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

Meeting abstrac

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

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

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

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

Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.MethodsRECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes.DiscussionRECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC

Application of the contour method to determine axial residual stresses in cold extruded steel rods

Residual stresses in cold extruded parts play an important role in both component lifetime and succeeding in manufacturing performance. When a cold extruded part is used directly, the lifetime of the part depends on the residual stresses induced during cold extrusion. On the other hand, if the part is exposed to post operations such as machining, residual stresses may cause distortions. Despite their importance, there are only a few residual stress measurement methods to assess axial residual stresses in full cylindrical thick components of massive forming. As high-energy X-ray and neutron diffraction methods are less available and considerably expensive, the contour method may be an alternative providing the accurate assessment of residual stresses without requiring specialized facilities. In the present work, residual stresses in cold extruded rods are determined via the contour method for various extrusion ratios. The finite element analyses for the same conditions are also carried out to provide the comparison to the contour method. The results indicate that the contour method can be a valuable candidate for the measurement of axial residual stresses in cold extruded thick components.</jats:p