LabMed doi: 10.3390/labmed3020014

Authors: Yujin Han Kap No Lee Jinsang Kim In Tae Kim Y. I. Cho

Whole blood viscosity (WBV) is a key hemorheological property influenced by cellular and biochemical factors and is associated with cardiovascular, cerebrovascular, and microcirculatory disorders. Despite its clinical relevance, comprehensive reference intervals for WBV and oxygen delivery indices—the ODI (oxygen delivery index) and TODI (tissue oxygen delivery index)—in healthy male and female adults have not been established. The objectives of this study were to (1) determine sex-specific reference intervals of WBV in healthy adults, (2) establish reference intervals for the ODI and TODI, and (3) evaluate the influence of hematologic, biochemical, lipid, and non-lipid determinants—as well as the effects of age—on systolic and diastolic blood viscosity (SBV and DBV). WBV was measured across nine shear rates (1–1000 s−1) in 150 healthy men and 150 healthy women using an automated scanning capillary tube viscometer (SCTV). Hematologic and biochemical profiles were obtained, and correlations with DBV and SBV were assessed. Reference intervals were calculated using CLSI-recommended nonparametric methods. WBV was consistently higher in men than women across all shear rates, with sex-based differences accentuated at low shear. Hemoglobin and hematocrit showed the strongest positive correlations with WBV (r ≈ 0.77–0.80), while RDW and HDL cholesterol showed negative associations. Triglycerides exhibited strong viscosity-enhancing effects in men, whereas total cholesterol, LDL, and triglycerides were all significantly increased viscosity in women. Protein-related determinants (total protein, albumin, and γ-gap) displayed striking sex divergence, with strong positive associations in men but attenuated or negative associations in women. Age showed no meaningful relationship with WBV in either sex. Reference intervals for the ODI and TODI revealed modest sex differences with tighter distributions in women. WBV, ODI, and TODI demonstrate clear sex-specific physiological patterns in healthy adults. Hematocrit remains the dominant determinant of blood viscosity, while lipid and protein-related factors contribute differently in men and women. These newly established reference intervals provide essential benchmarks for clinical interpretation and for understanding viscosity-related risk in cardiovascular and microcirculatory disease.

LabMed doi: 10.3390/labmed3020013

Authors: Janka Klingová Bianka Prokopová Barbora Šipková Vanesa Bujková Pavol Sulo

Helicobacter pylori is the leading cause of chronic gastrointestinal tract diseases, with a worldwide prevalence of around 50%. For identification in medical practice, non-invasive methods such as the immunochromatographic test for antigen in stool (SAT) and the urease breath test (UBT) are widely used. Recently, we developed a highly sensitive and specific nested PCR (NPCR) that involves two amplification reactions and uses primers designed to target the variable regions of the 16S rRNA gene to amplify a short 148 bp amplicon. The aim of this study was to compare two classical methods, SAT and UBT, with the 148 bp amplicon NPCR. We examined samples from 137 volunteers, and found 46 positives with NPCR using stool samples, 34 with UBT, and only 24 with SAT. H. pylori origin of the 148 bp amplicons was confirmed by sequencing. NPCR had the highest detection rate in this cohort, suggesting that a portion of the population may be misdiagnosed, particularly by SAT. Due to the cost and simple performance in practice, SAT is a method of choice for initial screening. However, in cases of negative results and persistent digestive problems, we recommend the more sensitive UBT. NPCR may be a useful complementary method, especially in discordant or clinically suspicious cases.

LabMed doi: 10.3390/labmed3020012

Authors: Joseph Osoga Missiani Ochwoto Gladys Tuitoek Lilian Ogonda

Hepatitis B virus (HBV) is the smallest partially double-stranded, reverse-transcribing DNA virus, with four open reading frames (ORFs) encoding viral proteins. It is classified into nine geographically distributed genotypes (A–I). In Kenya, the molecular characterization of HBV among patients seeking medical care remains poorly defined. This observational study aimed to characterize HBV among patients seeking medical care in Kenya’s endemic region, focusing on circulating genotypes and ORF mutations. Serum samples were collected from the outpatient departments of selected health facilities, with demographic and clinical information extracted from patients’ medical records. Hepatitis B surface antigen (HBsAg) was tested at the facilities, and 85 HBsAg-positive samples were collected for molecular analysis. The basal core promoter and pre-core (BCP/PC), polymerase, and surface regions of the viral genome were amplified and sequenced to determine genotypes and to profile their mutations. Out of 85 HBsAg-positive samples, 38 samples tested positive for HBV DNA, and 26 samples were successfully sequenced. HBV genotype A was prevalent at 73.1% (19/26), followed by genotype D at 23.1% (6/26), and genotype E at 3.8% (1/26). Genotype A sequences clustered with both A1 Asian and African subgenotypes, whereas genotype D clustered with subgenotypes D6 and D1. All HBV genotype A, D, and E sequences were serotypes adw2, ayw2, and ayw4, respectively. HBV core promoter mutations (A1762T/G1764A) were detected in both genotype D and genotype A isolates. The pre-core G1896A mutation was highly prevalent in genotype D samples (5/6; 83.3%) but was not observed in genotypes A or E. Analysis of mutations within the “a” determinant region revealed genotype-specific patterns: genotype A predominantly harbored V14A, P46H, S58C, and P67Q substitutions; genotype E showed N59S; and genotype D exhibited V14A, C69stop, S104T, and W182stop mutations. Two drug resistance mutations (V191I and A194T) were present in two chronic patients, one with genotype A and the other with genotype D. In conclusion, HBV genotypes A and D are the most prevalent among Kenyan patients with chronic HBV infection. The presence of point mutations in the ORFs among patients seeking medical care highlights the need for molecular surveillance to better understand the viral diversity and its potential clinical and public health implications.

LabMed doi: 10.3390/labmed3020011

Authors: Elisabetta Bretto Liseth Rivero-Sánchez

A 34-year-old healthy man was referred for colonoscopy due to tenesmus and rectal bleeding in the absence of systemic or immunosuppressive conditions. Incomplete bowel preparation limited the examination, but rectal inspection revealed a well-demarcated erythematous lesion with a granular, micronodular surface and fibrinous areas. The mucosa appeared friable and bled with minimal contact. The differential diagnosis included infectious and inflammatory etiologies. Histologic analysis showed granulation tissue with moderate lymphoplasmacytic infiltration, and C-reactive protein (CRP) confirmed Herpes Simplex Virus type 2 (HSV-2). This case underscores the importance of considering sexually transmitted infections (STIs) such as HSV in the differential diagnosis of rectal bleeding, even in immunocompetent individuals.

LabMed doi: 10.3390/labmed3020010

Authors: Dipti Tiwari Wann Jia Loh Tar Choon Aw

The ADA 2026 Standards of Care in Diabetes introduces pivotal updates that refine diagnostic and therapeutic workflows. Expanding upon the 2025 guidelines, the 2026 edition broadens continuous-glucose-monitoring (CGM) eligibility to include all individuals on insulin or non-insulin therapies where CGM aids management. Significant new guidance addresses hyperglycemia management in oncology, identifying metformin as the preferred first-line intervention for drug-induced glycemic excursions. Additionally, type 1-diabetes (T1D) risk stratification is refined; a confirmed single IA-2 autoantibody now warrants monitoring levels similar to the Stage 2 disease. Furthermore, prerequisites for automated-insulin-delivery (AID) initiation have been removed to streamline technology access. For laboratory professionals, these revisions emphasize the critical role of advanced glycemic metrics and precise autoantibody profiling in complex clinical contexts.

LabMed doi: 10.3390/labmed3020009

Authors: Ioanna Kotsiri Dimitrios Theodoridis Angeliki Tsifi Emmanouil Magiorkinis

Sepsis is a life-threatening syndrome caused by dysregulated host response to infection and remains a major global health challenge with high healthcare burden. Early recognition is critical for improving outcomes, yet current diagnostic tools and conventional biomarkers such as C-reactive protein and procalcitonin have important limitations related to kinetics, specificity, and cost. This review examines Monocyte Distribution Width (MDW), a novel hematologic parameter derived from routine complete blood count analysis, as an emerging biomarker for early sepsis detection and prognostic assessment. MDW reflects monocyte morphological heterogeneity associated with innate immune activation and rises early in the inflammatory cascade, often at the time of initial clinical presentation. Evidence from emergency department and intensive care unit studies demonstrates that MDW provides high sensitivity and negative predictive value for early sepsis screening and performs comparably to or better than established biomarkers, particularly when integrated with clinical scoring systems and other laboratory indices. Beyond diagnosis, elevated MDW correlates with disease severity, organ dysfunction, and adverse outcomes, suggesting prognostic utility. Although promising, current evidence is limited by heterogeneity and the need for standardized cut-off values and multicenter validation. Overall, MDW represents a rapid, cost-effective adjunct that may enhance multimodal sepsis assessment and clinical decision-making.

LabMed doi: 10.3390/labmed3010008

Authors: Massimo Berdini Gianluca Clementi Marco Torcianti Donatella Del Bianco Isabella Cantori Roberto Procaccini Antonio Gigante

Platelet-rich plasma (PRP) is widely used in orthopedics and sports medicine as an autologous product; however, substantial heterogeneity in manufacture and incomplete reporting of preparation parameters limits reproducibility and inter-study comparability.: We performed a PRISMA-guided methodological review of studies describing PRP preparation, subsequently focusing on orthopedic applications. MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, Web of Science, and Google Scholar were searched. 7330 records were retrieved; following merging and de-duplication, more than 2500 unique records were screened. The inclusion criteria for our study required studies on PRP that focused on orthopedic use of this preparation and studies that reported a defined methodology for PRP, reported in the abstract or in the manuscript. Extracted variables covered collection and anticoagulation, centrifugation strategy, cellular composition, activation/lysis, processing environment, storage, and time-to-use. Twenty-three orthopedic studies met the inclusion criteria. Whole blood draw volume and anticoagulant were reported in 15/23 studies each; centrifugation parameters (relative centrifugal force/RPM and duration) in 12/23; and PRP phenotype (e.g., leukocyte-poor vs. leukocyte-rich) in 15/23. Platelet metrics (baseline and/or final platelet count/concentration) were reported in 6/23. Sterility/environmental controls were mentioned in 17/23, whereas storage conditions and time-to-use were described in only 3/23. An explicit exogenous activation agent was reported on 1/23. Orthopedic PRP studies frequently omit critical manufacturing and handling descriptors—particularly platelet dose, leukocyte/lymphocyte handling, temperature control, storage/freezing conditions, and time-to-administration—impairing reproducibility and dose comparability. We propose a pragmatic, standardized protocol for preparation of leucocyte/lymphocyte-depleted PRP for orthopedic use (PRP only, without gelification), together with a minimum set of data and parameters to be evaluated. In our opinion these parameters should be included in future studies in order to standardize the production process. The quality of PRP itself could be impacted by such standardization, and the ability to objectively evaluate the results of studies could be enhanced by facilitating the comparison of data emerging from the literature.

LabMed doi: 10.3390/labmed3010007

Authors: Abdullah Bin Zahid Fakhar Un Nisa Ahmad Kamran Malik Nafees Qamar

Lung cancer remains one of the most formidable health challenges globally, with significant morbidity and mortality rates. Despite advancements in diagnostic and treatment technologies, the disease’s high prevalence, late-stage detection, and complex variations continue to hinder effective management. Early detection and accurate diagnosis play a pivotal role in improving survival rates. Crucially, the clinical and translational relevance of AI-based prediction lies in its potential to significantly reduce the incidence of late-stage diagnoses, thus increasing the chance of successful intervention. Lung cancer was first identified by medical professionals in the mid-19th century. Today, cancer remains a significant global health challenge, affecting an estimated 14 million individuals annually and causing 8.2 million fatalities worldwide. Lung cancer ranks among the leading causes of death associated with cancer. This research aims to bridge gaps in lung cancer diagnosis by exploring various learning methodologies. By focusing on studies from the last 10 years, this survey provides a contemporary understanding of the field, emphasizing the importance of automated diagnostic systems in reducing human error and improving efficiency. The selection of relevant research is based on a rigorous methodology, including specific inclusion and exclusion criteria, which are later discussed in detail with supporting figures and comparative data. Ultimately, this work underscores the critical need for innovative diagnostic solutions and comprehensive screening programs to combat lung cancer, save lives, and advance the field of medical research.

LabMed doi: 10.3390/labmed3010006

Authors: Bianca Santonastaso Hannah Spector Christine Cahill Khaled Refaai Frank Akwaa Jainulabdeen J. Ifthikharuddin Gahyun Gim Majed A. Refaai

A 75-year-old male was admitted with worsening anemia and spontaneous bruising in the left abdominal wall and paraspinal region. Laboratory workup revealed low factor XIII (FXIII) activity levels. Cryoprecipitate transfusions raised his FXIII level, but still fluctuated drastically, ranging from 4 to 43% was discharged 3 days later once his bleeding was managed. Three days later, he was readmitted for severe pain and new bruising in his latissimus dorsi and lateral right thigh. CT-scan revealed hemothorax and arterial bleeding requiring an urgent angiogram with embolization. Chromogenic and functional FXIII assays were unable to elucidate an inhibitor at this time. Management included FXIII concentrate, rituximab, and prednisone; the patient was discharged 12 days later with FXIII levels of 50%. After prednisone tapering, FXIII levels decreased drastically. This case exemplified that higher levels of FXIII are required to prevent bleeding diatheses rather than the previously reported minimum of 5% activity. Despite the diagnostic uncertainty of laboratory testing, the shortened half-life of FXIII activity following replacement therapy and favorable response to immunotherapy indicates that the bleeding diathesis was caused by an acquired inhibitor.

LabMed doi: 10.3390/labmed3010005

Authors: Missiani Ochwoto Raphael O. Ondondo Lydia Moraa Matoke Gladys Tuitoek Elizabeth Ogwora Samuel W. Omari Haron Mong’are Francis Otieno Onoka Esther Sigilai James Hungo Kimotho Robert Rono Amos Otedo Vincent Were Damaris Matoke-Muhia

Hepatitis B virus (HBV) infection is a silent epidemic; many infected people are asymptomatic and not aware of the infection. In 2022, it was reported that approximately 254 million people were living with chronic HBV infection globally, majority being in sub-Saharan Africa and Asia. In Kenya, the national HBV prevalence is estimated to be 3.5%. Our study was aimed at identifying key predictors and transmission trends that could inform the development of sustainable prevention models needed to address existing gaps in the national framework towards HBV elimination. We targeted participants seeking health services in Baringo and Kisumu county health facilities and conducted community mass testing in the two counties. Participants were interviewed using a study questionnaire and were tested for hepatitis B surface antigen (HBsAg) using an HBsAg rapid test. Venous blood was collected from participants who tested HBsAg+ for further infection confirmation and linkage to care. Logistic regression was performed to assess factors correlated with HBV infection. Out of 3034 participants, 192 tested positive for HBsAg and the prevalence of HBV infection was 6.3% (95% CI = 0.055–0.072). Intrafamilial infections in Baringo were 15.0%. HBV infection prevalence exceeded 10% among those aged 25–49 years, peaking at 13.1% in the 45–49-year age group and lowest at 1.8% in the 16–19-year age group. Overall, males had a higher prevalence in younger ages, while females above 60 years old were more affected. In multivariable logistic regression, individuals residing in Baringo (aPR = 8.1; 95% CI = 2.2–29.4), users of other injectable drugs (aPR = 6.7; 95% CI = 1.3–204.0), those traditionally circumcised (aPR 1.02; 95% CI = 0.56, 1.88), and staying >5 km from a health care facility (aPR = 10.4; 95% CI = 2.2–49.4) had significantly higher prevalence ratios of being infected with HBV. These different infection predictors underscore the need for different care and prevention approach models.

LabMed doi: 10.3390/labmed3010004

Authors: Miriam Demtschuk Priska Heinz

Measurement of vitamin E levels is used to evaluate the health status in humans. For routine analytics in clinical laboratories, an accurate, quick, and simple determination method is required. An option for the quantification of vitamin E (α-tocopherol) in human blood samples is the use of high-performance liquid chromatography (HPLC) in combination with a UV detector. Several sample preparation methods for this purpose have been reported in the literature. Our aim was to generate an overview and comparison of the different methods. The online database PubMed was searched for published HPLC methods. Of 77 reports screened, 16 methods were selected and summarized in tables. These present the parameters of the sample preparation procedure, HPLC settings, and some validation criteria (limit of detection (LOD), limit of quantification (LOQ), and intra- and inter-assay values, recovery rates) of the reported methods. In the frame of our methodological review, we could find some extraction approaches. The liquid–liquid extraction with hexane or the double extraction with hexane were often used. Another possibility is the single extraction approach. This systematic review highlights the similarities and differences in methods, and it can therefore be used to develop and establish methods in a laboratory.

LabMed doi: 10.3390/labmed3010003

Authors: Glen L. Hortin

Plasma cell disorders often have urinary excretion of monoclonal immunoglobulins and renal injury that are evaluated using total protein assays and electrophoresis. Proteinuria was evaluated for 100 patients with plasma cell disorders and 24 h collections. A turbidimetric method on the Abbott Alinity quantified protein. Electrophoresis used agarose gels. Most specimens (66%) had protein concentrations below the manufacturer’s limit of quantitation (LOQ), 6.8 mg/dL (68 mg/L). After validating an LOQ of 3 mg/dL (30 mg/L), 34% of urine specimens still were below the LOQ. After excluding 40 patients with other causes of increased protein excretion (decreased estimated glomerular filtration rate (eGFR), diabetes mellitus, or overflow proteinuria), almost all patients had protein excretion below an upper reference limit of 150 mg/d. Median total protein excretion for these 60 patients was 75 mg/d; only one patient excreted >132 mg/d. However, 32% of these patients without increased total protein excretion had albumin excretion ≥ 30 mg/d, suggestive of kidney injury. Electrophoretic patterns included glomerular, tubular, and overflow proteinuria; 32 specimens contained monoclonal immunoglobulins. Protein concentrations of urine are often below LOQs of total protein assays, raising questions about whether LOQs should be improved. Urine albumin measurements and electrophoretic patterns may serve as more sensitive indicators of kidney injury in patients with plasma cell disorder than measurements of total protein excretion or increased serum creatinine.

LabMed doi: 10.3390/labmed3010002

Authors: Ankush U. Patel Ryan McDougall Samir Atiya

Source plasma centers sustain hematology therapeutics by safeguarding testing, traceability, and cold-chain integrity before fractionation. Despite regulatory requirements (21 CFR 606/640; EU Directive 2005/62/EC), published pre-operational validation frameworks demonstrating deviation-readiness before first collections remain sparse. We conducted a simulation-based pre-operational validation of an electronic quality management system (eQMS) with an Incident → Deviation → Corrective Action and Preventive Action (CAPA) pathway at a new source plasma center, performing 20 chairside mock runs, 3 freezer-alarm drills, and a document-control stress test. Primary endpoints were anomaly rate, alarm-response time relative to a 15 min service-level agreement (SLA), and deviation-closure SLA compliance. Analyses were descriptive and designed to demonstrate system functionality, not long-term process stability. Minor anomalies occurred in 6/20 mock runs (30.0%; 95% CI 11.9–54.3); no major/critical events were observed (0/20; 95% CI 0–16.8). Deviation-closure SLAs were met in 6/6 tests (100%; 95% CI 54.1–100). Alarm-response times averaged 7.0 min (SD 1.0; range 6–8 min; 95% CI 4.5–9.5), and all drills met the 15 min vendor SLA, illustrating a preliminary readiness margin (Cpu ≈ 2.7) rather than a statistically stable capability estimate. Simulation-based pre-operational validation produced inspection-ready documentation and quantitative acceptance criteria aligned to U.S./EU expectations, supporting reproducible multi-site deployment. By protecting cold-chain integrity and traceability before first collections, the validated QMS helps preserve supply reliability for plasma-derived therapeutics central to hematology care and establishes the measurement infrastructure for post-operational performance validation.

LabMed doi: 10.3390/labmed3010001

Authors: Mehak Bhatia Katherine Davanzo Paul Kim Jyothik Varun Inampudi Mazhar Shapoo Marco Scipione Sorabh Dhar Lea Monday

The Infectious Diseases Society of America (IDSA) guidelines for community-acquired pneumonia (CAP) recommend pneumococcal urinary antigen testing (UAT) for a subset of inpatients admitted with pneumonia. Despite this, UAT testing is frequently performed on inpatients who do not meet the official IDSA criteria, and current evidence regarding antibiotic de-escalation in UAT-positive cases remains inconclusive. To explore this further, we conducted a retrospective cohort study examining antibiotic de-escalation patterns among hospitalized CAP patients who underwent UAT over a 60-day period during peak respiratory illness season (November and December, 2023). Patients with positive UAT results were compared to those who had negative UAT; the primary outcome was whether a positive UAT impacted antibiotic de-escalation prescribing. A total of 268 patients were analyzed—235 UAT-negative and 33 UAT-positive. Both groups were comparable in terms of disease severity, underlying health conditions, and readmission rates. Empiric therapy targeting Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) was used in 40% of patients (36% in the UAT-positive group and 46% of the UAG-negative group). The use of atypical coverage, MRSA coverage, or anti-pseudomonal β-lactams was frequently de-escalated in both cohorts (p < 0.05); however, the UAT-positive group had significantly shorter durations of anti-pseudomonal therapy (p = 0.03) and anti-MRSA therapy (p = 0.02). Despite this, the UAT-positive group was more commonly given fluoroquinolones, such as levofloxacin or moxifloxacin, over narrow-spectrum β-lactams for final antibiotic coverage (p = 0.021). Overall, positive UAT appeared to support earlier discontinuation of anti-MRSA and anti-pseudomonal antibiotics; however, it did not impact fluoroquinolone use. Future antimicrobial stewardship efforts may benefit from promoting greater use of narrow-spectrum β-lactams in these patients.

LabMed doi: 10.3390/labmed2040027

Authors: Giuseppe Lippi

Artificial intelligence (AI) has become increasingly integrated into scientific publishing, performing a vast array of tasks for enhancing research efficiency, analysis, and dissemination [...]

LabMed doi: 10.3390/labmed2040026

Authors: Ivan Brukner Matthew Oughton

Antibiotic susceptibility testing (AST) reports classify isolates as “susceptible” despite potential undetected resistant subpopulations—a phenomenon termed susceptibility heterogeneity (SH). Found in 15–97% of clinical isolates of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, SH arises from heteroresistance or polyclonal diversity and may evade standard low-inoculum protocols. Clinically, this can lead to treatment failure, particularly in high-risk cases including immunocompromised patients, bloodstream infections, transplant recipients, and situations where minor resistant subpopulations significantly affect outcome. We argue that ethical principles of non-maleficence, transparency, and equity now compel laboratories to acknowledge this limitation. A simple annotation—“Limited susceptibility possible; resistant subpopulations may not be detected”—should accompany “susceptible” results in immunocompromised patients. High-risk cases warrant enhanced testing. This commentary calls for zone inspection, staff training, and Clinical and Laboratory Standards Institute (CLSI)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline updates to reflect SH. Transparency enhances clinical decision-making without implying diagnostic fault.

LabMed doi: 10.3390/labmed2040025

Authors: Gustavo Barcelos Barra Ticiane Henriques Santa Rita Rafael Henriques Jácomo Lídia Freire Abdalla Nery

In the original publication [...]

LabMed doi: 10.3390/labmed2040024

Authors: Viola Ceconi Valentina Kiren Flora Maria Murru Andrea Bon Danica Dragovic Lorenzo Zandonà Alice Fachin Gianluca Tamaro Gianluca Tornese

Alpha-fetoprotein (AFP) is a biomarker commonly used in the diagnosis of various malignancies but may also be elevated in non-neoplastic conditions, including hypothyroidism. We report the case of a 3-year-old girl with Down syndrome (DS) and newly diagnosed hypothyroidism, who presented with a hypoechoic oval lesion adjacent to the thymic parenchyma on ultrasound and markedly elevated AFP levels (169.2 ng/mL). Further investigations, including MRI, excluded the presence of germ cell tumors. Following initiation of levothyroxine therapy, AFP levels normalized in parallel with thyroid function. No evidence of malignancy was detected despite the initial suspicion. This case underscores the association between elevated AFP and hypothyroidism, highlighting the importance of evaluating thyroid status in patients with increased AFP to avoid unnecessary oncological investigations. In particular, elevated AFP in the context of hypothyroidism and DS warrants careful thyroid assessment and follow-up to prevent redundant diagnostic procedures and reduce patient and family anxiety. Thyroid function testing should be considered before extensive oncological evaluation in children with elevated AFP.

LabMed doi: 10.3390/labmed2040023

Authors: Diana Gabriela Ilaș Sebastian Ciurescu Raluca Ibănescu Diana-Alexandra Mîțu Daniel Florin Lighezan

Chronic heart failure (CHF) carries high morbidity and mortality. Circulating biomarkers of myocardial stretch, injury, and remodelling aids diagnosis and prognosis, but utility varies, especially in HFpEF, where natriuretic peptide (NP) values may be lower or normal in obesity. We systematically searched PubMed, Scopus, and Web of Science (2010–2025) for primary adult chronic-HF studies evaluating blood-based biomarkers: NPs, high-sensitivity troponins (hs-cTn), galectin-3, soluble ST2 (sST2), and microRNAs. Secondary sources (reviews/meta-analyses/guidelines) informed context only. Acute-HF studies were not pooled with chronic-HF analyses. Where appropriate, log hazard ratios were meta-analysed with random effects models. Twenty-nine studies met criteria. NT-proBNP remained the diagnostic/prognostic reference; across five prognostic cohorts, the pooled HR was 1.68 (95% CI 1.54–1.82; I2 ≈ 55%). hs-cTn consistently improved risk stratification. Galectin-3 and sST2 were associated with adverse outcomes but typically provided modest incremental value beyond NPs/hs-cTn; galectin-3 is influenced by renal function, and sST2 is commonly interpreted around ~28–35 ng/mL. MicroRNAs (e.g., miR-21, miR-210-3p, miR-22-3p) showed promising yet heterogeneous signals across platforms and preanalytical workflows; therefore, findings were synthesised narratively without pooling. NT-proBNP and hs-cTn form the evidence-based backbone for biomarker-guided assessment in chronic HF. Galectin-3 and sST2 add adjunct prognostic information, while microRNAs remain investigational, pending standardised methods and external validation. Overall, evidence supports a multimarker, phenotype-tailored approach, with core NPs + hs-cTn and selective adjunct use of sST2/galectin-3 in context (HFrEF vs. HFpEF, obesity, renal function) to refine risk stratification and guide clinical decision-making.

LabMed doi: 10.3390/labmed2040022

Authors: Victoria González Soler Gema Fernández-Rivas Héctor Martínez Riveros Pablo Pillado Alonso Yesika Díaz Rodríguez Marcos Montoro Fernández Miquel Saña Miralles Pere Joan Cardona Iglesias Jordi Casabona Barbarà C. Agusti

Dried blood spots (DBSs) are a practical tool for diagnosing infectious diseases, especially in remote or resource-limited settings. This study assessed the efficacy of DBS-based serological assays for syphilis screening. EDTA blood samples from 171 syphilis-seropositive and 122 seronegative individuals were used to prepare DBSs by spotting whole blood onto filter paper. After drying, 12 mm disks were punched, incubated overnight in buffered solution, and centrifuged. Syphilis serological screening was conducted using the Liaison® Treponema Screen assay, Macro-Vue™ Reagin Plasma Rapid (RPR) card test, and Dual Path Platform (DPP) Syphilis Screen and Confirm test. The Liaison® assay demonstrated 100% sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with an optimized cut-off. The nontreponemal RPR test showed very low sensitivity (2.9%) on DBS but perfect specificity (100%). The DPP test for treponemal antibodies achieved high sensitivity (92.1%) and specificity (98.2%) with microreader adjustment. Visual reading of the DPP test had variable accuracy, with sensitivity reaching 100% but lower specificity (42.1%). Nontreponemal antibody detection by DPP showed moderate sensitivity and specificity. Although nontreponemal testing requires refinement, DBS testing combined with point-of-care tests like DPP holds promise for expanding syphilis screening accessibility and decentralization globally, particularly in resource-constrained environments.

LabMed doi: 10.3390/labmed2040021

Authors: Shelley Robin Latchem Benedict K. Jikong Heather L. Phillips Eleanor K. Jator

A 39-question survey targeting recent graduates was deployed by the American Society for Clinical Pathology (ASCP) to its membership nationwide by email. Participants were prompted to reflect on clinical educators from whom they had learned the most and least. This survey was open for approximately six weeks with 177 respondents. Participants included medical laboratory scientists (71.8%), medical laboratory technicians (21.8%), phlebotomists (4.5%), blood bank specialists (0.9%) and laboratory administration (0.9%). This paper focuses on three survey questions. The first question asked participants to reflect on clinical educators from whom they had learned the most and explain why. Themes included teaching ability (37.2%), engagement (25.6%), passion (18.6%) and knowledge (16.3%). The second question asked participants to reflect on educators they had learned the least from and explain why. Themes included teaching challenges (48.8%), disengagement (29.3%) and unprofessionalism (19.5%). The third question asked about barriers to clinical training. Main themes included staffing shortages (25.8%), COVID-19-related issues (12.9%) and work culture (12.9%). Little research has been published on the student perspective of clinical training in laboratory sciences. This research provides insight into what students consider helpful in their training and what hinders their learning.

LabMed doi: 10.3390/labmed2040020

Authors: Dona Benadof Agustin Zamorano Judith Aguirre Abigail Veas Esteban Araneda Gustavo Saint-Pierre

Timely reporting of microbiological results is critical for clinical decision-making, particularly in pediatric hospitals where delays can significantly impact outcomes. Despite advances in laboratory automation, workflow inefficiencies and resistance to change remain barriers to improvement in Latin America. This study aimed to evaluate the effect of implementing a Kaizen-based change management strategy on reducing turnaround time (TAT) in the microbiology laboratory of Hospital Roberto del Río, Santiago, Chile. We conducted a prospective, pre–post intervention study focusing on blood culture processing. The baseline period (July 2022) included 961 cultures processed with the BacT/ALERT® 3D system. A Kaizen/LEAN intervention was designed, comprising workflow redesign, staff training, and installation of the BACT/ALERT® Virtuo® (bioMerieux, Marcy l’Etoile, France) continuous-loading blood culture system. The intervention engaged all technical and professional staff in a five-day Kaizen immersion, followed by eight months of monitoring. Outcomes were assessed by comparing TAT for positive blood cultures before and after implementation (June 2023, 496 samples). Statistical analysis was performed using the Mann–Whitney U test, with p < 0.05 considered significant. The intervention achieved a median reduction in TAT from 68.22 h (IQR 56.14–88.59) pre-intervention to 51.52 h (IQR 41.17–66.57) post-intervention, corresponding to a 24.48% improvement (p < 0.001), surpassing the 20% target. Time to preliminary Gram reporting also decreased, and workflow standardization enhanced staff productivity and culture validation frequency. Implementation of Kaizen principles in a pediatric microbiology laboratory significantly reduced blood culture TAT and improved workflow efficiency. Beyond technological upgrades, active staff engagement and structured change management were key to success. These findings support the applicability of Kaizen-based interventions to optimize laboratory performance in resource-constrained public healthcare systems.

LabMed doi: 10.3390/labmed2040019

Authors: Nqobile Mthembu Sureshnee Pillay Hastings Twalie Musopole Shirelle Janine Naidoo Nokukhanya Msomi Bertha Cinthia Baye Derek Tshiabuila Nokulunga Zamagambu Memela Thembelihle Tombo Tulio de Oliveira Jennifer Giandhari

Acute respiratory infections (ARIs) continue to pose a major global health threat, particularly among vulnerable populations. These infections often present with similar clinical symptoms, complicating accurate diagnosis and facilitating unmonitored transmissions. Genomic surveillance has emerged as an invaluable tool for pathogen identification and monitoring of such infectious pathogens; however, its implementation is frequently limited by high costs. The widespread use of high-throughput sequencing during the COVID-19 pandemic has created an opportunity to repurpose existing genomic platforms for broader respiratory virus surveillance. In this study, we evaluated the feasibility of adapting the Illumina COVIDSeq assay—initially designed for SARS-CoV-2 whole-genome sequencing—for use with Influenza A/B, Respiratory Syncytial Virus (RSV), and Rhinovirus. Positive control samples were processed using two approaches for library preparation: four virus-specific multiple workflows and a combined rapid workflow. Both workflows incorporated pathogen-specific primers for amplification and followed the Illumina COVIDSeq protocol for library preparation and sequencing. Sequencing quality metrics were analysed, including Phred scores, read length distribution, and coverage depth. The study did not identify significant differences in genome coverage and genetic diversity metrics between workflows. Genome Detective consistently identified the correct species across both methods. The findings of this study demonstrate that the COVIDSeq assay can be effectively adapted for multi-pathogen genomic surveillance and that the combined rapid workflow can offer a cost- and labour-efficient alternative with minimal compromise to data quality.

LabMed doi: 10.3390/labmed2040018

Authors: Jiahui Zhuo Pengyun Wang Chengqi Xu

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, significantly elevates the risk of stroke and heart failure. The etiology of AF is complex and multifactorial, involving genetic predisposition, environmental risk factors, and their potential interactions. A previous genome-wide association study (GWAS) of AF in a Korean population has identified an association between the rs3737883 single-nucleotide polymorphism (SNP) in the PPFIA4 gene and an increased risk of AF. However, the association needs to be replicated in other populations. In this paper, we conducted a case–control association study including 724 AF cases and 1475 controls, and successfully validated the association between SNP rs3737883 with the risk of AF in a Chinese population (OR = 1.33 with an adjusted p was 2.83 × 10−11). Given that the PPFIA4 variant has been reported to influence high-sensitivity cardiac troponin T (hs-cTnT) levels, we further investigated the relationship between rs3737883 and hs-cTnT in 48 AF patients. Notably, we observed that the risk allele was also associated with elevated hs-cTnT levels. Our findings provide further genetic substantiation for the association of rs3737883 with AF. These results suggest a potential association between the PPFIA4 gene variant, hs-cTnT levels, and AF risk, although further studies are needed to clarify the underlying mechanisms.

LabMed doi: 10.3390/labmed2030017

Authors: Marios A. Diamantopoulos Michaela A. Boti Triantafyllia Sarri Andreas Scorilas

Non-coding RNAs (ncRNAs) are critical regulators of gene expression, taking part in the modulation of multiple biological functions across a range of cell types. Initially dismissed as transcriptional noise, ncRNAs are now recognized for their significant roles in key cellular mechanisms, including differentiation, apoptosis, and proliferation, as well as their profound implications for the pathogenesis of numerous human diseases. Due to their remarkable stability, tissue-specific expression patterns, and abundance in body fluids, ncRNAs hold significant promise as non-invasive biomarkers for diagnosis, prognosis, and therapeutic monitoring. Furthermore, advances in RNA-targeted therapeutics have introduced novel strategies to modulate ncRNA activity, although challenges related to delivery efficiency, specificity, and clinical validation remain. This review comprehensively summarizes the classification, biogenesis, and molecular functions of ncRNAs, elucidates their involvement in health and disease, and evaluates their potential as clinical biomarkers and therapeutic targets. Additionally, it discusses the emerging technologies for RNA manipulation, including CRISPR-based RNA editing, that can advance ncRNA research and revolutionize ncRNA-based therapeutics.

LabMed doi: 10.3390/labmed2030016

Authors: Mayukh K. Sarkar

Quality assurance in a clinical laboratory is essential to ensure reliable, accurate and precise laboratory test results all the time. A hemostasis laboratory is an important part of a clinical laboratory setting in a hospital or a healthcare center, and clinical laboratory tests play a crucial role in diagnosis and management of conditions related to bleeding or clotting of diseased individuals. This review discusses all aspects of coagulation laboratory testing from pre-analytical, analytical, and post-analytical variables as part of daily quality assurance processes undertaken as well as the quality management process of assay validation and implementation in a laboratory prior to patient testing. The internal and external quality processes that drive a hemostasis laboratory will be discussed that shows a rigorous process in assurance of testing that is reliable and accurate every time, at all times.

LabMed doi: 10.3390/labmed2030015

Authors: James V. Harte Ciara Hoy Vitaliy Mykytiv

Cell population data (CPD) parameters generated by Sysmex XN-series analysers are promising biomarkers for a variety of disease states. Routine use of CPD parameters, however, will require extensive evaluation of potential pre-analytical variables that may affect reliability. At present, no information on the comparability of CPD parameters generated using different blood collection tubes is available. In this preliminary study, we evaluated the impact of four commonly used blood collection tubes—dipotassium (K2) EDTA, tripotassium (K3) EDTA, trisodium citrate, and lithium heparin—on the generation of CPD parameters in whole blood from a cohort of 10 healthy donors. We also evaluated the stability of the CPD parameters generated at 4 h post-collection. Statistically significant differences in the CPD were observed across all blood collection tubes: whole blood anticoagulated with K3EDTA induced minimal biases and was comparable to whole blood anticoagulated with K2EDTA at collection; however, whole blood anticoagulated with citrate and heparin were associated with more substantial and more widespread biases in several parameters with potential clinical relevance. Notably, the biases observed in whole blood anticoagulated with K3EDTA increased in both number and magnitude at 4 h post-collection, whilst the CPD parameters generated with whole blood anticoagulated with K2EDTA remained stable. Although further confirmatory investigations are required, these findings highlight the importance of anticoagulant selection, as well as the need for further pre-analytical research, to support the integration of CPD parameters generated by Sysmex XN-series analysers into routine diagnostic workflows.

LabMed doi: 10.3390/labmed2030014

Authors: Julie Martinez Rezak Drali Amira Doudou Chalom Sayada Ronan Boulmé Dimitri Gonzalez Laurent Deblir Matthieu Barralon Jérome Wautrin Jonathan Porzio Arnaud Reffay Mohamed Errafyqy Jonathan Kolsch Jonathan Léonard Giuseppina Zuco Aitor Modol Sofiane Mohamed

In recent years, antiviral therapy has proved crucial in the treatment of infectious diseases, particularly infections by highly variable viruses such as human immunodeficiency virus, hepatitis B, hepatitis C, SARS-CoV-2 or bacteria such as Mycobacterium tuberculosis. Under the effect of selection pressure, this variability induces mutations that lead to resistance to antiviral and antibacterial drugs, and thus to escape from treatment. The use of Advanced Biological Laboratories (ABL) assays technology combined with next-generation sequencing (NGS) and automatized software to detect majority and minority variants involved in treatment resistance has become a mainstay for establishing therapeutic strategies. The present study demonstrated high concordance between majority and minority subtypes and mutations identified in 15 samples across four NGS platforms: ISeq100 (Illumina (San Diego, CA, USA)), MiSeq (Illumina), DNBSEQ-G400 (MGI (Santa Clara, CA, USA)) and Mk1C MinION (Oxford Nanopore (Oxford Science Park, UK)). However, nanopore technology showed a higher number of minority mutations (<20%). The analysis also validated the pooling of microbiological samples as a method for detecting mutations and genotypes in viral and bacterial organisms, using the easy-to-use DeepChek® bioinformatics software, compatible with all four sequencing platforms. This study underlines the constant evolution of microbiological diagnostic research and the need to adapt rapidly to improve patient care.

LabMed doi: 10.3390/labmed2030013

Authors: Syed Bukhari

Cardiac amyloidosis (CA) results from the deposition of either immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid fibrils in the myocardium, causing restrictive cardiomyopathy and, if left untreated, can lead to early death. Advancements in non-invasive diagnostic modalities have led to an increased recognition of the disease. Monoclonal gammopathy plays a pivotal role in the diagnostic algorithm for CA, particularly in differentiating AL from ATTR. This review highlights the importance of monoclonal protein detection through serum protein electrophoresis, immunofixation electrophoresis, and serum free light chain assays as initial screening tools. However, these tests alone are insufficient for a definitive diagnosis due to the complexities associated with coexisting monoclonal gammopathies and the potential for false negative and positive results. Advanced imaging modalities, such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, along with tissue biopsy, are crucial for confirming CA and accurately determining the CA subtype.

LabMed doi: 10.3390/labmed2030012

Authors: Ivan Brukner Matthew Oughton

Rapid, safe, and field-deployable molecular diagnostics are crucial for the effective management of infectious disease outbreaks, particularly those involving highly infectious pathogens, which can produce clinical symptoms similar to less infectious pathogens, thus raising potential biosafety concerns. In this study, we evaluated DNA/RNA Defend Pro (DRDP) buffer, a novel viral-inactivating transport medium designed to stabilize nucleic acids and allow direct PCR without nucleic acid extraction. To ensure critical qPCR parameters were not compromised by using DRDP, we conducted serial dilution tests using herpes simplex viruses 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV), comparing DRDP to standard universal transport medium (UTM). Detection sensitivity, determined by cycle quantification (Cq) values, favored DRDP, as UTM samples required a 2–3-fold dilution to mitigate PCR inhibition. DRDP maintained reliable PCR compatibility at reaction volumes containing up to 25% buffer. At higher DRDP concentrations (30–35%), PCR inhibition occurred due to EDTA content but was fully reversible by adding supplemental magnesium. Furthermore, DRDP samples did not require an initial 95 °C thermal lysis step, thus simplifying the procedure without reducing PCR sensitivity or efficiency.

LabMed doi: 10.3390/labmed2030011

Authors: Saavi Reddy Pellakuru Neha Nischal Hasaam Uldin Nathan Jenko Anshu Firake David Beale Karthikeyan P. Iyengar Rajesh Botchu

Fluid-sensitive sequences on MRI [Magnetic Resonance Imaging] have widely been used to assess soft tissue oedema. Windowing techniques play a significant role in adjusting the contrast to highlight the pathology. The purpose of this study is to establish the impact of modified MRI window parameters, with a narrower window width than window level, in assessing soft tissue oedema in a plethora of musculoskeletal pathologies. Fifty randomly selected patients with a range of musculoskeletal pathologies resulting in soft tissue oedema on MRI were included in the study. Two separate images of each MRI study were taken on a PD fat suppressed sequence, one with default windowing range and another with window width lower than that of window level. Both images were reviewed by two radiologists and were assessed for diagnostic effectiveness in terms of image resolution and depiction of pathology. Assessment was semi-quantitatively compared and graded on the Likert scale, from 1 to 5, with 1 indicating poor quality and 5 indicating excellent quality. Friedman’s test was then conducted to compare the scores of both images. In most of the cases, the image with the modified window/level setting was significantly better in terms of depicting pathology and having better resolution, though some cases showed no clear preference. Friedman’s test showed that the score for images with modified window settings was significantly higher. Images with modified windowing in conjunction with standard imaging protocols help to assess soft tissue oedema.

LabMed doi: 10.3390/labmed2020010

Authors: Eleni C. Georgiadi Apostolos Nousias Paraskevi Kotsi

Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10–15% of patients receiving oral anticoagulants will undergo an interventional procedure, and expert groups have issued several guidelines for perioperative management in such situations. According to the PAUSE study, the proposed randomized strategy of stopping DOACs without bridging therapy in patients with atrial fibrillation was associated with low rates of major bleeding and arterial thromboembolism so that its implementation is increasingly safe. The present study was carried out in order to investigate the efficacy and safety of the standardized perioperative DOAC management strategy by measuring the residual activity of oral anticoagulants when stopping them preoperatively in daily practice in a regional hospital. Thirty-two patients were included in the present study. They were patients who suffered from atrial fibrillation or deep vein thrombosis and were receiving an oral anticoagulant, rivaroxaban or apixaban at the indicated dose. These patients underwent an elective surgery or invasive procedure at the Karditsa General Hospital between May 2022 and April 2023. The results showed that in a percentage of >90% of the patients on the day of surgery they had a residual anti-Xa activity below 0.5 U/mL. This rate is considered high and confirms the safety and efficacy of the guideline-recommended protocol for perioperative discontinuation of DOACs.

LabMed doi: 10.3390/labmed2020009

Authors: Lauren Frisbie Ann E. Salm Jeff Radcliff Scott J. Weissman Hema Kapoor Peter Rabinowitz

This study included deidentified antibiotic susceptibility results from outpatient urinary Escherichia coli isolates from Washington state which were tested at a large clinical laboratory during 2013–2019. Isolates were categorized as representing the first, second, third, or fourth-or-greater occurrence of infection in data from individual patients. We used logistic regression with the outcome of resistance, adjusting for year of antimicrobial susceptibility test, patient sex, patient age, and facility type. In cases of subsequent infection, we found a significant risk of resistance to levofloxacin, ciprofloxacin, ceftriaxone, trimethoprim-sulfa, nitrofurantoin, ampicillin, gentamicin, and amoxicillin-clavulanate. Our findings suggest that Escherichia coli isolates from recurrent urinary tract infections have a higher rate of resistance to most tested antibiotics than isolates from the first urinary tract infection in a given year. However, susceptibility frequencies did not differ significantly between antibiograms constructed using only the first occurrence in a patient and those constructed using all subsequent occurrences. These findings suggest that the traditional approach of including only the first occurrence of urinary Escherichia coli in a patient may underestimate levels of antibiotic resistance in a community. Such underestimation could negatively affect empiric therapeutic choices, health outcomes, and treatment costs.

LabMed doi: 10.3390/labmed2020008

Authors: Laura Jane Coleman John L. Byrne Stuart Edwards Rosemary O’Hara

Objective: This study employed advanced biostatistical methods to investigate Interleukin-6 (IL-6), Tumour Necrosis Factor Alpha (TNF-α), and Myeloperoxidase (MPO) levels in serum and plasma samples from patients with severe osteoarthritis (OA) compared to volunteers. The primary aim was to evaluate the diagnostic potential of these biomarkers and address statistical challenges, including non-normal data distribution and non-aged-matched groups. Design: Using Enzyme-Linked Immunosorbent Assays (ELISAs), IL-6, TNF-α, and MPO concentrations were analysed in 58 OA patients and 28 volunteers. Statistical analyses included Shapiro–Wilk tests to assess normality, a Mann–Whitney U (MWU) test to compare biomarker levels, and sensitivity analyses using Rank-based ANCOVA, and regression models were used to address non-normal data distributions and to validate the findings under adjustments for age and gender. Levene’s test was used to evaluate the homogeneity of variables. Results: Serum TNF-α and plasma MPO were significantly higher in OA patients than in volunteers (p < 0.05), while IL-6 levels were non-significant (p = 0.160). MWU tests confirmed significant differences for TNF-α (p = 0.045) and MPO (p = 0.0001). Sensitivity analysis using Rank-based ANCOVA and regression models confirmed the robustness of these biomarkers, with TNF-α (p = 0.037) and MPO (p = 0.0099) retaining statistical significance after adjusting for covariates. IL-6 remained non-significant across all analyses. Conclusions: TNF-α and MPO emerged as statistically robust biomarkers for severe OA, with the serum samples better reflecting inflammation than plasma. These findings underscore the importance of using advanced biostatistical methods such as Rank-based ANCOVA and regression to validate biomarkers, particularly in heterogenous datasets. Future research should incorporate larger, more diverse cohorts and detailed demographic profiling to explore the early diagnostic potential of these biomarkers and further understand OA progression.

LabMed doi: 10.3390/labmed2020007

Authors: Jeonghwa Kim Taewon Kim

Background: In vitro blood circulation loop systems are utilized to assess the hemocompatibility and performance of medical devices that come into contact with blood, in accordance with the international standards ASTM F1830 and ASTM F1841. However, a method for evaluating the specific type of anticoagulant and the blood characteristics of each animal species is necessary to ensure consistent and reliable results. Methods: Blood was collected from healthy rabbits, pigs, rhesus monkeys, and cynomolgus monkeys to evaluate whole blood preserved in anticoagulants (ACD-A, CPDA-1, and heparin). For each sample, red blood cells were monitored over time, and their morphological characteristics were documented. Results: The morphological grade of erythrocytes gradually decreased over time. Significant differences were observed based on the type of anticoagulant used in the experiment, and variations were noted among different animal species. Conclusions: The hemocompatibility of in vitro blood circulation loop systems may vary depending on the animal species. Observing erythrocyte morphology can serve as a control measure to ensure reproducible results.

LabMed doi: 10.3390/labmed2020006

Authors: Divya Mamilla Stevephen Hung Gizachew Demessie Deneen Nault Carla Ayala Soriano Salome Mendoza Rebecca Yee

Identification of mycobacterial infections for both Mycobacterium tuberculosis and non-tuberculosis mycobacteria is important for effective patient care. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a promising tool that is used in many clinical laboratories for the identification of bacteria and yeast. This study evaluates the impact of growth media on the performance of the MALDI Biotyper® MBT smart MS for mycobacteria identification. Increased rates of identification, particularly in non-rapid growers and pigment producers, and higher confidence scores were generated in mycobacteria isolated from solid agar, rather than liquid broth. Testing each isolate in triplicate can increase yield of detection. Using the Bruker MBT Mycobacteria Kit to process our samples for testing on the Bruker MALDI Biotyper® instrument generated precise and accurate mycobacteria identification. These findings emphasize the importance of optimizing mycobacterial specimen processing workflows to include appropriate culture media, which can enhance mycobacterial identification and improve diagnostic accuracy.

LabMed doi: 10.3390/labmed2010005

Authors: Amber Coussee Johan Robbrecht Karel Maelegheer Wouter Vandewal Lisa Florin

The objective of this study was to assess the performance characteristics of the new automated haematology analyser from Sysmex Corporation, the Sysmex XR-Series, compare its performance to the Sysmex XN-Series through method comparison, and compare our results to previously published literature. Analytical performance of the new Sysmex XR-20 consisting of precision, bias, and total error, a method comparison with the Sysmex XN-2000, and the flagging performance evaluation were conducted on a Sysmex XR-20 analyser in the AZ Sint-Lucas Hospital (Bruges, Belgium) several months before its launch in Europe. We conclude that the Sysmex XR-Series is an excellent successor to the Sysmex XN-Series for routine haematology analysis. Analytical performance and flagging efficiency are comparable to the Sysmex XN-analyser.

LabMed doi: 10.3390/labmed2010004

Authors: Gustavo Barcelos Barra Ticiane Henriques Santa Rita Rafael Henriques Jácomo Lídia Freire Abdalla Nery

Cell-free DNA (cfDNA) analysis is a pivotal tool in non-invasive diagnostics, including cancer monitoring and prenatal testing. However, the preanalytical phase, particularly the choice of anticoagulant, significantly impacts cfDNA integrity and yield. This study aims to compare cfDNA yield, stability, and DNase activity in plasma-citrate and plasma-heparin, using plasma-EDTA and serum as established controls, to explore more deeply the impact of blood DNAse activity on cfDNA in these specimens. Blood samples from 15 healthy volunteers were collected in four types of tubes (citrate, heparin, EDTA, and serum). cfDNA was extracted and quantified using qPCR, and endogenous DNase activity was assessed through hydrolysis probe assays. Samples were incubated at 37 °C for 24 h to evaluate cfDNA degradation rates. Heparin-plasma exhibited the highest DNase activity, with baseline cfDNA levels intermediate—higher than EDTA but lower than serum—leading to substantial cfDNA degradation (85.3%). Combined with its known PCR inhibition, this renders heparin-plasma unsuitable for cfDNA analysis. Citrate-plasma, with baseline cfDNA levels similar to EDTA, showed partial DNase inhibition, resulting in intermediate cfDNA degradation (13.3%), a limitation that diminishes its viability compared to EDTA-plasma. Serum, with the highest baseline cfDNA levels, exhibited high DNase activity and significant cfDNA degradation (55.6%), making it unsuitable for cfDNA preservation. EDTA-plasma demonstrated complete DNase inhibition and minimal cfDNA degradation (8%), confirming it as the most suitable specimen for cfDNA analysis. These findings emphasize the importance of anticoagulant selection, highlighting critical limitations of heparin-plasma and citrate-plasma while reinforcing EDTA-plasma as the gold standard for preserving cfDNA integrity in diagnostic applications.

LabMed doi: 10.3390/labmed2010003

Authors: Amy Fountain Natalie Williams-Bouyer Ping Ren Carol Carman Jose H. Salazar Rajkumar Rajendran

Recent initiatives have discouraged the treatment of asymptomatic bacteriuria in specific patient populations due to its lack of clinical benefit, no improvement in morbidity or mortality, and its contribution to antibiotic overuse. This study aimed to evaluate whether an intervention at order entry, combined with DCLS laboratory consultation for urine cultures and urinalyses, could reduce unnecessary lab tests and inappropriate antibiotic use, thereby improving patient outcomes. Our research design was a quasi-experimental study with a retrospective and prospective chart review on non-pregnant adult patients 18 years of age and older from July 2021 to September 2022. Data collected for both reviews included patient demographics, provider demographics, patient signs and symptoms, laboratory test results, test order type, test order utilization and antibiotic prescriptions. Our study included 6372 patients, with 3408 in the retrospective review and 2964 in the prospective review. Before the intervention, 60% (n = 2053) of test orders were inappropriate, which decreased to 20% (n = 591) post-intervention. In asymptomatic patients, reflexed urine cultures decreased from 51% to 13% post-intervention. Lastly, in asymptomatic patients, antibiotic therapy at discharge dropped from 54% to 25% after the intervention. Post-intervention ordering practices improved, decreasing the number of inappropriate orders across all patient and provider types. Overall, this initiative showed a significant reduction in the treatment of asymptomatic bacteriuria, which has been linked to the overuse of antibiotic therapy.

LabMed doi: 10.3390/labmed2010002

Authors: Ishan Bhatia Lloyd Hutchinson Jan Cerny

Acute promyelocytic leukemia (APML) is one of the most curable leukemia subtypes, where the majority of patients achieve complete remission and also deep molecular remission after therapy, characterized by a PCR-undetectable state. Similarly, chronic myelogenous leukemia (CML) is a leukemia where, thanks to effective targeted treatment with tyrosine kinase inhibitors (TKIs), deep remission detectable only by PCR has become part of the routine management of these patients. Here, we describe a patient who was PCR-negative after induction and consolidation with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) and stayed PCR-undetectable for 13 months post-consolidation, later experiencing molecular relapse following mild SARS-CoV-2 infection. The patient was able to reestablish molecular remission again without anti-leukemic therapy several weeks later. She remained PCR-negative for the next 42 months. Viral infection-triggered immunosuppression, as in our case, offers a possible explanation for the temporary loss of molecular remission seen in leukemia patients monitored by PCR. Our first case illustrates this period of convalescence from viral infection, which was maybe accompanied by loss of molecular response. Viral infections and temporary immunosuppression may be a culprit in cases where molecular responses are lost temporarily. This loss of the PCR-undetectable state may have implications for other cancer patients where PCR monitoring is used. Thus, our observation may have broader implications for other patients, especially those with CML. We further enforce these findings by describing a second patient with CML who experienced temporary molecular relapse in the setting of post-viral syndrome.

LabMed doi: 10.3390/labmed2010001

Authors: Alfredo Giovannelli Massimo Pieri Eleonora Nicolai Martina Pelagalli Cinzia Calabrese Flaminia Tomassetti Jacopo Maria Legramante Alessandro Terrinoni Sergio Bernardini Marilena Minieri

Sepsis is a life-threatening condition, and clinicians should diagnose it as soon as possible to enable rapid intervention. The study aims to validate the AIA-360 Presepsin (PSEP) test for its use in determination in the diagnosis of septic patients after admission to emergency departments (ED). A total of 97 blood samples were collected from patients at the ED and from blood donors of Tor Vergata Hospital. Here, 15 samples were obtained from patients with a confirmed diagnosis of sepsis, and 44 samples with non-septic inflammatory condition. A control group of 38 samples from healthy subjects was also included. The non-septic inflammatory condition group and the confirmed sepsis group had a median of 874.40 pg/mL and 1467.10 pg/mL, respectively, while the control group showed a PSEP median value of 473.90 pg/mL, thus showing a significant statistical difference among all groups. The ROC curves highlighted a good sensitivity (93.33%) and specificity (76.19%) for PSEP values, suggesting the best cut-off point of 890 pg/mL. (p-value < 0.001; Mann–Whitney test). The PSEP test can improve and speed up the diagnosis of sepsis after admission to the ED with respect to other biomarkers, mainly due to its early kinetics.

LabMed doi: 10.3390/labmed1010006

Authors: James V. Harte Gavin T. Buckley

Anticoagulants can complicate the interpretation of routine and specialised coagulation assays. Several methodologies have been developed to minimise or eliminate anticoagulant-associated interferences; however, no ‘universal methodology’ that encompasses different anticoagulant classes is currently available. Ciraparantag is a promising reversal agent that can bind both direct oral anticoagulants (DOACs) and heparin-like anticoagulants. As such, we aimed to investigate whether ciraparantag could be employed as a ‘universal’ anticoagulant chelator in vitro. Human plasma was spiked with ascending concentrations of ciraparantag, with or without DOACs or heparin, and assayed for routine coagulation parameters. Ciraparantag had minimal effects on coagulation testing when added to human plasma at concentrations similar to pharmacokinetic maxima; however, ciraparantag did not remove DOAC- or heparin-associated activities in vitro, which was likely due to the preferential chelation of anionic substances in the coagulation reagents. In contrast, DOAC-Stop™, a commercial activated charcoal-based adsorbent, efficiently removed both DOAC- and ciraparantag-associated interferences. In conclusion, although ciraparantag is not effective as a ‘universal’ anticoagulant chelator in vitro, we report that activated charcoal-based adsorbents may be clinically useful in situations where laboratory investigations are complicated by the presence of DOACs and/or ciraparantag.

LabMed doi: 10.3390/labmed1010005

Authors: Hannes Dörfler John Daniels Shekhar Wadekar Quentin Pagneux Dennis Ladage Georg Greiner Ojan Assadian Rabah Boukherroub Sabine Szunerits

In this study, we present a novel face mask engineered for the collection of exhaled breath condensate (EBC) and its application and performance in a clinical study of COVID-19 infection status assessment versus the gold standard polymerase chain reaction (PCR) nasopharyngeal swab testing. EBC was collected within a clinical trial of COVID-19-infected and non-infected patients and analyzed by reverse transcription quantitative (RT-q) PCR, with the results being compared with nasopharyngeal sampling of the same patient. The cycle threshold (Ct) values of the nasopharyngeal samples were generally lower than those of EBC, with viral loads in EBC ranging from 1.2 × 104 to 5 × 108 viral particles mL−1 with 5 min of breathing. From the 60 clinical patients’ samples collected, 30 showed a confirmed SARS-CoV-2 infection. Of these 30 individuals, 22 (73%) had Ct values < 40 (representing the threshold for SARS-CoV-2 infectivity) using both amplification of ORF1a/b and the E-gene. The 30 EBC samples from non-infected participants were all identified as negative, indicating a 100% specificity. These first results encourage the use of the face mask as a noninvasive sampling method for patients with lung-related diseases, especially with a view to equipping the face mask with miniaturized sensing devices, representing a true point-of-care solution in the future.

LabMed doi: 10.3390/labmed1010004

Authors: Brittany Larkin Laura Mahaney Samuel Abegunde Jennifer L. Shea

Quantifying M-proteins is an important part of diagnosing and monitoring patients with monoclonal gammopathies. Historically, laboratories use one of two methods to accomplish this. The splice method utilizes a perpendicular drop on each side of the M-protein on the electrophoretogram. In contrast, the skim method applies a tangent skimming line connecting the points above the polyclonal background. In this study, we compared the bias between these two methods across two different instruments (Helena SPIFE 3000 and Sebia Capillarys 3) in 118 patients. First, we compared the splice technique on both instruments and observed a significant average bias of 58.3% (slope = 1.437, y-intercept = 0.76, and r = 0.9682). We next compared the splice technique on the SPIFE 3000 to the skim technique on the Capillarys 3 and observed an average bias of only −2.10% (slope = 1.363, y-intercept = −1.98, and r = 0.9716), although there was significant scatter along the line of best fit. Lastly, we compared splice vs. skim on the Capillarys 3 and observed an average bias of −38.2% (slope = 0.947, y-intercept = −2.65, and r = 0.9686). Based on these results, care should be taken when switching instruments or integration techniques to ensure consistent monitoring of patients.

LabMed doi: 10.3390/labmed1010003

Authors: Holly Hosking Wayne Pederick Paul Neilsen Andrew Fenning

The assessment and modelling of DNA double-strand break damage and repair is widely investigated throughout the literature. This optimisation study investigated the requirement of cell proliferation prior to treatment with chemotherapeutic agents to damage DNA and the optimal window of analysis for DNA double-strand break repair measurements with γ-H2AX. Peripheral blood mononuclear cells were collected from healthy volunteers and incubated with phytohaemagglutinin at final concentrations of 0, 0.25, 0.5, 1, 2.5, 5 and 10 µg/mL for 0, 24, 48, 72 and 168 h at 37 °C, 5% CO2, and proliferation was measured via spectrometry (MTS assay). This study, detailed in this methodology paper, found that peripheral blood mononuclear cells must be proliferated prior to the chemical induction of DNA double-strand breaks. The window for assessment of early DNA double-strand break repair was determined to be one hour after removal of the DNA damaging agent.

LabMed doi: 10.3390/labmed1010002

Authors: Glen L. Hortin

LabMed is a new open access electronic journal supported by one of the world’s leading electronic publishers MDPI, the Multidisciplinary Digital Publishing Institute, and by an international editorial board with diverse expertise in laboratory medicine [...]

LabMed doi: 10.3390/labmed1010001

Authors: Weiyong Liu

It is my great honor and pleasure to announce the launch of LabMed (ISSN: 2813-9038) [...]