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Introduction: The diagnosis of plasma cell neoplasms depends on the accurate quantification of plasma cells, traditionally done by immunohistochemical CD138 staining of bone marrow biopsies. Currently, there is no fully satisfactory reference method for this quantification. In our previous study, we compared the commonly used overview estimation method (method A) with a novel method for counting plasma cells in three representative areas (method B). Results showed comparable concordance parameters between the two methods. In this follow‐up study, we compared the previously evaluated methods with a digital analysis method (method C) that uses artificial intelligence in open‐source software, QuPath. Methods: Archived CD138 immunohistochemically stained trephine sections of bone marrow samples used in our previous study were used (n = 33). Reviewers selected three representative areas on each sample by taking images with a light microscope and camera. Digital analysis was performed using the positive cell detection function in QuPath. The entire process was repeated by each reviewer to test intraobserver concordance (concordance correlation coefficient [CCC]) in addition to interobserver concordance (intraclass correlation coefficient [ICC]). Results: Intraobserver concordance of method C showed strong agreement for all reviewers with the lowest CCC = 0.854. Interobserver concordance for method C using ICC was 0.909 and 0.949. This showed high interobserver agreement with significant differences between method C and previously assessed method A (ICC = 0.793 and 0.713) and method B (ICC = 0.657 and 0.658). Conclusion: We were able to successfully count CD138‐positive plasma cells in bone marrow biopsies using artificial intelligence. This method is superior to both manual counting and overview estimation, regardless of tumour load. [ABSTRACT FROM AUTHOR]

The quantitation of plasma cells in bone marrow (BM) is crucial for diagnosing and classifying plasma cell neoplasms. Various methods, including Romanowsky-stained BM aspirates (BMA), immunohistochemistry, flow cytometry, and radiological imaging, have been explored. However, challenges such as patchy infiltration and sample haemodilution can impact the reliability of BM plasma cell percentage estimates. Bone marrow plasma cell percentage varies across methods, with immunohistochemically stained biopsies consistently yielding higher values than Romanowsky-stained BMA or flow cytometry alone. CD138 or MUM1 immunohistochemistry and artificial intelligence image analysis on whole-slide images are emerging as promising tools for accurate plasma cell identification and quantification. Radiological imaging, particularly with advanced technologies like dual-energy computed tomography and radiomics, shows potential for multiple myeloma diagnosis, although standardisation remains a challenge. Molecular techniques, such as allele-specific oligonucleotide quantitative polymerase chain reaction and next-generation sequencing, offer insights into clonality and measurable residual disease. While no consensus exists on a gold standard method for BM plasma cell quantitation, CD138-stained biopsies are favoured for accurate estimation and play a pivotal role in diagnosing and assessing multiple myeloma treatment responses. Combining multiple methods, such as BMA, BM biopsy, and flow cytometry, enhances accuracy of diagnosis and classification of plasma cell neoplasms. The quest for a gold standard requires ongoing research and collaboration to refine existing methods. Furthermore, the rise of digital pathology is anticipated to reshape laboratory medicine and the role of pathologists in the digital era. What this study adds: This article adds a comprehensive review and comparison of different methods for plasma cell estimation in the bone marrow, highlighting their strengths and limitations. The goal is to contribute valuable insights that can guide the selection of optimal techniques for accurate plasma cell estimation. [ABSTRACT FROM AUTHOR]

Introduction: Verification of blood collection tubes is essential for clinical laboratories. The aim of this study was to assess performance of candidate tubes from four alternative suppliers for routine diagnostic haematology testing during an impending global shortage of blood collection tubes. Methods: A multicentre verification study was performed in Cape Town, South Africa. Blood from 300 healthy volunteers was collected into K2EDTA and sodium citrate tubes of BD Vacutainer® comparator tubes and one of four candidate tubes (Vacucare, Vacuette®, V‐TUBE™ and Vacutest®). A technical verification was performed, which included tube physical properties and safety. Routine haematology testing was performed for clinical verification. Results: Vacucare tubes did not have a fill‐line indicator, Vacuette® tubes had external blood contamination on the caps post‐venesection and Vacutest® tubes had hard rubber stoppers. K2EDTA tubes of Vacuette®, Vacucare and Vacutest® performed similarly to the comparator. Unacceptable constant bias was seen for PT in Vacucare (95% CI −2.38 to −0.10), Vacutest® (95% CI −1.91 to −0.49) and Vacuette® (95% CI 0.10–1.84) tubes and for aPTT in Vacuette® (95% CI 0.22–2.00) and V‐TUBE™ (95% CI −2.88 to −0.44). Unacceptable %bias was seen for aPTT in Vacucare (95% CI 2.78–4.59) and Vacutest® tubes (95% CI 2.53–3.82; desirable ±2.30), and in V‐TUBE™ for mean cell volume (95% CI 1.15–1.47, desirable ±0.95%) and mean cell haemoglobin concentration (95% CI −1.65 to −0.93, desirable ±0.43%). Conclusion: Blood collection tubes introduce variability to routine haematology results. We recommend that laboratories use one brand of tube. Verification of new candidate tubes should be performed to ensure consistency and reliable reporting of results. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify arterial blood gas (ABG) abnormalities, with a focus on a high anion gap (AG) metabolic acidosis and evaluate outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU. Methods: A retrospective, observational study was conducted in a tertiary hospital in Cape Town during the first and second COVID-19 waves. Age, gender, sodium (Na), potassium (K), chloride (Cl), bicarbonate (HCO3std), pH, partial pressure of carbon dioxide (pCO2), creatinine, estimated glomerular filtration rate (eGFR), lactate levels and ABG results were obtained. The Pearson χ2 test or Fisher exact test and the Wilcoxon rank-sum test were used to compare mortality and survival. To identify factors associated with non-survival, a multivariable model was developed. Results: This study included 465 patients, 226 (48%) of whom were female. The sample population's median (IQR) age was 54.2 (46.1–61.3) years, and 63% of the patients died. ABG analyses found that 283 (61%) of the 465 patients had alkalosis (pH ≥ 7.45), 65 (14%) had acidosis (pH ≤ 7.35) and 117 (25%) had normal pH (7.35–7.45). In the group with alkalosis, 199 (70.3%) had a metabolic alkalosis and in the group with acidosis, 42 (64%) had a metabolic acidosis with an increased AG of more than 17. Non-survivors were older than survivors (56.4 years versus 50.3 years, p <.001). Conclusion: Most of the COVID-19 patients admitted to the ICU had an alkalosis, and those with acidosis had a much worse prognosis. Higher AG metabolic acidosis was not associated with patients' characteristics. [ABSTRACT FROM AUTHOR]

Many Africans may have a gene that predisposes them to iron overload when they consume large amounts of dietary iron. Africans in sub-Sahara drink a locally-produced beer that is fermented in steel drums. The beer contains 80 milligrams of iron per liter, and many Africans drink several liters a day. The average iron content of a typical Western diet is 15 to 20 milligrams per day. Relatives of 36 patients with documented iron overload were studied. Blood tests on relatives who regularly drank the beer showed increased transferrin saturation, a measure of iron overload. Transferrin saturation was higher in first-degree relatives than in other relatives. Genetic analysis of the families supported the presence of an iron-loading gene that interacts with dietary iron.

Background: Bone marrow biopsy (BMB) plays a crucial role in the diagnosis and assessment of treatment response in patients with multiple myeloma (MM). 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been shown to be a complimentary measure of marrow involvement in patients with Hodgkin and diffuse large B cell lymphomas. However, only limited information is available on its relationship with BMB in MM. Aim: To assess the association between bone marrow involvement on 18F-FDG PET/CT, and BMB in patients with MM and other plasma cell neoplasms. Setting: Cape Town, South Africa. Methods: Hundred and three patients undergoing 18F-FDG PET/CT and BMB were included. Plasma cell infiltration (PCI) on BMB was compared for three visual patterns of 18F-FDG bone marrow uptake (irregular, diffuse less than or equal to the liver and diffuse greater than liver). Results: Eighty-four patients had diffuse bone marrow uptake. Of these, 25/84 had uptake greater than liver, all having PCI ≥ 60% and a median value of 85%. Of the 84 patients, the 59 patients with uptake less than or equal to liver had PCI < 10% in 57.6% (34/59), and ≥ 10% in 42.4% (25/59) with a median value of 8%. Nineteen patients had irregular bone marrow uptake. Of these, 4/19 (21.1%) had PCI of < 10% and 15/19 (78.9%) had PCI ≥ 10%, with the median value of 23%. The median percentage of PCI across the three described patterns of FDG uptake was significantly different (p = 0.0001). Conclusion: 18F-fluorodeoxyglucose positron emission tomography/computed tomography might avoid the need of repeat BMB in most of the patients with diffuse and irregular patterns of 18F-FDG uptake. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukaemia (AML) is a heterogeneous group of myeloid neoplasms for which two international classification systems exist: the 2022 World Health Organization (WHO) and international consensus classification of myeloid neoplasms (ICC), with an emphasis on molecular abnormalities. Aim: To determine the molecular-genetic profile of AML in the South African public sector. Setting: The Charlotte Maxeke Johannesburg Academic Hospital, Somatic Cell Genetics Unit, National Health Laboratory Service, South Africa. Methods: All newly diagnosed AML cases analysed with next generation sequencing (NGS) between January 2019 and December 2022 were retrospectively reviewed. Clinical and laboratory data were obtained from the laboratory information system. Results: In total, 194 AML cases were tested by NGS (162 classifiable), with a median age of 42 years for adults and 7 years for the paediatric cohort. There were 21 cases of AML with mutated TP53 (ICC), 5 of which were unclassifiable with the WHO classification system. In t(8;21) (q22;q22.1), KIT and FLT3-ITD mutations were present in 43% and 20% of cases respectively; FLT3-ITD in 50% of acute promyelocytic leukaemia (APL) and ~20% of AML with NPM1 were triple mutated (NPM1, DNMT3A, FLT3-ITD). Conclusion: This study revealed a high proportion of exon 17 KIT mutations in t(8;21), FLT3-ITD mutations in APL and triple mutated AML with mutated NPM1, all of which are likely to be driving the poor outcomes seen in these AML subgroups in our setting. Contribution: This is the first nationwide description of the molecular-genetic landscape of AML in the South African public sector. [ABSTRACT FROM AUTHOR]

In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hussey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure., Methods: We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity., Findings: Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35)., Interpretation: The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19., Funding: Wellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health.