Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Point-of-care testing: state-of-the art and perspectives.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e., presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups.

OBJECTIVES: Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. METHODS: Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. RESULTS: The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. CONCLUSIONS: Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

Point-of-care testing performed by healthcare professionals outside the hospital setting: consensus based recommendations from the IFCC Committee on Point-of-Care Testing (IFCC C-POCT).

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Point-of-Care Testing (C-POCT) supports the use of point-of-care testing (POCT) outside of the hospital setting performed by healthcare professionals without formal laboratory education because of its numerous benefits. However, these benefits are associated with risks that must be managed, to ensure the provision of reliable test results and minimize harm to the patient. Healthcare professionals, local regulatory bodies, accredited laboratories as well as manufacturers should actively be engaged in education, oversight and advice to ensure that the healthcare professional selects the appropriate equipment and is able to analyze, troubleshoot and correctly interpret the point-of-care (POC) test results.

Salivary testing of COVID-19: evaluation of serological testing following positive salivary results.

BACKGROUND: Salivary detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as an alternative to nasopharyngeal or oropharyngeal swab testing. Our group previously published a study demonstrating that both testing methods identified SARS-CoV-2 using polymerase chain reaction (PCR)-based detection methodology. We therefore conducted a follow-up study using antibody testing to evaluate the accuracy of saliva versus swabs for COVID-19 detection and the durability of antibody response. METHODS: Venous blood samples were collected from consenting participants and the presence of serum antibodies for SARS-CoV-2 was evaluated on a large, automated immunoassay platform by the Roche anti-SARS-CoV-2 qualitative assay (Roche Diagnostics, Laval Quebec). Individuals with a serum antibody cut-off index (COI) ≥ 1.0 were considered positive. RESULTS: In asymptomatic and mildly symptomatic patients with a previously positive standard swab and/or saliva SARS-CoV-2 PCR-test, 42 demonstrated antibodies with 13 patients positive by swab alone, and 8 patients positive by saliva alone. CONCLUSIONS: Despite their status as 'current standard' for COVID-19 testing, these findings highlight limitations of PCR-based tests.

Assessing Structural Quality Elements of Pediatric Emergency Care.

BACKGROUND AND OBJECTIVE: Emergency departments must have appropriate resources and equipment available to meet the unique needs of children. We assessed the availability of stakeholder-endorsed quality structure performance measures for pediatric emergency department patients. METHODS: A survey of Child Health Corporation of America member hospitals was conducted. Six broad equipment groups were queried: general, monitoring, respiratory, vascular access, fracture-management, and specialized pediatric trays. Equipment availability was determined at the level of the individual item, 6 broad groups, and 44 equipment subgroups. The survey queried the availability of 8 protocol/procedure elements: method to identify age-based abnormal vital signs, patient-centered care advisory council, bronchiolitis evidence-based guideline, pediatric radiation dosing standards, suspected child abuse protocols, use of validated pediatric triage tool, and presence of nurse and physician pediatric coordinators. RESULTS: Fifty-two percent (22/42) of sites completed the survey. Forty-one percent reported availability of all 113 recommended equipment items. Every hospital reported complete availability of equipment in 77% of the subgroups. The most common missing items were adult-sized lumbar puncture needles, hypothermia thermometers, and various sizes of laryngeal mask airways. Regarding the protocol/procedure elements, a method to identify age-based abnormal vital signs, pediatric radiation dosing standard, and nurse and physician pediatric coordinators were present in 100%. Ninety-five percent used a validated triage tool and had suspected child abuse protocols. CONCLUSIONS: Presence of necessary pediatric emergency equipment is better in the surveyed hospitals than in prior reports. Most responding hospitals have important protocol/procedures in place. These data may provide benchmarks for optimal care.

Group work: Facilitating the learning of international and domestic undergraduate nursing students.

BACKGROUND: Devising innovative strategies to address internationalization is a contemporary challenge for universities. A Participatory Action Research (PAR) project was undertaken to identify issues for international nursing students and their teachers. The findings identified group work as a teaching strategy potentially useful to facilitate international student learning. METHODS: The educational intervention of structured group work was planned and implemented in one subject of a Nursing degree. Groups of four to five students were formed with one or two international students per group. Structural support was provided by the teacher until the student was learning independently, the traditional view of scaffolding. The group work also encouraged students to learn from one another, a contemporary understanding of scaffolding. Evaluation of the group work teaching strategy occurred via anonymous, self-completed student surveys. The student experience data were analysed using descriptive statistical techniques, and free text comments were analysed using content analysis. RESULTS: Over 85% of respondents positively rated the group work experience. Overwhelmingly, students reported that class discussions and sharing nursing experiences positively influenced their learning and facilitated exchange of knowledge about nursing issues from an international perspective. DISCUSSION: This evaluation of a structured group work process supports the use of group work in engaging students in learning, adding to our understanding of purposeful scaffolding as a pathway to enhance learning for both international and domestic students. By explicitly using group work within the curriculum, educators can promote student learning, a scholarly approach to teaching and internationalization of the curriculum.

Outcomes of an Asynchronous Care Model for Chronic Conditions in a Diverse Population: 12-Month Retrospective Chart Review Study.

BACKGROUND: Diabetes and hypertension are some of the most prevalent and costly chronic conditions in the United States. However, outcomes continue to lag behind targets, creating further risk of long-term complications, morbidity, and mortality for people living with these conditions. Furthermore, racial and ethnic disparities in glycemic and hypertension control persist. Flexible telehealth programs leveraging asynchronous care allow for increased provider access and more convenient follow-up, ultimately improving critical health outcomes across demographic groups. OBJECTIVE: We aim to evaluate the 12-month clinical outcomes of participants in the 9amHealth web-based clinic for diabetes and hypertension. We hypothesized that participation in the 9amHealth program would be associated with significant improvements in glycemic and blood pressure (BP) control across a diverse group of individuals. METHODS: We enrolled 95 patients in a completely web-based care clinic for diabetes and hypertension who received nutrition counseling, health coaching, and asynchronous physician consultations for medication prescribing. Patients received standard or cellular-connected glucose meters and BP cuffs in order to share data. Laboratory tests were completed either with at-home phlebotomy draws or a self-administered test kit. Patients' first and last hemoglobin A1c (HbA1c) and BP results over the 12-month period were compared, and analyses were repeated across race and ethnicity groups. RESULTS: Among all 95 patients, the average HbA1c decreased by -1.0 (from 8.2% to 7.2%; P<.001) over 12 months of program participation. In those with a baseline HbA1c >8%, the average HbA1c decreased by -2.1 (from 10.2% to 8.1%; P<.001), and in those with a baseline HbA1c >9%, the average HbA1c decreased by -2.8 (from 11% to 8.2%; P<.001). Among participants who identified as a race or ethnicity other than White, the HbA1c decreased by -1.2 (from 8.6% to 7.4%, P=.001). Further examination of subgroups confirmed HbA1c lowering within each race or ethnicity group. In the overall population, the average systolic BP decreased by 17.7 mm Hg (P=.006) and the average diastolic BP decreased by 14.3 mm Hg (P=.002). Among participants self-identifying as a race or ethnicity other than White, the results similarly showed a decrease in BP (average reduction in systolic BP of 10 mm Hg and in diastolic BP of 9 mm Hg). CONCLUSIONS: A fully web-based model leveraging all-asynchronous physician review and prescribing, combined with synchronous and asynchronous coaching and nutrition support, was associated with clinically meaningful improvement in HbA1c and BP control over a 12-month period among a diverse group of individuals. Further studies should prospectively evaluate the effectiveness of such models among larger populations, assess the longer-term sustainability of these outcomes, and explore financial models to make these types of programs broadly accessible.

Accuracy of point-of-care testing devices for haemoglobin in the operating room: meta-analysis.

BACKGROUND: Point-of-care tests (POCT) for haemoglobin are increasingly used to guide intraoperative transfusion. However, their accuracy compared to central laboratory tests is unknown. The objective was to perform a systematic review and meta-analysis of method comparison studies assessing the accuracy of POCT versus central laboratory haemoglobin tests in patients undergoing surgery. METHODS: Electronic databases were searched from inception to April 2020 (updated August 2023). Any methodological approach comparing haemoglobin measurements between POCT and central laboratory in patients undergoing surgery under anaesthesia in the operating room were included. Data abstraction was guided by PRISMA and risk of bias was assessed by QUADAS-2. Data were extracted independently and in duplicate by two reviewers. Outcomes included mean differences between POCT and central laboratory haemoglobin with associated standard deviations and 95% limits of agreement (LOA). RESULTS: Of 3057 citations, 34 studies were included (n = 2427, 6857 paired measurements). Several devices were compared (pulse co-oximetry, n = 25; HemoCue, n = 10; iSTAT, n = 6; blood gas analysers, n = 10; haematology analyser, n = 2). Median sample size was 41 patients, and 11 studies were funded by device manufacturers. Fifteen of 34 studies had low risk of bias. Pooled mean differences (95% LOA) were: pulse co-oximeters 2.3 g/l (-25.2-29.8), HemoCue -0.3 g/l (-11.1-10.5), iSTAT -0.3 g/l (-8.4-7.8) and blood gas analysers -2.6 g/l (-17.8-12.7). CONCLUSION: All POCT examining intraoperative haemoglobin measurement yielded pooled mean difference LOAs larger than the allowable limit difference of ±4 g/dl. Intraoperative haemoglobin measured by POCT should not be considered interchangeable with central laboratory values and caution is necessary when using these tests to guide intraoperative transfusion.

Pediatric reference intervals: challenges and recent initiatives.

The clinical laboratory plays a critical role in healthcare delivery by providing objective data on specific biomarkers that directly aid in the diagnosis and monitoring of a wide range of clinical disorders. Reliable and accurate reference intervals for laboratory analyses are integral for correct interpretation of clinical laboratory test results and, therefore, for appropriate clinical decision-making. Ideally, reference intervals should be established based on a healthy population and stratified for key covariates including age, gender and ethnicity. However, establishing reference intervals can be challenging as it requires the collection of large numbers of samples from healthy individuals. This challenge is further augmented in pediatrics, where dynamic changes due to child growth and development markedly affect circulating levels of disease biomarkers. As a result, even larger reference populations are required to reliably calculate reference intervals. In this review, we outline the challenges specific to establishing pediatric reference intervals and highlight recent initiatives aimed at closing existing gaps in current knowledge. We also outline recommended approaches to the development of reference intervals and detail several alternative approaches. Finally, reference intervals for emerging and novel biomarkers of pediatric disease are discussed along with a number of potential alternative sample types.

Complex biological pattern of fertility hormones in children and adolescents: a study of healthy children from the CALIPER cohort and establishment of pediatric reference intervals.

BACKGROUND: Pediatric endocrinopathies are commonly diagnosed and monitored by measuring hormones of the hypothalamic-pituitary-gonadal axis. Because growth and development can markedly influence normal circulating concentrations of fertility hormones, accurate reference intervals established on the basis of a healthy, nonhospitalized pediatric population and that reflect age-, gender-, and pubertal stage-specific changes are essential for test result interpretation. METHODS: Healthy children and adolescents (n = 1234) were recruited from a multiethnic population as part of the CALIPER study. After written informed parental consent was obtained, participants filled out a questionnaire including demographic and pubertal development information (assessed by self-reported Tanner stage) and provided a blood sample. We measured 7 fertility hormones including estradiol, testosterone (second generation), progesterone, sex hormone-binding globulin, prolactin, follicle-stimulating hormone, and luteinizing hormone by use of the Abbott Architect i2000 analyzer. We then used these data to calculate age-, gender-, and Tanner stage-specific reference intervals according to Clinical Laboratory Standards Institute C28-A3 guidelines. RESULTS: We observed a complex pattern of change in each analyte concentration from the neonatal period to adolescence. Consequently, many age and sex partitions were required to cover the changes in most fertility hormones over this period. An exception to this was prolactin, for which no sex partition and only 3 age partitions were necessary. CONCLUSIONS: This comprehensive database of pediatric reference intervals for fertility hormones will be of global benefit and should lead to improved diagnosis of pediatric endocrinopathies. The new database will need to be validated in local populations and for other immunoassay platforms as recommended by the Clinical Laboratory Standards Institute.

Comparison of Three Methods for LDLC Calculation for Cardiovascular Disease Risk Categorisation in Three Distinct Patient Populations.

BACKGROUND: Limitations of the Friedewald equation for low-density-lipoprotein cholesterol (F-LDLC) calculation led to the Martin-Hopkins (M-LDLC) and Sampson-National Institutes of Health (S-LDLC) equations. We studied these newer calculations of LDLC for correlation and discordance for stratification into the Canadian Cardiovascular Society (CCS) 2021 Dyslipidemia Guidelines' cardiovascular disease (CVD) risk categories. METHODS: We performed analyses on lipid profiles from 3 populations: records of a hospital biochemistry laboratory (population 1), lipid clinic patients without select monogenic dyslipidemias (population 2A), and lipid clinic patients with familial hypercholesterolemia (FH; population 2B). RESULTS: There was very strong correlation among the 3 calculated LDLC. In populations 1 and 2A, M-LDLC and S-LDLC were progressively higher than F-LDLC as triglyceride (TG) levels increased from normal to ∼ 5 mmol/L. In population 2B, M-LDLC was higher than F-LDLC, but S-LDLC was progressively lower than F-LDLC. Using the CCS 2021 guidelines' 4 CVD risk categories, 7.0% (population 2A) to 7.2% (population 1) of cases for M-LDLC vs F-LDLC and 3.9% (population 2A) to 4.4% (population 1) of cases for S-LDLC vs F-LDLC were reclassified to an adjacent CVD risk category, mostly from a lower to a higher risk category. CONCLUSIONS: Switching from F-LDLC to S-LDLC or M-LDLC can reclassify up to ∼ 4.4% or 7.2% of patients, respectively, to another CCS CVD risk category. The difference between F-LDLC and M-LDLC or S-LDLC is greater with higher TG, and with lower LDLC. We recommend that clinical laboratories switch to reporting results from either M-LDLC or S-LDLC, but S-LDLC should not be used in FH patients, pending further studies.

Point-of-care haemoglobin accuracy and transfusion outcomes in non-cardiac surgery at a Canadian tertiary academic hospital: protocol for the PREMISE observational study.

INTRODUCTION: Transfusions in surgery can be life-saving interventions, but inappropriate transfusions may lack clinical benefit and cause harm. Transfusion decision-making in surgery is complex and frequently informed by haemoglobin (Hgb) measurement in the operating room. Point-of-care testing for haemoglobin (POCT-Hgb) is increasingly relied on given its simplicity and rapid provision of results. POCT-Hgb devices lack adequate validation in the operative setting, particularly for Hgb values within the transfusion zone (60-100 g/L). This study aims to examine the accuracy of intraoperative POCT-Hgb instruments in non-cardiac surgery, and the association between POCT-Hgb measurements and transfusion decision-making. METHODS AND ANALYSIS: PREMISE is an observational prospective method comparison study. Enrolment will occur when adult patients undergoing major non-cardiac surgery require POCT-Hgb, as determined by the treating team. Three concurrent POCT-Hgb results, considered as index tests, will be compared with a laboratory analysis of Hgb (lab-Hgb), considered the gold standard. Participants may have multiple POCT-Hgb measurements during surgery. The primary outcome is the difference in individual Hgb measurements between POCT-Hgb and lab-Hgb, primarily among measurements that are within the transfusion zone. Secondary outcomes include POCT-Hgb accuracy within the entire cohort, postoperative morbidity, mortality and transfusion rates. The sample size is 1750 POCT-Hgb measurements to obtain a minimum of 652 Hgb measurements <100 g/L, based on an estimated incidence of 38%. The sample size was calculated to fit a logistic regression model to predict instances when POCT-Hgb are inaccurate, using 4 g/L as an acceptable margin of error. ETHICS AND DISSEMINATION: Institutional ethics approval has been obtained by the Ottawa Health Science Network-Research Ethics Board prior to initiating the study. Findings from this study will be published in peer-reviewed journals and presented at relevant scientific conferences. Social media will be leveraged to further disseminate the study results and engage with clinicians.

Development of a multiplex selected reaction monitoring assay for quantification of biochemical markers of down syndrome in amniotic fluid samples.

Down syndrome (DS) is one of the most common chromosomal abnormalities affecting about 1 of every 700 fetuses. Current screening strategies have detection rates of 90-95% at a 5% false positive rate. The aim of this study was to discover new biomarkers of DS in amniotic fluid by using a multiplex selected reaction monitoring assay. Nine proteins were analyzed: CEL, CPA1, MUC13, CLCA1, MUC5AC, PLUNC, and HAPLN1, and CGB as positive control and serotransferrin as negative control. One proteotypic peptide for each protein was selected, and internal heavy isotope-labeled peptide standards were spiked into the samples. Fifty-four samples from pregnant women carrying normal (n = 37) or DS-affected (n = 17) fetuses were analyzed. The median protein concentrations for DS and normal samples, respectively, were as follows: 20 and 49 ng/mL (p < 0.01) for CEL; 3.7 and 14 ng/mL (p < 0.001) for CPA1; 80 and 263 ng/mL (p < 0.001) for MUC13; 46 and 135 ng/mL (p < 0.001) for CLCA1; 0.65 and 0.93 µg/mL (p < 0.05) for MUC5AC; 61 and 73 ng/mL (p > 0.05) for PLUNC; 144 and 86 ng/mL (p < 0.01) for HAPLN1; 0.89 and 0.54 µg/mL (p = 0.05) for CGB; 91 and 87 µg/mL (p > 0.05) for serotransferrin. Statistically significant differences were found in six out of the seven candidate proteins analyzed, reflecting a different regulation in DS.

Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFκB activation resulting in a microenvironment predisposed to ectopic pregnancy.

Chlamydia trachomatis and smoking are major risk factors for tubal ectopic pregnancy (EP), but the underlying mechanisms of these associations are not completely understood. Fallopian tube (FT) from women with EP exhibit altered expression of prokineticin receptors 1 and 2 (PROKR1 and PROKR2); smoking increases FT PROKR1, resulting in a microenvironment predisposed to EP. We hypothesize that C. trachomatis also predisposes to EP by altering FT PROKR expression and have investigated this by examining NFκB activation via ligation of the Toll-like receptor (TLR) family of cell-surface pattern recognition receptors. PROKR2 mRNA was higher in FT from women with evidence of past C. trachomatis infection than in those without (P < 0.05), and was also increased in FT explants and in oviductal epithelial cell line OE-E6/E7 infected with C. trachomatis (P < 0.01) or exposed to UV-killed organisms (P < 0.05). The ability of both live and dead organisms to induce this effect suggests ligation of a cell-surface-expressed receptor. FT epithelium and OE-E6/E7 were both found to express TLR2 and TLR4 by immunohistochemistry. Transfection of OE-E6/E7 cells with dominant-negative TLR2 or IκBα abrogated the C. trachomatis-induced PROKR2 expression. We propose that ligation of tubal TLR2 and activation of NFκB by C. trachomatis leads to increased tubal PROKR2, thereby predisposing the tubal microenvironment to ectopic implantation.

Routine Screening for Central and Primary Adrenal Insufficiency during Immune-Checkpoint Inhibitor Therapy: An Endocrinology Perspective for Oncologists.

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated hypothalamic-pituitary-adrenal axis disruption can lead to hypocortisolism. This is a life-threatening but difficult to diagnose condition, due to its non-specific symptoms that overlap with symptoms of malignancy. Currently, there is no consensus on how to best screen asymptomatic patients on ICI therapy for hypophysitis with serum cortisol. METHODS: A retrospective chart review of patients treated with ICI in a tertiary care centre was conducted to assess the rate of screening with cortisol and whether this had an impact on diagnosis of ICI-hypophysitis in the preclinical stage. Patients were identified as having hypophysitis with an adrenocorticotropin hormone (ACTH) deficiency based on chart review of patients with cortisol values ≤ 140 nmol/L (≤5 mcg/dL). We also assessed what proportion of cortisol values were drawn at the correct time for interpretation (between 6 AM and 10 AM). RESULTS: Two hundred and sixty-five patients had 1301 cortisol levels drawn, only 40% of which were drawn correctly (between 6 and 10 AM). Twenty-two cases of hypophysitis manifesting with ACTH deficiency were identified. Eight of these patients were being screened with cortisol following treatment and were detected in the outpatient setting. The remaining 14 patients were not screened and were diagnosed when symptomatic, after an emergency room visit or hospital admission. Sixty percent of the cortisol tests were uninterpretable as they were not drawn within the appropriate time window. CONCLUSION: Measuring morning serum cortisol in asymptomatic patients on ICI therapy is a fast and inexpensive way to screen for hypophysitis and should become the standard of care. Random serum cortisol measurement has no clinical value. Education needs to be provided on when to correctly perform the test and how to interpret it and we provide an algorithm for this purpose. The adoption and validation of such an algorithm as part of routine practice could significantly reduce morbidity and mortality in patients, especially as ICI therapy is becoming increasingly commonplace.

High-Anion-Gap Metabolic Acidosis During a Prolonged Hospitalization Following Perforated Diverticulitis: An Educational Case Report.

Rationale: The metabolic acidoses are generally separated into 2 categories on the basis of an anion gap calculation: high-anion-gap and normal anion-gap metabolic acidosis. When a high-anion-gap metabolic acidosis (HAGMA) is not clearly explained by common etiologies and routine confirmatory testing, specialized testing can definitively establish rare diagnoses such as 5-oxoproline, d-lactate accumulation, or diethylene glycol toxicity. Presenting Concerns of the Patient: A 56-year-old woman had a prolonged hospital admission following perforated diverticulitis requiring sigmoid resection. Her hospitalization was complicated by feculent peritonitis and surgical wound dehiscence needing prolonged broad-spectrum antibiotics and wound debridements. She developed acute kidney injury and HAGMA in the hospital. Diagnoses: Chart review showed that she received a large cumulative dose of acetaminophen during her hospital stay. Laboratory studies showed markedly increased serum 5-oxoproline causing HAGMA. Interventions Including Prevention and Lifestyle: Patient was admitted to the intensive care unit and treated with N-acetylcysteine and renal replacement therapy. Outcomes: After admission to the intensive care unit, the patient continued to require vasopressor and ventilatory support for septic shock and a ventilator-associated pneumonia. After an initial recovery and resolution of her HAGMA, she subsequently suffered recurrent aspirations which were fatal. Teaching points: 1. The acronym GOLD MARK is useful when assessing patients with HAGMA and most causes of HAGMA can be established with routine testing.2. When the etiology of HAGMA remains unclear, additional testing can be required to diagnose rare causes of HAGMA.3. Rare causes of HAGMA are diethylene glycol, 5-oxoproline, and d-lactate accumulation.4. Acidosis secondary to 5-oxoproline accumulation can occur even with "therapeutic" doses of acetaminophen in patients receiving it regularly for a prolonged period and who have depleted glutathione stores.5. Risk factors for glutathione depletion include malnutrition, older age, sepsis, pregnancy, multiple chronic illnesses, and chronic kidney disease.

Justification: Les acidoses métaboliques sont généralement classées en deux catégories sur la base d'un calcul de trou anionique : les acidoses métaboliques à trou anionique élevé (HAGMA ­ High anion gap metabolic acidosis) et les acidoses métaboliques à trou anionique normal. Lorsque l'acidose métabolique à trou anionique élevé n'est pas clairement expliquée par des étiologies courantes et des tests de confirmation de routine, des tests spécialisés peuvent établir de façon définitive des diagnostics rares tels que l'accumulation de 5-oxoproline, l'accumulation de D-lactate ou une toxicité du diéthylène glycol. Présentation du cas: Une femme de 56 ans hospitalisée de façon prolongée à la suite d'une diverticulite perforée nécessitant une résection du sigmoïde. L'hospitalisation a été compliquée par une péritonite purulente et une déhiscence de la plaie chirurgicale ayant nécessité un débridement de la plaie et une antibiothérapie à large spectre prolongée. La patiente a développé une insuffisance rénale aiguë (IRA) et une HAGMA durant son séjour à l'hôpital. Diagnostic: L'examen du dossier a montré que la patiente avait reçu une dose cumulative importante d'acétaminophène pendant son séjour à l'hôpital. Des analyses en laboratoire ont montré une augmentation marquée de la 5-oxoproline sérique ayant causé l'HAGMA. Interventions y compris prévention et mode de vie: La patiente a été admise à l'unité des soins intensifs et traitée par N-acétylcystéine et thérapie de remplacement rénal (TRR). Résultats: Après son admission à l'USI, la patiente a continué d'avoir besoin de vasopresseur et d'assistance respiratoire en raison d'un choc septique et d'une pneumonie associée au ventilateur. Après un rétablissement initial et la résolution de son HAGMA, la patiente a ensuite dû subir des aspirations récurrentes qui lui ont été fatales. Enseignements tirés: 1. L'acronyme GOLD MARK est utile lors de l'évaluation des patients atteints d'HAGMA; la plupart des causes d'HAGMA peuvent être établies avec des tests de routine.2. Lorsque l'étiologie de l'HAGMA reste incertaine, des tests supplémentaires peuvent être nécessaires pour diagnostiquer les causes rares de l'HAGMA.3. Les causes rares de HAGMA sont une accumulation de diéthylène glycol, de 5-oxoproline et de D-lactate.4. L'acidose secondaire à une accumulation de 5-oxoproline peut se produire même avec des doses « thérapeutiques ¼ d'acétaminophène chez les patients qui l'ont reçu régulièrement pendant une période prolongée et qui ont épuisé leurs réserves de glutathion.5. Les facteurs de risque pour l'épuisement des réserves de glutathion incluent la malnutrition, l'âge plus avancé, la septicémie, la grossesse, les maladies chroniques multiples et l'insuffisance rénale chronique.

Point of care molecular and antigen detection tests for COVID-19: current status and future prospects.

INTRODUCTION: Detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been critical to support and management of the COVID-19 pandemic. Point of care testing (POCT) for SARS-CoV-2 has been a widely used tool for detection of SARS-CoV-2. AREAS COVERED: POCT nucleic acid amplification tests (NAATs) and rapid antigen tests (RATs) have been the most readily used POCT for SARS-CoV-2. Here, current knowledge on the utility of POCT NAATs and RATs for SARS-CoV-2 are reviewed and discussed alongside aspects of quality assurance factors that must be considered for successful and safe implementation of POCT. EXPERT OPINION: Use cases for implementation of POCT must be evidence based, regardless of the test used. A quality assurance framework must be in place to ensure accuracy and safety of POCT.

Practical application of mathematical calculations and statistical methods for the routine haematology laboratory.

BACKGROUND: Statistical analyses are embedded as critical functions in the routine haematology laboratory. AIM: This educational article is aimed at providing an overview of these topics and practical application examples. MATERIALS, METHODS, AND RESULTS: Topics covered include mathematical conversion between units, maintaining a quality control (QC) system, statistical methods for reagent validation, and determining uncertainty of measurement (UoM). DISCUSSION: Additional considerations may be required when a regional laboratory program is in place, such as the harmonization of INR results and determination of therapeutic reference intervals for unfractionated heparin therapy. CONCLUSION: The coauthors of this manuscript are fortunate to be part of regional network of hospital laboratories, the Eastern Ontario Regional Laboratory Association (EORLA).

Cotinine exposure increases Fallopian tube PROKR1 expression via nicotinic AChRalpha-7: a potential mechanism explaining the link between smoking and tubal ectopic pregnancy.

Tubal ectopic pregnancy (EP) is the most common cause of maternal mortality in the first trimester of pregnancy; however, its etiology is uncertain. In EP, embryo retention within the Fallopian tube (FT) is thought to be due to impaired smooth muscle contractility (SMC) and alterations in the tubal microenvironment. Smoking is a major risk factor for EP. FTs from women with EP exhibit altered prokineticin receptor-1 (PROKR1) expression, the receptor for prokineticins (PROK). PROK1 is angiogenic, regulates SMC, and is involved in intrauterine implantation. We hypothesized that smoking predisposes women to EP by altering tubal PROKR1 expression. Sera/FT were collected at hysterectomy (n=21). Serum levels of the smoking metabolite, cotinine, were measured by enzyme-linked immunosorbent assay. FTs were analyzed by q-RT-PCR, immunohistochemistry, and Western blotting for expression of PROKR1 and the predicted cotinine receptor, nicotinic acetylcholine receptor α-7 (AChRα-7). FT explants (n=4) and oviductal epithelial cells (cell line OE-E6/E7) were treated with cotinine and an nAChRα-7 antagonist. PROKR1 transcription was higher in FTs from smokers (P<0.01). nAChRα-7 expression was demonstrated in FT epithelium. Cotinine treatment of FT explants and OE-E6/E7 cells increased PROKR1 expression (P<0.05), which was negated by cotreatment with nAChRα-7 antagonist. Smoking targets human FTs via nAChRα-7 to increase tubal PROKR1, leading to alterations in the tubal microenvironment that could predispose to EP.