7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor.

For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177Lu-[DOTA0-Tyr3]-octreotate (177Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177Lu-octreotate PRRT of NETs.