The Practicality of the Use of Liquid Biopsy in Early Diagnosis and Treatment Monitoring of Oral Cancer in Resource-Limited Settings

An important driving force for precision and individualized medicine is the provision of tailor-made care for patients on an individual basis, in accordance with best evidence practice. Liquid biopsy(LB) has emerged as a critical tool for the early diagnosis of cancer and for treatment monitoring, but its clinical utility for oral squamous cell carcinoma (OSCC) requires more research and validation. Hence, in this review, we have discussed the current applications of LB and the practicality of its routine use in Africa; the potential advantages of LB over the conventional “gold-standard” of tissue biopsy; and finally, practical considerations were discussed in three parts: pre-analytic, analytic processing, and the statistical quality and postprocessing phases. Although it is imperative to establish clinically validated and standardized working guidelines for various aspects of LB sample collection, processing, and analysis for optimal and reliable use, manpower and technological infrastructures may also be an important factor to consider for the routine clinical application of LB for OSCC. LB is poised as a non-invasive precision tool for personalized oral cancer medicine, particularly for OSCC in Africa, when fully embraced. The promising application of different LB approaches using various downstream analyses such as released circulating tumor cells (CTCs), cell free DNA (cfDNA), microRNA (miRNA), messenger RNA (mRNA), and salivary exosomes were discussed. A better understanding of the diagnostic and therapeutic biomarkers of OSCC, using LB applications, would significantly reduce the cost, provide an opportunity for prompt detection and early treatment, and a method to adequately monitor the effectiveness of the therapy for OSCC, which typically presents with ominous prognosis

Evaluation of blood cell count parameters as predictors of treatment failure of malaria in Angola: An observational study

Background- Despite the guidelines provided by the World Health Organization for the treatment of malaria, treatment failure occurs in many hospitalized patients. Objective- Evaluate whether blood cell count parameters may serve as predictors for malaria treatment. Methodology- A cross-sectional study with a quantitative approach. Results- Of the 219 patients, 21.5% showed failure to antimalarial treatment, Patient with 21 and 40 years (72.6%), male (53.4%), from peri-urban area (47.5%), with high parasitemia (59.8%), treated with Arthemeter (90.9%) and the mortality were 5.9%. Significant associations were observed between occupation, level of parasitemia and outcome with resistance to antimalarial treatment (p<0.05). Patients with normal Hb [OR: 0.75 (95% CI: 0.39–1.44), p = 0.393], RBC [OR: 0.83 (95% CI: 0.40–1.72), p = 0.632], RDW [OR: 0.54 (95% CI: 0.27–1.09), p = 0.088], MCV [OR: 0.61 (95% CI: 0.28–1.31), p = 0.204] were less likely to have malaria treatment failures after artemisinin-based therapy failure. In contrast, those with normal values of segmented neutrophils [OR: 0.32 (95% CI: 0.11–0.96), p = 0.042] and lymphocyte counts [OR: 0.24 (95% CI: 0.05–1.04), p = 0.055]. We also found that patients with significant low levels of Hct [OR: 0.31 (95% CI: 0.15–0.64) p = 0.002], and high leukocytes [OR: 8.88 (95% CI: 2.02–37.2), p = 0.004] and normal platelet values [OR: 1.42 (95% CI: 0.73–2.95), p = 0.280] demonstrated high probability of treatment failure. Conclusion- The importance of blood cell count parameters in monitoring malaria therapy necessitates the urgent need to re-evaluate Artemether-based therapy. Future studies involving more participants in different settings are needed to provide further evidence

TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

BACKGROUND: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. METHODS: We generated neuron-specific TNF-deficient (NsTNF / ) mice and compared outcomes of disease against TNF f/f control and global TNF / mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracerebral M. tuberculosis infection of TNF / mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF / mice were resistant to infection and presented with a phenotype similar to that in TNF f/f control mice. Impaired immunity in TNF / mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. CONCLUSION: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The application of CAR-T cell therapy in hematological malignancies: advantages and challenges

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies. KEY WORDS: Chimeric antigen receptor T cell, Clinical applications, Immunotherapy, Malignancie

Use of Honey in the Management of Chemotherapy-Associated Oral Mucositis in Paediatric Patients

Background: Oral mucositis (OM) is a critical condition during chemotherapy in both adult and child cancer patients. Paediatric cancer patients have a higher prevalence of OM than adult cancer patients. Honey is a natural product that has been reported to have the best tissue healing properties. The present mini-review focused on the evaluation of the effectiveness of oral care with honey products in the treatment and prophylaxis of chemotherapy-induced OM in child patients. Methods: A network of electronic English databases including CINAHL, CENTRAL, EMBASE, MEDLINE and PubMed, were used for primary search from April 2010 to April 2020. We have also considered data collected from ClinicalTrials.gov, Web of Science and Google Scholar. PRISMA software was used to build collective data. Controlled trials were included in this review and were critically appraised by Down and Black. The narrative synthesis was performed. Results: A total number of 346 data of children and adolescents with cancer were considered in this short review. All patients were from three randomized controlled trial articles and two were non-randomised controlled trial articles. Based on the evidence so far revealed, honey may show an effect in the treatment and prophylaxis of OM. The analysis of collected data revealed that the probability value P< 0.05. The honey enhanced recovery time and severity of OM were significantly compared with those without honey treatment receiving group of pediatric patients. Conclusion: Honey not only has been shown to have the capability for healing injured tissues but it is also a more economical treatment, and it has fewer side effects compared to synthetic drugs. Honey or honey products can prevent chemotherapy-induced OM (CIOM) and be the best treatment to grade I, II and III CIOM. However, it is disappointing that studies involving children as patients were few, and limited data available so far

A retrospective study

Funding Information: Thanks to the research team of INIS/CISA (Joana Sebastião, Joltim Quivinja, Joana Paixão, António Mateus, and Zinga David), Instituto Nacional de Sangue (Eunice Manico, Alberto Sozinho, and Deodete Machado), and Clínica Girassol (Alice Teixeira, Domingos Alfredo, and Ngueza Loureiro) for the data collection, technical/administrative support, and testing. Publisher Copyright: © 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.Background and Aims: Hypertension is a public health concern, mainly in resource-limited countries. We investigated the characteristics and risk factors related to high blood pressure in healthy blood donors from, Luanda, the capital city of Angola. Methods: This was a retrospective study that included 343 healthy donors from December 2019 to September 2020. Results: The mean age was 32 ± 9 years. Men represented 93% of the population. Mean systolic blood pressure (SBP) was 131 ± 12.3 mmHg (ranging from 100 to 160 mmHg) and diastolic blood pressure (DBP) was 80.1 ± 9.72 mmHg (from 56.0 to 100 mmHg). DBP was related to age and gender (p 140/90 mmHg). Age between 20 and 40 years (odds ratio [OR]: 2.52, p = 0.043), women (OR: 1.87, p = 0.548), nonurbanized areas (OR: 0.39, p = 0.067), high educational level (OR: 0.76, p = 0.637), employed (OR: 0.49, p = 0.491), voluntary donors (OR: 0.87, p = 0.799), blood group B (OR: 2.06, p = 0.346), and Rh- (OR: 0.26, p = 0.104), were potentially related with high-pressure. The high-pressure cases increased from December 2019 (4%) to September 2020 (28%) (p = 0.019). Conclusion: We showed high pressure among the healthy blood donors population. Demographic characteristics, ABO/Rh blood group, and year period are features that should be considered in cardiovascular disease control strategies. Biological and nonbiological features related to blood pressure changes should be considered for further studies in the Angolan population.publishersversionpublishe

Early Evidence of Circulating SARS-CoV-2 in Unvaccinated and Vaccinated Measles Patients, September 2019–February 2020

Funding Information: This study was funded as a donation from the Ministry of Health, Angola. Publisher Copyright: © 2022 Paixao et al.Background: The global emergence of coronavirus disease 2019 (COVID-19) has challenged healthcare and rapidly spread over the globe. Early detection of new infections is crucial in the control of emerging diseases. Evidence of early recorded COVID-19 cases outside China has been documented in various countries. In this study, we aimed to identify the time of SARS-CoV-2 infection circulation by retrospectively analyzing sera of measles patients, weeks before the reported first COVID-19 cases in Angola. Materials and Methods: We examined the humoral response against SARS-CoV-2 by using an enzyme-linked immunosorbent assay (ELISA)-based assay on a combined two-step sandwich enzyme immunoassay method. In total, we received 568 study patients with blood specimens collected from 23 September 2019 to 28 February 2020, 442 sera samples that met the criteria of the study were withdrawn and selected from the overall 568 received samples. In this study, we considered seropositives, patients who tested positive for SARS-CoV-2 immunoglobulin G (IgG) and M (IgM) antibodies with the index value >1. Results: Of the 442 sera samples that met the criteria of the study, 204 were measles seropositive. Forty out of 204 were confirmed reactive to SARS-CoV-2 viral proteins using IgG and IgM more than 2 weeks before the first reported case in Angola. The humoral response analysis showed significant differences (p = 0.01) between the IgG and IgM indexes in the unvaccinated measles patients. Similarly, a significant difference (p = 0.001) was seen between the IgG and IgM indexes in the vaccinated measles patients. Conclusion: Here, using the humoral response analysis, we report the identification of early circulation SARS-CoV-2 infection weeks before the first recognized cases in the Republic of Angola.publishersversionpublishe