Survey of Laboratory Medicine's national response to the HSE cyberattack in the Republic of Ireland.

BACKGROUND: On Friday 14 May 2021, the Health Service Executive (HSE) was subjected to a serious cyberattack on their information technology (IT) infrastructure. Healthcare workers lost access to HSE-provided clinical and non-clinical IT systems, including laboratory systems. AIM: The aim of this national survey was to capture Laboratory Medicine's response across the Republic of Ireland during the HSE cyberattack. METHOD: An electronic survey developed using Microsoft Forms® was emailed on 24 September 2021 to 58 local representatives of the PeriAnalytic and Laboratory Medicine Society (PALMSoc). RESULTS: The survey was sent to 43 clinical laboratories across the Republic of Ireland. A total of 41 responses from 43 laboratories across all laboratory disciplines were received (95% response rate). From these, 55% did not have access to a functioning LIS, with 56% of these not having access to a LIS for greater than 2 weeks. A decrease in specimen requests received during this period was reported by 74% of laboratories, with 32% experiencing a reduction that lasted in excess of one month. Over half of the laboratories (55%) experienced a reduction of > 30% in requests, indicating that clinicians stopped investigating patients (87% reduction in primary care), further escalating the disruption to healthcare. CONCLUSION: The cyberattack burdened the HSE and laboratories at a time when healthcare staffs were coming to terms with the impact of the COVID-19 pandemic. Despite this, the survey confirms the agility of laboratory staff in meeting the demands placed on it during this time.

The CELTIC ranges project (comprehensive and effective laboratory test reference intervals for Irish children) methodology and results for renal profile tests in plasma on the Roche modularTM system.

BACKGROUND: The CELTIC ranges project aims to deliver a comprehensive range of reference intervals for commonly ordered laboratory investigations suitable for use in an Irish population as well as enabling comparison with relevant international studies. In this paper, we describe our methodology used throughout the entire project and present paediatric reference intervals for renal profile tests in plasma (sodium, potassium, urea and creatinine). METHODS: 1023 children aged up to 17 years were recruited from our hospital's general practitioner paediatric phlebotomy clinic. Clinical chemistry analyses were performed on the Roche modular system and statistical analysis was completed in line with CLSI guideline EP28-A3c. RESULTS: The plasma reference interval for sodium for ages 0.45-16.99 years was 137-143 mmol/L in 1000 subjects (combined genders). For plasma potassium, the corresponding ranges between 1 and 16.99 years (combined genders) were 3.6-4.8 mmol/L. Apart from neonates and in keeping with other studies, age partitioning for electrolytes was not required. Data for plasma creatinine (enzymatic methodology) and urea is also presented and, as anticipated, required partitioning for both age and gender. CONCLUSIONS: Our renal profile findings are broadly consistent with those of international studies, for example, CALIPER, HAPPI, NORDIC, PRINCE and KiGGs. Moreover, the CELTIC ranges study is also based on over 1000 subjects whose samples were analysed on the widely used Roche modular analytics system. We also expect the findings will improve knowledge of children's metabolic health in Ireland.

Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents.

OBJECTIVES: Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. METHODS: Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. RESULTS: Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [ß: 3.00; 95% confidence interval (CI): 2.32-3.70; P < .001] and 6 months (ß: 3.59; 95% CI: 2.89-4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (ß: -0.05; 95% CI: -0.08 to -0.02; P < .001) and frailty (ß: -0.22; 95% CI: -0.33 to -0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. CONCLUSIONS AND IMPLICATIONS: In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity.

BACKGROUND: Paediatric traumatic brain injury (TBI) is recognised to have significant longer-term neurocognitive effects. Childhood is a time of high risk for head injury. Functional recovery is variable with a combination of any or all of physical, cognitive and emotional impairment. Immune activation and alteration in cytokine levels are present following TBI which may differ from adults. METHODS: Pro- and anti-inflammatory cytokines including Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-17A, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were examined at baseline and following in vitro treatment with endotoxin of whole blood, in the following children: severe TBI (sTBI: initial Glasgow coma scale(GCS) ≤ 8), mild TBI (mTBI; GCS 14/15) at 0-4d and at 10-14d post-TBI and compared to healthy age-matched controls. RESULTS: The study enrolled 208 children, including 110 with TBI cohort (n = 104 mild; 6 severe) and controls (n = 98). At baseline all children with TBI had increased IL-6. The mTBI group had significantly increased IFN-γ versus controls. In sTBI at baseline, IFN-γ was decreased compared to controls. At baseline IL-8, IL-10, IL-17A, and TNF-α were decreased in mTBI compared to controls. This persisted at 2 week post-mTBI. The AUC for detecting mTBI was 0.801 CI (0.73-086) using IL6/IL10 ratio. mTBI showed a greater fold change in IL-8 and TNF-α in response to endotoxin stimulation, a response that persisted at 2 weeks. Children with sTBI did not have a significant IL-6 response to endotoxin, but did show an increase in IL-17A. CONCLUSION: Children with all TBI including mTBI show altered cytokine profiles and altered endotoxin responses. Although cytokines increased in sTBI especially in response to endotoxin, suppressed responses were found in mTBI coupled with persistent immune dysfunction post-injury.

Traumatic Brain Injury in Children: Glial fibrillary Acidic Protein and Clinical Outcomes.

OBJECTIVES: Glial fibrillary acidic protein (GFAP) is a neuronal protein released after traumatic brain injury (TBI) and detectable in serum samples. GFAP correlates with symptom severity in adults and may be a marker of brain injury in children with milder symptoms or preverbal children. METHODS: GFAP was examined in children with severe TBI (initial Glasgow Coma Scale score <8), with mild TBI (Glasgow Coma Scale score 14/15), and at 0 to 4 and at 10 to 14 days after TBI and was compared with healthy age-matched controls. Mechanism, time points from injury, and symptoms were recorded. RESULTS: The study enrolled 208 children including 110 with TBI (n = 104 mild, 6 severe) and controls (n = 98). GFAP was higher in mild TBI than in controls and highest in the severe TBI cohort, with a maximum value at 6 hours from injury. Vomiting was significantly associated with higher GFAP levels, but no association was found with amnesia, loss of consciousness, and the Sports Concussion Assessment Tool. Children reporting >1-point changes from their preinjury functioning on the Post-Concussive Symptom Inventory had higher initial GFAP but not total Post-Concussive Symptom Inventory score changes. CONCLUSIONS: GFAP identifies children with TBI, even at the milder end of the spectrum, and is strongly associated with postinjury vomiting. It may be a useful marker of pediatric TBI; however, sampling is time critical.

High anti-SARS-CoV-2 antibody seroprevalence in healthcare workers in an Irish university teaching hospital.

INTRODUCTION: Healthcare workers are at very high risk for SARS-CoV-2 exposure and infection. This study evaluated anti-SARS-CoV-2 seroprevalence in healthcare workers in a tertiary care hospital and then correlated seroprevalence with confirmed or suspected SARS-CoV-2 infection in this population since the onset of the COVID-19 pandemic. METHOD: The study was approved by our institution's Joint Research Ethics Committee in June 2020. All volunteers were provided with a consent form, an information leaflet and a questionnaire on the day before phlebotomy. Serum samples were collected from 1176 participants over a 3-month period and analysed using the Elecsys Anti-SARS-CoV-2 assay (Roche Diagnostics GmbH, Mannheim, Germany) which detects total antibodies against the nucleocapsid protein of SARs-COV-2. RESULTS: Overall anti-SARS-CoV-2 seroprevalence among participating healthcare workers was 17.9%. The rate of confirmed infection by real-time polymerase chain reaction molecular testing prior to participation was 12.2%. Of 211 participants who had a reactive antibody test result, 37% did not have COVID-19 infection confirmed at any point prior to participation in this study, either having had a swab which did not detect SARS-CoV-2 RNA or having never been tested. Seropositivity was the highest (30%) in the youngest quintile of age (20-29 years old). Staff with more patient contact had a higher seroprevalence of 19.5% compared to 13.4% in staff with less patient contact. CONCLUSION: This study demonstrates that a substantial proportion of SARS-CoV-2 infections in healthcare workers may be asymptomatic or subclinical and thus potentially represent a significant transmission risk to colleagues and patients.

Survey of laboratory medicine's national response to the Covid-19 pandemic in the Republic of Ireland.

BACKGROUND: The global SARS-CoV-2 pandemic placed Irish Laboratory Medicine services under sustained and massive strain. Rapid reconfiguration was required to introduce new assays at high capacity for diagnosis and monitoring of COVID-19, while maintaining existing services. AIM: The aim of this national survey was to capture Laboratory Medicine's response across the Republic of Ireland during the first wave of the COVID-19 pandemic. METHODS: An electronic survey developed using Microsoft Forms® was emailed on 5 October 2020 to 53 local representatives of the PeriAnalytic and Laboratory Medicine Society (PALMSoc), reaching 38 separate pathology departments in the country. RESULTS: A total of 45 responses from 38 laboratories were received (72% response rate) representing a range of departments and disciplines. Most laboratories (63%) introduced new tests, and in a time frame of less than 6 weeks (80%). Point-of-care testing (POCT) played a significant role in the response to COVID-19, with almost half of respondents (47%) reporting that additional equipment was introduced. Maintenance of the Quality Management System (QMS) proved challenging, with 60% of respondents indicating that not all aspects were sustained. When asked about changes to staff rostering, 98% of respondents reported that changes were made. All adjustments were made despite staffing challenges; only 18% of respondents described the staffing levels in their department as 100% prior to the onset of the first wave. CONCLUSIONS: This study confirms an agile and resilient response to the COVID-19 pandemic from Ireland's Laboratory Medicine services despite many economic and staffing challenges.

Sweat testing in the modern era: A national survey of sweat testing practice in the Republic of Ireland.

BACKGROUND: The sweat test has been the "gold standard" diagnostic test for cystic fibrosis for more than 40 years. We hypothesized that there would be a change in the pattern of sweat testing in Ireland since the introduction of cystic fibrosis newborn screening in 2011, when practices were last reviewed. This is a follow up survey looking at sweat testing numbers and practices. METHODS: A national survey compiled data on sweat collection, conductivity and sweat chloride testing in all hospitals previously identified as performing sweat tests. RESULTS: All 13 centres in Ireland performing sweat testing in 2018 responded to the survey (100% return rate). Our results indicate that 1007 sweat tests were performed in 2018 compared to 2555 in 2011, equating to a 61% reduction. Seven out of 13 centres are performing less than 50 sweat tests per year. Nine out of 13 centres (69%) had a sweat test failure rate greater than the recommended allowable rate of ≤ 10%. We detected a trend of sweat testing in patients with an existing diagnosis of CF who had commenced cystic fibrosis transmembrane conductance regulator (CFTR) modulators. CONCLUSIONS: There has been a significant reduction in the number of sweat tests performed in Ireland since the introduction of newborn screening for CF. There remains a lack of standardisation in many aspects of the service ranging from sample collection to reporting of results. We have identified a new trend of sweat testing in the cystic fibrosis transmembrane conductance regulator modulator era.

Colon capsule endoscopy is a viable alternative to colonoscopy for the investigation of intermediate- and low-risk patients with gastrointestinal symptoms: results of a pilot study.

Background and study aims Colon capsule endoscopy (CCE) is a recommended viable alternative to colonoscopy for colonic visualisation in a variety of clinical settings with proven efficacy in polyp detection, surveillance, screening and Inflammatory Bowel Disease (IBD) assessment. CCE efficacy in an unselected average risk symptomatic cohort has yet to be established. The aim of this study was to determine the feasibility of CCE imaging assessment in average risk symptomatic patients as an alternative to colonoscopy with and without additional biomarker assessment. Patients and methods This was a prospective, single-center comparison study of colonoscopy, CCE and biomarker assessment. Results Of 77 invited subjects, 66 underwent both a CCE and colonoscopy. A fecal immunochemical test (FIT) and fecal calprotectin (FC) were available in 56 and 59 subjects. In all 64 % (n = 42) had any positive finding with 16 (24 %) found to have significant disease (high-risk adenomas, IBD) on colonoscopy. The CCE completion rate was 76 %, five (8 %) had an inadequate preparation, the CCE polyp detection rate was high at 35 %. The sensitivity, specificity, positive and negative predictive values of CCE for significant disease were 81 %, 98 %, 93 % and 94 % respectively. In addition, three (5 %) significant small bowel diagnoses were made on CCE. FC and FIT were frequently elevated in patients with both colitis (5/7, 71 %) and high-risk adenomas (4/7 57 %). While both had a low positive predictive value for clinically significant disease, FIT 32 % and FC 26 %. Conclusions CCE is a safe and effective alternative to colonoscopy in symptomatic average risk patients with or without the addition of biomarker screening.

Growth hormone replacement may influence the biological action of thyroid hormone on liver and bone tissue.

OBJECTIVE: Growth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues. DESIGN: We prospectively studied twenty GH deficient men before and after GH replacement in a tertiary referral endocrine center. Serum biochemical measurements included insulin like growth factor-1 (IGF-1), thyroid hormones (free & total T3, free & total T4 and reverse T3) and TSH. Changes in thyroid hormone concentration were compared to alterations in hepatic and bone biomarkers of thyroid hormone action. RESULTS: GH replacement provoked a decline in serum free T4 concentration (-1.09 ± 1.99 pmol/L; p = 0.02) and an increase in free T3 (+0.34 ± 0.15 pmol/L; p = 0.03); therefore, the free T3:free T4 ratio increased from 0.40 ± 0.02 to 0.47 ± 0.02 (p = 0.002). Sex hormone binding globulin (SHBG) level was unchanged. However, a decline in serum ferritin (-26.6 ± 8.5 ng/mL; p = 0.005) correlated with a fall in freeT4. Alterations in lipid profile, including a rise in large HDL sub-fractions and Lp (a) (+2.1 ± 21.1 nmol/L; p = 0.002) did not correlate with thyroid hormone levels. Significant increases were recorded in serum bone turnover markers - procollagen type 1 amino-terminal propeptide +57.4%; p = 0.0009, osteocalcin +48.6%; p = 0.0007; c-terminal telopeptides of type 1 collagen +73.7%; p = 0.002. Changes in bone formation markers occurred in parallel with fluctuations in thyroid hormone. CONCLUSION: GH-induced alterations in the thyroid axis are associated with complex, tissue specific effects on thyroid hormone action. Modulation of bone turnover markers suggests that GH may improve the biological action of thyroid hormone on bone.

HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study.

AIMS/HYPOTHESIS: The prevalence of atherosclerosis is increased in type 1 diabetes despite normal-to-high HDL-cholesterol levels. The cholesterol efflux capacity (CEC) of HDL is a better predictor of cardiovascular events than static HDL-cholesterol. This cross-sectional study addressed the hypothesis that impaired HDL function contributes to enhanced CVD risk within type 1 diabetes. METHODS: We compared HDL particle size and concentration (by NMR), total CEC, ATP-binding cassette subfamily A, member 1 (ABCA1)-dependent CEC and ABCA1-independent CEC (by determining [3H]cholesterol efflux from J774-macrophages to ApoB-depleted serum), and carotid intima-media thickness (CIMT) in 100 individuals with type 1 diabetes (37.6 ± 1.2 years; BMI 26.9 ± 0.5 kg/m2) and 100 non-diabetic participants (37.7 ± 1.1 years; 27.1 ± 0.5 kg/m2). RESULTS: Compared with non-diabetic participants, total HDL particle concentration was lower (mean ± SD 31.01 ± 8.66 vs 34.33 ± 8.04 µmol/l [mean difference (MD) -3.32 µmol/l]) in participants with type 1 diabetes. However, large HDL particle concentration was greater (9.36 ± 3.98 vs 6.99 ± 4.05 µmol/l [MD +2.37 µmol/l]), resulting in increased mean HDL particle size (9.82 ± 0.57 vs 9.44 ± 0.56 nm [MD +0.38 nm]) (p < 0.05 for all). Total CEC (14.57 ± 2.47%CEC/4 h vs 12.26 ± 3.81%CEC/4 h [MD +2.31%CEC/4 h]) was greater in participants with type 1 diabetes relative to non-diabetic participants. Increased HDL particle size was independently associated with increased total CEC; however, following adjustment for this in multivariable analysis, CEC remained greater in participants with type 1 diabetes. Both components of CEC, ABCA1-dependent (6.10 ± 2.41%CEC/4 h vs 5.22 ± 2.57%CEC/4 h [MD +0.88%CEC/4 h]) and ABCA1-independent (8.47 ± 1.79% CEC/4 h vs 7.05 ± 1.76% CEC/4 h [MD +1.42% CEC/4 h]) CEC, were greater in type 1 diabetes but the increase in ABCA1-dependent CEC was less marked and not statistically significant in multivariable analysis. CIMT was increased in participants with type 1 diabetes but in multivariable analysis it was only associated negatively with age and BMI. CONCLUSIONS/INTERPRETATION: HDL particle size but not HDL-cholesterol level is independently associated with enhanced total CEC. HDL particle size is greater in individuals with type 1 diabetes but even after adjusting for this, total and ABCA1-independent CEC are enhanced in type 1 diabetes. Further studies are needed to understand the mechanisms underlying these effects, and whether they help attenuate progression of atherosclerosis in this high-risk group. Graphical abstract.

Metabolic dysfunction and diabetes mellitus during long-term follow-up of severe acute pancreatitis: A case-matched study.

BACKGROUND/OBJECTIVES: Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT). METHODS: Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models. RESULTS: The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint. CONCLUSIONS: Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.

Monitoring and capturing patient identification errors in laboratory medicine.

BACKGROUND: Specimen labelling and patient identification are significant contributors to the rate of error in the preanalytical phase of laboratory medicine. This study aimed to investigate the prevalence and nature of preanalytical quality monitoring practices for patient identification and specimen labelling errors in Irish clinical laboratories. METHODS: A survey was developed by the Clinical Biochemistry Unit, Trinity College Dublin and the Irish External Quality Assessment Scheme (IEQAS), with the intention of gathering key information from each laboratory. Thirty-nine questions were organized into seven subsections covering general information, labelling requirements, information availability, rejection criteria, error monitoring, error reporting and interest in participation in an external quality assessment scheme. The survey was sent electronically to 63 laboratory quality managers at 55 laboratories in Ireland. RESULTS: A total of 39 responses (61% response rate) provided information on 94 separate laboratory departments or disciplines. Laboratories reported varying practices and requirements for labelling specimens and all accepted handwritten preprinted request forms. All (100%) respondents had defined rejection criteria both for specimen labelling and request form completion. Unsurprisingly, the rejection criteria differed between the various laboratory disciplines. Almost all respondents provided information to clinical staff on labelling requirements, but just over half provided training on the same. A large percentage of laboratories (74%) monitored the rate of specimen-labelling errors; however, only 46% had defined target limits for acceptable rates of error. CONCLUSION: The survey observed a wide variation in collection, recording and monitoring of errors but also confirmed significant interest in improving preanalytical monitoring and data collection.

Outcomes of the short Synacthen test: what is the role of the 60 min sample in clinical practice?

In recent years, the short Synacthen test (SS) has become the most widely used test to assess adrenal reserve. Despite its frequent use, there are still several areas related to the short Synacthen test (SST), which have no consensus including the optimum sampling times, that is, whether a 60 min post-Synacthen administration cortisol is necessary or not. METHODOLOGY: We performed a retrospective data analysis of 492 SSTs performed on adult patients in a tertiary referral teaching hospital in Ireland. The SSTs were performed in the inpatient and outpatient setting and included patients across all medical disciplines and not exclusively to the endocrinology department. RESULTS: 313 patients had 0, 30 and 60 min samples available for analysis. A total of 270/313 (82%) were deemed to pass the test, that is, cortisol ≥500 nmol/L at both 30 and 60 min. Of the 313 patients, 19 (6%) patients had an indeterminate response, cortisol <500 nmol/L at 30 min, but rising to ≥500 nmol/L on the 60 min sample. Of these 19 patients, only 9/19 patients had a serum cortisol level at 30 min <450 nmol/L, requiring clinical treatment with glucocorticoid replacement. All 24/313 (8%) patients who had insufficient responses at 60 min were also insufficient at 30 min sampling. No individuals passed (≥500 nmol/L) at 30 min and then failed (<500 nmol/L) at 60 min. CONCLUSION: Using the 30 min cortisol sample post-Synacthen administration alone identifies clinically relevant adrenal insufficiency in the majority of cases. A small subset of patients have a suboptimal response at 30 min but have a 60 min cortisol concentration above the threshold for a pass. Data regarding the long-term outcomes and management of such patients are lacking and require further study.

Spectrum of rhabdomyolysis in an acute hospital.

Rhabdomyolysis is a state of muscle necrosis with the hallmark being elevated creatine kinase that may cause acute kidney injury with serious consequences. It happens in many clinical settings. We sought to investigate all cases of rhabdomyolysis admitted to an acute hospital in Ireland over one calendar year. All cases of rhabdomyolysis admitted to a tertiary hospital over a 12-month period were reviewed. It was defined as serum creatine kinase greater than five times upper limit normal. The incidence, presenting characteristics and clinical outcomes, was collected from electronic records, electronic consult system and discharge summaries. Rhabdomyolysis was observed in 306 (1.7%) of all 18,297 admissions. It was seen most commonly in the setting of acute coronary syndrome (19.6%), post-operative state (18.0%), long-term confinement in the same position (16.3%), infection (9.2%) and seizures (6.5%). Overall mortality in this group was 16%. Acute kidney injury occurred in 43% of patients. Those with severe acute kidney injury (stage 3) had a mortality of 50%. Length of stay was significantly prolonged in the presence of acute kidney injury (p < 0.001). Surprisingly, in 44% of those with acute kidney injury, nephrology advice was not requested. Rhabdomyolysis is a common and a serious clinical condition across many specialties in an acute hospital that would likely benefit from nephrology involvement should acute kidney injury supervene.

In women with PCOS, waist circumference is a better surrogate of glucose and lipid metabolism than disease status per se.

OBJECTIVE: Cardiometabolic abnormalities are recognized in polycystic ovary syndrome (PCOS). However, over-emphasis on PCOS as a risk factor potentially results in over-investigation and treatment of some women with and under-recognition of cardiometabolic risk in obese women without PCOS. Our objective was to explore the association between waist circumference (WC) and indices of glucose and lipid metabolism in women with and without PCOS. DESIGN, PATIENTS AND MEASUREMENTS: (i) An exploratory cross-sectional study investigating association of potential cardiometabolic risk markers (PCOS status, anthropometric measures, hsCRP, HOMA-IR, SHBG, testosterone) with indices of glucose (frequently sampled intravenous glucose tolerance test) and lipid metabolism (postprandial studies and lipoprotein particle size) in 61 women with (n = 29) and without (n = 32) PCOS; (ii) a cross-sectional study in 103 PCOS women and 102 BMI-matched controls to explore if between-group differences in indices of lipid and glucose metabolism persist after adjusting for WC. NIH criteria were used for PCOS diagnosis. RESULTS: Study 1: Univariate correlations and stepwise regression modelling identified waist circumference (WC), as a better surrogate than PCOS status, independently predicting multiple variables of glucose and lipid metabolism. Study 2: Fasting insulin and triglyceride, hsCRP and insulin resistance (according to HOMA-IR and SiM [Avignon index]) were greater, while fasting HDL was lower in women with PCOS compared to BMI-matched women without PCOS. None of these differences persisted when a subset of 80 women with PCOS was compared with 80 women without PCOS, pair-matched for WC. CONCLUSION: Some cardiometabolic abnormalities in PCOS are related to central obesity, and following adjustment for WC does not differ from normal subjects. Waist circumference measurement has potential to take precedence over PCOS status as part of the assessment of cardiometabolic risk in reproductive-age women.

Lactic acidosis: an update.

Lactate is one of the most crucial intermediates in carbohydrate and nonessential amino acid metabolism. The complexity of cellular interactions and metabolism means that lactate can be considered a waste product for one cell but a useful substrate for another. The presence of elevated lactate levels in critically ill patients has important implications for morbidity and mortality. In this review, we provide a brief outline of the metabolism of lactate, the pathophysiology of lactic acidosis, the clinical significance of D-lactate, the role of lactate measurement in acutely ill patients, the methods used to measure lactate in blood or plasma and some of the methodological issues related to interferences in these assays, especially in the case of ethylene glycol poisoning.

Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism.

Context: Intestinal cholesterol metabolism is important in influencing postprandial lipoprotein concentrations, and might be important in the development of vascular disease. Objective: This study evaluated associations between expression of intestinal cholesterol metabolism genes, postprandial lipid metabolism, and endothelial function/early vascular disease in human subjects. Design/Patients: One hundred patients undergoing routine oesophago-gastro-duodenoscopy were recruited. mRNA levels of Nieman-Pick C1-like 1 protein (NPC1L1), ABC-G5, ABC-G8, ABC-A1, microsomal tissue transport protein (MTTP), and sterol-regulatory element-binding protein (SREBP)-2 were measured in duodenal biopsies using quantitative reverse transcription polymerase chain reaction. Postprandially, serum lipid and glycemic profiles were measured, endothelial function was assessed using fasting, and postprandial flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT). Subjects were divided into those above and below the median value of relative expression of each gene, and results were compared between the groups. Results: There were no between-group differences in demographic variables or classical cardiovascular risks. For all genes, the postprandial triglyceride incremental area under the curve was greater (P < 0.05) in the group with greater expression. Postprandial apolipoprotein B48 (ApoB48) levels were greater (P < 0.05) in groups with greater expression of NPC1L1, ABC-G8, and SREBP-2. For all genes, postprandial but not fasting FMD was lower (P < 0.01) in the group with greater expression. Triglyceride and ApoB48 levels correlated significantly with postprandial FMD. Carotid artery IMT was greater (P < 0.05) in groups with greater expression of MTTP, ABC-A1, and SREBP-2. Conclusion: Intestinal cholesterol metabolism gene expression is significantly associated with postprandial increment in triglycerides, intestinal ApoB48, and reduced postprandial FMD. Some genes were also associated with increased IMT. These findings suggest a role of intestinal cholesterol metabolism in development of early vascular disease.

Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome.

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4 ± 1.2 years (mean ± SEM), body mass index (BMI) 36.8 ± 1.5 kg/m(2)) and 26 non-PCOS subjects (age 34.1 ± 0.9 years, BMI 31.5 ± 1.0 kg/m(2)) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (S I), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.