Living fully, choosing wisely: Exploring patient-centred approaches to palliative care and MAiD - Part I.

With increasing numbers of individuals presenting with advanced cancer, strong recommendations for the integration of palliative care in oncology, and the availability and acceptance of medical assistance in dying, oncology nurses must be informed and prepared to provide patient-centred care in advanced cancer. This is part one of a two-part case report presenting an exploration of early palliative care and medical assistance in dying in the setting of advanced cancer. It focuses on the patient and family experience throughout the illness trajectory, from diagnosis to death, and incorporates some of the common challenges seen in supporting someone with advanced cancer.

Different elemental infant formulas show equivalent phosphorus and calcium bioavailability in healthy volunteers.

Retrospective chart reviews have reported hypophosphatemia associated with elemental formula use in infants and children with systemic disease involving multiple diagnoses. The present study aims to evaluate the bioavailability of phosphorus from 2 commercial elemental formulas and to test our hypothesis of bioequivalence of the 2 products in healthy volunteers receiving gastric acid-suppressive medication. A single-center, double-blind, randomized, cross-over study was conducted in healthy volunteers with esomeprazole-induced hypochlorhydria.

Ethics Consultations at a Major Academic Medical Center: A Retrospective, Longitudinal Analysis.

Background: Evidence suggests that healthcare professionals feel inadequately equipped to manage ethical issues that arise, resulting in ethics-related stress. Clinical ethics consultation, and preventive ethics strategies, have been described as ways to decrease ethics-related stress, however information is limited regarding specific sources of ethical concern.

Methods: The purpose of this study was to conduct a retrospective, longitudinal analysis of a comprehensive database of ethics consultations, at a major academic medical center in the Northeast United States in order to: (1) Discern major sources of ethical concern, (2) Evaluate how these have changed over time in their content and frequency, (2a) Evaluate trends in nurse versus physician-initiated requests.

Amino Acid Availability of a Dairy and Vegetable Protein Blend Compared to Single Casein, Whey, Soy, and Pea Proteins: A Double-Blind, Cross-Over Trial.

Protein quality is important for patients needing medical nutrition, especially those dependent on tube feeding. A blend of dairy and vegetable proteins (35% whey, 25% casein, 20% soy, 20% pea; P4) developed to obtain a more balanced amino acid profile with higher chemical scores, was compared to its constituent single proteins. Fourteen healthy elderly subjects received P4, whey, casein, soy, and pea (18 g/360 mL bolus) on five separate visits.

Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study.

Objective: Estetrol (E4) is an estrogen produced exclusively by the human fetal liver during pregnancy. In this study the pharmacodynamic effects of escalating doses of E4 in postmenopausal women were investigated.

Methods: This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women.

Clinical effects of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women.

Objective: Estetrol (E4) is a natural fetal estrogen. The safety of increasing doses of E4 and its preliminary effects on the vagina, endometrium and menopausal vasomotor symptoms were investigated.

Study Design: This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women.

A quantitative non-invasive assessment of femoroacetabular impingement with CT-based dynamic simulation--cadaveric validation study.

Background: Femoroacetabular impingement (FAI) is caused by an anatomic deviation of the acetabular rim or proximal femur, which causes chronic groin pain. Radiological identification of FAI can be challenging. Advances in imaging techniques with the use of computed tomography (CT) scan enable 3D simulation of FAI.

Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer.

Estetrol (E4) is a fetal estrogen with estrogenic effects on reproductive organs and bone in preclinical models and in postmenopausal women. However, E4 exerts antiestrogenic effects on breast cancer (BC) cell growth in vitro and in vivo. We have investigated the effect of 14 days preoperative treatment with 20mg E4 per day on tumor proliferation markers, sex steroid receptor expression and endocrine parameters in a prospective, randomized, placebo-controlled, preoperative window trial in 30 pre- and post-menopausal women with estrogen-receptor positive early BC.

Detection of Clostridium difficile in retail ground meat products in Manitoba.

The aim of the present study was to determine whether Clostridium difficile was present in uncooked retail ground beef and ground pork products sold in Winnipeg, Manitoba. Using an alcohol treatment protocol and inoculation of cultures on C difficile Moxalactam Norfloxacin (CDMN), toxigenic C difficile was found in 6.3% of 48 meat samples.

Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model.

Background: Estetrol (E4) is a pregnancy-specific estrogenic steroid hormone produced by the human fetal liver in both male and female fetuses. During pregnancy, E4 plasma values increase exponentially until parturition and decrease thereafter. The synthesis of E4 in the liver of a newborn ceases during the first weeks after birth.

Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient mice.

Purpose: Radiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of (111)In-octreotide.

Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.

Unlabelled: High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with β-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal radiation dose. In rat PRRT studies, renal protection by the coadministration of lysine was confirmed by histologic examination of kidney specimens indicating nephrotoxicity. In the current study, we investigated dedicated small-animal SPECT/CT renal imaging in rats to monitor renal function in vivo during follow-up of PRRT, with and without lysine.

Nephrotoxicity in mice after repeated imaging using 111In-labeled peptides.

Unlabelled: We determined the renal radiation dose of a series of (111)In-labeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed.

Methods: Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention after injection of 40-50 MBq of (111)In-diethylenetriaminepentaacetic acid-labeled peptides (octreotide, exendin, octreotate, neurotensin, and minigastrin analogs), and the absorbed kidney radiation doses were estimated.

Androgen-regulated gastrin-releasing peptide receptor expression in androgen-dependent human prostate tumor xenografts.

Human prostate cancer (PC) overexpresses the gastrin-releasing peptide receptor (GRPR). Radiolabeled GRPR-targeting analogs of bombesin (BN) have successfully been introduced as potential tracers for visualization and treatment of GRPR-overexpressing tumors. A previous study showed GRPR-mediated binding of radiolabeled BN analogs in androgen-dependent but not in androgen-independent xenografts representing the more advanced stages of PC.

Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours.

Purpose: Peptide receptor radionuclide therapy using β-emitting radiolabelled somatostatin analogues like DOTA,Tyr3-octreotate shows beneficial results in patients suffering from somatostatin receptor overexpressing tumours. However, after high-dose therapy partial renal reabsorption of radiopeptides may lead to nephrotoxicity. Co-infusion of lysine/arginine lowers renal retention of these radiopeptides without affecting tumour uptake.

Versatile conjugation of octreotide to dendrimers by cycloaddition ("click") chemistry to yield high-affinity multivalent cyclic Peptide dendrimers.

The somatostatin analogue Tyr(3)-octreotide, which has a high binding affinity for the SSTR2 receptor (somatostatin receptor subtype 2) expressed on tumor cells, is used clinically for the diagnosis and treatment of a variety of neuroendocrine tumors and gastrointestinal disorders. There is growing interest in the development of multivalent peptide systems, because they may have enhanced binding affinity compared to monovalent analogues. In this report, we describe the design and synthesis of a series of Tyr(3)-octreotide-containing monomeric, dimeric, and tetrameric dendrimeric conjugates.

Clinical applications for estetrol.

In this paper the potential clinical applications for the human fetal estrogen estetrol (E(4)) are presented based on recently obtained data in preclinical and clinical studies. In the past E(4) has been classified as a weak estrogen due to its rather low estrogen receptor affinity. However, recent research has demonstrated that due to its favorable pharmacokinetic properties, especially the slow elimination and long half-life, E(4) is an effective orally bioavailable estrogen agonist with estrogen antagonistic effects on the breast in the presence of estradiol.

Update: improvement strategies for peptide receptor scintigraphy and radionuclide therapy.

Somatostatin receptor-targeting peptides are widely used for the imaging and therapy of neuroendocrine tumors. Peptide-receptor radionuclide therapy (PRRT) in neuroendocrine tumor patients with radiolabeled somatostatin analogs has resulted in symptomatic improvement, prolonged survival, and enhanced quality of life. The side-effects of PRRT are few and mostly mild, certainly when using kidney protective agents.

Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences.

Introduction: During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice.

Molecular imaging of gastrin-releasing peptide receptor-positive tumors in mice using 64Cu- and 86Y-DOTA-(Pro1,Tyr4)-bombesin(1-14).

Bombesin is a tetradecapeptide neurohormone that binds to gastrin-releasing peptide receptors (GRPR). GRPRs have been found in a variety of cancers including invasive breast and prostate tumors. The peptide MP2346 (DOTA-(Pro(1),Tyr(4))-bombesin(1-14)) was designed to bind to these GRP receptors.

Androgen-dependent expression of the gastrin-releasing peptide receptor in human prostate tumor xenografts.

Unlabelled: Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observation suggests that GRP receptors may be used as new visualization and treatment modalities for these tumors. Radiolabeled GRP receptor-targeting analogs of GRP and bombesin (BN) have successfully been developed for these purposes.

Long-term toxicity of [(177)Lu-DOTA (0),Tyr (3)]octreotate in rats.

Purpose And Methods: Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [(177)Lu-DOTA(0),Tyr(3)]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models.