Blood Screening Research Articles

REASONS OF DONOR DEFERRAL FOR A SINGLE DONOR PLATELETPHERESIS IN A PUBLIC SECTOR BLOOD TRANSFUSION CENTRE OF LAHORE: A CROSS-SECTIONAL STUDY

Background and Objective: Plateletpheresis is a process by which platelets are extracted from the donor. Donor selection is critical since donors are the sole supply of blood available to satisfy demand. The goal of this study is to investigate the causes behind plateletpheresis donor deferral in order to ensure safe blood donation. Materials and Methods: The research was carried out at the department of Haematology and Transfusion Medicine University of Child Health Sciences, The Children Hospital Lahore. 50 plateletpheresis donors who voluntarily came for donation were considered for the procedure as per guidelines and departmental standard operating procedure. The details of the procedure of plateletpheresis were explained to each donor. Donor questionnaire was filled including brief history, general physical examination, Haematological parameters such as haemoglobin and the donor blood screening was done to be considered fit for procedure. The reasons for deferral of donors were noted after all work up was done. Informed consent was taken before the procedure. Plateletpheresis was done using COM.TEC Cell Separator instrument. Results: In this study 50 donors were included. Out of 50 donors 34 were approved for procedure and 16 were deferred due to different temporary and permanent reasons. The age of the donors were in between 18 to 50 years. Major reason for temporary deferral was poor venous access (n=7, 14%) followed by the low haemoglobin value (n=4, 8%). Other reasons for temporary deferral were history of medication (n=3, 6%), low platelet count (n=4,8%), history of blood transfusion (n=1, 2%), history of vaccination n=2, 4%), leucocytosis (n=1, 2%), underweight (n=4, 8%), fever (n=1, 2%), refusal after questionnaire (n=1, 2%), seropositive for malaria and VDRL (n=3, 6%), high blood pressure (n=1, 2%), and anxiety (n=1, 2%). Permanent reasons for deferral were seropositive for HbsAg (n=2, 4%), seropositive for HCV (n=4, 8%) and tattoo (n=1, 2%). Conclusion: This study found a pattern of donor deferral in single donor platelet apheresis that was our experience in single centre. In conclusion during the selection of donors, Transfusion services should be very careful related to donor safety measures and these causes of deferral should be kept in mind.

Change in Antinuclear Antibody Titers during Biologic Treatment for Psoriasis.

We previously evaluated blood screening data, including antinuclear antibodies (ANA), before initiating biologic treatment for patients with psoriasis in a real-world setting. However, we did not analyze change in ANA titers after the start of biologics. No previous study has comprehensively investigated change in ANA titers over time in individual patients or the effectiveness of certolizumab pegol or tildrakizumab. This study evaluated change in ANA titers in individual patients during treatment with biologics, including certolizumab pegol and tildrakizumab. 111 patients were included in this study. Change in ANA was regarded as significant when the ANA titer was ×80 or more in patients with a previously undetectable ANA titer or when it increased by fourfold or more in those with a detectable ANA titer before treatment. The ratios of patients with a significant change in ANA titer who were treated with a tumor necrosis factor (TNF) inhibitor, interleukin (IL) -17 inhibitor, or IL-23 inhibitor were 34.9% (15/43), 0.0% (0/32), and 0.0% (0/36), respectively. There were 4 patterns of significant change in ANA titer: (i) an increase (n=8), (ii) a decrease after an increase (n=4), (iii) a decrease after an increase with a drug change (n=2), and (iv) an increase after a decrease after an increase (n=1). No symptom suggesting lupus syndrome was noted. ANA titers must be carefully monitored throughout treatment with biologics, especially TNF inhibitors, and the possibility of lupus-like syndrome should be excluded.

Screening for possible hypopituitarism following mild traumatic brain injury: The first all-female study. Who do we need to evaluate further?

Studies on hypopituitarism (HP) following mild traumatic brain injury (mTBI) have focused on male populations although women may be more susceptible to the sequelae of mTBI. This is, to the best of our knowledge, the first all-female study screening for HP following mTBI. Screening for possible HP in female athletes reporting a history of one or more mTBI. Pituitary hormone screening blood tests (SBT) were performed in 133 of the 151 female athletes included. Repeated results outside the reference value (O-RV) were considered abnormal necessitating further endocrinological evaluation. Repeated SBT were O-RV in 88 women (66.2%). Decreased levels of serum insulin growth factor 1 (S-IGF1) were found in 55.6% of participants and elevated levels of serum prolactin (S-prolactin) in 22.6%. Serum cortisol levels were below the RV in 6.0% and thyroid hormonal levels in 11.3%. Lower age and increased number of mTBI symptoms correlated significantly with the risk of hormonal results O-RV. The majority of the study population had SBT O-RV, warranting further workup of possible HP. Decreased levels of S-IGF1 were most commonly observed followed by elevated S-prolactin possibly indicating hypothalamic-pituitary impairment. Lower age and increased number of symptoms of mTBI may indicate the need to screen for HP.

Risk of Target Organ Damage in Children With Primary Ambulatory Hypertension: A Systematic Review and Meta-Analysis.

Target organ damage (TOD) such as left ventricular hypertrophy (LVH), abnormal pulse wave velocity, and elevated carotid intima-media thickness are common among adults with hypertension and are associated with overt cardiovascular events. The risk of TOD among children and adolescents with hypertension confirmed by ambulatory blood pressure monitoring is poorly understood. In this systematic review, we compare the risks of TOD among children and adolescents with ambulatory hypertension to normotensive individuals. A literature search was conducted to include all relevant English-language publications from January 1974 to March 2021. Studies were included if patients underwent 24-hour ambulatory blood pressure monitoring and ≥1 TOD was reported. Ambulatory hypertension was defined by society guidelines. Primary outcome was the risk of TOD, including LVH, left ventricular mass index, pulse wave velocity, and carotid intima-media thickness among children with ambulatory hypertension compared with those with ambulatory normotension. Meta-regression calculated the effect of body mass index on TOD. Of 12 252 studies, 38 (n=3609 individuals) were included for analysis. Children with ambulatory hypertension had an increased risk of LVH (odds ratio, 4.69 [95% CI, 2.69-8.19]), elevated left ventricular mass index (pooled difference, 5.13 g/m2.7; [95% CI, 3.78-6.49]), elevated pulse wave velocity (pooled difference, 0.39 m/s [95% CI, 0.20-0.58]), and elevated carotid intima-media thickness (pooled difference, 0.04 mm [95% CI, 0.02-0.05]), compared with normotensive children. Meta-regression showed a significant positive effect of body mass index on left ventricular mass index and carotid intima-media thickness. Children with ambulatory hypertension have adverse TOD profiles, which may increase their risk for future cardiovascular disease. This review highlights the importance of optimizing blood pressure control and screening for TOD in children with ambulatory hypertension. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020189359.

A Novel Approach on the Use of Samples from Faecal Occult Blood Screening Kits for Metabolomics Analysis: Application in Colorectal Cancer Population.

The incidence of colorectal cancer (CRC) is increasing, and currently it is the third most common cancer. Early CRC diagnosis is still difficult and relies on an invasive colonoscopy and tissue biopsy. The globally observed tendency demands non-invasive, specific, and accurate diagnostic tools for early diagnosis and prognosis. In this work, the main aim was to evaluate for the first time the feasibility of using extracts from the non-invasive sample collection from faecal occult blood (FOB) kits for its use in metabolomics studies taking advantage in this way of the high sensitivity of this technology. Then, a cohort of 131 samples from control individuals (CTL), adenoma (AD) and CRC patients were analysed using a semitargeted approach by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry (UHPLC-ToF-MS). Multivariate and univariate statistical analysis revealed that cholesteryl esters (ChoE) with polyunsaturated fatty acids (PUFAs) together with FOB were relevant metabolites that could clearly separate CRC patients from AD and CTL individuals, whereas the metabolic profiles of CTL and AD were very similar. These results are in agreement with previous findings and reveal the advantage of using the same FOBT samples for several analyses, which would facilitate sample collection and improve direct connection between FOB measurements and metabolomics analysis. Although the sample size and the number of metabolites should be enhanced to cover a wider range of metabolites, alterations in lipid metabolism clearly point out for future perspectives.

A mathematical and exploratory data analysis of malaria disease transmission through blood transfusion

Malaria is a mosquito-borne disease spread by an infected vector (infected female Anopheles mosquito) or through transfusion of plasmodium-infected blood to susceptible individuals. The disease burden has resulted in high global mortality, particularly among children under the age of five. Many intervention responses have been implemented to control malaria disease transmission, including blood screening, Long-Lasting Insecticide Bed Nets (LLIN), treatment with an anti-malaria drug, spraying chemicals/pesticides on mosquito breeding sites, and indoor residual spray, among others. As a result, the SIR (Susceptible—Infected—Recovered) model was developed to study the impact of various malaria control and mitigation strategies. The associated basic reproduction number and stability theory is used to investigate the stability analysis of the model equilibrium points. By constructing an appropriate Lyapunov function, the global stability of the malaria-free equilibrium is investigated. By determining the direction of bifurcation, the implicit function theorem is used to investigate the stability of the model endemic equilibrium. The model is fitted to malaria data from Benue State, Nigeria, using R and MATLAB. Estimates of parameters were made. Following that, an optimal control model is developed and analyzed using Pontryaging's Maximum Principle. The malaria-free equilibrium point is locally and globally stable if the basic reproduction number (R0) and the blood transfusion reproduction number (Rα) are both less or equal to unity. The study of the sensitive parameters of the model revealed that the transmission rate of malaria from mosquito-to-human (βmh), transmission rate from humans-to-mosquito (βhm), blood transfusion reproduction number (Rα) and recruitment rate of mosquitoes (bm) are all sensitive parameters capable of increasing the basic reproduction number (R0) thereby increasing the risk in spreading malaria disease. The result of the optimal control shows that five possible controls are effective in reducing the transmission of malaria. The study recommended the combination of five controls, followed by the combination of four and three controls is effective in mitigating malaria transmission. The result of the optimal simulation also revealed that for communities or areas where resources are scarce, the combination of Long Lasting Insecticide Treated Bednets (u2), Treatment (u3), and Indoor insecticide spray (u5) is recommended. Numerical simulations are performed to validate the model's analytical results.

Rhesus (Rh) blood group antigens in multiparous women attending antenatal clinic in tertiary hospital, port harcourt, Nigeria

The routine blood screening test carried out for pregnant women attending antenatal clinic in Tertiary Hospital Port Harcourt, Nigeria especially with regards to blood group system is limited to ABO/Rh D antigen screening. This cross-sectional, hospital-based study was aimed at determining the prevalence of the Rh C, c, E and e blood group antigens in multiparous women attending antenatal clinic in Tertiary Hospital Port Harcourt, Nigeria. A total of one hundred and twenty (120) pregnant females within the age range of 18-40years were recruited randomly into the study between February-June, 2022. Blood samples were aseptically collected by venipuncture into EDTA sample bottle; Rh C, c, E and e blood group antigens were assay for using microwell agglutination technique. Data generated was statistically analyzed by simple percentage calculation and defining the percentage frequency of Rh antigens. Results obtained showed the percentage distribution of 17.5% for Rh C, 89.2% for Rh c, 39.2% for Rh E and 90.8% for Rh-e. Percentage distribution of Rh antigens amongst studied population based on parity showed that G3P2 group had the highest percentage positivity of 8(6.7%) for Rh-C antigen while those carrying their first pregnancy (prime) had the highest percentage positivity of 33(27.5%), 15(12.5%) and 36(30.0%) for Rh-c, Rh-E and Rh-e respectively. Distribution of Rh antigens with respect to previous transfusion history in studied participants showed 6 (5.0%), 15 (12.5%), 6 (5.0%) and 17 (14.2%) percentage positivity for Rh-C, Rh-c, Rh-E and Rh-e respectively. This study revealed a percentage positivity of 17.5%, 89.2%, 39.2 % and 90.8% for Rh-C, Rh-c, Rh-E and Rh-e respectively with high percentage expression for Rh-c, E and e antigens found on the red cells of Antennal Women carrying their first pregnancy. Furthermore, there is a high percentage expression of Rh antigens in previously transfused pregnant women in this study. Although routine phenotyping of these blood group antigens will be a financial burden in a resource limited country like Nigeria. It is expedient and needful to take into cognizance the fact that the presence of Rh C, c, E and e antigens may likely be the cause of some delayed transfusion reactions and haemolytic disease of the foetus and new born. Therefore, there is need for the inclusion of Rh C, c, E and e in routine antigen typing for pregnant women in other to help ameliorate red blood cell alloimmunization and delayed haemolytic transfusion reaction during pregnancy. Furthermore, there is need to promulgate policies that promote the optimum stocking of Rh-e, c antigen negative blood in blood banks in the area for emergency use.

ПРЕНАТАЛЬНЫЙ И НЕОНАТАЛЬНЫЙ СКРИНИНГ НОВОРОЖДЕННЫХ

Thorough observation after childbirth and additional examination of newborns based on prenatal and neonatal screening, including the screening of blood, hearing, congenital heart defects and other organs and systems, and in case of indications for hereditary diseases - the genetic examination, does allow not only at the clinical, but also at the pre-clinical stage the planning of preventive and therapeutic measures for newborns and early-age children. This read offers a working algorithm for prenatal and neonatal screening of newborns.

The Evolution of the Safety of Plasma Products from Pathogen Transmission-A Continuing Narrative.

Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is an essential part of the large-scale manufacture of these products and is required for good manufacturing practice (GMP). Early observations of the transmission of hepatitis by pooled plasma and serum led to the incorporation of heat treatment of the albumin solution produced by industrial Cohn fractionation of plasma. This led to an absence of pathogen transmission by albumin over decades, during which hepatitis continued to be transmitted by other early plasma fractions, as well as through mainstream blood transfusions. This risk was decreased greatly over the 1960s as an understanding of the epidemiology and viral aetiology of transfusion-transmitted hepatitis led to the exclusion of high-risk groups from the donor population and the development of a blood screening test for hepatitis B. Despite these measures, the first plasma concentrates to treat haemophilia transmitted hepatitis B and other, poorly understood, forms of parenterally transmitted hepatitis. These risks were considered to be acceptable given the life-saving nature of the haemophilia treatment products. The emergence of the human immunodeficiency virus (HIV) as a transfusion-transmitted infection in the early 1980s shifted the focus of attention to this virus, which proved to be vulnerable to a number of inactivation methods introduced during manufacture. Further developments in the field obviated the risk of hepatitis C virus (HCV) which had also infected chronic recipients of plasma products, including haemophilia patients and immunodeficient patients receiving immunoglobulin. The convergence of appropriate donor selection driven by knowledge of viral epidemiology, the development of blood screening now based on molecular diagnostics, and the incorporation of viral inactivation techniques in the manufacturing process are now recognised as constituting a "safety tripod" of measures contributing to safety from pathogen transmission. Of these three components, viral inactivation during manufacture is the major contributor and has proven to be the bulwark securing the safety of plasma derivatives over the past thirty years. Concurrently, the safety of banked blood and components continues to depend on donor selection and screening, in the absence of universally adopted pathogen reduction technology. This has resulted in an inversion in the relative safety of the products of blood banking compared to plasma products. Overall, the experience gained in the past decades has resulted in an absence of pathogen transmission from the current generation of plasma derivatives, but maintaining vigilance, and the surveillance of the emergence of infectious agents, is vital to ensure the continued efficacy of the measures in place and the development of further interventions aimed at obviating safety threats.

Analysis of clinical features, biochemical indices and genetic variants among children with Short/branched-chain acyl-CoA dehydrogenase deficiency detected by neonatal screening

To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.

Voles, shrews and red squirrels as sources of tick blood meals and tick-borne pathogens on an island in southwestern Finland

Molecular identification of the previous blood meal source of a questing tick (Acari: Ixodidae) from blood meal fragments was proposed a few decades ago. Following this, several blood meal assays have been developed and published, but none of them have been taken into widespread use. Recently, novel retrotransposon-based qPCR assays designed for detecting blood meal fragments of North American host species were published. We wanted to assess their function with host species present in Finland.Questing ticks were collected by cloth dragging in August-September 2021 from an island in southwestern Finland. DNA was extracted from Ixodes ricinus nymphs (n=438) and qPCR assays applied to identify larval blood meal sources (voles, shrews and red squirrels) and screen for several tick-borne human pathogens and other microbes with pathogenic potential [Borrelia spp. (including specific assays for Borrelia afzelii, Borrelia garinii, Borrelia valaisiana), Anaplasma phagocytophilum, Babesia spp., Rickettsia spp., and Neoehrlichia mikurensis].The probability of a nymph having fed as larva on either a vole, shrew or red squirrel was 0.34 (0.30 – 0.38; 95% confidence interval). Bacteria of the genus Borrelia were the most common pathogens detected, with host-specific probabilities of carrying Borrelia of 0.30 (0.18 – 0.44) for nymphs that had fed on voles, 0.23 (0.14 – 0.35) for nymphs that had fed on shrews, and 0.42 (0.28 – 0.58) for nymphs that had fed on red squirrels. Other microbes were rarely acquired from these hosts, apart from N. mikurensis from voles.This study highlights that shrews and red squirrels may equal voles as blood meal sources for I. ricinus larvae. Overall, variation in proportions of blood meals provided by these animals may be high across even proximate study areas. All studied host species appeared to be important sources for particularly Borrelia afzelii, and voles also for N. mikurensis.

Parasite detection and quantification in avian blood is dependent on storage medium and duration.

Studies of parasites in wild animal populations often rely on molecular methods to both detect and quantify infections. However, method accuracy is likely to be influenced by the sampling approach taken prior to nucleic acid extraction. Avian Haemosporidia are studied primarily through the screening of host blood, and a range of storage mediums are available for the short- to long-term preservation of samples. Previous research has suggested that storage medium choice may impact the accuracy of PCR-based parasite detection, however, this relationship has never been explicitly tested and may be exacerbated by the duration of sample storage. These considerations could also be especially critical for sensitive molecular methods used to quantify infection (qPCR). To test the effect of storage medium and duration on Plasmodium detection and quantification, we split blood samples collected from wild birds across three medium types (filter paper, Queen's lysis buffer, and 96% ethanol) and carried out DNA extractions at five time points (1, 6, 12, 24, and 36 months post-sampling). First, we found variation in DNA yield obtained from blood samples dependent on theirstorage medium which had subsequent negative impacts on both detection and estimates of Plasmodium copy number. Second, we found that detection accuracy (incidence of true positives) was highest for filter-paper-stored samples (97%), while accuracy for ethanol and Queen's lysis buffer-stored samples was influenced by either storage duration or extraction yield, respectively. Lastly, longer storage durations were associated with decreased copy number estimates across all storage mediums; equating to a 58% reduction between the first- and third-year post-sampling for lysis-stored samples. These results raise questions regarding the utility of standardizing samples by dilution, while also illustrating the critical importance of considering storage approaches in studies of Haemosporidia comparing samples subjected to different storage regimes and/or stored for varying lengths of time.

A rare case of clinically significant naturally occurring anti-Cw reported in a healthy male donor.

Anti-Cw antibody is an immunoglobulin against the red cell antigen Cw which is a low frequency red cell antigen that belongs to the Rh antigen system. It is a clinically significant antibody and may cause haemolysis on exposure to antigen positive red cells. Due to its low frequency, it is not included in routine antibody screening panels. A 32years healthy male donor with no history of transfusion donated whole blood at the department of Transfusion Medicine & Blood Centre of our institute. As a part of routine pre-transfusion testing, the donor's samples were subjected to automated blood grouping and screening for unexpected red cell antibodies using 3 cells panel on solid-phase red-cell adherence (SPRCA) (Galileo Neo, Immucor, Norcross, USA). The antibody screening came out to be positive with a reaction in cell I of the antibody screening panel. Further the antibody was identified as anti Cw in using 16 cells panel, select cells and phenotyping. In the present case, the anti-Cw antibody was found to be reactive at 37°C and AHG phase which could lead to haemolytic transfusion reaction. The fact that the male donor had no history of transfusion or transplant led us to the conclusion that it was a naturally occurring, but a clinically significant antibody. This case highlights the importance of performing an antibody screening for healthy donors as well and urges transfusion services to procure screening cells which incorporate Cw positive cells.

Modeling the Risk of HIV Transfusion Transmission.

Blood donations are routinely screened for HIV to prevent an infectious unit from being released to the blood supply. Despite improvements to blood screening assays, donations from infected donors remain undetectable during the window period (WP), when the virus has not yet replicated above the lower limit of detection (LOD) of a screening assay. To aid in the quantitative risk assessments of WP donations, a dose-response model describing the probability of transfusion-transmission of HIV over a range of viral RNA copies was developed. An exponential model was chosen based on data fit and parsimony. A data set from a HIV challenge study using a nonhuman primate model and another data set from reported human blood transfusions associated with HIV infected donors were separately fit to the model to generate parameter estimates. A Bayesian framework using No-U-Turn Sampling (NUTS) and Monte Carlo simulations was performed to generate posterior distributions quantifying uncertainty in parameter estimation and model predictions. The parameters of the exponential model for both nonhuman primate and human data were estimated with a mean (95% credible intervals) of 2.70 × 10 -2 (7.74 × 10 -3 , 6.06 × 10 -2 ) and 7.56 × 10 -4 (3.68 × 10 -4 , 1.31 × 10 -3 ), respectively. The predicted ID 50 for the animal and human models was 26 (12, 90) and 918 (529, 1886) RNA copies transfused, respectively. This dose-response model can be used in a quantitative framework to estimate the probability of transfusion-transmission of HIV through WP donations. These models can be especially informative when assessing risk from blood components with low viral load.

Clinical performance of a multimodal screening blood test for advanced adenomas and CRC in an average-risk cohort of 1,038 participants.

75 Background: The National Polyp Study and 2021 USPSTF CRC-update highlight that the detection and removal of precancerous advanced adenomas (AA) prevents colorectal cancer (CRC), decreases mortality, and leads to higher cost savings than early cancer detection. Performance of a multimodal blood-based test for the detection of CRC and AA that integrates sensitive and accurate detection of circulating gastrointestinal epithelial cells and somatic oncologic variants as well as SEER data of the impact of sex and age is described. Methods: The prospective study included average-risk, asymptomatic screening subjects from 18 geographically dispersed US colonoscopy centers with blood drawn before colonoscopy. Monte Carlo cross-validation (MCCV) methods were used to evaluate the robustness of test performance through 2000 iterations of independent training and validation using bootstrap resampling with stratification to balance patient histopathology, age, and gender. Results include point estimates, confidence intervals, and distributions of sensitivity and specificity to detect AA and CRC. Results: The study cohort (53.2% female; mean age 56.7 yrs.) consisted of 1,038 subjects (White 65.1%; Black 8.5%; Hispanic 24.8%; Asian 1.7%); of which 954 (92%) were asymptomatic, average-risk screening subjects without age enrichment (including 11 CRC and 93 AA) and 84 (8%) were enriched case-control (65 CRC and 19 AA) subjects. The algorithm derives a test score from 0 (low risk) to 100 (high risk) as a quantitative measure of AA and CRC risk. A pre-defined cut point of 47.2 yields a test specificity > 90%, and 92.1% and 54.5% sensitivity for the detection of CRC and AA, respectively. Estimated sensitivities and selected Clopper-Pearson (Exact) 95% confidence intervals based on validation results from MCCV are presented. A split analysis shows for the 954 intended-use, asymptomatic, average-risk screening subjects, the sensitivity for CRC and AA are 100% and 55.9%. Conclusions: A multi-site, prospective, average-risk CRC screening study using a multimodal assay had high sensitivity and specificity for AA and CRC. The quantitative correlation of test scores with disease pathology indicates that the modes of the assay interrogate the primary underlying pathophysiology of disease. The results demonstrate the potential of this novel test to meet the clinically unmet need for a noninvasive strategy for CRC screening and prevention that detects CRC and AA. Clinical trial information: NCT05127096 . [Table: see text]

Effectiveness of Using Nucleic Acid Amplification Test to Screen Blood Donors for Hepatitis B, Hepatitis C, and HIV: A Tertiary Care Hospital Experience From Pakistan.

Background Ensuring blood safety is the primary goal of transfusion medicine. Despite extensive serological tests and strict safety measures, the risk of transfusion-transmitted infections (TTIs) still exists. As applied to blood screening, Nucleic Acid Amplification Test (NAT)offers much higher sensitivity for detecting viral infections. It is, however, currently available to a handful of centers due to the high cost. This study aims to establish the Effectiveness of NAT by assessing the NAT yield and residual risk of transmission of Hepatitis B virus (HBV), hepatitis C virus (HCV)and HIV with and without NAT testing. Material and method This prospective cross-sectional study recruited blood donors from January 2020 to November 2022. All donors underwent routine serologic screening. Only serologically negative donors were tested for HBV, HCV, and HIV by NAT. The NAT yield and residual risk (RR) per million donors were computed for viral infections in seronegative blood donors and calculated using the incidence/window period model. Result A total of 59708 donors were included during the study period. The overall prevalence of TTI's were: For HCV 1.7% (n = 1018), HBV 1.5% (n = 918), HIV 0.07% (n = 47), Syphilis 1.2% (n = 758) and malaria 0.3% (n = 218). Out of 57759 seronegative donors, thirty-four NAT-reactive samples were identified, with 3 cases of HCV, 31 cases of HBV, and Nil HIV cases. NAT yield of HBV was 1 in 1863 with an RR of 8.6 per million, followed by HCV with a NAT yield of 1 in 19253 and RR of 0.8 per million donations. NAT testing reduced RR for HBV by 48.9% and HCV by 94.5%. Conclusion Our study showed that NAT detected 34 out of 57759 cases initially missed by serological tests. The study suggests that the parallel use of serology and NAT screening of donated blood would be beneficial.

Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis.

The association between Hymenoptera venom-triggered anaphylaxis (HVA) and clonal mast cell-related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom-triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from 'how many patients with cMCD have anaphylaxis?' to 'how many patients with anaphylaxis have cMCD?'. The discovery of hereditary α-tryptasemia (HαT)-a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene-, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk=2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β -tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell-related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.

Multicenter evaluation of the new Alinity s anti-HCV II assay for routine hepatitis C virus blood screening

BackgroundAnti-HCV immunoassays remain the primary serologic test for HCV screening among blood donors. Since 1990s, Anti-HCV assays have evolved and those currently available detect infection earlier and have improved sensitivity and specificity compared with older generation assays. The new Alinity s Anti-HCV II assay, with its innovative design, has improved sensitivity, which shall further enhance safety of blood. MethodsAlinity s Anti-HCV II assay was evaluated at 2 blood services (HKRCBTS & SNBTS). The overall sensitivity was evaluated using known positive samples (n = 5 at HKRCBTS; 50 at SNBTS) and 3 seroconversion panels (panel members =14 at each site). A total of 7,532 blood donor samples were tested to determine the clinical specificity. ResultsThe clinical sensitivity of the new assay was found to be 100% at both sites. HCV seroconversion panel detection rates were 57.1% (8/14) and 14.3% (2/14) for the Alinity s Anti-HCV II and Anti-HCV assays respectively, resulting in an improvement in seroconversion sensitivity of 42.8% for the Anti-HCV II assay over the Anti-HCV assay. The specificity of the Anti-HCV II assay was 100% at HKRCBTS, and 99.95% at SNBTS. ConclusionsThe Anti-HCV II assay detected all known positive specimens and was able to detect samples in seroconversion panels earlier compared to the Anti-HCV assay. The assay showed excellent clinical specificity and generated fewer false-reactive results and was found to be suitable for routine blood donor screening.

A chemiluminescence based approach to nucleic acid testing to detect HBV, HCV, and HIV-1 in blood screening

Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are life-threatening blood-borne infections that can be unintentionally transmitted in transfused blood products. Here, we optimized a method for detecting HBV, HCV, and HIV-1 in blood screening using magnetic nanoparticles (MNPs) and polymerase chain reaction (PCR)-chemiluminescence. Viral genomes were extracted from donated blood samples using MNPs. The isolated viral DNA and RNA were amplified in a one-step parallel reverse transcription-PCR (RT-PCR). HBV, HCV, and HIV-1 were detected using complementary nucleic acid probes and quantified using a chemiluminescent substrate. 10 422 donated blood samples were tested both with the above method and Roche Cobas TaqScreen MPX Test. The lengths of the amplified PCR products for HBV, HCV, and HIV-1 were 119 bp, 220 bp, and 174 bp, respectively, indicating that the extraction methods successfully separated high-quality viral genomes from the serum samples. The probes and reaction conditions used for the chemiluminescent detection of HBV, HCV, and HIV-1 genomes in unknown samples were empirically optimized. Of the 10 422 blood samples screened, 12 were HBV positive and 2 were HCV positive. These results were consistent with those of a parallel-controlled study using Roche Cobas TaqScreen MPX Test. The assay described here is fast, accurate, and sensitive for detecting HBV, HCV, and HIV, which runs in parallel and has broad implications for blood screening and epidemiological studies.

Brown Tumors of the Jaws: A Retrospective Study.

(1) Describe the clinical spectrum, imaging features, management, and outcome of brown tumors (BT) of the jaws. (2) Determine via a literature review the facts and controversies around the characteristics and management of this lesion. Our study was approved by the institutional committee of Sahloul University Hospital in accordance with the ethical standards of the Declaration of Helsinki. Sixteen patients with BT in the context of a primary, secondary, and tertiary hyperparathyroidism were treated and followed up during their recovery. This study reports 16 patients with a mean age of 48 years old. Brown tumor lesions were associated with primary hyperparathyroidism in 6 cases (38%), secondary hyperparathyroidism to chronic kidney failure in 5 cases (31%), and tertiary hyperparathyroidism in the context of a long lasting CRI in 5 cases. Their location was maxillary in 7 cases, mandibular in 5 cases, and bimaxillary in 4 cases. The treatment consisted of parathyroidectomy in 13 patients, maxillary resection in 3 cases, and vitamin D treatment in 2 cases. Favorable outcomes, characterized by tumor regression, were reported in 9 cases, whereas unfavorable evolution was observed among 7 patients. Parathyroidectomy is the gold standard treatment for primary hyperparathyroidism. It resulted in a total regression in all our cases. Regarding secondary hyperparathyroidism, blood screening and chronic renal insufficiency follow-up are critically valuable to detect this condition at an early stage, hence increasing the success rate of brown tumor regression. Our secondary and tertiary hyperparathyroidism results were miscellaneous; although it is important to emphasize the importance of the chronic renal insufficiency management to ensure a success. Brown tumors should be included in the differential diagnosis of giant cell lesions. Parathyroidectomy is usually sufficient to induce the total regression of the lesion in primary hyperparathyroidism cases. A more delicate approach is needed regarding secondary hyperparathyroidism. Meticulous control of chronic renal insufficiency is mandatory in addition to parathyroidectomy.