Journal of Clinical Pathology

ImportanceThe Verifying Accurate Leading-edge IVCT Development Act, if enacted, would create a unified regulatory oversight system for all in vitro clinical tests, including laboratory-developed tests. ObjectiveTo determine the frequency of use of laboratory-developed tests in an academic medical center system. DesignQuality improvement study analyzing 2021 test order data. SettingAcademic medical center (hospital, outpatient clinics, and cancer center) and non-profit national reference laboratory. Main Outcome(s) and Measure(s)Main outcome, not applicable; non-interventional study of retrospective data. Measures include assay type, assay methodology, compliance status (i.e., Food and Drug Administration cleared, approved, and/or authorized assay, laboratory-developed test, and standard method), test order volume, inpatient versus outpatient setting, and provider medical specialty. ResultsOf the 3,016,928 tests ordered in 2021, 2,831,489 (93.9%) were Food and Drug Administration cleared, approved, and/or authorized assays, 116,583 (3.9%) were laboratory-developed tests, and 68,856 (2.3%) were standard methods. Laboratory-developed tests were more commonly ordered in the outpatient versus inpatient setting and represented a higher proportion of the test volume at the cancer center compared to University Hospital (5.6% vs 3.6% respectively). The top 167 laboratory-developed test assays accounted for 90% of the laboratory-developed test volume (104,996 orders). Among the 20 most frequently ordered laboratory-developed tests were mass spectrometry assays and tests used in the care of immunocompromised patients. Internal/family medicine placed the greatest number of orders (1,044,642) and ordered one of the lowest proportions of laboratory-developed tests (3.2%). Non-infectious disease molecular testing made up 8.8% of laboratory-developed tests ordered. ConclusionsLaboratory-developed tests made up a small percentage of the total laboratory tests ordered within the academic health system studied. Regulatory reform proposals should consider the need for both safety and availability of laboratory-developed tests in clinical laboratory settings. KEY POINTSO_ST_ABSQuestionC_ST_ABSHow frequently are laboratory developed tests (LDTs) used in an academic medical center (AMC) setting? FindingsIn this quality improvement study looking at test orders in 2021, 93.9% of test orders were for FDA cleared, approved, or authorized assays, 3.9% were for LDTs, and 2.3% were for standard methods. The top 167 LDT assays accounted for 90% of the LTD volume. MeaningIn vitro diagnostic reform efforts will impact many LDTs assays with relatively low order volumes in AMC settings.

BackgroundUnited Kingdom Standards for Microbiology Investigations limits the pre-analytical delay of blood cultures to a maximum of four-hours between collection and incubation. Compliance with this delay standard is a measure of the ability of a microbiology service to support the management of sepsis which is a life-threatening complication of infection. A positive blood culture confirms the infection and an early result is critical to the effective management of the condition. Delayed results lead to the prolongation of empiric broad spectrum antimicrobial therapy which is considered a causal factor in the emergence of antimicrobial resistance. This retrospective observational study documents compliance with the standard by microbiology services in England in 2022/23. The impact of laboratory centralisation on the ability of microbiology services to comply with this standard is examined. MethodsFreedom of Information requests were submitted to 116 National Health Service Trusts/administrative units in England requesting retrospective audit data showing compliance with the recommended pre-analytical delay standard. Data relating to service configuration and cost were also requested. ResultsResponses were received from 89 Trusts (76.7%) managing 146 hospitals. Overall, the rate of compliance was low, with only four hospitals (2.7%) showing full compliance and 31.5% showing >80% compliance. ConclusionsPoor rates of compliance with the PAD standard are a concern as prompt attention to blood cultures improves patient outcomes from sepsis and supports antimicrobial stewardship. Laboratory centralisation has resulted in withdrawal of staff and facilities from some hospitals with insufficient investment in others, leading to a demonstrable inability of many hospitals to comply with this standard. Compliance will require investment in microbiology services. The financial implications of the improvements proposed should be evaluated in the context of overall health care and community benefits.

ObjectivesWe compared the Abbott ID NOW COVID-19 point-of-care test (POCT) with polymerase chain reaction (PCR)-based methods to assess the claimed sensitivity and specificity of POCT and to optimize test utilization in our regional health care system. MethodsAssuming PCR to be the gold standard, we used a convenience sampling of mostly symptomatic COVID-19 suspect hospital patients who had already been tested for internal validation and guideline development purposes by both PCR and POCT to calculate the sensitivity and specificity of POCT with Clopper-Pearson 95% confidence intervals (CI). ResultsDuring the study period, 113 paired patient samples met eligibility criteria. The sensitivity of POCT in this population was calculated to be 94.1% [CI 71.31-99.85%] and the specificity was 99.0% [CI 94.33-99.97%]. ConclusionsBased on the lower sensitivity of POCT and the estimated prevalence of COVID-19 in our symptomatic and asymptomatic hospital patients, we recommend a two-pronged testing approach in which COVID-19 suspect patients are tested by the more sensitive PCR, while asymptomatic patients with a low pre-test probability of infection are tested with POCT supplemented by PCR confirmation of positive results. Furthermore, isolation decisions should not be based on POCT results alone.

Public health emergency of SARS-CoV-2 has facilitated diagnostic testing as a related medical countermeasure against COVID-19 outbreak. Numerous serologic antibody tests have become available through an expedited federal emergency use only process. This paper highlights the analytical characteristic of an ELISA based assay by AnshLabs and three random access immunoassay (RAIA) by DiaSorin, Roche, and Abbott that have been approved for emergency use authorization (EUA), at a tertiary academic center in a low disease-prevalence area. The AnshLabs gave higher estimates of sero-prevalence, over the three RAIA methods. For positive results, AnshLabs had 93.3% and 100% concordance with DiaSorin or Abbott and Roche respectively. For negative results, AnshLabs had 69.7% and 73.0% concordance with DiaSorin and Roche or Abbott respectively. All discrepant samples that were positive by AnshLabs and negative by RAIA tested positive by all-in-one step SARS-CoV-2 Total (COV2T) assay performed on the automated Siemens Advia Centaur XPT analyzer. None of these methods, however, are useful in early diagnosis of SARS-CoV-2.

BackgroundHypercoagulability is becoming widely recognized as a major complication of COVID-19 infection as evidenced by high levels of fibrinogen degradation products and microthrombi identified within the lungs and kidneys of autopsy specimens from these patients. We report thromboelastography (TEG) testing on a cohort of patients with suspected COVID-19 infection at the time of admission to the intensive care unit. MethodsTEG testing was performed using the TEG 6s analyzer near or at the time of ICU admission. We also report the results of other coagulation or inflammatory related indices such as platelet count, prothrombin time, fibrinogen, D-dimer, C-reactive protein, ferritin, and procalcitonin. All laboratory testing was performed at the discretion of the attending physician in the course of normal patient care and retrospectively reviewed. ResultsWe found that maximum clot strength was consistently elevated in COVID-19 patients while normal in all patients found to be negative. We did not encounter significant prolongations of coagulation assays outside of those expectedly prolonged by heparin therapy nor was meeting the criteria for disseminated intravascular coagulation encountered. ConclusionsWe postulate that elevated maximum clot strength by TEG testing is predictive of COVID-19 status as within our cohort this perfectly predicted patients COVID-19 status despite a high level of suspicion in negative patients with normal TEG results. While these results require a larger cohort for confirmation, we feel that TEG testing could improve confidence in COVID-19 testing results in suspected patients possibly allowing for earlier de-escalation of infectious precautions and personal protective equipment utilization.

The development of a high through-put flow cytometric assay for the identification of clonal T cells has proved challenging. We assessed the surface expression of a specific T Cell Receptor {beta}-chain constant region using conjugated anti-JOV1.1 monoclonal antibodies to identify clonal T cell populations in a large diagnostic flow cytometry laboratory within a quaternary referral hospital. 37 cases were analysed. We identified 15 cases of clonal JOVI.1 expression, 7 of which had a consensus diagnosis of T-cell lymphoproliferative disease (TLPD). The remaining 22 cases had polyclonal JOVI.1 expression, none of which had a consensus diagnosis of TLPD, resulting in a sensitivity of 100% and specificity of 73%. When clonal NK-T cells were excluded, specificity further improves to 97%. These results provide real-world data and support the widespread adoption of this assay into diagnostic use.

BackgroundThe concept of sigma metrics & lean six sigma is well known in the field of healthcare. However not many labs utilize the six sigma metrics for maintenance of high quality laboratory performance. A minimum value of 3 {sigma} is desired in any clinical laboratory & values of {sigma}[≥] 6 are regarded as gold standard for obtaining high quality lab reports. Aims &ObjectivesTo calculate bias, cv & sigma metrics from the IQC & EQC data in order to ascertain extent of quality management in our lab. Materials &MethodsAn extensive study of sample processing and quality practices was carried out in the Central Laboratory of Department of Biochemistry; PGIMER &Dr. RML Hospital, New Delhi; from Feb 2020 to July 2020. The IQC used(both level I & level II) were from Biorad Laboratories India (lyphochek assayed chemistry control) & the EQC used was from Randox Laboratories, UK. All the controls were run on Beckman Coulter clinical chemistry analyser AU 680. Total 14 clinical parameters were analysed & subsequently; Mean, S.D., CV, bias & {sigma} were calculated through their respective formulas. ResultsSigma level was more than 6 for both levels of IQC was observed for Amylase. It indicates world class performance. Total bilirubin, AST, Triglyceride & HDL depicted {sigma} values between 3.1 - 6 for both L1 & L2. Iron showed {sigma} value of 5.5 in L1 whereas it was 3.78 in L2. ConclusionSigma metrics in clinical laboratory is an essential technique to ascertain poor assay performance, along with assessment of the efficiency of existing laboratory process.

BackgroundArtificial intelligence (AI) is rapidly fueling a fundamental transformation in the practice of pathology. However, AIs clinical integration remains challenging, with no AI algorithms to date enjoying routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. MethodsPerspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analyzed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. FindingsConsensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AIs role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. InterpretationThis is the first systematic consensus study detailing the expected short/mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AIs successful clinical implementation. FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

BackgroundBarth syndrome is an inherited disorder that results from pathogenic mutations in TAZ, the gene responsible for encoding tafazzin, an enzyme that remodels the mitochondrial phospholipid cardiolipin. Barth syndrome is characterized by heart and skeletal muscle myopathy, growth delay, and neutropenia among other features. The TAZPOWER clinical trial investigated the effects of the mitochondria-targeting peptide elamipretide in patients with Barth syndrome. Methods and findingsTAZPOWER included a randomized, double-blind, crossover study of 12 weeks treatment with elamipretide or placebo in 12 patients with Barth syndrome. A broad spectrum of plasma and urine metabolites were measured using liquid chromatography-tandem mass spectrometry at baseline and after 12 weeks treatment with elamipretide or placebo. Of 51 "energy-linked" metabolites analyzed, we highlight here the effects of elamipretide on the plasma and urinary concentrations of several metabolites previously observed to be abnormal in patients with Barth syndrome. Elamipretide treatment was associated with significantly lowered medium- and short-chain acylcarnitines in plasma and urine, respectively (p < 0.05). Acetylcarnitine, 3-hydroxybutyrate, and 3-methylglutaconate trended to decrease after 12 weeks of elamipretide, but these trends did not reach statistical significance. After 12 weeks of treatment, elamipretide had no discernible effect on four amino acids previously characterized as having abnormal concentrations in patients with Barth syndrome. Lastly, elamipretide caused a significant rise in plasma taurine concentrations, an amino acid which has been observed to be decreased in patients with Barth syndrome. ConclusionsAs evidenced by reduced plasma and urinary content of acylcarnitines and trends for lowered ketone body 3-hydroxybutyrate, fat metabolism in Barth syndrome appears to be modified after 12 weeks of elamipretide treatment. Overall, these data are consistent with the improved mitochondrial function that may precede functional benefits with a longer duration of therapy with elamipretide in patients with Barth syndrome. Trial registrationClinicalTrials.gov NCT03098797. Summary pointsO_LIExploratory targeted metabolomic analyses of plasma and urine were performed after a double-blind, crossover trial in patients with Barth syndrome receiving elamipretide or placebo for 12 weeks. C_LIO_LIAmong 51 "energy-linked" metabolites analyzed in both plasma and urine, prominent changes were observed in metabolites associated with fat metabolism. C_LIO_LICollectively, plasma medium-chain (C6-C12) acylcarnitines were reduced after 12 weeks of elamipretide treatment in patients with Barth syndrome. C_LIO_LIUrinary acylcarnitine concentrations were also lowered with elamipretide in Barth syndrome patients, most prominently for shorter chain acylcarnitines. C_LIO_LIElamipretide for 12 weeks also trended to lower 3-methylglutaconate and the ketone body 3-hydroxybutyrate, although these decreases did not reach statistical significance. C_LIO_LIElamipretide also caused a significant rise in plasma taurine, which has been previously reported to be low in Barth syndrome patients. C_LIO_LIThese metabolite changes may be consistent with improved mitochondrial function that precedes the functional benefits observed in patients with Barth syndrome after longer-term therapy. C_LI

Backgroundto investigate endometrial carcinoma prognostic value of some histopathological and immunohistochemical factors, fairly easily accessible in every routinely pathology lab set. Methodswe considered patients affected by endometrial carcinoma with available clinical and radiological follow-up data after radical hysterectomy (S. Martino Polyclinic Hospital, Genoa, Italy, period 1/1/2013 - 1/7/2016). We analyzed the following histopathological items: histotype, stage (FIGO), type of infiltration (infiltrative/espansive), desmoplasia, intratumoral necrosis, tumor infiltrating lymphocytes and lymph vascular spaces invasion. Moreover, each case has been investigated with a panel of immunohistochemistry including estrogen receptor , progesteron receptor, Ki67, p53, {beta}-catenin, e-cadherin, bcl-2 and cyclin D1. Primary endpoints were disease free survival and overall survival. Resultsout of 99 cases eligible for our purpose, we found 69 low-grade endometrioid, 8 high-grade endometrioid and 22 other high-grade endometrial carcinomas. Disease free survival multivariate analysis showed a strong significant correlation between poor prognosis and advanced stage (p=0.0042). Advanced stage (p=0.0003) and presence of desmoplasia (p=0.04) resulted significantly correlated to a worse prognosis in overall survival multivariate analysis. In univariate model, the non-endometrioid histotype was significantly correlated with an unfavorable prognosis when compared to the endometriod type. Same for progesteron receptor low expression. Conclusionthe multivariate analysis confirmed the central prognostic role of stage in endometrial carcinoma. Moreover, other immunohistochemical markers in univariate analysis, have confirmed their easily reproducible usefulness, well integrating the recent TGCA molecular classification.

The current gold standard for clinical pathogen identification relies on a combination of culture-based methods, target-specific molecular techniques, and antigen-detection assays1. Known limitations of the first method include the requirement for viable and culturable microorganisms, while the second approach is constrained to a limited number of predefined targets. These constraints reduce their diagnostic success, as not all pathogens are culturable, easily isolated from commensal microbiota, or represented in the selected detection panels. While culture-based methods are widely recognized for their limited sensitivity, updated quantifications of their actual performance in real-world clinical settings are scarce. To address this gap, we conducted a retrospective survey of all lower respiratory tract (LRT) samples processed by either culture or target-based molecular methods over a five-year period at a Portuguese hospital centre, providing a quantitative assessment of current diagnostic performance.

In March 2020, the World Health Organization (WHO) declared a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the absence of effective treatment or biomedical prevention, understanding potential post infection immunity has important implications for epidemiologic assessments. For this reason, increasing number of in vitro diagnostic companies are developing serological assays to detect antibodies against SARS-CoV-2, but most of them lack the validation by third parties in relation to their quality, limiting their usefulness. We submitted to serological screening by two different immunochromatographic (IC) rapid testing for detection of IgG and IgM against SARS-CoV-2, 151 asymptomatic or minimally symptomatic healthcare workers previously tested positive for SARS-CoV-2 RT-PCR in order to evaluate the performance of rapid assays. Results showed discrepancies between molecular and IC results, and an inconsistency of immunoglobulins positivity patterns when compared to ELISA/CLIA results, highlighting the absolute necessity of assays performance validation before their marketing and use, in order to avoid errors in the results evaluation at both clinical and epidemiological level.

BackgroundNowadays, the detection of therapy-guiding aberrations such as EGFR mutations and ALK fusion genes in tumor tissue is common practice for lung cancer patients. The aim of this study is to explore the feasibility of detecting common therapy-guiding aberrations in RNA isolated from platelets. MethodsWe applied a single primed enrichment-based targeted next generation sequencing (NGS) approach on 10 platelet RNA samples isolated from patients with active disease. In parallel, we applied RNA-based ddPCR focusing on EGFR p.(T790M), p.(L858R) and E19del, on KRAS codon 12 and 13 and on ALK-EML4/KIF5B fusions on 22 platelet RNA samples from patients with tumors known to harbor one of these drivers. For 11 cases ddPCR analysis of circulating cell free (cf)DNA from the same blood sample was performed in parallel. ResultsDespite having good quality NGS data, none of the variants detected in the tumor biopsy were observed in platelet-derived RNA samples. Using the more sensitive ddPCR, we detected known aberrations in three of 22 platelet-derived RNA samples. EGFR mutant droplets were not observed in any of the seven platelet samples, while these mutations were detected in three of six cfDNA samples of which five were extracted from the same blood sample. KRAS mutant droplets were detected in three out of nine platelet RNA samples with fractional abundances of 0.07%, 0.11% and 0.55%. Analysis of five cfDNA samples from the same blood samples revealed KRAS-mutant droplets in four of them. Two of the four corresponding platelet RNA samples were also positive for mutant KRAS. No ALK fusion droplets were detected in seven platelet derived RNA samples. ConclusionsThe level of tumor-derived RNA transcripts in platelets of non-small cell lung cancer patients was too low to be measured reliably for clinically relevant alterations in EGFR, KRAS and ALK fusion gene transcripts.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529), creates a diagnostic vacuum, since differentiation of Omicron from Delta relies on relatively slow next generation sequencing (NGS) technology delaying epidemiologic understanding and therapeutic intervention. The RUO SARS-CoV-2 Variant Set 1 Test (RSCov2V1) RT-PCR for detection of spike gene N501Y, E484K and del69-70 was designed to differentiate Alpha from Beta and Gamma variants. While Delta lacks these three variants, Omicron has the N501Y and del69-70 mutation. We submitted 88 samples for RSCov2V1 identifying 9 samples with the N501Y and del69-70 mutations while all other samples (79) were negative for all three variants. 9/9 samples with the del69-70 and N501Y were identified by NGS to be Omicron while 47/47 other samples assessed by NGS were confirmed to be Delta family variants. We demonstrate here that an immediately available RT-PCR assay for detection of spike gene N501Y and del69-70 can be utilized to rapidly differentiate Omicron from Delta variants in the proper epidemiologic context

IntroductionThe impact of workflow changes and total laboratory automation (TLA) on microbiology culture processing time was evaluated in an academic-affiliated regional hospital. Materials and MethodsA retrospective analysis of microbiological data in a research database was performed to compare turnaround time (TAT) for organism identification (ID) before and after implementation of TLA (2013 versus 2016, respectively). TAT was compared using the {chi}2 test for categorical variables and log-transformed t-test for continuous variables. ResultsA total of 9,351 predefined common and clinically important positive mono-bacterial culture results were included in the analysis. Shorter TAT (hours) in 2016 compared to 2013 (p<0.0001) for positive result pathogen ID were observed in specimen types including blood (51.2 vs. 70.6), urine (40.7 vs. 47.1), wound (39.6 vs. 60.2), respiratory (47.7 vs. 67), and all specimen types combined (43.3 vs. 56.8). Although shorter TATs were not observed from all specimen categories for negative result pathogen ID, TAT for all specimen types combined was shorter (p[&le;]0.001) in 2016 compared to 2013 (94 vs. 101). ConclusionsTotal laboratory automation and workflow changes--including process standardization--facilitate shorter organism ID TAT across specimen sources.

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. In the present study potential histopathological and immunohistochemical prognostic markers are investigated Consecutive cases of high grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. Each surgical specimen has been routinely processed, the most representative block has been selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, {beta}-catenin, Bcl-2 and cyclin D1. For each immunomarker the percentage of positive tumor cells were evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). 33 cases were eligible: 19 resulted FIGO I-II, 14 resulted FIGO III-IV. 12 patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). Women with recurrent disease demonstrated a significant higher bcl2% (35.84{+/-}30.96% vs 8.09{+/-}11.56% p=0.0032) while DOD patients had higher ki67% (75{+/-}13.09% vs 58.6{+/-}19.97% p=0.033) and bcl2% of border significance (34.37{+/-}34.99% vs 13{+/-}17.97% p=0.078). As expected FIGO III-IV had a worse DFS (HR=3.34; 95%CI:1.1-10.99; p=0.034) and OS (HR=5.19; 95%CI: 1.27-21.14 p= 0.0217). Bcl2-high patients (bcl2>10%) demonstrated a significant worse DFS (HR=9.11; 95%CI: 2.6-32.4; p=0.0006) and OS (HR=7.63; 95%CI:1.7-34; p=0.0084); also PR low patients (PR[&le;]10%) had a significant worse DFS (HR=3.74; 95%CI:1.2-11.9; p=0,02). HG-NEC represent an heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis often at an advanced stage at presentation. Bcl2 and PR may represent promising markers to identify a sub-group of patients having an even worse prognosis requiring a careful and close follow-up.

AbstarctO_ST_ABSBackgroundC_ST_ABSThe COVID-19 serological tests for IgG and IgM have been developed with several methodologies: Immunoenzymatic Assay (ELISA), Chemiluminescence, Electro Chemiluminescence, Fluorescent Lateral Flow Immunoassays and Immunochromatography. None of these tests should be used for the diagnosis or population screening of the disease, considering that the antibodies appear only on the 8th - 14th day of the disease onset. The present study evaluates a sample of immunofluorescent and immunochromatographic rapid tests to show their agreement in relation to Chemiluminescence. MethodsA diagnostic test evaluation assay was performed to establish the performance of five "rapid" tests (4 immunochromatographic and 1 immunofluorescent tests) for IgG and IgM serology for SARS-CoV-2 using a panel of 30 serum samples from patients received in the laboratory analysis routine. For the evaluation of clinical performance, the qualitative results of the "rapid" tests were compared against those obtained by chemiluminescence, dichotomized as positives ([&ge;] 10 AU / mL) or negative (<10 UA / mL). FindingsThe best agreement is seen in the immunofluorescent assay, for the IgG contrast, with a particularly good kappa index (0.85), without positive disagreements and a negative disagreement of about 15%. In the immunochromatographic methods Kappa index was 0.61 at best, with disagreements in negative findings of {approx}35% and in positive cases of up to {approx}70%. The IgM concordance behavior, on the other hand, reflects a weak to moderate Kappa concordance value (Kappa 0.2 to 0.6), with negative disagreements reaching up to 55% and positives of up to 84%, without any evaluated test reaching Kappa performance equal to or greater than 0.8. InterpretationSerological studies should be used in the clinical and epidemiological context and of other diagnostic tests. Given the high demand and supply in the market of "rapid serological tests", its evaluation against panels of serologically positive or negative samples established by Chemiluminescence or Electro chemiluminescence is essential to authorize its extensive use in populations FundingNone

BackgroundNeonatal sepsis, a significant cause of morbidity and mortality, is a systemic response to infection in the first month of life. Its early diagnosis is challenging due to nonspecific clinical manifestations and the time-intensive nature of blood cultures, the diagnostic gold standard. The Hematological Sepsis Scoring (HSS) system, introduced in 1988, offers a rapid diagnostic alternative using hematological parameters. To enhance diagnostic accuracy, the Modified HSS incorporates additional parameters, such as nucleated RBC, and assigns higher weightage to neutropenia. This study evaluates the utility of the Modified HSS in the early diagnosis of neonatal sepsis, aiming to facilitate prompt treatment and reduce neonatal mortality. MethodsThis descriptive analytical study was conducted over a year at B.P. Koirala Institute of Health Sciences, involving neonates >34 weeks of gestation within four weeks of birth, clinically suspected of sepsis. Blood samples were analyzed using Modified Hematological Sepsis Scoring (HSS) and BacT/ALERT for culture. Purposive sampling selected 147 cases. Ethical clearance was obtained, and informed consent secured. Hematological parameters, including TLC, ANC, IT ratio, and nucleated RBC, were assessed, and cultures were processed for microbial identification and susceptibility. ResultsThe study included 147 neonates with suspected sepsis (male:female ratio 1.33). Blood cultures were positive in 21 cases, with early-onset sepsis predominant (81%). Modified Hematological Sepsis Scoring (HSS) showed high diagnostic accuracy: sensitivity (90.48%), specificity (96.83%), and accuracy (95.91%) for HSS [&ge;]4. Among hematological parameters, degenerative changes had the highest sensitivity (95.23%), and nucleated RBC showed the highest accuracy (91.15%). Staphylococcus aureus (52.3%) was the most common pathogen. Modified HSS proved effective for early sepsis diagnosis. ConclusionModified HSS is an effective and accurate tool for early neonatal sepsis diagnosis, with high sensitivity, especially when using a score [&ge;]4 as the cutoff. The inclusion of nucleated RBC enhances sensitivity, while the systems diagnostic accuracy is improved by recalibrating parameters. Modified HSS, utilizing common hematological parameters, shows significant potential for clinical application.

BackgroundAn endometrial sampling procedure is a gold standard for the diagnostic evaluation of women with abnormal uterine bleeding (AUB) with primary aim to identify the cause, especially to determine whether carcinoma or premalignant lesions are present. The objective of the study is therefore to review endometrial biopsy specimen histopathological findings and associated factors at a tertiary referral hospital in urban Ethiopia. MethodologyThis is a two years retrospective analysis of cases of patients for whom endometrial biopsy was taken at a territory referral hospital in urban Ethiopia. Odds ratios, 95% confidence interval and p-value set at 0.05 were used to determine the statistical significance of the associations. ResultsA total of 277 patient records were analyzed and mean and the median age of the study patients were 41.89 and 40.00 years respectively. The commonest histopathologic finding was endometrial polyp 66 (23.83%), followed by proliferative endometrium 47 (16.97%) and secretory endometrium 25(9.03%). Endometrial hyperplasia, endometrial malignancy, and pregnancy complications were reported in 9 (3.25%), 13 (4.69%), and 25 (9.03%) of cases respectively. Endometritis was detected in 20(7.22%), while Tuberculous (TB) endometritis was reported in 3(1.08%) of cases only. Inconclusive and inadequate sample was reported in 30 (10.83%) and 34 (12.27%) of cases respectively. Endometrial polyp was associated with 40-49 years of age (OR= 12.56, 95% CI: 2.58-61.23). ConclusionsEndometrial polyp was the commonest histopathologic finding followed by proliferative and secretory endometrium respectively. Rate of sample inadequacy is higher than most of the study reports which mandates to improve sampling technique to increase sample adequacy and routine transvaginal ultrasound for endometrial evaluation especially for those postmenopausal women to decide the necessity of endometrial sampling.

Background: External Quality Assurance (EQA) is an essential component of modern laboratory medicine. Current scientific evidence on EQA focuses primarily on the analyses carried out by EQA providers while relatively little research has been conducted in individual clinical laboratories. Methods: In this retrospective single-center observational study in a clinical laboratory, EQA results were analyzed over a period of four years (2021-2024). The evaluation was based on EQA action reports documented in the institutes internal quality management system. Deviations were classified according to department, type of discrepancy, root cause category (analytical, preanalytical, systemic, unidentifiable), and measures taken. Results: A total of 7226 EQA participations were evaluated during the observation period. The overall error rate remained consistently low, ranging between 0.8% and 1.6%, with no significant change over time (p = 0.87). Most deviations occurred in the departments of clinical chemistry and immuno/autoimmune diagnostics (p < 0.001). These were predominantly quantitative discrepancies (false low/false negative or false high/false positive). Root cause analysis showed a clear dominance of analytical causes (p < 0.001), while preanalytical and systemic causes were identified less frequently. In most cases, corrective measures, such as re-analyses, recalibrations, process adjustments, or staff training, were implemented promptly. Hard structural measures, such as changing methods or discontinuing tests, were rarely necessary. Conclusion: In a clinical laboratory, EQA is an important tool for structured error analysis and continuous quality improvement. Consistent processing of deviating EQA results goes hand in hand with stable analytical performance and a low error rate.