Robotic and Laparoscopic Adrenalectomy for Pheochromocytoma: An International Multicenter Study.

BACKGROUND AND OBJECTIVE: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients. METHODS: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed. We analyzed baseline characteristics and postoperative complications at discharge, 90 d, and 1 yr. We conducted propensity score matching (PSM; 1:1 ratio) and multivariable analyses to evaluate outcomes and risk factors for the occurrence of complications and higher Comprehensive Complication Index (CCI). KEY FINDINGS AND LIMITATIONS: Of 1755 patients, 1613 (91.9%) underwent LA and 142 (8.1%) underwent RA. Estimated blood loss, conversion rate, complication rate, and CCI at discharge, 90 d, and 1 yr were similar between the groups. However, RA was associated with a longer operative time in comparison to LA (100 vs 123 min; p < 0.001), but not after PSM (p = 0.120). Multivariable analysis revealed that Charlson comorbidity index (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.29; p = 0.001), and tumor size per 1-cm increment (OR 1.13, 95% CI 1.07-1.21; p < 0.001) were independently associated with the incidence of complications, but there was no significant difference in complication rates between the LA and RA groups (OR 1.09, 95% CI 0.63-1.87; p = 0.767). After PSM, RA was associated with a lower rate of severe (grade ≥3a) complications in comparison to LA (p = 0.023). CONCLUSIONS AND CLINICAL IMPLICATIONS: RA is a safe alternative to LA and yields similar outcomes for patients with pheochromocytoma. RA may be associated with a lower likelihood of severe complications. Further studies are warranted to determine the role of robotic surgery in pheochromocytoma. PATIENT SUMMARY: Pheochromocytoma is a rare tumor in the adrenal gland and the gold-standard treatment is surgical removal. We assessed patient outcomes after robot-assisted surgery compared with laparoscopic surgery and found that outcomes are similar, but the rate of severe complications may be lower if a surgical robot is used.

A study of variation in therapeutic approach to low-risk differentiated thyroid cancer in the UK.

BACKGROUND: The British Thyroid Association and American Thyroid Association guideline definitions for low-risk differentiated thyroid cancers are susceptible to differing interpretations, resulting in different clinical management in the UK. OBJECTIVE: To explore the national effect of these guidelines on the management of low-risk differentiated thyroid cancers. METHODS: Anonymised questionnaires were sent to multidisciplinary teams performing thyroidectomies in the UK. Risk factors that multidisciplinary teams considered important when managing low-risk differentiated thyroid cancers were established. RESULTS: Most surgeons (71 out of 75; 94.7 per cent) confirmed they were core multidisciplinary team members. More than 80 per cent of respondents performed at least 30 hemi- and/or total thyroidectomies per annum. A majority of multidisciplinary teams (50 out of 75; 66.7 per cent) followed British Thyroid Association guidelines. Risk factors considered important when managing low-risk differentiated thyroid cancers included: type of tumour histology findings (87.8 per cent), tumour size of greater than 4 cm (86.5 per cent), tumour stage T3b (85.1 per cent) and central neck node involvement (85.1 per cent). Extent of thyroid surgery (e.g. hemi- or total thyroidectomy) was highly variable for low-risk differentiated thyroid cancers. CONCLUSION: Management of low-risk differentiated thyroid cancers is highly variable, leading to a heterogeneous patient experience.

Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.

Risk factors for postoperative hypotension after adrenalectomy for phaeochromocytoma: derivation of the PACS risk score.

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

The role of C-reactive protein as a prognostic marker in COVID-19.

BACKGROUND: C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality. METHODS: Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell's C statistic and Akaike information criterion (AIC)]. RESULTS: The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable). CONCLUSIONS: The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.

Impact of Surgery on Older Patients Hospitalized With an Acute Abdomen: Findings From the Older Persons Surgical Outcome Collaborative.

Background: The impact of surgery compared to non-surgical management of older general surgical patients is not well researched. Methods: We examined the association between management and adverse outcomes in a cohort of emergency general surgery patients aged > 65 years. This multi-center study included 727 patients (mean+/-SD, 77.1 ± 8.2 years, 54% female) admitted to five UK hospitals. Data were analyzed using multi-level crude and multivariable logistic regression. Outcomes were: mortality at Day 30 and 90, length of stay, and readmission within 30 days of discharge. Covariates assessed were management approach, age, sex, frailty, polypharmacy, anemia, and hypoalbuminemia. Results: Approximately 25% of participants (n = 185) underwent emergency surgery. Frailty and albumin were associated with mortality at 30 (frailty OR = 3.52 [95% CI 1.66-7.49], albumin OR = 3.78 ([95% CI 1.53-9.31]), and 90 days post discharge (frailty OR = 3.20 [95% CI 1.86-5.51], albumin OR=3.25 [95% CI 1.70-6.19]) and readmission (frailty OR = 1.56 [95% CI (1.04-2.35)]). Surgically managed patients and frailty had increased odds of prolonged hospitalization (surgery OR = 5.69 [95% CI 3.67-8.80], frailty OR = 2.17 [95% CI 1.46-3.23]). Conclusion: We found the impact of surgery on length of hospitalization in older surgical patients is substantial. Whether early comprehensive geriatric assessment and post-op rehabilitation would improve this outcome require further evaluation.

The Clinical Frailty Scale: Estimating the Prevalence of Frailty in Older Patients Hospitalised with COVID-19. The COPE Study.

Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical events including mortality in older people. CFS is also an essential criterion for determining ceilings of care in people with COVID-19. Our aims were to assess the prevalence of frailty in older patients hospitalised with COVID-19, their sex and age distribution, and the completion rate of the CFS tool in evaluating frailty. Methods: Data were collected from thirteen sites. CFS was assessed routinely at the time of admission to hospital and ranged from 1 (very fit) to 9 (terminally ill). The completion rate of the CFS was assessed. The presence of major comorbidities such as diabetes and cardiovascular disease was noted. Results: A total of 1277 older patients with COVID-19, aged ≥ 65 (79.9 ± 8.1) years were included in the study, with 98.5% having fully completed CFS. The total prevalence of frailty (CFS ≥ 5) was 66.9%, being higher in women than men (75.2% vs. 59.4%, p < 0.001). Frailty was found in 161 (44%) patients aged 65-74 years, 352 (69%) in 75-84 years, and 341 (85%) in ≥85 years groups, and increased across the age groups (<0.0001, test for trend). Conclusion: Frailty was prevalent in our cohort of older people admitted to hospital with COVID-19. This indicates that older people who are also frail, who go on to contract COVID-19 may have disease severity significant enough to warrant hospitalization. These data may help inform health care planners and targeted interventions and appropriate management for the frail older person.

Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association between prior NSAID use and time to mortality (adjusted HR (aHR) = 0.89, 95% CI 0.52-1.53, p = 0.67) or length of stay (aHR 0.89, 95% CI 0.59-1.35, p = 0.58). This study found no evidence that routine NSAID use was associated with higher COVID-19 mortality in hospitalised patients; therefore, patients should be advised to continue taking these medications until further evidence emerges. Our findings suggest that NSAID use might confer a modest benefit with regard to survival. However, as this finding was underpowered, further research is required.

The Prevalence of Delirium in An Older Acute Surgical Population and Its Effect on Outcome.

BACKGROUND: With an ageing population, an increasing number of older adults are admitted for assessment to acute surgical units. Older adults have specific factors that may influence outcomes, one of which is delirium (acute cognitive impairment). OBJECTIVES: To establish the prevalence of delirium on admission in an older acute surgical population and its effect on mortality. Secondary outcomes investigated include hospital readmission and length of hospital stay. METHOD: This observational multi-centre study investigated consecutive patients, ≥65 years, admitted to the acute surgical units of five UK hospitals during an eight-week period. On admission the Confusion Assessment Method (CAM) score was performed to detect delirium. The effect of delirium on important clinical outcomes was investigated using tests of association and logistic regression models. RESULTS: The cohort consisted of 411 patients with a mean age of 77.3 years (SD 8.1). The prevalence of admission delirium was 8.8% (95% CI 6.2-11.9%) and cognitive impairment was 70.3% (95% CI 65.6-74.7%). The delirious group were not more likely to die at 30 or 90 days (OR 1.1, 95% CI 0.2 to 5.1, p = 0.67; OR 1.4, 95% CI 0.4 to 4.1. p = 0.82) or to be readmitted within 30 days of discharge (OR 0.9, 95% CI 0.4 to 2.2, p = 0.89). Length of hospital stay was significantly longer in the delirious group (median 8 vs. 5 days respectively, p = 0.009). CONCLUSION: Admission delirium occurs in just under 10% of older people admitted to acute surgical units, resulting in significantly longer hospital stays.

Accreditation of endocrine surgery units.

BACKGROUND/PURPOSE: A key measure to maintain and improve the quality of healthcare is the formal accreditation of provider units. The European Society of Endocrine Surgeons (ESES) therefore proposes a system of accreditation for endocrine surgical centers in Europe to supplement existing measures that promote high standards in the practice in endocrine surgery. METHODS: A working group analyzed the current healthcare situation in the field of endocrine surgery in Europe. Two surveys were distributed to ESES members to acquire information about the structure, staffing, caseload, specifications, and technology available to endocrine surgery units. Further data were sought on tracer diagnoses for quality standards, training provision, and research activity. Existing accreditation models related to endocrine surgery were included in the analysis. RESULTS: The analysis of existing accreditation models, available evidence, and survey results suggests that a majority of ESES members aspire to a two-level model (termed competence and reference centers), sub-divided into those providing neck endocrine surgery and those providing endocrine surgery. Criteria for minimum caseload, number and certification of staff, unit structure, on-site collaborating disciplines, research activities, and training capacity for competence center accreditation are proposed. Lastly, quality indicators for distinct tracer diagnoses are defined. CONCLUSIONS: Differing healthcare structures, existing accreditation models, training models, and varied case volumes across Europe are barriers to the conception and implementation of a pan-European accreditation model. However, there is consensus on accepted standards required for accrediting an ESES competence center. These will serve as a basis for first-stage accreditation of endocrine surgery units.

Mice with a Brd4 Mutation Represent a New Model of Nephrocalcinosis.

Nephrolithiasis (NL) and nephrocalcinosis (NC), which comprise renal calcification of the collecting system and parenchyma, respectively, have a multifactorial etiology with environmental and genetic determinants and affect ∼10% of adults by age 70 years. Studies of families with hereditary NL and NC have identified >30 causative genes that have increased our understanding of extracellular calcium homeostasis and renal tubular transport of calcium. However, these account for <20% of the likely genes that are involved, and to identify novel genes for renal calcification disorders, we investigated 1745 12-month-old progeny from a male mouse that had been treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for radiological renal opacities. This identified a male mouse with renal calcification that was inherited as an autosomal dominant trait with >80% penetrance in 152 progeny. The calcification consisted of calcium phosphate deposits in the renal papillae and was associated with the presence of the urinary macromolecules osteopontin and Tamm-Horsfall protein, which are features found in Randall's plaques of patients with NC. Genome-wide mapping located the disease locus to a ∼30 Mbp region on chromosome 17A3.3-B3 and whole-exome sequence analysis identified a heterozygous mutation, resulting in a missense substitution (Met149Thr, M149T), in the bromodomain-containing protein 4 (BRD4). The mutant heterozygous (Brd4+/M149T ) mice, when compared with wild-type (Brd4+/+ ) mice, were normocalcemic and normophosphatemic, with normal urinary excretions of calcium and phosphate, and had normal bone turnover markers. BRD4 plays a critical role in histone modification and gene transcription, and cDNA expression profiling, using kidneys from Brd4+/M149T and Brd4+/+ mice, revealed differential expression of genes involved in vitamin D metabolism, cell differentiation, and apoptosis. Kidneys from Brd4+/M149T mice also had increased apoptosis at sites of calcification within the renal papillae. Thus, our studies have established a mouse model, due to a Brd4 Met149Thr mutation, for inherited NC. © 2019 American Society for Bone and Mineral Research.

An N-Ethyl-N-Nitrosourea (ENU)-Induced Tyr265Stop Mutation of the DNA Polymerase Accessory Subunit Gamma 2 (Polg2) Is Associated With Renal Calcification in Mice.

Renal calcification (RCALC) resulting in nephrolithiasis and nephrocalcinosis, which affects ∼10% of adults by 70 years of age, involves environmental and genetic etiologies. Thus, nephrolithiasis and nephrocalcinosis occurs as an inherited disorder in ∼65% of patients, and may be associated with endocrine and metabolic disorders including: primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, and hyperoxaluria. Investigations of families with nephrolithiasis and nephrocalcinosis have identified some causative genes, but further progress is limited as large families are unavailable for genetic studies. We therefore embarked on establishing mouse models for hereditary nephrolithiasis and nephrocalcinosis by performing abdominal X-rays to identify renal opacities in N-ethyl-N-nitrosourea (ENU)-mutagenized mice. This identified a mouse with RCALC inherited as an autosomal dominant trait, designated RCALC type 2 (RCALC2). Genomewide mapping located the Rcalc2 locus to a ∼16-Mbp region on chromosome 11D-E2 and whole-exome sequence analysis identified a heterozygous mutation in the DNA polymerase gamma-2, accessory subunit (Polg2) resulting in a nonsense mutation, Tyr265Stop (Y265X), which co-segregated with RCALC2. Kidneys of mutant mice (Polg2+/Y265X ) had lower POLG2 mRNA and protein expression, compared to wild-type littermates (Polg2+/+ ). The Polg2+/Y265X and Polg2+/+ mice had similar plasma concentrations of sodium, potassium, calcium, phosphate, chloride, urea, creatinine, glucose, and alkaline phosphatase activity; and similar urinary fractional excretion of calcium, phosphate, oxalate, and protein. Polg2 encodes the minor subunit of the mitochondrial DNA (mtDNA) polymerase and the mtDNA content in Polg2+/Y265X kidneys was reduced compared to Polg2+/+ mice, and cDNA expression profiling revealed differential expression of 26 genes involved in several biological processes including mitochondrial DNA function, apoptosis, and ubiquitination, the complement pathway, and inflammatory pathways. In addition, plasma of Polg2+/Y265X mice, compared to Polg2+/+ littermates had higher levels of reactive oxygen species. Thus, our studies have identified a mutant mouse model for inherited renal calcification associated with a Polg2 nonsense mutation. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Is anemia associated with cognitive impairment and delirium among older acute surgical patients?

AIM: The determinants of cognitive impairment and delirium during acute illness are poorly understood, despite being common among older people. Anemia is common in older people, and there is ongoing debate regarding the association between anemia, cognitive impairment and delirium, primarily in non-surgical patients. METHODS: Using data from the Older Persons Surgical Outcomes Collaboration 2013 and 2014 audit cycles, we examined the association between anemia and cognitive outcomes in patients aged ≥65 years admitted to five UK acute surgical units. On admission, the Confusion Assessment Method was carried out to detect delirium. Cognition was assessed using the Montreal Cognitive Assessment, and two levels of impairment were defined as Montreal Cognitive Assessment <26 and <20. Logistic regression models were constructed to examine these associations in all participants, and individuals aged ≥75 years only. RESULTS: A total of 653 patients, with a median age of 76.5 years (interquartile range 73.0-80.0 years) and 53% women, were included. Statistically significant associations were found between anemia and age; polypharmacy; hyperglycemia; and hypoalbuminemia. There was no association between anemia and cognitive impairment or delirium. The adjusted odds ratios of cognitive impairment were 0.95 (95% CI 0.56-1.61) and 1.00 (95% CI 0.61-1.64) for the Montreal Cognitive Assessment <26 and <20, respectively. The adjusted odds ratio of delirium was 1.00 (95% CI 0.48-2.10) in patients with anemia compared with those without. Similar results were observed for the ≥75 years age group. CONCLUSIONS: There was no association between anemia and cognitive outcomes among older people in this acute surgical setting. Considering the retrospective nature of the study and possible lack of power, findings should be taken with caution. Geriatr Gerontol Int 2018; 18: 1025-1030.

Prevalence of multimorbidity and its association with outcomes in older emergency general surgical patients: an observational study.

OBJECTIVES: Multimorbidity is the presence of 2 or more medical conditions. This increasingly used assessment has not been assessed in a surgical population. The objectives of this study were to assess the prevalence of multimorbidity and its association with common outcome measures. DESIGN: A cross-sectional observational study. SETTING: A UK-based multicentre study, included participants between July and October 2014. PARTICIPANTS: Consecutive emergency (non-elective) general surgical patients admitted to hospital, aged over 65 years. OUTCOME MEASURES: The outcome measures were (1) the prevalence of multimorbidity and (2) the association between multimorbidity and frailty; the rate and severity of surgery; length of hospital stay; readmission to hospital within 30 days of discharge; and death at 30 and 90 days. RESULTS: Data were collected on 413 participants aged 65-98 years (median 77 years, (IQR (70-84)). 51.6% (212/413) participants were women. Multimorbidity was present in 74% (95% CI 69.7% to 78.2%) of the population and increased with age (p<0.0001). Multimorbidity was associated with increasing frailty (p for trend <0.0001). People with multimorbidity underwent surgery as often as those without multimorbidity, including major surgery (p=0.03). When comparing multimorbid people with those without multimorbidity, we found no association between length of hospital stay (median 5 days, IQR (1-54), vs 6 days (1-47), (p=0.66)), readmission to hospital (64 (21.1%) vs 18 (16.8%) (p=0.35)), death at 30 days (14 (4.6%) vs 6 (5.6%) (p=0.68)) or 90-day mortality (28 (9.2%) vs 8 (7.6%) (p=0.60)). CONCLUSIONS AND IMPLICATIONS: Multimorbidity is common. Nearly three-quarters of this older emergency general surgical population had 2 or more chronic medical conditions. It was strongly associated with age and frailty, and was not a barrier to surgical intervention. Multimorbidity showed no associations across a range of outcome measures, as it is currently defined. Multimorbidity should not be relied on as a useful clinical tool in guidelines or policies for older emergency surgical patients.

The prevalence of hyperglycaemia and its relationship with mortality, readmissions and length of stay in an older acute surgical population: a multicentre study.

BACKGROUND: The purpose of the study is to examine the prevalence of hyperglycaemia in an older acute surgical population and its effect on clinically relevant outcomes in this setting. METHODS: Using Older Persons Surgical Outcomes Collaboration (OPSOC) multicentre audit data 2014, we examined the prevalence of admission hyperglycaemia, and its effect on 30-day and 90-day mortality, readmission within 30 days and length of acute hospital stay using logistic regression models in consecutive patients, ≥65 years, admitted to five acute surgical units in the UK hospitals in England, Scotland and Wales. Patients were categorised in three groups based on their admission random blood glucose: <7.1, between 7.1 and 11.1 and ≥11.1 mmol/L. RESULTS: A total of 411 patients (77.25±8.14 years) admitted during May and June 2014 were studied. Only 293 patients (71.3%) had glucose levels recorded on admission. The number (%) of patients with a blood glucose <7.1, 7.1-11.1 and ≥11.1 mmol/L were 171 (58.4), 99 (33.8) and 23 (7.8), respectively. On univariate analysis, admission hyperglycaemia was not predictive of any of the outcomes investigated. Although the characteristics of those with no glucose level were not different from the included sample, 30-day mortality was significantly higher in those who had not had their admission glucose level checked (10.2% vs 2.7%), suggesting a potential type II error. CONCLUSION: Despite current guidelines, nearly a third of older people with surgical diagnoses did not have their glucose checked on admission highlighting the challenges in prognostication and evaluation research to improve care of older frail surgical patients.

A Retroperitoneal Leiomyosarcoma Presenting as an Adrenal Incidentaloma in a Subject on Warfarin.

Adrenal incidentalomas (AIs) are mostly benign and nonsecretory. Management algorithms lack sensitivity when assessing malignant potential, although functional status is easier to assess. We present a subject whose AI was a retroperitoneal leiomyosarcoma (RL). Case Presentation. A woman on warfarin with SLE and the antiphospholipid syndrome, presented with left loin pain. She was normotensive and clinically normal. Ultrasound scans demonstrated left kidney scarring, but CT scans revealed an AI. MRI scans later confirmed the AI without significant fat and no interval growth. Cortisol after 1 mg dexamethasone, urinary free cortisol and catecholamines, plasma aldosterone renin ratio, and 17-hydroxyprogesterone were within the reference range. Initially, adrenal haemorrhage was diagnosed because of warfarin therapy and the acute presentation. However, she underwent adrenalectomy because of interval growth of the AI. Histology confirmed an RL. The patient received adjuvant radiotherapy. Discussion. Our subject presented with an NSAI. However, we highlight the following: (a) the diagnosis of adrenal haemorrhage in this anticoagulated woman was revised because of interval growth; (b) the tumour, an RL, was relatively small at diagnosis;

Routine coagulation screening is an unnecessary step prior to ERCP in patients without biochemical evidence of jaundice: a cross-centre study.

INTRODUCTION: Guidelines suggest that all patients with choledocholithiasis should have a coagulation screen prior to endoscopic retrograde cholangiopancreatography (ERCP). This study aims to establish the incidence of deranged coagulation in such patients and its relationship with bleeding complications. METHODS: Analysis of consecutive patients undergoing ERCP procedures at two NHS sites was undertaken. Exclusion criteria were anti-coagulation use, bleeding disorders or incomplete data. Demographic data, pre-procedure bilirubin and prothrombin time (PT), ERCP procedural information, and bleeding complications were recorded for each. The cohort was divided into jaundice and non-jaundiced groups. Statistical analysis was performed using the student's t-test, Chi-squared test and Fisher's exact test. RESULTS: 793 patients (419 jaundiced; 374 non-jaundiced) were included. PT was significantly higher in the jaundiced group (greater by 2 (1.35-2.64) seconds; p < 0.001). PT was prolonged in 26.7 per cent of the jaundiced group; 28 patients (6.7 per cent) had a PT of >16.8 s 5.9 per cent of the non-jaundiced group had prolonged PT, with 1 patient having a PT >16.8 s. There were 5 major, and 32 minor bleeding complications with no differences between groups. In those with abnormal coagulation, only 1 minor bleeding complication occurred in a jaundiced patient. DISCUSSION: Normal pre-ERCP bilirubin was 99.7% (98.5-100) sensitive to predict a PT <16.8 s. Cost savings of £14,350 could have been achieved with judicial use of coagulation screening. CONCLUSION: Pre-ERCP coagulation screening should only be indicated in patients with a raised bilirubin or individuals on anticoagulation therapy or with a history of bleeding diathesis.

The prevalence of cognitive impairment in emergency general surgery.

OBJECTIVES: Rates of all surgical procedures are increasing at a faster rate than the population is ageing. However, this encouraging statistic, necessitates a robust evidence base. The epidemiological evidence base in acute general surgery in the older person is sparse. This is the first assessment of the prevalence of cognitive impairment measured using the Montreal Cognitive Assessment tool (MoCA) in acute general surgery. METHODS: In three sites in Wales, England and Scotland comprising rural and urban populations, we studied consecutive patients aged over 65 years. We considered any older person admitted to the acute general surgical unit. We assessed them for baseline demographic data. They each underwent a MoCA assessment. RESULTS: We collected data on 245 people, mean age 76.9 years (8.1, standard deviation), 136 (55.5%) were women. Of these 201 completed the MoCA test, mean score of 18.9 and median score 20 (range 0-30). There were 37 (15.1%) MoCA scores in the normal range (≥26) and 44 (18%) people were unable to attempt (or complete) the MoCA. Increasing age (p < 0.01) but not sex (p = 0.14) predicted an abnormal MoCA. Considering only the 44 people who were unable to attempt the MoCA assessment, 11 (25%) were known to have a diagnosis of dementia, 9 (20.5%) were too unwell and the remainder unable to complete the assessment to due pre-existing disability. CONCLUSIONS: In a representative UK wide population, a high proportion of older people admitted with an acute general surgical problem had cognitive impairment when assessed using the MoCA.

Autosomal dominant hypercalciuria in a mouse model due to a mutation of the epithelial calcium channel, TRPV5.

Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1). Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5) and 6 (Trpv6) genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P). Compared to wild-type littermates, heterozygous (Trpv5(682P/+)) and homozygous (Trpv5(682P/682P)) mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5(682P/682P) mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D(3) concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5(682P/+) and Trpv5(682P/682P) mice consistent with a trafficking defect. In addition, Trpv5(682P/682P) mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D(28K), consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings indicate that the TRPV5 S682P mutant is functionally significant and study of HCALC1, a novel model for autosomal dominant hypercalciuria, may help further our understanding of renal calcium reabsorption and hypercalciuria.