Point-of-care testing, near-patient testing and patient self-testing: warning points.

Point-of-care testing (POCT), near-patient testing (NPT) and patient self-tests (PST) are diagnostic examinations performed at the time and place of patient care. While POCT and NPT are performed and analyzed by medical professionals, PST are based on samples and parameters directly collected and analyzed by lay users. These tests are spreading both in high income countries and in low to middle income countries as they are expected to improve healthcare efficiency and equity, by saving resources, releasing pressure from hospitals and reducing logistical barriers. However, accurate multidisciplinary assessment is mandatory to ensure that what they promise is real. We reviewed some important ethical aspects, international standards and regulations. The current risks associated with alternative ways of testing are explained by the principles of respect for patient autonomy and non-maleficence. Further evidence from multidisciplinary assessment is needed to evaluate pros and cons in light of the principles of beneficence and justice. Although POCT or NPT need common regulation and accurate provider training to ensure safe and appropriate interpretation of results, PST needs even more attention as they are subject to direct patient use. Randomized controlled trails including patient education should be conducted in order to provide reliable evidence on clinical outcomes, patient acceptance and cost-effectiveness. Mandatory regulation is needed to avoid harm and EU regulation should help different countries maintain a safe use of devices in a global population of producers and users.

Palladium-Catalyzed Regioselective Synthesis of 2-SF5 -Indenols and Further Derivatizations.

A palladium-catalyzed synthesis of 2-SF5 -indenols has been developed by reacting commercially available boronic acid derivatives and readily accessible SF5 -alkynes. The present methodology is fully regioselective thanks to the intrinsic polarization of SF5 -alkynes. A selection of downstream functionalizations has been performed to highlight the versatility of 2-SF5 -indenols and indenones as platforms for the design of more complex SF5 -containing molecules.

Kynurenine pathway in Coronavirus disease (COVID-19): Potential role in prognosis.

BACKGROUND: It is known that inflammatory responses play an important role in the pathophysiology of COVID-19. AIMS: In this study, we aimed to examine the role of kynurenine (KYN) metabolism on the severity of COVID-19 disease AQ5. MATERIALS & METHODS: Seventy COVID-19 patients of varying severity and 30 controls were included in the study. In addition to the classical laboratory parameters, KYN, tryptophan (TRP), kynurenic acid (KYNA), 3 hydroxykynurenine (3OHKYN), quinolinic acid (QA), and picolinic acid (PA) were measured with mass spectrometry. RESULTS: TRP, KYN, KYN:TRP ratio, KYNA, 3OHKYN, PA, and QA results were found to be significantly different in COVID-19 patients (p < 0.001 for all). The KYN:TRP ratio and PA of severe COVID-19 patients was statistically higher than that of mild-moderate COVID-19 patients (p < 0.001 for all). When results were examined, statistically significant correlations with KYN:TRP ratio, IL-6, ferritin, and procalcitonin were only found in COVID-19 patients. ROC analysis indicated that highest AUC values were obtained by KYN:TRP ratio and PA (0.751 vs 0.742). In determining the severity of COVID-19 disease, the odd ratios (and confidence intervals) of KYN:TRP ratio and PA levels that were adjusted according to age, gender, and comorbidity were determined to be 1.44 (1.1-1.87, p = 0.008) and 1.06 (1.02-1.11, p = 0.006), respectively. DISCUSSION & CONCLUSION: According to the results of this study, KYN metabolites play a role in the pathophysiology of COVID-19, especially KYN:TRP ratio and PA could be markers for identification of severe COVID-19 cases.

The diagnostic value of serum hepcidin in acute appendicitis.

BACKGROUND: Acute appendicitis (AA) is the primary cause of acute abdomen in patients presenting to the emergency department with abdominal pain. Limited studies have explored the relationship between serum hepcidin levels and AA. This study aimed to measure serum hepcidin levels in patients undergoing surgery with a preliminary diagnosis of AA and to assess whether these levels can serve as a biochemical marker for diagnosing AA. METHODS: This study included patients aged 18 or older who presented to the emergency department between April 2018 and May 2019 and underwent surgery with a diagnosis of AA. The cohort comprised 94 patients with surgical pathology results compatible with AA (Group A), 16 patients with results not compatible with AA (Group B), and 42 healthy controls. Serum hepcidin levels were measured from venous blood samples. RESULTS: Mean hepcidin levels were 1750±285 pg/mL in Group A, 1349±381 pg/mL in Group B, and 1066±225 pg/mL in the control group. Statistically significant differences in serum hepcidin levels were observed between Group A and the control group (p<0.05). CONCLUSION: Hepcidin levels were significantly higher in patients with AA compared to both the control group and patients with surgically confirmed non-AA pathology. Therefore, hepcidin may serve as a useful adjunct in diagnosing acute appendicitis.

Evaluation of serum galectin-3 levels at Alzheimer patients by stages: a preliminary report.

BACKGROUND AND AIMS: Neuroinflammation has a critic role in the pathophysiology of neurological diseases. The activation of microglia is the main actor in this process. The aim of this study to collect data on the role of microglial activation in the etiology, and the possible continuum at the stage of disease through the evaluation of serum galectin-3 levels in patients with Alzheimer's disease (AD). METHODS: This was a prospective and cross-sectional study conducted on patients who were diagnosed as having AD using the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and stages determined with the scales of Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) with healthy controls. RESULTS: In our study, we studied 118 people, 57 with AD and 61 healthy people as a control group. In the AD patient group, serum galectin-3 levels were higher compared with the control group (p = 0.003). There were no significant differences in either group in other collected parameters (p > 0.05). It was observed that in all patients with AD, parallel to the stage of the disease, serum galectin-3 levels, patience's age, and duration of disease were statically and significantly increased (p < 0.05). CONCLUSION: In conclusion, serum galactin-3 levels may be associated with AD and maybe a potential biomarker for the identification of disease in the early stages. In future years, serum galectin-3 levels may become an important biomarker and therapeutic agent for chronic neurodegenerative diseases such as AD.

Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies.

Calculating the sample size in scientific studies is one of the critical issues as regards the scientific contribution of the study. The sample size critically affects the hypothesis and the study design, and there is no straightforward way of calculating the effective sample size for reaching an accurate conclusion. Use of a statistically incorrect sample size may lead to inadequate results in both clinical and laboratory studies as well as resulting in time loss, cost, and ethical problems. This review holds two main aims. The first aim is to explain the importance of sample size and its relationship to effect size (ES) and statistical significance. The second aim is to assist researchers planning to perform sample size estimations by suggesting and elucidating available alternative software, guidelines and references that will serve different scientific purposes.

Efficacy of ultrasound-guided Transversus Abdominis Plane (TAP) block in inguinal hernia surgery and the immunomodulatory effects of proinflammatory cytokines: prospective, randomized, placebo-controlled study.

BACKGROUND: Tumor Necrosis Factor-α (TNF-α) and Interleukin-1ß (IL-1ß) are among the cytokines released secondary to the surgical stress response. The objective of this study was to investigate the effect of a Transversus Abdominis Plane (TAP) block on postoperative pain and its immunomodulatory activity through proinflammatory cytokines. METHODS: TAP (study group; n=40) or p-TAP (placebo group; n=40). Patients in the TAP group underwent an Ultrasound (US) guided unilateral TAP block using 20-cc 0.5% bupivacaine solution. Patients in the p-TAP group underwent a sham block using 20-cc isotonic solution. The TNF-α and IL-1ß levels were measured three times at preoperative hour-0 and postoperative hours 4 and 24. Visual Analog Scale (VAS) scores were recorded at 0-hours, 30-minutes, 4-hours, and 24-hours. Analgesic use within the first 24-hours following surgery was monitored. RESULTS: The postoperative VAS score was decreased in the TAP group at all time points (0, 4, and 24hours), and the differences between groups were statistically significant (p< 0.001 for all comparisons). In the TAP group, the TNF-α and IL-1ß levels at 4 and 24 hours post operation were significantly lower than the preoperative levels (p< 0.001 for all comparisons). CONCLUSION: The TAP block for pre-emptive analgesia enabled effective hemodynamic control during the intraoperative period, provided effective pain control in the postoperative period, and decreased inflammation and surgical stress due to the decreased levels of the proinflammatory cytokines TNF-α and IL-1ß in the first postoperative 24hours, indicating immunomodulatory effect.

A preliminary data: Evaluation of serum Galectin-3 levels in patients with Idiopathic Parkinson's Disease.

AIM: In our study, we aimed to collect data for the hypothesis that Galectin-3 might be used as a new prognostic and therapeutic biomarker in Idiopathic Parkinson's Disease (IPD). METHOD: In this prospective and cross-sectional study, the Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn and Yahr (H&Y) scales were applied to each patient diagnosed as IPD according to the UK Brain Bank diagnostic criteria. The control group consisted of healthy individuals with the same age, gender, and body mass index characteristics as the patients meeting the exclusion criteria. RESULTS: A total of 111 cases were included in the study, 48 were IPD, and 63 were healthy controls. There were no statistically significant differences between the IPD and control groups in terms of demographic, anthropometric, and blood parameters (p > 0.05). Serum galectin-3 levels were significantly higher in IPD than the control group (p < 0.001). Serum galectin-3 levels, UPDRS scores, and duration of disease were significantly higher in patients with IPD in parallel with the progression of the disease (p < 0.001; 0.001; 0.009). No significant relationship was detected between the stage of the disease and other parameters (p < 0.05). CONCLUSION: Our study supports the hypothesis that serum galectin-3 level might be associated with IPD. Our data suggest that serum galectin-3 levels might be an accessible biomarker for the detection and prevention of chronic, progressive diseases such as IPH.

The diagnostic value of serum urokinase-type plasminogen activator receptor in acute appendicitis.

BACKGROUND: To measure serum uPAR levels in patients operated with a preliminary diagnosis of acute appendicitis (AA) and to investigate whether these parameters can be used as a biochemical marker in the diagnosis of AA. METHODS: Patients aged 18 or over, presenting to the emergency department between May and December 2018 and operated with a diagnosis of AA were enrolled. This study included 84 patients with surgical pathology results compatible with AA (Group A), 26 patients with surgical pathology results were not compatible with AA (Group B) and 55 healthy control groups. Serum uPAR levels were measured from venous blood samples taken at admission. RESULTS: Mean uPAR levels were 4.53±3.47 ng/mL in the Group A, 1.13±1.63 ng/mL in the Group B and 0.80±1.21 ng/mL in the control group. Serum uPAR levels differed statistically significantly from Group A in Group B and the control group, (p<0.05). CONCLUSION: uPAR was found to be significantly higher in the AA patients compared to the control group and patients with surgically determined non-AA pathologies. uPAR can be used as an aid in the diagnosis of acute appendicitis.

Rapid access to information resources in clinical biochemistry: medical applications of Personal Digital Assistants (PDA).

Laboratory specialists currently need to access scientific-based information at anytime and anywhere. A considerable period of time and too much effort are required to access this information through existing accumulated data. Personal digital assistants (PDA) are supposed to provide an effective solution with commercial software for this problem. In this study, 11 commercial software products (UpToDate, ePocrates, Inforetrive, Pepid, eMedicine, FIRST Consult, and 5 laboratory e-books released by Skyscape and/or Isilo) were selected and the benefits of their use were evaluated by seven laboratory specialists. The assessment of the software was performed based on the number of the tests included, the software content of detailed information for each test-like process, method, interpretation of results, reference ranges, critical values, interferences, equations, pathophysiology, supplementary technical details such as sample collection principles, and additional information such as linked references, evidence-based data, test cost, etc. In terms of technique, the following items are considered: the amount of memory required to run the software, the graphical user interface, which is a user-friendly instrument, and the frequency of new and/or up-date releases. There is still no perfect program, as we have anticipated. Interpretation of laboratory results may require software with an integrated program. However, methodological data are mostly not included in the software evaluated. It seems that these shortcomings will be fixed in the near future, and PDAs and relevant medical applications will also become indispensable for all physicians including laboratory specialists in the field of training/education and in patient care.

Conventional and non-conventional coronary risk factors in male premature coronary artery disease patients already having a low Framingham risk score.

BACKGROUND: Individual risk factors and, more importantly, global risk assessment tools such as the Framingham risk score have been used successfully for risk prediction especially in older patients. However, there is paucity of data about the coronary heart disease prediction in premature coronary artery disease patients with a low Framingham risk score. METHODS AND RESULTS: We recruited 102 consecutive young patients without hypertension and diabetes mellitus in the study. All subjects had had chest pain and underwent coronary angiography since non-invasive diagnostic test results suggested ischaemia. Forty-five patients having at least one coronary lesion independent of severity were included in the study group.The remaining fifty-seven subjects without any coronary lesion were used as control group. Conventional and non-conventional risk factors were evaluated both in patients and control subjects. Framingham risk score and absolute 10-year hard CHD events risk were also calculated for each individual. The coronary heart disease group had a significantly higher smoking frequency as compared to the control group.They also had higher plasma levels of triglycerides, apolipoprotein B and apo B/AI ratio but a smaller LDL particle size.We failed to find any independent CHD predictor after logistic regression analysis. However, individual ROC curve analysis of risk factors revealed that apolipoprotein B, triglycerides and apo B/AI ratio have the highest area under the curve for coronary artery disease prediction. CONCLUSIONS: The Framingham risk score may underestimate the true risk of an individual. Incorporating non-conventional risk factors such as apolipoprotein B and apo B/apo AI ratio may provide valuable information in these patients.

Chitotriosidase levels in healthy elderly subjects.

Chitotriosidase (CHIT) belongs to the family of glycosylhydrolases and is highly homologous to chitinases from lower organisms. The enzyme CHIT is of interest for clinical reasons, because it is selectively expressed in chronically activated tissue macrophages. In most ethnic groups, approximately 6% of all individuals are homozygous for CHIT deficiency. Pathological tissue macrophages in several disease conditions massively express CHIT. A shared feature of such cells in the different conditions is the accumulation of lipid material in the lysosomal apparatus. Serum CHIT activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker. Our objective is to determine the levels of serum CHIT activity in healthy elderly subjects. Healthy 90 (between 65-94 years old) elderly people and 69 (between 20-44 years old) young people were chosen. Serum CHIT enzymatic activity was determined with the flurometric enzyme activity assay using artificial 4-MU substrate. We found CHIT activity 270 +/- 21 (nmol/mL/h) (values are mean +/- SD) in elderly people and 136 +/- 17 in young people. There are statistical differences between elderly and young subjects.

Determination of 5-fluorouracil and dihydrofluorouracil levels by using a liquid chromatography-tandem mass spectrometry method for evaluation of dihydropyrimidine dehydrogenase enzyme activity.

PURPOSE: 5-Fluorouracil (5-FU), acting as a pyrimidine antagonist, is a major chemotherapy drug used for the treatment of tumors such as gastrointestinal, breast, ovary, and head and neck cancers. The key and rate-limiting enzyme in 5-FU catabolism is dihydropyrimidine dehydrogenase (DHPDH), whose partial or complete deficiency exposes to a severe 5-FU toxicity in patients. The determination of DHPDH activity in patients before the treatment and setting up a personalized therapy for each patient receiving the drug can help us to prevent the possible risk of toxicity. METHODS: To isolate peripheral blood mononuclear cells (PBMCs), EDTA-anticoagulated blood samples were collected from randomly selected 47 patients and examined for 5-FU and its metabolite dihydrofluorouracil (FUH2) by using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) to observe DHPDH activity at different intervals (0 and 4th hour) indirectly. RESULTS: Intra-assay and interassay CV % values of samples from the measurements of the modified methods are found 1.3-11.9, 2.3-9.4 for 5-FU and 3.1-14.4, 3.3-12.6 for FUH2, respectively. The reference values derived from 45 patients treated with 5-FU are 1.84 ± 0.34 ug/gr protein for 5-FU, 40.15 ± 11.43 ng/gr protein for FUH2, respectively. FUH2/5-FU ratio is 21.9 ± 3.72. In addition, the results determined from two patients, in which the lack of DHPDH is considered, were 3.24 and 4.16 ug/gr protein for 5-FU, 4.1 and 6.7 ng/gr protein for FUH2. FUH2/5-FU ratio is 1.26 and 1.61. CONCLUSION: The measurements of 5-FU, FUH2, and especially their ratio (FUH2/5-FU) by the modified LC-MS/MS method could be used to determine DHPDH enzyme activity.

The effect of insulin resistance and obesity on low-density lipoprotein particle size in children.

OBJECTIVE: In adults, it was shown that obesity and insulin resistance affect low-density lipoprotein (LDL) particle size and small dense (sd) LDL is associated with cardiovascular diseases. In this study, we investigated the effect of obesity and insulin resistance on LDL particle size. METHODS: Twenty-six obese children (13 girls, 13 boys) with a median age of 10.5 years and 27 healthy control subjects (17 girls, 10 boys) with a median age of 11.5 were enrolled in the study. RESULTS: The number of patients with insulin resistance in the obese group was 15 out of 26. In the control group, there was no subject with insulin resistance. Serum triglyceride and very LDL (VLDL) levels were higher and serum high-density lipoprotein levels (HDL) were lower in the obese patients than in the controls. There was no statistical difference in the LDL particle size between the two groups (medians: 26.6 vs. 26.7 nm (p=0.575)). The size of LDL particle was not correlated with body mass index (BMI) standard deviation score (SDS), homeostasis model assessment of insulin resistance (HOMA-IR), or serum lipids. CONCLUSION: Measurement of LDL particle size as a routine procedure is not necessary in childhood obesity.