Associations Between Transcranial Doppler Flow Velocities, Laboratory Parameters, and Clinical Features in Turkish Children With Sickle Cell Disease.

OBJECTIVE: Stroke is one of the major complications of sickle cell disease (SCD). Stroke features either occlusion of, or stenosis at, the origin of one of the large intracerebral arteries, the internal carotid artery (ICA), and/or the middle cerebral artery (MCA). PURPOSE: We sought correlations between cerebral blood flow velocities and the laboratory and clinical findings of patients with SCD. MATERIALS AND METHODS: Fifty-three pediatric SCD patients (39 with HbSS, 14 with HbSß0) were analyzed. The mean patient age was 12.9±3.9 years. The control group contained 24 healthy individuals. The time-averaged maximum mean velocity (TAMMV) and resistive index (RI) of the MCA, the TAMMVs of the ICA and vertebral artery (VA), and the diameter of the VA were estimated through transcranial Doppler ultrasonography using a 2.5 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. We evaluated the relationships between the TAMMVs, laboratory parameters, and clinical findings. RESULTS: The mean±SD MCA TAMMV was 161.2±35.4 cm/s in patients with HbSS and 185.8±62.9 cm/s in patients with HbSß0. The mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 168.5±43.9 cm/s, 0.63±0.06, 116.8±25.5 cm/s, 69.2±18.5 cm/s, and 3.5±0.61 mm for all SCD patients, respectively. In the control group, the mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 103.8±28.8 cm/s, 0.53±0.04, 96.4±27.8 cm/s, 40.3±12.1 cm/s, and 3.4±0.6 mm, respectively. Although the differences were not significant, TAMMVs were higher in HbSß0 patients taking hydroxyurea; those with hemoglobin levels <8 g/dL, ferritin levels >1000 ng/dL, mean platelet volume >12 fL, or red cell distribution width >18%; or required chelation, or were below the third percentiles of weight and height. The TAMMV was significantly higher only in SCD patients who complained of headache. CONCLUSIONS: High ferritin and low hemoglobin levels, a high mean platelet volume, a high red cell distribution width, low weight (below the third percentile), and a short height (below the third percentile) may be associated with elevated cerebral blood flow velocities and an increased stroke risk in children with SCD. Children with such features should be closely followed-up through transcranial Doppler ultrasonography examination.

Pathological Features in 100 Deceased Patients With COVID-19 in Correlation With Clinical and Laboratory Data.

Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 post-mortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.

A Triple-Parameter-Based Laboratory-Friendly Fluorescence Imaging to Identify Apoptosis in Live Cells.

Cellular signals to resist apoptosis have been attributed as one of the mechanisms of tumorigenesis. Hence, apoptosis is a cardinal target for drug development in cancers, and several antitumor drugs have been designed to induce apoptosis in tumor cells. Recently, venetoclax, a Bcl2 inhibitor that induces apoptosis, has been approved by the FDA for the treatment of CLL and SLL patients. Proapoptotic antitumor drugs have been traditionally developed and tested, targeting apoptosis in tumor cells. The mechanism of such drug actions has been functionally connected to the mechanism of apoptosis. The identification of apoptosis in a tumor cell takes into account different characteristics in several steps of apoptosis. Thus, it is understandable that modes of identification of apoptosis observed in tumor cells in a laboratory have also been tuned to different characteristics in several parameters of apoptosis. Here, we present a detailed methodology for a triple-parameter-based co-fluorescence imaging to identify apoptosis in live tumor cells. The procedure involves co-fluorescence staining specific for three cardinal features of apoptosis in live cells. The procedure is simple, time-sensitive, and can be performed successfully in a laboratory-friendly manner.

Frequency and type of adverse analytical findings in athletics: Differences among disciplines.

Athletics is a highly diverse sport that contains a set of disciplines grouped into jumps, throws, races of varying distances, and combined events. From a physiological standpoint, the physical capabilities linked to success are quite different among disciplines, with varying involvements of muscle strength, muscle power, and endurance. Thus, the use of banned substances in athletics might be dictated by physical dimensions of each discipline. Thus, the aim of this investigation was to analyse the number and distribution of adverse analytical findings per drug class in athletic disciplines. The data included in this investigation were gathered from the Anti-Doping Testing Figure Report made available by the World Anti-Doping Agency (from 2016 to 2018). Interestingly, there were no differences in the frequency of adverse findings (overall,~0.95%, range from 0.77 to 1.70%) among disciplines despite long distance runners having the highest number of samples analysed per year (~9812 samples/year). Sprinters and throwers presented abnormally high proportions of adverse analytical findings within the group of anabolic agents (p < 0.01); middle- and long-distance runners presented atypically high proportions of findings related to peptide hormones and growth factors (p < 0.01); racewalkers presented atypically high proportions of banned diuretics and masking agents (p = 0.05). These results suggest that the proportion of athletes that are using banned substances is similar among the different disciplines of athletics. However, there are substantial differences in the class of drugs more commonly used in each discipline. This information can be used to effectively enhance anti-doping testing protocols in athletics.

Determination of ochratoxin A in edible pork offal: intra-laboratory validation study and estimation of the daily intake via kidney consumption in Belgium.

Pork-derived products can contribute to the overall ochratoxin A (OTA) intake via carry-over from contaminated feed or via mould spoilage of meat products (salami, dry-cured ham, sausage). An analytical method using liquid chromatography coupled with mass spectrometry (LC-MS/MS) was developed and validated in accordance with the specifications laid down by European Commission. It offered quantification limits of 0.2 for kidney, liver and 0.4 µg/kg for black sausage. Spiking experiments of blank samples at 5-10 µg/kg showed recoveries ranging from 88 to 101%, 89 to 97% and 80 to 85% for kidney, liver and black sausage, respectively. The respective intra-laboratory repeatabilities ranged between 9.8-11.1%, 9.4-14.4% and 9.7-14.2%, and extended measurement uncertainties MU(k = 2) were 33%, 35% and 43% for kidney, liver and black sausage. Next, the validated method was applied to kidney (110), liver (20) and black sausage (20) samples collected in Belgium in the period 2012-2019. Neither liver nor black sausage samples were contaminated with OTA. Kidney samples (37.3%) were OTA contaminated at the mean level of 0.22 ± 0.25 µg/kg (up to 1.91 µg/kg). These data combined with the offal consumption in the Belgian population revealed average daily OTA exposures ranged from 0.167 and 0.319 ng/kg bw for 3 age groups (3-9, 10-17 and 18-64 years). Taking into account, the OTA non-neoplastic and neoplastic effects, risk characterization assessed via the margin of exposure for reference endpoints revealed no potential health risk for the consumers. As the presence of low OTA content in foods together with other mycotoxins or derivatives may interactively potentiate its toxicity, monitoring of OTA and its metabolites in meat and meat by-products is advised.

Harsh and Sweet Sensations Predict Acute Liking of Electronic Cigarettes, but Flavor Does Not Affect Acute Nicotine Intake: A Pilot Laboratory Study in Men.

INTRODUCTION: Electronic cigarette use is increasing in popularity, and thousands of flavors are available. Adolescent vaping rates in the United States have nearly doubled in the past year. Unlike combustible tobacco, added flavors are not currently regulated for some types of electronic cigarette products. Here, we investigated the role of flavor in electronic cigarette liking and acute intake. METHODS: Men (n = 39) aged 18-45 vaped in a controlled laboratory setting after being randomized to one of four e-liquids: 6 mg nicotine/mL cherry, 18 mg/mL cherry, 6 mg/mL chocolate, or 18 mg/mL chocolate. They completed several questionnaires, and vaped ad libitum for 10 minutes. After the first puff, participants rated sensations (sweetness, bitterness, coolness, harshness/irritation) on general labeled magnitude scales (gLMS) and rated overall liking on a generalized hedonic scale. Once the 10-minute session ended, participants made another set of ratings. RESULTS: Liking was generally stable across the vaping session and liking varied substantially across the four conditions. Across all conditions, sensory ratings predicted liking: harshness/irritation was negatively associated with first puff liking, whereas perceived sweetness was positively associated with first puff liking. First puff liking associated with increased amount of e-liquid vaped, but not total nicotine intake. Participants appeared to titrate their nicotine intake regardless of assigned condition. CONCLUSION: Flavored e-liquids affect acute liking ratings, but not acute nicotine intake. IMPLICATIONS: These data suggest individuals who regularly vape may titrate their nicotine intake, regardless of flavor, and contrary to expectations, acute liking did not predict total nicotine intake. However, more-liked flavors may potentially make higher nicotine levels more tolerable by adding pleasant sensations directly, rather than by perceptual masking that reduces aversive sensations.

The impact of biosafety enhancement on stat laboratory quality metrics: Lessons from the COVID-19 pandemic.

OBJECTIVE: It is unclear if implementation of biosafety action plans in response to the COVID-19 pandemic has affected laboratory quality metrics. METHODS: This retrospective study used quality data, including turnaround time (TAT) and number/type of unacceptable specimens from a stat laboratory supporting an outpatient medical clinic serving predominantly elderly cancer patients. Four months of data from the height of the COVID-19 pandemic (March-June 2020) were compared to the same months in 2019. RESULTS: March-May 2020 test volumes were decreased compared to 2019. June 2020 test volume was slightly increased compared to 2019. TATs in 2020 were similar/ slightly improved compared to the same months in 2019, due to shortened collect to receive and receive to verify TATs. The number and types of unacceptable specimens were similar in 2020 and 2019. CONCLUSIONS: Despite the challenges to the system caused by the pandemic, laboratory quality metrics were maintained.

Comparability of laboratory-developed and commercial PD-L1 assays in non-small cell lung carcinoma.

PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to treatment with PD-1 and PD-L1 inhibitors. Different inhibitors have been developed with different PD-L1 assays, which use different PD-1 antibody clones on different immunohistochemistry platforms. Depending on instrument and reagent availability, laboratory-developed tests with cross-platform use of PD-L1 antibodies may have practical benefits over commercial assays. The 22C3 pharmDx Assay (referred to as 22C3 DAKO), the VENTANA PD-L1 SP263 Assay (referred to as SP263 VENTANA) and a lab-developed test using the 22C3 antibody on the VENTANA BenchMark ULTRA IHC/ISH system (referred to as 22C3 VENTANA) were performed on whole sections of 85 NSCLC surgical resections. All sections were independently scored by three pathologists using tumor proportion scores. Correlation coefficients for continuous scores in pairwise comparisons between assays ranged from 0.976 to 0.978. When using a 1% positivity threshold (dichotomous scores), the 22C3 DAKO assay and 22C3 VENTANA assays showed the greatest agreement (93% agreement, κ = 0.86, 95% CI 0.75-0.97), and the 22C3 DAKO and SP263 VENTANA assays tended to show slightly less agreement (84% agreement, κ = 0.66, 95% CI 0.50-0.82). When using a 50% positivity threshold (dichotomous scores), all pairwise comparisons showed similar agreement (96-99% agreement, κ = 0.89-0.97). Overall, there was no significant difference between assays at 1% or 50% thresholds (P = .77). These data are consistent with potential interchangeability of these assays, which may widen the scope of PD-L1 assays available to laboratories and reduce logistical barriers to testing.

Avaliação externa da qualidade da identificação entomológica de triatomíneos realizada na Rede de Laboratórios Públicos em Pernambuco, 2017 / Evaluación externa de la calidad en la identificación entomológica de triatominos realizada en la red de laboratorios públicos en Pernambuco, Brasil, 2017 / External quality assessment of entomological identification of triatomines carried out in the Pernambuco Public Health Laboratory network, Brazil, 2017

Objetivo: Avaliar a qualidade da identificação de triatomíneos na rede de laboratórios do estado de Pernambuco, Brasil. Métodos: Os nove laboratórios participantes receberam material de apoio com as chaves dicotômicas e um painel composto por sete insetos triatomíneos conhecidos no estado, para identificação da situação do espécime no recebimento (estrutura completa ou danificada), espécie e sexo. Resultados: Nove laboratórios de 12 aderiram ao estudo. A proporção de acerto para identificação do sexo foi de 56/63, e para espécie, 45/63, não apresentando relação direta com a ocorrência de danos nas estruturas morfológicas durante o transporte dos insetos. Para Panstrongylus megistus, houve acerto em todos os espécimes (9/9), enquanto para espécies do gênero Rhodnius a proporção foi menor (3/9). Conclusão: Apesar do bom desempenho na identificação entomológica, as fragilidades observadas poderão orientar ações para melhoria na rede de laboratórios e serão essenciais para os programas de controle vetorial da doença de Chagas.

Objetivo: Evaluar la calidad de la identificación de triatominos en la red de laboratorios del estado de Pernambuco, Brasil. Métodos: Los nueve laboratorios participantes recibieron material de apoyo con claves dicotómicas y un panel conformado por siete insectos triatominos conocidas en el estado, para identificar la situación del espécimen al recibirlo (estructura completa o dañada), especie y sexo. Resultados: La adherencia al laboratorio fue del 9/12. La proporción de aciertos para la identificación del sexo fue del 56/63, y para las especies 45/63, no mostraron relación directa con la ocurrencia de daños en las estructuras morfológicas durante el transporte de insectos. Solo Panstrongylus megistus logró el 9/9 de precisión, mientras que para las especies del género Rhodnius fue el más pequeño (3/9). Conclusión: A pesar del buen desempeño en identificación entomológica, la evaluación indicó debilidades que permitirán implementar acciones correctivas para mejorar la red de laboratorios, esenciales para los programas de control vectorial de la enfermedad de Chagas.

Objective: To assess the quality of triatomine identification in the laboratory network of the state of Pernambuco, Brazil. Methods: The participating laboratories received support material with dichotomous keys and a panel made up of seven triatomine insects known in the Pernambuco, in order to identify specimen status on receipt (intact or damaged structure), as well as species and sex. Results: Nine out of 12 laboratories took part of the study. The proportion of correct answers was 56/63 for sex identification, and 45/63, for species. The answers did not present a direct relationship with occurrence of damage to morphological structures during insect transportation. Panstrongylus megistus identification was correct for all specimens (9/9 laboratories), while correct identification of species of the Rhodnius genus was the lowest (3/9 laboratories). Conclusion: Despite the good performance in entomological identification, the weaknesses observed may guide improvements in the laboratory network and will be essential for Chagas disease vector control programs.

Is It Time to Remove Total Calcium from the Basic and Comprehensive Metabolic Panels? Assessing the Effects of American Medical Association-Approved Chemical Test Panels on Laboratory Utilization.

BACKGROUND: The necessity of individual tests within the most commonly used disease-oriented test panels has not been well established. We evaluated test-ordering practices for total calcium, both before and after implementation of American Medical Association (AMA)-approved panels (basic metabolic panel [BMP] and comprehensive metabolic panel [CMP]) in our electronic ordering system. METHODS: We performed a retrospective review of all total calcium orders placed during April and June 2018, before and after implementation of the panels. Orders from inpatient, outpatient, and emergency department (ED) care units were totaled, and the percentage of abnormal test results was calculated. We then queried institutional databases to determine the number of unique patients with calcium-related diagnoses and compared the rates from a 5-month period both before and after implementation of the panels. RESULTS: Total test volumes and tests per unique patient increased by more than 3-fold after implementation of calcium-containing AMA-approved panels, with the majority of those orders coming from BMPs and CMPs. The rate of low calcium values increased because of the shift toward more inpatient testing; however, the percentage of abnormal results within each patient population (inpatient, outpatient, ED) decreased. The prevalence of hypo- and hypercalcemia-related diagnoses among patients in the 5 months after implementation did not change significantly (1.29% before implementation vs 1.27% after implementation). CONCLUSIONS: Implementation of BMPs and CMPs dramatically increased total calcium testing volumes without changing the rate of calcium-related diagnoses. The results suggest that the increase in total calcium orders associated with panel-based testing largely constitutes excess or unnecessary testing.

New information flows for cancer registries: testing the use of laboratory data in the province of Reggio Emilia, Italy.

INTRODUCTION: Haematological malignancies often escape the standard information flows of cancer registries because diagnosis is not always based on bone marrow histology but, rather, on other laboratory tests. OBJECTIVE: To quantify incident haematological malignancies identified exclusively through the laboratory information system and to measure the impact of that source on the sensitivity and accuracy of registering these malignancies. METHODS: We collected data from the only provincial laboratory of Reggio Emilia on molecular biology, flow cytometry tests and bone marrow smears to detect specific markers of some chronic haematological malignancies. We carried out a record linkage between laboratory reports (period 2013-2017) of patients resident in the province of Reggio Emilia and the Cancer Registry of Reggio Emilia. RESULTS: Of the 303 patients who underwent at least one of these tests, 85 were not included in our Cancer Registry. Of these 85 patients, 42 had received a diagnosis of cancer: 34 myeloproliferative neoplasms, 3 chronic myeloid leukaemias, 3 myelodysplastic neoplasms, 1 multiple myeloma and 1 chronic lymphocytic leukaemia. We recovered 4.2% of the total number of chronic haemolymphopoietic cancers registered in the study period, accounting for 15% of myeloproliferative neoplasms. For 30% of prelinkage cases, the specificity of the morphological code improved. CONCLUSIONS: Although the laboratory information system's contribution to the completeness of Cancer Registry incident cases was modest, it is useful to add laboratory data to routine cancer registry information flows due to the increasing use of molecular characterisation and to the phenomenon of dehospitalisation.

[Employee Safety and Biosafety Applications in Microbiology Laboratories; A Multicenter Evaluation in Turkey]. / Mikrobiyoloji Laboratuvarlarinda Çalisan Güvenligi ve Biyogüvenlik Uygulamalari Açisindan Türkiye'de Çok Merkezli Bir Degerlendirme.

Medical laboratory personnel may be exposed to various hazards, especially biological and chemical, during their routine activities. In this multicenter study, which could reflect the nation wide results, it was aimed to determine the safety and biosecurity practices of the employee working in medical microbiology laboratories and to reveal the current situation. A total of 1072 personnel working in the Medical Microbiology Laboratory of 23 hospitals (14 medical faculty hospitals, seven ministry of health training and research hospitals and two state hospitals) from different provinces were provided with a questionnaire consisting of 33 questions inquiring about the rules, opinions, attitudes and behaviors regarding safety and biosafety practices. Statistical analyses were made with institutions, age groups, gender, educational background, working time and occupational groups in terms of exposure to biological and chemical hazards. It was determined that approximately 50% personnel of the university/ training and research hospitals and 2/3 of the state hospitals personnel consumed food and beverages in the laboratories (p<0.05). Compared with other hospitals, it was determined that in state hospitals; the absence of separate resting room (35%), the personnel finding their own knowledge and practices inadequate (28.9%), laboratory coats washed at home (95%), educational organization and participation rates (90%) and medical waste information levels of the personnel were higher (p< 0.05). It was determined that as the age progresses, the rate of education, food and beverage consumption in the laboratory, not being outside the laboratory with protective equipment (gloves, masks and laboratory coats) and the history of laboratory acquired infections were increased (p< 0.05). It was observed that washing the laboratory coats at home was higher in the younger age group and hospital washing was higher in the elderly group (p< 0.05). There was no significant difference between the genders in terms of food and beverage consumption in the laboratory (p= 0.09). It was determined that periodic health checks were not performed in 1/3 of both sexes, but the use of gloves and compliance with medical waste rules was lower in men. Female employees find themselves inefficient in terms of knowledge and practices (p< 0.05). The rate of those who did not have their periodic checkups at regular intervals was higher in the high school and master of science education groups; While non-compliance with medical waste rules, food and beverage consumption in the laboratory was highest in the primary and high school graduates, the lowest rates were found in the master and doctorate groups (p< 0.05). The rate of those who had regular health checkups was higher in the group of specialist physicians and technicians (p< 0.05). It was observed that the rule of not going out of the laboratory with protective equipment was fully observed in the 35+ years working group, while compliance was 70-85% in other groups (p< 0.05), hepatitis B vaccination rate was highest in specialist doctors and lowest in cleaning and other personnel group (p< 0.05). Highest non-compliance rate with medical waste rules was observed in the cleaning personnel group (p< 0.05). As a result, although advances have been made in employee safety practices in medical microbiology laboratories in our country in recent years, it has been found that it is not yet sufficient. The results indirectly reflected the profile of medical laboratories in our country. In the laboratories, physical space and equipment deficiencies should be eliminated, periodic health checkups and vaccination should be provided, non-staff entrance to the laboratory and food, beverage and cigarette consumption should be prevented, laboratory coats should be washed in the hospital, in-service trainings, including medical waste training, should be conducted and these trainings should be developed through mechanisms that will change the behavior.

Reliability of liquid biopsy analysis: an inter-laboratory comparison of circulating tumor DNA extraction and sequencing with different platforms.

Liquid biopsy, the analysis of circulating tumor DNA (ctDNA), is a promising tool in oncology, especially in personalized medicine. Although its main applications currently focus on selection and adjustment of therapy, ctDNA may also be used to monitor residual disease, establish prognosis, detect relapses, and possibly screen at-risk individuals. CtDNA represents a small and variable proportion of circulating cell-free DNA (ccfDNA) which is itself present at a low concentration in normal individuals and so analyzing ctDNA is technically challenging. Various commercial systems have recently appeared on the market, but it remains difficult for practitioners to compare their performance and to determine whether they yield comparable results. As a first step toward establishing national guidelines for ctDNA analyses, four laboratories in Switzerland joined a comparative exercise to assess ccfDNA extraction and ctDNA analysis by sequencing. Extraction was performed using six distinct methods and yielded ccfDNA of equally high quality, suitable for sequencing. Sequencing of synthetic samples containing predefined amounts of eight mutations was performed on three different systems, with similar results. In all four laboratories, mutations were easily identified down to 1% allele frequency, whereas detection at 0.1% proved challenging. Linearity was excellent in all cases and while molecular yield was superior with one system this did not impact on sensitivity. This study also led to several additional conclusions: First, national guidelines should concentrate on principles of good laboratory practice rather than recommend a particular system. Second, it is essential that laboratories thoroughly validate every aspect of extraction and sequencing, in particular with respect to initial amount of DNA and average sequencing depth. Finally, as software proved critical for mutation detection, laboratories should validate the performance of variant callers and underlying algorithms with respect to various types of mutations.

Survey on request form content and result reporting in therapeutic drug monitoring service among laboratories in Czechia and Slovakia.

INTRODUCTION: The aim of the study was to investigate current practice and policies of therapeutic drug monitoring (TDM) service requesting and result reporting in Czechia and Slovakia. MATERIALS AND METHODS: All 149 laboratories that measure plasma drug concentrations were given an online questionnaire during a regular external quality assessment TDM cycle. The questionnaire consisted of 17 questions. The optimal TDM practice was defined as the application of all elements (age, body weight, time of sampling, date of the first administration, time of the last dose administration, the dose, the dosing interval, the route of administration, information on reason of testing, and information on other co-administered drugs) needed for reporting a recommendation for further drug dosing (positive response to question number 16). RESULTS: The response rate was 69%, 103 out of 149 laboratories measuring drug concentrations. Only 12% (12 out of 103 laboratories) of the laboratories implemented all elements needed for optimal TDM practice and reported a recommendation. Both paper and electronic request forms were used by 77 out of 103 (75%) laboratories. A total of 69 out of 103 laboratories (67%) specified the type of sampling tube on their request form. Cystatin C was used for prediction of renal drug elimination by 24% (25 out of 103) of participants. CONCLUSIONS: Small number of laboratories implemented all elements needed for optimal TDM practice and report a recommendation on further dosing. Further efforts in education on optimal TDM practice as well as harmonization of service are desirable.

A Practical Approach to Preventing Renal Complications in the Catheterization Laboratory.

Contrast-induced acute kidney injury is a common complication in patients undergoing invasive procedures and is associated with increased mortality and morbidity. There is no effective approach to the management of this complication, and prevention remains of paramount importance. The 3 pillars of prevention are identification of high-risk patients, appropriate hydration before and after contrast exposure, eGFR-based contrast dosing and use of ultra-low contrast volume in high-risk patients. Most evidence supporting these practices is derived from patients undergoing coronary angiography or percutaneous coronary intervention but these basic principles can be applied to most patients undergoing contrast-based procedures in the catheterization laboratory.

Significant inter- and intra-laboratory variation in grading of invasive breast cancer: A nationwide study of 33,043 patients in the Netherlands.

Accurate, consistent and reproducible grading by pathologists is of key-importance for identification of individual patients with invasive breast cancer (IBC) that will or will not benefit from adjuvant systemic treatment. We studied the laboratory-specific grading variation using nationwide real-life data to create insight and awareness in grading variation. Synoptic pathology reports of all IBC resection-specimens, obtained between 2013 and 2016, were retrieved from the nationwide Dutch Pathology Registry (PALGA). Absolute differences in laboratory-proportions of Grades I-III were compared to the national reference. Multivariable logistic regression provided laboratory-specific odds ratios (ORs) for high- vs. low-grade IBC. 33,792 IBC pathology reports of 33,043 patients from 39 laboratories were included, of which 28.1% were reported as Grade I (range between laboratories 16.3-43.3%), 47.6% as Grade II (38.4-57.8%), and 24.3% as Grade III (15.5-34.3%). Based on national guidelines, the indication for adjuvant chemotherapy was dependent on histologic grade in 29.9% of patients. After case-mix correction, 20 laboratories (51.3%) showed a significantly deviant OR. Significant grading differences were also observed among pathologists within laboratories. In this cohort of 33,043 breast cancer patients, we observed substantial inter- and intra-laboratory variation in histologic grading. It can be anticipated that this has influenced outcome including exposure to unnecessary toxicity, since choice of adjuvant chemotherapy was dependent on grade in nearly a third of patients. Better standardization and training seems warranted.

Risk assessment in academic laboratories in the west of Iran: compare the CHRA and the RSLs methods.

In the laboratories staffs, there is potential for adverse health effects in exposure to chemicals. Therefore, risk assessment is one of the main issues to prevent these effects. The purpose of this study was to assess the health risk of laboratory staffs and compare the two methods, including 'Chemical Health Risk Assessment' (CHRA) and 'Regional Screening Levels' (RSLs), that developed by the Department of Occupational Safety and Health of Malaysia and the Environmental Protection Agency respectively. Using these two methods, the places with the highest risk were identified. Comparisons showed that RSLs is a precise method without personal judgment. The CHRA is a simple method for wider chemicals that categorize risk. But CHRA includes fewer parameters compared to RSLs, as well as personal judgment. The results of the present study showed that two methods did not compatible. According to the characteristics of these two methods, it is recommended to use them as a compliment each other to obtain accurate results.

The Mouse Mammary Gland: a Tool to Inform Adolescents About Environmental Causes of Breast Cancer.

Adolescence is a vulnerable period of breast development, and environmental chemical exposures that occur during this period can increase the risk of breast cancer in adulthood. Discussing breast health with adolescent girls can be difficult for several reasons. In this project, we worked to not only inform adolescent researchers about environmental risks for breast cancer but to also involve them in research studies. We taught adolescents about the stages of mammary gland development using samples collected from mice, with a specific focus on pre-pubertal and pubertal stages of development. Our analysis shows that adolescent researchers, with relatively modest training, can collect reliable and reproducible data on aspects of mammary gland biology that are known to be disrupted by environmental chemicals, with coefficients of variation < 2.5% for basic mammary gland parameters and 5-7% for more complex measures. Finally, we provided these adolescents with information about environmental risk factors for breast cancer that they could share with their peers and community and action items to potentially modify their individual risk. We hope that researchers working in this field will engage adolescent researchers in projects to evaluate chemicals that influence breast cancer risk. Summer research programs that inform young adolescents about breast cancer risk factors not only benefit these novice researchers individually but also benefit their communities when they are encouraged to talk about the value of basic science studies, discuss vulnerable periods of mammary gland development, and share what they have learned about cancer and the environment.