Haematological and biochemical pathology markers for a predictive model for ITU admission and death from COVID-19: A retrospective study.

Coronavirus disease (COVID-19) caused by SARS-CoV-2 has affected over 227 countries. Changes in haematological and biochemical characteristics in patients with COVID-19 are emerging as important features of the disease. This study aims to identify the pathological findings of COVID-19 patients at Bedford Hospital by analysing laboratory parameters that were identified as significant potential markers of COVID-19. Patients who were admitted to Bedford Hospital from March-July 2020 and had a positive swab for COVID were selected for this study. Clinical and laboratory data were collected using ICE system. Multiple haematological and biochemistry biomarkers were analysed using univariate and multivariate logistic regression to predict intensive therapy unit (ITU) admission and/or survival based on admission tests. Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein were elevated in most patients, irrespective of ITU status, representing a common outcome of COVID-19. This was driven by lymphopenia in 80% and neutrophilia in 42% of all patients. Multivariate logistic regression identified an increase in mortality associated with greater age, elevated NLR, alkaline phosphatase activity and hyperkalaemia. With the area under the receiver operating characteristic (ROC) curve of 0.706 +/- 0.04117, negative predictive value (NPV) 66.7% and positive predictive value (PPV) 64.9%. Analysis also revealed an association between increases in serum albumin and potassium concentrations and decreases in serum calcium, sodium and in prothrombin time, with admission to ITU. The area under the ROC curve of 0.8162 +/- 0.0403, NPV 63.3% and PPV 80.5%. These data suggest that using admission (within 4 days) measurements for haematological and biochemical markers, that we are able to predict outcome, whether that is survival or ITU admission.

A UK national audit of the laboratory investigation of phaeochromocytoma and paraganglioma.

BACKGROUND: Phaeochromocytomas and paragangliomas (PPGL) are catecholamine secreting tumours associated with significant morbidity and mortality. Timely diagnosis and management are essential. A range of laboratory tests can be utilised in the investigation of PPGL. There is scope for significant variation in practice between centres. We aimed to investigate how the laboratory investigation of PPGL is performed in laboratories across the United Kingdom. METHODS: A questionnaire consisting of 21 questions was circulated to Clinical Biochemistry laboratories in the United Kingdom via the Association for Clinical Biochemistry and Laboratory Medicine office. The survey was designed to allow audit against Endocrine Society Guidelines on the Investigation and Management of PPGL and to obtain information on other important aspects not included in these guidelines. RESULTS: Responses were received from 58 laboratories and the data were compiled. The majority of laboratories use either urine or plasma metanephrines in first-line testing for PPGL, although a number of different combinations of biochemistry tests are utilised in different centres. All laboratories measuring metanephrines or catecholamines in-house use LC or LC-MS/MS methods. There are some marked differences between laboratories in urine metanephrines reference ranges used and sample requirements. CONCLUSIONS: There is evidence of good practice in UK laboratories (as assessed against Endocrine Society Guidelines) such as widespread use of urine/plasma metanephrines and appropriate analytical methodologies used. However, there is also evidence of variations in practice in some areas that should be addressed.

Steroid metabolism and excretion in severe anorexia nervosa: effects of refeeding.

BACKGROUND: To our knowledge, changes in steroid metabolism in subjects with anorexia nervosa (AN) after weight gain have not been elucidated. OBJECTIVE: We characterized urinary steroid excretion and metabolism in AN patients and investigated the effects of refeeding. DESIGN: In an intervention study, we recruited 7 women with life-threatening weight loss upon admission and after a median [interquartile range (IQR)] of 95 d (88-125 d) of intensive refeeding; 15 age-matched women were recruited as control subjects. The major urinary metabolites were quantified in 24-h collections by capillary gas chromatography. A single examiner measured weights, heights, and skinfold thicknesses. RESULTS: The median (IQR) age of patients was 24 y (21-26 y), and the duration of AN was 4.0 y (3.3-8.0 y). Body mass index (BMI; in kg/m(2)) increased from 12.8 (12.7-13.1) to 18.6 (18.0-19.6) after refeeding (P < 0.0001). Steroid values [median pre-, post-refeeding (P value)] were as follows: androgen metabolites [472, 1017 µg/24 h (0.93)], cortisol metabolites [1960, 3912 µg/24 h (0.60)], and ratios of androsterone (5α)/etiocholanolone (5ß) [0.28, 0.63 (<0.001)], 5α-/5ß-tetrahydrocortisol [0.20, 0.48 (0.02)], tetrahydrocortisols/tetrahydrocortisone [0.87, 0.61 (0.09)], 20-hydroxy-/20-oxocortisol metabolites [0.29, 0.47 (0.01)], and 20α-/20ß-reduced cortisol metabolites [1.18, 1.89 (≥1.00)]. BMI change was positively correlated with 5α-/5ß-tetrahydrocortisol (r = 0.95, P < 0.001). Before refeeding, the following metabolites were lower in patients than in control subjects: androsterone, 5α-tetrahydrocortisol, α-cortolone and α-cortol, 5α-/5ß-tetrahydrocortisol, androsterone/etiocholanolone, and 20-hydroxy/20-oxocortisol (all P < 0.05). After refeeding, all steroid metabolites in patients were at concentrations that were comparable with those in control subjects. CONCLUSIONS: Significant changes in urine steroid-metabolite excretion occurred upon starvation, which were reversed upon refeeding. For cortisol, there were decreases in 5α-/5ß-tetrahydrocortisol and 20-hydroxy-/20-oxometabolites; for androgen, there was a decrease in androsterone/etiocholanolone.

Primary hyperparathyroidism in the older person.

Primary hyperparathyroidism (PHPT) is a common condition which may have few symptoms. One of the principal concerns in the older person with minimally symptomatic PHPT is restoration of bone mineral density and prevention of fracture. Other important considerations are cardiovascular risk and quality of life. Surgery, the traditional treatment of choice, may not always correct these factors. We present a review of the literature and advice of medical therapies which should be of benefit, with emphasis on a multifaceted approach in protecting the patient from PHPT.

Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is a hereditary disorder characterised by uni- or multiglandular parathyroid disease. A subset of families are likely to be genetic variants of other familial tumour syndromes in which PHPT is the main feature, for example multiple endocrine neoplasia type 1 (MEN 1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT). OBJECTIVE: To investigate seven families diagnosed with FIHP, each with two to eight affected family members, to clarify the underlying genetic mechanism. METHODS: The entire MEN1 gene was sequenced for germline mutations and, in addition, tumour specimens were analysed in comparative genomic hybridisation and loss of heterozygosity studies. RESULTS: Two families exhibited MEN1 mutations, L112V and 1658delG, which were associated with loss of the wild-type 11q13 alleles in all tumours analysed. In the remaining five families, no MEN1 mutation was identified. CONCLUSION: These results support the involvement of the MEN1 tumour suppressor gene in the pathogenesis of some of the FIHP kindreds. However, loss on chromosome 11 was seen in all tumours exhibiting somatic deletions, although in two families the tumour deletions involved 11q distal to MEN1. We conclude that the altered MEN1 gene function is of importance in the development of FIHP.