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OBJECTIVE: To assess for improvement in diagnostic efficiency following implementation of an institutional pediatric stroke alert protocol at a quaternary children's hospital, and to compare characteristics of in-hospital (IH) and out-of-hospital (OH) stroke alert activations. STUDY DESIGN: We retrospectively reviewed data from pediatric stroke alerts called for children between age 1 month to 21 years of age at our quaternary children's hospital between October 2016 and October 2022 after implementation of an institutional stroke alert protocol. Generalized linear models assessed code-to-image (CTI) time over the study period, with and without interaction terms for alert location. Demographic, clinical, and imaging characteristics between IH and OH alerts were compared using Fisher's exact test or Mann-Whitney U test. RESULTS: Of 206 total stroke activations, 129 (62.6%) occurred IH and 77 (37.4%) occurred OH. Overall mean CTI time decreased by 4.56 minutes per year (p = 0.007) after adjusting for confounders. The association between year and mean CTI time was significantly stronger for IH alerts (decrease of 8.33 minutes/year) compared with OH alerts (increase of 1.90 minutes/year). Subgroup analyses showed that CTI for computed tomography (CT) ± CT angiography and magnetic resonance imaging (MRI) without sedation improved, although CTI time for MRI with sedation did not change over time. IH/OH divergent trends were consistent for CT ± CTA and non-sedated MRI. CONCLUSION: After implementation of a pediatric stroke alert protocol, we observed a steady and significant improvement in CTI times for IH, but not OH alerts.
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Cancer develops when multiple systems fail to suppress uncontrolled cell proliferation. Breast cancers and oesophageal squamous cell carcinoma (OSCC) are common cancers prone to genetic instability. They typically occur in acidic microenvironments which impacts on cell proliferation, apoptosis, and their influence on surrounding cells to support tumour growth and immune evasion. This study aimed to evaluate the impact of the acidic tumour microenvironment on the production of pro-tumorigenic and immunomodulatory factors in cancer cell lines. Multiple factors that may mediate immune evasion were secreted including IL-6, IL-8, G-CSF, IP-10, GDF-15, Lipocalin-2, sICAM-1, and myoglobin. Others, such as VEGF, FGF, and EGF that are essential for tumour cell survival were also detected. Treatment with moderate acidity did not significantly affect secretion of most proteins, whereas very low pH did. Distinct differences in apoptosis were noted between the cell lines, with WHCO6 being better adapted to survive at moderate acid levels. Conditioned medium from acid-treated cells stimulated increased cell viability and proliferation in WHCO6, but increased cell death in MCF-7. This study highlights the importance of acidic tumour microenvironment in controlling apoptosis, cell proliferation, and immune evasion which may be different at different anatomical sites. Immunomodulatory molecules and growth factors provide therapeutic targets to improve the prognosis of individuals with cancer.
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Neoplasias de la Mama , Neoplasias Esofágicas , Humanos , Femenino , Supervivencia Celular , Línea Celular Tumoral , Neoplasias de la Mama/patología , Proliferación Celular/genética , Neoplasias Esofágicas/metabolismo , Ciclo Celular , Microambiente TumoralRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) infection is prevalent in Africa and causes morbidity and mortality despite antiretroviral therapy (ART). Non-communicable complications of HIV infection include cardiovascular disease (CVD) with thromboses throughout the vascular tree. Ongoing inflammation and endothelial dysfunction in people living with HIV (PLWH) probably contribute significantly to HIV-related CVD. OBJECTIVES: A systematic review was conducted to inform interpretation of 5 biomarkers commonly measured in PLWH namely interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), D-dimers, and soluble intracellular and vascular adhesion molecules-1 (sICAM-1 and sVCAM-1) to attempt to define a range for these values in ART naïve PLWH without overt CVD or additional comorbid diseases. METHODS: A systematic search was conducted for all studies documenting the levels of the above biomarkers in ART naïve PLWH published on the PubMed database from 1994 to 2020. RESULTS: The number of publications that reported medians above the assay values was: 4/15 for D-dimer; 0/5 for TNF-α, 8/16 for IL-6, 3/6 for sVCAM-1, and 4/5 for sICAM-1. CONCLUSION: The clinical utility of biomarkers is reduced by the lack of standardisation of the measurement of these parameters, absence of normal reference indices and the lack of uniformity of study protocols in different research centres. This review supports the ongoing use of D-dimers to predict thrombotic and bleeding events in PLWH since the weighted averages across study assays suggest that the median levels do not exceed the reference range. The role of inflammatory cytokine monitoring and measurement of endothelial adhesion markers is less clear.
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Enfermedades Cardiovasculares , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Interleucina-6 , Factor de Necrosis Tumoral alfa/uso terapéutico , Biomarcadores , VIHRESUMEN
Current biomarkers to assess the risk of complications of both acute and chronic viral infection are suboptimal. Prevalent viral infections like human immunodeficiency virus (HIV), hepatitis B and C virus, herpes viruses, and, more recently, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may be associated with significant sequelae including the risk of cardiovascular disease, other end-organ diseases, and malignancies. This review considers some biomarkers which have been investigated in diagnosis and prognosis of key viral infections including inflammatory cytokines, markers of endothelial dysfunction and activation and coagulation, and the role that more conventional diagnostic markers, such as C-reactive protein and procalcitonin, can play in predicting these secondary complications, as markers of severity and to distinguish viral and bacterial infection. Although many of these are still only available in the research setting, these markers show promise for incorporation in diagnostic algorithms which may assist to predict adverse outcomes and to guide therapy.
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COVID-19 , Virosis , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Virosis/diagnóstico , Biomarcadores , CitocinasRESUMEN
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a serious thrombotic microangiopathy (TMA), is prevalent in the South African HIV-infected population. The exact pathogenesis of HIV-associated TTP (HIV-TTP) is however still unclear with diagnostic and therapeutic inconsistancies. METHODS: A systematic review of the published literature regarding HIV-TTP was performed. RESULTS: HIV-TTP is still associated with significant morbidity and mortality in Africa despite the availability of anti-retroviral therpy (ART). Diagnosis of HIV-TTP requires the presence of a micro-angiopathic haemolytic anaemia with significant red blood cell schistocytes and thrombocytopenia in the absence of another TMA but background activation of the coagulation system and inflammation in HIV infected people can result in diagnostic anbiguity. Plasma therapy in the form of infusion or exchange is successful but expensive, associated with side-effects and not widely available. Adjuvant immunosuppression therapy may of benefit in patients with HIV-TTP and ART must always be optimised. Endothelial dysfunction caused by chronic inflammation and complement activation most likely contributes to the development of HIV-TTP. CONCLUSION: The role of adjuvant immunomodulating therpy, the therapeutic targets and pathogenic contribution from endothelial dysfunction in HIV-TTP requires further investigation.
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Infecciones por VIH , Púrpura Trombocitopénica Trombótica , Infecciones por VIH/complicaciones , Humanos , Inflamación , Plasma , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/terapiaRESUMEN
Coeliac disease (CD) is an autoimmune disorder and one of the few gastroenteropathies with accurate serological testing. CD serology has decreased accuracy for patients on a gluten-free diet and for monitoring mucosal healing. New ancillary tests would, therefore, be useful. Intestinal Fatty Acid Binding Protein (I-FABP) and CX3CL1 (Fractalkine) are two promising biomarkers for CD but haven't been examined in patients who are at a high-risk for CD such as patients with type one diabetes (TID). This study, therefore, aimed to investigate serum levels of I-FABP and CX3CL1 in a cohort of South African patients with TID at a high-risk of developing CD. The serum I-FABP levels were significantly higher in CD-positive patients compared to CD-negative individuals (p = 0.03). No significant differences in the serum CX3CL1 levels were detected although this may reflect the impact of the comorbid autoimmune diseases had on the serum CX3CL1 levels. In conclusion, this study is the first to assess the levels of these biomarkers in a multiethnic population with comorbid autoimmune disease and determined I-FABP to be the more promising biomarker in such clinical contexts. Future research should focus on a diverse biomarker panel and longitudinal follow-up of patients at a high-risk for CD.
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Enfermedad Celíaca , Biomarcadores , Enfermedad Celíaca/diagnóstico , Quimiocina CX3CL1 , Dieta Sin Gluten , Proteínas de Unión a Ácidos Grasos , Humanos , SudáfricaRESUMEN
BACKGROUND: Patients with Human Immunodeficiency Virus (HIV) infection are at risk of thrombotic microangiopathies (TMAs) notably thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). Overlap between laboratory results exists resulting in diagnostic ambiguity. METHODS: Routine laboratory results of 71 patients with HIV-associated TTP (HIV-TTP) and 81 with DIC with concomitant HIV infection (HIV-DIC) admitted between 2015 and 2021 to academic hospitals in Johannesburg, South Africa were retrospectively reviewed. Both the PLASMIC and the International Society of Thrombosis and Haemostasis (ISTH) DIC scores were calculated. RESULTS: Patients with HIV-TTP had significantly (P < .001) increased schistocytes and features of hemolysis including elevated lactate dehydrogenase (LDH)/upper-limit-of-normal ratio (median of 9 (interquartile range [IQR] 5-12) vs 3 (IQR 2-5)) but unexpectedly lower fibrinogen (median 2.8 (IQR 2.2-3.4) vs 4 g/L (IQR 2.5-9.2)) and higher D-dimer (median 4.8 (IQR 2.4-8.1) vs 3.6 g/L (IQR 1.7-6.2)) levels vs the HIV-DIC cohort. Patients with HIV-DIC were more immunocompromised with frequent secondary infections, higher platelet and hemoglobin levels, more deranged coagulation parameters and less hemolysis. Overlap in scoring systems was however observed. CONCLUSION: The laboratory parameter overlap between HIV-DIC and HIV-TTP might reflect a shared pathogenesis including endothelial dysfunction and inflammation and further research is required. Fibrinogen in DIC may be elevated as an acute phase reactant and D-dimers may reflect the extensive hemostatic activation in HIV-TTP. Inclusion of additional parameters in TMA scoring systems such the LDH/upper-limit-of-normal ratio, schistocytes count and wider access to ADAMTS-13 testing may enhance diagnostic accuracy and ensure appropriate utilization of plasma.
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Coagulación Intravascular Diseminada , Infecciones por VIH , Hemostáticos , Púrpura Trombocitopénica Trombótica , Microangiopatías Trombóticas , Proteína ADAMTS13 , Proteínas de Fase Aguda , Coagulación Intravascular Diseminada/diagnóstico , Infecciones por VIH/complicaciones , Hemoglobinas , Hemólisis , Humanos , Lactato Deshidrogenasas , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Estudios Retrospectivos , Sudáfrica , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiologíaRESUMEN
BACKGROUND: Guidelines recommend evaluation for electrographic seizures in neonates and children at risk, including after cardiopulmonary bypass (CPB). Although initial research using screening electroencephalograms (EEGs) in infants after CPB found a 21% seizure incidence, more recent work reports seizure incidences ranging 3-12%. Deep hypothermic cardiac arrest was associated with increased seizure risk in prior reports but is uncommon at our institution and less widely used in contemporary practice. This study seeks to establish the incidence of seizures among infants following CPB in the absence of deep hypothermic cardiac arrest and to identify additional risk factors for seizures via a prediction model. METHODS: A retrospective chart review was completed of all consecutive infants ≤ 3 months who received screening EEG following CPB at a single center within a 2-year period during 2017-2019. Clinical and laboratory data were collected from the perioperative period. A prediction model for seizure risk was fit using a random forest algorithm, and receiver operator characteristics were assessed to classify predictions. Fisher's exact test and the logrank test were used to evaluate associations between clinical outcomes and EEG seizures. RESULTS: A total of 112 infants were included. Seizure incidence was 10.7%. Median time to first seizure was 28.1 h (interquartile range 18.9-32.2 h). The most important factors in predicting seizure risk from the random forest analysis included postoperative neuromuscular blockade, prematurity, delayed sternal closure, bypass time, and critical illness preoperatively. When variables captured during the EEG recording were included, abnormal postoperative neuroimaging and peak lactate were also highly predictive. Overall model accuracy was 90.2%; accounting for class imbalance, the model had excellent sensitivity and specificity (1.00 and 0.89, respectively). CONCLUSIONS: Seizure incidence was similar to recent estimates even in the absence of deep hypothermic cardiac arrest. By employing random forest analysis, we were able to identify novel risk factors for postoperative seizure in this population and generate a robust model of seizure risk. Further work to validate our model in an external population is needed.
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Puente Cardiopulmonar , Paro Cardíaco , Puente Cardiopulmonar/efectos adversos , Niño , Electroencefalografía , Paro Cardíaco/complicaciones , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Convulsiones/diagnóstico , Convulsiones/epidemiología , Convulsiones/etiologíaRESUMEN
BACKGROUND: Kidney transplants are the only curative therapeutic intervention for end-stage kidney disease (ESKD). The current organ shortage in South Africa makes recipient risk assessments and effective laboratory workup crucial to assist in better organ assignment and increase the likelihood of better transplant outcomes. HLA typing is a step in the pre-transplant workup for performing virtual crossmatches and matching donors and recipients. Sequence Specific Oligonucleotide (SSO) PCR is a relatively fast and inexpensive method for determining genotypic HLA types at a 2- to 4-digit resolution. This study aimed to validate the SSO technique for achieving a 4-digit resolution when determining HLA types to improve virtual crossmatches. METHODS: DNA was extracted from 33 samples. After PCR amplification, the samples were hybridized to oligonu-cleotide probes and the HLA A, B, C, DRB1, DQA1/B1, DRB3, DRB4, DRB5, and DPA1/B1 types were identified. These results were compared to results from external laboratories. RESULTS: The kappa coefficient calculated for the low-resolution comparison suggested a perfect agreement between the two results (p = 0.32). CONCLUSIONS: SSO was successfully validated for HLA typing in the Johannesburg kidney transplant setting. This will improve the specificity of virtual crossmatches on an automated system by matching the resolution of the HLA typing and the HLA antibody testing. Additionally, common HLA types were identified in this donor cohort. Future research into these common HLA types and haplotypes in a South African population will inform the feasibility of reintroducing HLA matching into the pretransplant workup.
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Trasplante de Riñón , Alelos , Antígenos HLA/genética , Prueba de Histocompatibilidad , Humanos , Oligonucleótidos/genética , SudáfricaRESUMEN
BACKGROUND: Verification of the performance of analytical platforms is indicated prior to adoption of new Technology for patient sample analysis. Acceptance criteria for the performance of coagulation analytical platforms are not always readily available and is complicated by the multiple assays and test principles in this section of the clinical laboratory. Coagulation samples are also prone to pre-analytical, post-sample collection variables potentially interfering with accuracy analysis. METHODS: This verification study assessed the accuracy of the automated STAGO STA-R Max® coagulation analyzers by means of a comparison study of results obtained on the previously validated STAGO STA-R Evolution® analyzer for 22 coagulation parameters on 40 individual patient samples for each parameter. Within- and between- run reproducibility on commercial control material, carry-over from abnormal to normal samples and the interference of bilirubin, hemoglobin and lipids on the chromogenic analytical channel were also assessed. Ongoing evaluation of the analyzer performance was assessed by External Quality Assurance (EQA) scheme participation. RESULTS: The reproducibility (precision) on 2 levels (Normal and Pathological) commercial control material was acceptable with co-efficient of variance (CV) results below the manufacturer target % CVs. The correlation study demonstrated accuracy of results obtained on the analyzers for all parameters except for D-dimers and coagulation Factor VII. Subsequent EQA performance for these two parameters were however satisfactory. Interference from bilirubin, hemoglobin and lipids did occur in the chromogenic channel. No clinically significant carry over from abnormal to normal samples were observed. CONCLUSIONS: The performance of the STAGO STA-R Max® analyzer is acceptable across the full coagulation test repertoire with the exception of the von Willebrand activity assay. Participation in EQA scheme assessments will be an integral part of ongoing monitoring of the performance of this automated analyzer.
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Automatización de Laboratorios/instrumentación , Pruebas de Coagulación Sanguínea/instrumentación , Coagulación Sanguínea , Técnicas de Laboratorio Clínico/instrumentación , Garantía de la Calidad de Atención de Salud , Automatización de Laboratorios/métodos , Automatización de Laboratorios/normas , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Servicios de Laboratorio Clínico/normas , Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/normas , Humanos , Laboratorios/normas , Reproducibilidad de los Resultados , SudáfricaRESUMEN
BACKGROUND: Von Willebrand disease requires laboratory confirmation with quantitative and qualitative measurements of von Willebrand factor (VWF). Qualitative VWF-activity (VWF-Ac) tests have poor inter- and intra-laboratory reproducibility with coefficients of variation (CVs) as high as 64%, often lacking accuracy at low VWF-Ac levels. METHODS: This study evaluated the recently launched immunoturbidometric STAGO® STA-VWF:RCo® reagent for VWF-Ac. Accuracy was evaluated on 32 samples by comparing results using the Siemens® Innovance® reagent. An intra-run reproducibility study was performed on controls. Linearity and lower limit of detection was studied on external-quality-assurance (EQA) material with a known VWF-Ac level. RESULTS: STA-VWF:RCo® reagent results were within clinical interpretation agreement with Siemens® Innovance®. The reproducibility study yielded % CVs of 8.41 for normal and 11.46 for abnormal controls and the assay was linear between 73 and 14.6% and remained linear to 2% with extrapolation. CONCLUSIONS: The STAGO® STA-VWF:RCo® reagent showed clinically meaningful accuracy and acceptable precision.
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Pruebas de Coagulación Sanguínea/métodos , Técnicas de Laboratorio Clínico , Inmunoturbidimetría/métodos , Enfermedades de von Willebrand/diagnóstico , Factor de von Willebrand/análisis , Pruebas de Coagulación Sanguínea/normas , Femenino , Humanos , Inmunoturbidimetría/normas , Límite de Detección , Modelos Lineales , Masculino , Reproducibilidad de los Resultados , Enfermedades de von Willebrand/sangreRESUMEN
BACKGROUND: The G202010A prothrombin gene mutation is a documented prothrombotic risk factor in Caucasian patients. Several other mutations have been described within the prothrombin gene, predominantly in non-Caucasians, including the C20209T mutation. The clinical significance of this mutation is uncertain, but it has been associated with thrombotic events and pregnancy complications. METHODS: We describe a 28-year-old black South African woman who presented with pulmonary embolism during pregnancy. She was investigated for underlying prothrombotic biomarkers. RESULTS: Genetic screening for the prothrombin G202010A mutation by real-time polymerase chain reaction and melting curve analysis demonstrated an atypical mutant peak. Sequencing confirmed a variant C20209T prothrombin mutation. CONCLUSIONS: This is the first report of the C20209T mutation in the Southern African population. It remains uncertain whether genetic testing should be offered routinely to non-Caucasian patients in a resource-limited setting.
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Mutación , Complicaciones Hematológicas del Embarazo/genética , Protrombina/genética , Embolia Pulmonar/genética , Adulto , Población Negra/genética , Femenino , Humanos , Embarazo , Complicaciones Hematológicas del Embarazo/etnología , Embolia Pulmonar/etnología , SudáfricaRESUMEN
BACKGROUND: The thrombotic microangiopathies (TMAs) is a heterogeneous group of relatively uncommon but serious disorders presenting with thrombocytopenia and microangiopathic haemolysis. Thrombotic thrombocytopenic purpura (TTP) is one of these microangiopathic processes. HIV infection is an acquired cause of TTP but the pathogenesis is poorly understood. HIV-associated TTP was previously described to be associated with advanced immunosuppression. The incidence of HIV-related TTP was expected to decline with access to anti-retroviral therapy (ART). METHODS: We undertook an observational study of patients with a diagnosis of TTP admitted to our hospital (CMJAH). The patient demographics, laboratory test results and treatment outcomes were recorded. RESULTS: Twenty-one patients were admitted with a diagnosis of TTP during the study period. All patients had schistocytes and severe thrombocytopaenia. The presenting symptoms were non-specific and renal dysfunction and neurological compromise were uncommon. 77% of the patients were HIV-infected and, in 7 patients, TTP was the index presentation. The remainder of the HIV infected patients were on ART and the majority were virologically suppressed. A significant female preponderance was present. Only 4 of the 21 patients tested HIV negative with a positive Coombs test in 2. All patients in this cohort received treatment with plasma exchange therapy for a median period of 12 days with a 96.5% survival rate. Neither the baseline laboratory features nor the degree of immunosuppression was predictive of the duration of therapy needed for remission. CONCLUSION: HIV-related TTP is still a cause of morbidity and the clinical presentation is heterogeneous which may present a diagnostic challenge in the absence of sensitive biomarkers. Early treatment with plasma exchange is effective but expensive and invasive.
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BACKGROUND: Autoimmune paraphenomena, are associated with B-cell lymphoproliferative disorders, including monoclonal gammopathy of uncertain significance. These paraphenomena can rarely include acquired bleeding disorders. CASE PRESENTATION: This case study reports an unusual clinical presentation of 2 acquired bleeding disorders, Acquired von Willebrand syndrome (disease) and Acquired Glanzmann's thrombasthenia, in an elderly patient with monoclonal gammopathy of uncertain significance. CONCLUSIONS: Acquired bleeding disorders are often underdiagnosed and a high degree of clinical suspicion is required. The patient in this study demonstrated platelet aggregometry which was atypical for isolated Glanzmann's thrombosthenia because of the severe concomitant endogenous decrease in von Willebrand factor. There was an absence of platelet aggregation to all tested agonists including ristocetin. Once the diagnosis was made, however, the patient showed a partial response to intravenous immunoglobulin confirming the immunological pathogenesis in this case. This case highlights the need to consider acquired bleeding disorders in patients with a possible predisposing factor.
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BACKGROUND: Suitable laboratory testing prior to transplantation ensures that a patient's immunological risk is understood and allows the transplantation team to make the correct decisions on donor-recipient pairing. Preformed donor-specific anti-HLA antibodies mediate rejection in transplanted patients. Improved laboratory testing is needed to increase the chances of successful organ allocation. In this study, we show how Luminex™ single antigen assays are vital in determining immunological risk to transplantation and in predicting waiting time to transplantation. METHODS: Potential recipients awaiting renal transplantation (deceased donor) were tested using Luminex™ single antigen testing. HLA class I and II antibody specificities were determined, and patient demographics were analyzed for each blood group. Antibody reactivity was compared between patients who were transplanted or not transplanted in each blood group. Immunological risk to successful transplantation was determined retrospectively for all patients. RESULTS: Patient demographics were reported for the cohort. More males await renal transplantation than females (male:female ratio of 1.84:1). The median age of the patients was similar between the blood groups (between 41 and 44.5 years), as was the median time spent on the waiting list (between 3 - 4 years). Patients who were transplanted had significantly reduced HLA antibody expression compared to those who were not transplanted (total median reactivity 2 versus 8%, p = 0.0006). Patients were retrospectively stratified according to HLA antibody expression as a surrogate marker for immunological risk. Those in the high-risk group spent longer on the waiting list and had a low chance of being transplanted. CONCLUSIONS: Risk stratification can be used as a tool in predicting likelihood of successful transplantation. Laboratories in South Africa should move towards implementing highly sensitive, highly specific diagnostic assays in order to improve successful organ allocation. This will aid in standardizing testing algorithms in order to transplant more recipients.
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Antígenos HLA/inmunología , Prueba de Histocompatibilidad/métodos , Trasplante de Riñón/estadística & datos numéricos , Donantes de Tejidos , Listas de Espera , Adolescente , Adulto , Anciano , Niño , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sudáfrica , Adulto JovenRESUMEN
BACKGROUND: The validity of laboratory results depends on pre-analytical variables not detected by conventional quality control. Recommendations are for post-centrifugation coagulation samples to remain capped with cappiercing primary tube analysis. Total laboratory automation integrates analytical platforms with potential incompatibilities necessitating changes including pre-analytical uncapping of samples. METHODS: Samples analyzed for Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), D-dimers, Antithrombin and Fibrinogen at baseline, and after 60 and 120 minutes were left at ambient temperature, either re-capped or uncapped, in order to simulate changes from baseline that could occur in uncapped samples on an automation track prior to analysis. Changes were compared to the maximal permissible bias. RESULTS: Sample uncapping for up to 120 minutes at ambient temperature post-centrifugation did not result in clinically significant changes in routine coagulation parameters. CONCLUSIONS: Routine coagulation parameters will not change significantly if the primary citrate tubes are uncapped after centrifugation prior to analysis.
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Automatización de Laboratorios/métodos , Pruebas de Coagulación Sanguínea/métodos , Coagulación Sanguínea , Manejo de Especímenes/métodos , Antitrombinas/análisis , Pruebas de Coagulación Sanguínea/instrumentación , Centrifugación/métodos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Humanos , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Control de Calidad , Reproducibilidad de los Resultados , Manejo de Especímenes/instrumentación , Temperatura , Factores de TiempoRESUMEN
Cancer cells influence their microenvironment by secreting factors that promote tumour growth and survival while evading immune-mediated destruction. We previously determined the expression of secreted factors in breast and oesophageal squamous cell carcinoma cell lines (MCF-7 and WHCO6, respectively) using Luminex assays. These cells were subsequently treated with low pH medium to mimic in vivo acid exposure, and the effects on cell viability, proliferation, and secretion of cytokines, chemokines and growth factors were described [1]. Here, we present the datasets from these experiments in addition to data obtained from treating cell lines with conditioned medium from apoptotic cell cultures.
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Medical professionals, particularly in regions with a high burden of human immunodeficiency virus (HIV), should be alert to the hematological complications of HIV, which may include cytopenias, malignancy, and coagulation disturbances. Patients may present with these conditions as the first manifestation of HIV infection. Hematological abnormalities are often multifactorial with opportunistic infections, drugs, malignancy, and HIV infection itself contributing to the clinical presentation, and the diagnosis should consider all these factors. Life-threatening hematological complications requiring urgent diagnosis and management include thrombotic thrombocytopenic purpura, superior mediastinal syndrome, spinal cord compression, and tumor lysis syndrome due to aggressive lymphoma. Antiretroviral therapy is the therapeutic backbone, including for patients with advanced HIV, in addition to specific therapy for the complication. This article reviews the impact of HIV on the hematological system and provides a clinical and diagnostic approach, including the role of a bone marrow biopsy, focusing on perspectives from sub-Saharan Africa.
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People with HIV (PWH) experience endothelial dysfunction (ED) that is aggravated by chronic inflammation and microbial translocation across a damaged gut barrier. Although this paradigm is well-described, downstream pathways that terminate in endothelial dysfunction are only partially understood. This study found increased expression of granulocyte macrophage colony stimulating factor (GM-CSF), toll-like receptor-4 (TLR4), and myeloperoxidase in the aortic endothelium of PWH compared to those without HIV. Bacteria-derived lipopolysaccharide (LPS) heightened glucose uptake and induced GM-CSF expression in primary human endothelial cells. Exposure to sodium-glucose cotransporter-2 (SGLT2) inhibitors reduced glucose uptake, GM-CSF release, and ED in LPS-activated endothelial cells ex vivo, and PWH treated with SGLT2 inhibitors for diabetes had significantly lower plasma GM-CSF levels than non-diabetic PWH not on this medication. The findings suggest that microbial products trigger glucose uptake and GM-CSF expression in the endothelium, contributing to localized inflammation in PWH. Modifying this altered state could offer therapeutic benefits.