Maximal care considerations when treating patients with end-stage heart failure: ethical and procedural quandaries in management of the very sick

Deciding who should receive maximal technological treatment options and who should not represents an ethical, moral, psychological and medico-legal challenge for health care providers. Especially in patients with chronic heart failure, the ethical and medico-legal issues associated with providing maximal possible care or withholding the same are coming to the forefront. Procedures, such as cardiac transplantation, have strict criteria for adequate candidacy. These criteria for subsequent listing are based on clinical outcome data but also reflect the reality of organ shortage. Lack of compliance and non-adherence to lifestyle changes represent relative contraindications to heart transplant candidacy. Mechanical circulatory support therapy using ventricular assist devices is becoming a more prominent therapeutic option for patients with end-stage heart failure who are not candidates for transplantation, which also requires strict criteria to enable beneficial outcome for the patient. Physicians need to critically reflect that in many cases, the patient’s best interest might not always mean pursuing maximal technological options available. This article reflects on the multitude of critical issues that health care providers have to face while caring for patients with end-stage heart failure

Outcomes after urgent thyroidectomy following rapid control of thyrotoxicosis in Graves’ disease are similar to those after elective surgery in well-controlled disease

Background Surgery for Graves’ disease (GD) is usually performed after adequate control with medical treatment. Occasionally, rapid pre-operative optimization is required. The primary objective was to compare the outcomes of patients undergoing elective surgery for well-controlled GD with those undergoing rapid pre-operative treatment. We also propose a formal treatment protocol for future use. Methods A retrospective cohort study in a tertiary referral centre included 247 patients with well-controlled GD undergoing elective surgery and 19 patients with poorly controlled disease undergoing surgery after rapid optimization. The latter group did not respond well to thionamides (carbimazole and/or propylthiouracil) or had intolerance or side effects to thionamides and were treated with a range of non-thionamide drugs, including Lugol’s iodine, cholestyramine, beta blockers and steroids (with or without thionamides), and closely monitored for 1–2 weeks before surgery. Outcome measures included thyroid storm, hypoparathyroidism and recurrent laryngeal nerve palsy. Results In total, 266 patients with male-to-female ratio of 1:6 and median (interquartile range) age of 39 (31–51) were included. Overall, long-term recurrent laryngeal palsy and hypoparathyroidism occurred in 1 (0.38%) and 13 (4.9%) patients, respectively. No patient had thyroid storm. There was no significant difference in hypoparathyroidism (p = 1), vocal cord palsy (p = 0.803) and post-operative bleeding (p = 0.362), between elective surgery and rapid optimization groups. Conclusion Rapid pre-operative treatment is effective, safe and is associated with similar outcomes compared to usual treatment. A rapid pre-operative optimization protocol is proposed

In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

<p>Abstract</p> <p>Background</p> <p>Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties.</p> <p>Methods</p> <p>The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated.</p> <p>Results</p> <p>The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor.</p> <p>Conclusions</p> <p>These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma tumor initiating cells.</p

Atypical glandular cells in conventional cervical smears: Incidence and follow-up

BACKGROUND: Atypical glandular cells on cervical smears are often associated with clinically significant uterine lesions. The frequency and accuracy of AGC-NOS (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of the gland cell type or the degree of suspicion, and their outcome were investigated. METHODS: From January 1, 1990 to December 31, 1999 a total of 261 patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou smear interpretation representing 0.05% of all Pap-smears analyzed at the national level. 191 (73.2%) patients had a subsequent histological examination, 8 samples were not representative by origin and were excluded. RESULTS: Out of 183 AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven precancerous and/or cancerous lesions, 44% being of endocervical and 56% of endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the patients with subsequent invasive endocervical adenocarcinoma (AC) and 56% (28/50) of those patients with invasive endometrial AC were without clinical symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or endometrial AC respectively recorded by the national Morphologic Tumour Registry (MTR) were first identified by a cytological AGC-NOS diagnosis. CONCLUSION: Our findings emphasize the importance of the cytological AGC-category even in the absence of a precise origin or cell type specification. 56% of the AGC-diagnoses being associated with significant cancerous or precancerous conditions, a complete and careful evaluation is required

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Recent advances in hydrothermal carbonisation:from tailored carbon materials and biochemicals to applications and bioenergy

Introduced in the literature in 1913 by Bergius, who at the time was studying biomass coalification, hydrothermal carbonisation, as many other technologies based on renewables, was forgotten during the "industrial revolution". It was rediscovered back in 2005, on the one hand, to follow the trend set by Bergius of biomass to coal conversion for decentralised energy generation, and on the other hand as a novel green method to prepare advanced carbon materials and chemicals from biomass in water, at mild temperature, for energy storage and conversion and environmental protection. In this review, we will present an overview on the latest trends in hydrothermal carbonisation including biomass to bioenergy conversion, upgrading of hydrothermal carbons to fuels over heterogeneous catalysts, advanced carbon materials and their applications in batteries, electrocatalysis and heterogeneous catalysis and finally an analysis of the chemicals in the liquid phase as well as a new family of fluorescent nanomaterials formed at the interface between the liquid and solid phases, known as hydrothermal carbon nanodots