Immune biomarker evaluation of sequential tyrosine kinase inhibitor and nivolumab monotherapies in renal cell carcinoma: the phase I TRIBE trial.

Background: Predictive biomarkers for immune checkpoint blockade in the second-line treatment of metastatic renal cell carcinoma (mRCC) are lacking. Materials and methods: Patients with histologically confirmed RCC who started nivolumab after at least 4 months of tyrosine kinase inhibitors (TKIs) were recruited for this study. Serial tissue and blood samples were collected for immune biomarker evaluation. The primary endpoint was to determine the association of specific T-cell subsets with clinical outcomes tested using Wilcoxon rank sum for clinical benefit rate (CBR) and log-rank test for progression-free survival (PFS). Results: Twenty patients were included in this trial with a median age of 64 years and followed-up for a median of 12 months. The median PFS for patients who received TKI was 13.8 months, while for those subsequently treated with nivolumab following TKI therapy, the median PFS was 2.6 months. CBR of nivolumab was 20% with two partial responses. Functionally active programmed cell death protein 1+ CD4+ T cells were enriched in non-responders (q = 0.003) and associated with worse PFS on nivolumab (P = 0.04). Responders showed a significant reduction in the effector CD4+T-cell (TEF) fraction compared to non-responders at 3 months on nivolumab (0.40 versus 0.80, P = 0.0005). CD127+CD4+ T cells were enriched in patients who developed immune-related adverse effects (q = 0.003). Using in-house validated multiplex immunohistochemistry for six markers, we measured tumour-associated immune cell densities in tissue samples. Responders to nivolumab showed a significantly higher mean of immune cell densities in tissue samples compared to non-responders (346 versus 87 cells/mm2, P = 0.04). Conclusions: In this small study, analysis of tissue-based and peripheral blood immune cell subsets predicted clinical outcomes of nivolumab. Further studies are warranted with larger populations to validate these observations.

Instituting coronavirus disease 2019 testing: opportunities and challenges of molecular laboratory diagnosis in a Southern Nigerian teaching hospital.

The coronavirus disease 2019 pandemic emphasised the importance of laboratory preparedness, including molecular diagnostic capacity, in the control of infectious disease outbreaks. This article reflects on diagnostic capacity-building opportunities presented by the pandemic, the challenges experienced along the way and the lessons learned from the perspective of a university teaching hospital in Southern Nigeria. We advocate for these lessons to inform strategic planning for laboratory preparedness at subnational, national and continental levels.

Improving cancer incidence evaluation through local government area matching: a study of the Edo-Benin cancer registry in Nigeria.

BACKGROUND: Cancer registries in Nigeria, as well as in other sub-Saharan African countries, face challenges in adhering to international cancer registration standards. We aimed to improve cancer incidence estimation by identifying under-reporting of new cancers through matching patient-reported local government areas (LGAs) in Edo state, Nigeria, to their respective catchment populations. METHODS: Information on cancers was obtained from records of hospitals, medical clinics, pathology laboratories, and death certificates according to IARC guidelines. We utilized normalized scores to establish consistency in the number of cancers by calendar time, and standardized incidence ratios (SIR) to assess the variation in cancer incidence across LGAs compared to Edo state average. Subsequently, we estimated sex- and site-specific annual incidence using the average number of cancers from 2016 to 2018 and the predicted mid-year population in three LGAs. Age-standardization was performed using the direct method with the World Standard Population of 1966. RESULTS: The number of incident cancers consistent between 2016-2018 in Egor, Oredo, and Uhunmwonde showed a significantly increased SIR. From 2016 to 2018 in these three LGAs, 1,045 new cancers were reported, with 453 (42.4%) in males and 592 (57.6%) in females. The average annual age-standardized incidence rate (ASR) was 50.6 (95% CI: 45.2 - 56.6) per 105. In men, the highest incidence was prostate cancer (ASR: 22.4 per 105), and in women, it was breast cancer (ASR: 16.5 per 105), and cervical cancer (ASR: 12.0 per 105). Microscopically verified cancers accounted for 98.1%. CONCLUSIONS: We found lower age-standardized incidence rates than those reported earlier for the Edo state population. Collecting information on the local government areas of the cancers allows better matching with the respective target population. We recommend using LGA information to improve the evaluation of population-based cancer incidence in sub-Saharan countries.

The Effectiveness of Common Interventions in the Management of Sickle Cell Disease in Primary Care Settings: A Review.

Sickle cell disease (SCD), a chronic condition that affects men and women equally, continues to present a public health burden in the United States due to its associated morbidity and complications. Despite advances in medical knowledge and the design of novel therapies for managing the disease, its burden remains compounded because of increasing rates of immigration arising from global displacements and economic unrest in many countries. We thus conducted a comprehensive literature review of publications from 2000 to 2022 to gather guidelines on managing SCD, with a search through four databases, PubMed, Embase, Google Scholar, and Cochrane; 42 articles met the final inclusion criteria after the full-text article screening process. In the United States healthcare system, primary care physicians (PCPs) are generally providers who cater to the lifelong management of chronic medical conditions, SCD not being an exception. While more SCD patients now present to primary care clinics, many PCPs still lack the confidence and adequate experience necessary to manage the condition effectively. The gap created by the shortage of PCPs extensively equipped to provide comprehensive SCD care leads to poor health outcomes for patients. It is imperative now more than ever to continue to raise awareness about this condition at the provider level, to ensure that patients receive well-rounded care to improve their quality of life and clinical outcomes. Providing up-to-date knowledge about existing and novel therapies and/or modalities of SCD treatment would undoubtedly equip the PCPs with self-assurance to manage the condition adeptly. Thus, we explore various public health interventions such as hydroxyurea therapy, pneumococcal vaccination, penicillin therapy, iron chelation therapy, and clinical decision support tools that have been implemented in primary healthcare settings and shown to be effective in improving SCD care. We also discuss recent advancements that can lead to improved outcomes for SCD patients in the future.

A Review of 10-Year Survivability of Immunotherapy in the Management of Colon Cancer.

Colon cancer is one of the most common cancers in the United States of America. In addition to conventional treatment approaches such as surgery, chemotherapy, and radiation for colorectal cancer, immunotherapy has gained recognition over the past few years. However, its effectiveness in colorectal cancer treatment is controversial. Our study investigates the survival and progression-free rates of immunotherapy for different types of colorectal cancer over the last 10 years. We conducted literature reviews from various clinical trials and research studies to evaluate immunotherapy's role in colorectal cancer treatment. We also investigated how it affects clinical outcomes. We discovered a range of effective immunotherapy approaches targeting various growth factors and signaling pathways. These modalities include monoclonal antibodies aimed at growth factors such as epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), human epidermal growth factor receptor 2 (HER2), and downstream signaling pathways such as mitogen-activated protein kinase (MAPK), kirsten rat sarcoma viral oncogene (KRAS), B-raf proto-oncogene, serine/threonine kinase (BRAF), and phosphatase and tensin homolog (PTEN). Additionally, we identified immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors, as well as target therapy and adoptive cell therapy as promising immunotherapeutic options. Nevertheless, the application of immunotherapy remains highly limited due to various factors influencing survival and progression-free rates, including tumor microenvironment, microsatellite instability, immune checkpoint expression, and gut microbiome. Additionally, its effectiveness is restricted to a small subgroup of patients, accompanied by side effects and the development of drug resistance mechanisms. To unlock its full potential, further clinical trials and research on molecular pathways in colorectal cancer are imperative. This will ultimately enhance drug discovery success and lead to more effective clinical management approaches.

Evaluation of Bronchiolitis in the Pediatric Population in the United States of America and Canada: A Ten-Year Review.

Bronchiolitis is a well-known viral infection among the pediatric population, significantly impacting hospitalization rates. The COVID-19 pandemic profoundly affected respiratory viral infections, including bronchiolitis, as various mitigation measures were implemented. In this study, we analyzed bronchiolitis cases during the pandemic and post-pandemic period, aiming to identify changes in management guidelines and their incidence and management over the last 10 years. Moreover, we explored the relationship between bronchiolitis and COVID-19, a virus that gained rapid notoriety worldwide. By analyzing data from pediatric populations in Canada and the USA, we sought to understand the role of varying seasons in the peak periods of bronchiolitis infections. The comprehensive review's results will provide valuable insights into bronchiolitis dynamics within the context of the COVID-19 pandemic. Our aim is to better comprehend the interplay between bronchiolitis, COVID-19, and seasonal variations, ultimately contributing to a deeper understanding of this respiratory viral infection and informing future management strategies. Furthermore, these findings can assist healthcare professionals in preparing for and responding to potential fluctuations in bronchiolitis cases in the post-pandemic era.

Correction: Implementation of a COVID-19 screening tool in a southern Nigerian tertiary health facility.

[This corrects the article DOI: 10.1371/journal.pgph.0000578.].

Immune Checkpoint Inhibitors as a Treatment Option for Bladder Cancer: Current Evidence.

Bladder cancer is a prevalent disease, and treatment options for advanced bladder cancer remain limited. However, immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) have shown promise in treating bladder cancer. These drugs work by blocking receptors and ligands, disrupting signaling, and allowing T cells to recognize and attack cancer cells. ICIs have been found to be effective in treating bladder cancer, especially in cases of metastatic urothelial carcinoma (UC) that have progressed after chemotherapy. Furthermore, combination therapy with ICIs and chemotherapy or radiation therapy has shown promise in treating bladder cancer. While there are challenges associated with ICIs, including adverse effects, immune-related adverse events, and lack of efficacy in some patients, they remain a promising option for bladder cancer treatment, especially in cases where other treatment options have failed. This review paper focuses on the current role, challenges, and future trends of immunotherapy in the management of bladder cancer.

The Role of Biomarkers in the Diagnosis and Prognosis of Different Stages of Melanoma.

Melanoma is a skin cancer arising from melanocytes, the cells responsible for synthesizing melanin pigment, which gives the skin its color. Early diagnosis and treatment of melanoma increase survival rates. Clinical examination and biopsy are the primary tools used to diagnose melanoma. However, distinguishing between pre-malignant melanocytic lesions and early invasive melanoma histopathologically remains challenging. Therefore, additional modalities such as a detailed clinical history, imaging, genetic testing, and biomarkers have been applied to diagnose melanoma. This review discusses the current trends in biomarker advancements over the last 10 years to assist in the early detection and diagnosis of melanoma. Biomarkers such as melanoma-associated antigens (MAAs), S100B, microRNAs (miRNAs), and circulating tumor cells (CTCs) have the potential to aid in the detection, diagnosis, and prognosis of melanoma. However, the application of biomarkers in the diagnosis of melanoma is still evolving.

EPIC: an evaluation of the psychological impact of early-phase clinical trials in cancer patients.

BACKGROUND: Anxiety and depression in patients with cancer is associated with decreased quality of life and increased morbidity and mortality. However, these are often overlooked and untreated. Early-phase clinical trials (EPCTs) recruit patients with advanced cancers who frequently lack future treatment options, which may lead to increased anxiety and depression. Despite this, EPCTs do not routinely consider psychological screening for patients. PATIENTS AND METHODS: This prospective observational study explored levels of anxiety and depression alongside impact of trial participation in the context of EPCTs. The Hospital Anxiety and Depression Scale and the Brief Illness Perceptions Questionnaire were completed at the point of EPCT consent, the end of screening and at pre-specified time points thereafter. RESULTS: Sixty-four patients (median age 56 years; median Eastern Cooperative Oncology Group performance status 1) were recruited. At consent, 57 patients returned questionnaires; 39% reported clinically relevant levels of anxiety whilst 18% reported clinically relevant levels of depression. Sixty-three percent of patients experiencing psychological distress had never previously reported this. Males were more likely to be depressed (P = 0.037) and females were more likely to be anxious (P = 0.011). Changes in anxiety or depression were observed after trial enrolment on an individual level, but not significant on a population level. CONCLUSIONS: Patients on EPCTs are at an increased risk of anxiety and depression but may not seek relevant support. Sites offering EPCTs should consider including psychological screening to encourage a more holistic approach to cancer care and consider the sex of individuals when tailoring psychological support to meet specific needs.

[How can participation in health promotion projects be encouraged ? Professionals' views on the key factors at play.] / Comment promouvoir la participation dans les projets de promotion de la santé ? Les facteurs clés selon les professionnels.

INTRODUCTION: The participation of the stakeholders concerned by health promotion interventions targeting health determinants is a founding principle of integral importance. Notwithstanding the potential benefits of these approaches, their implementation is still quite limited and field practices are highly varied, if not totally heterogeneous. Such limitations can be considered in conjunction with the poorly defined outlines of participation, which can lead to variable interpretations of what it entails, and also to the different contextual factors potentially affecting its implementation. This study therefore aims: (1) to identify the various perceptions and experiences of participation, and (2) to identify the factors impacting the implementation of participation in support and development of health promotion. METHODOLOGY: All in all, 34 professionals participated in this qualitative research, in which triangulation was associated with analysis of the written productions collected during creativity workshops (Cube activity) and semi-structured interviews and observations. All participants gave their informed consent to participate, and the data were anonymized and remained accessible to one and all. The data were subjected to content analysis (Bardin, 2003) focusing on types of factors contributing to the implementation (or non-implementation) the of participation. RESULTS: Data analysis led to the emergence of 7 categories of factors: stakeholder characteristics, the individual characteristics of professionals and decision-makers, relations between professionals among themselves and with stakeholders, the methods and form of the approach implemented, the local organization and its missions, and the national context. DISCUSSION: The representations and experiences of participatory approaches among health promoters are very heterogeneous. Implementation depends largely on how stakeholder characteristics are taken into account, on the ability of professionals to adapt to them, on the development of favorable interpersonal relationships through reflexive work on posture, and on the use of relevant and scientifically validated methods. CONCLUSIONS: To strengthen the openness and motivation of field professionals to undertake participatory actions, awareness-raising and training in specific skills seems relevant, the objective being to enable them to anticipate risks and to make the most of whatever opportunities appear.

Implementation of a COVID-19 screening tool in a southern Nigerian tertiary health facility.

Screening for coronavirus disease 2019 (COVID-19) in emergency rooms of health facilities during outbreaks prevents nosocomial transmission. However, effective tools adapted for use in African countries are lacking. This study appraised an indigenous screening and triage tool for COVID-19 deployed at the medical emergency room of a Nigerian tertiary facility and determined the predictors of a positive molecular diagnostic test for COVID-19. A cross-sectional study of all patients seen between May and July 2020 at the Accident and Emergency of the University of Benin Teaching Hospital was conducted. Patients with any one of the inputs- presence of COVID-19 symptoms, history of international travel, age 60 years and above, presence of comorbidities and oxygen saturation < 94%- were stratified as high-risk and subjected to molecular testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Data was obtained from the screening record book patterned after a modified screening tool for COVID-19, deidentified and entered into IBM-SPSS version 25.0. Binary logistic regression was conducted to determine significant predictors of a positive SARS-CoV-2 test. The level of significance was set at p < 0.05. In total, 1,624 patients were screened. Mean age (standard deviation) was 53.9±18.0 years and 651 (40.1%) were 60 years and above. One or more symptoms of COVID-19 were present in 586 (36.1%) patients. Overall, 1,116 (68.7%) patients were designated high risk and tested for SARS-CoV-2, of which 359 (32.2%) were positive. Additional inputs, besides symptoms, increased COVID-19 detection by 108%. Predictors of a positive test were elderly age [AOR = 1.545 (1.127-2.116)], co-morbidity [AOR = 1.811 (1.296-2.530)] and oxygen saturation [AOR = 3.427 (2.595-4.528)]. This protocol using additional inputs such as oxygen saturation improved upon symptoms-based screening for COVID-19. Models incorporating identified predictors will be invaluable in resource limited settings.

Setting up a molecular diagnostic laboratory for SARS-CoV-2 testing: Experience of a single centre in a resource-constrained setting.

BACKGROUND: Molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is at the forefront of the global response to the coronavirus disease 2019 (COVID-19) pandemic. However, molecular diagnostic capabilities are poorly developed in many African countries. Efforts by the Nigeria Centre for Disease Control and other public health agencies to scale up facilities for molecular testing across the continent are well documented, but there are few accounts from the laboratories at the frontline. INTERVENTION: As part of an institutional response to the COVID-19 pandemic, the University of Benin Teaching Hospital, Benin City, Nigeria, signed a memorandum of understanding with a World Bank-supported institution to obtain a non-proprietary testing platform, renovated an existing molecular virology laboratory and validated the test process to make SARS-CoV-2 testing readily available for decision-making by frontline health workers. These efforts resulted in the University of Benin Teaching Hospital's inclusion in the Nigeria Centre for Disease Control COVID-19 molecular laboratory network. The laboratory achieved a turnover of 12 123 tests within 7 months of operation. Challenges faced and dealt with include incompatible equipment, limited skilled manpower, unstable (unreliable) electric power supply, disrupted procurement and supply chain, and significant overhead costs. LESSONS LEARNT: Molecular diagnostic capability is essential in laboratory preparedness for pandemic response and can be achieved by establishing collaborative networks in low-resource settings. RECOMMENDATIONS: Molecular diagnostic capabilities attained during the COVID-19 pandemic should be maintained by governmental support of the local biotechnology sector, collaboration with partners and stakeholders and the expansion of diagnostics to include other diseases of public health importance.

Preparedness and response of a tertiary hospital to the COVID-19 pandemic in Nigeria: challenges, opportunities and lessons.

Africa was the last continent to be affected by the COVID-19 pandemic. Much of the discourse on Africa's response captured in scientific journals revolves around nations, public health agencies and organizations, but little is documented about how individual healthcare facilities have fared. This article reports the challenges faced in a tertiary hospital in Nigeria, including space constraints, diagnostic challenges, shortages in personal protective equipment and health worker infections. The opportunities and strengths that aided the response are also highlighted. The lessons learned will be useful to similar facilities. More information about health facility response at various levels is needed to comprehensively assess Africa's response to the pandemic.

Facility-Based Surveillance Activities for COVID-19 Infection and Outcomes among Healthcare Workers in a Nigerian Tertiary Hospital.

COVID-19 in healthcare workers (HCWs) can result in nosocomial transmission, depletion in available workforce, and enhanced community transmission. This article describes surveillance for COVID-19 in HCWs at a tertiary healthcare facility, and documents the outcomes. A descriptive cross-sectional study of all HCWs identified from surveillance for COVID-19 from March 31 to August 31, 2020 was conducted. Healthcare workers were categorized as high risk and low risk using an adapted WHO Risk Assessment tool. Nasopharyngeal and oropharyngeal swab specimens obtained from high-risk subjects were tested by a reverse transcriptase PCR method. Data were analyzed with IBM SPSS version 25.0 software (IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY), and results were presented as frequencies and percentages. The level of significance was set at P < 0.05. During 5 months of surveillance, 1,466 HCWs with a mean age of 38.1 ± 9.7 years were identified as contacts. On risk assessment, 328 (22.4%) were adjudged high risk. High risk was associated with increasing age (P < 0.001), male gender (P = 0.001), and nonclinical staff (P = 0.002). Following testing, 78 (5.3%) in the high-risk category were confirmed to have COVID-19. There was no record of COVID-19 in HCWs adjudged low risk. Forty-four (56.4%) cases were epidemiologically linked to the community, 20 (25.7%) to patients, and 14 (17.9%) to another HCW. Surveillance and risk assessment are crucial to COVID-19 response in healthcare facilities and revealed HCW infections with predominantly nonoccupational epidemiological links in this study.

Supportive Care: An Indispensable Component of Modern Oncology.

The advent of new cancer therapies, alongside expected growth and ageing of the population, better survival rates and associated costs of care, is uncovering a need to more clearly define and integrate supportive care services across the whole spectrum of the disease. The current focus of cancer care is on initial diagnosis and treatment, and end of life care. The Multinational Association of Supportive Care in Cancer defines supportive care as 'the prevention and management of the adverse effects of cancer and its treatment'. This encompasses the entire cancer journey, and necessitates involvement and integration of most clinical specialties. Optimal supportive care can assist in accurate diagnosis and management, and ultimately improve outcomes. A national strategy to implement supportive care is needed to acknowledge evolving oncology practice, changing disease patterns and the changing patient demographic.

Cardiac rhabdomyoma in a neonate with supraventricular tachycardia.

Cardiac rhabdomyoma (CR) is a rare tumor commonly associated with tuberous sclerosis. They are often detected prenatally or in early infancy. The case of a Nigerian human immunodeficiency virus (HIV)-exposed neonate with CR who presented with supraventricular tachycardia and cardiovascular collapse is presented. The infant was born to a mother on highly active antiretroviral therapy (HAART). The possible role of HIV and HAART in CR etiology and the difficulty in the management of this case are highlighted.

Ultraviolet and visible imaging and spectrographic imaging instrument.

The Ultraviolet and Visible Imaging and Spectrographic Imaging experiment consists of five spectrographic imagers and four imagers. These nine sensors provide spectrographic and imaging capabilities from 110 to 900 nm. The spectrographic imagers share an off-axis design in which selectable slits alternate fields of view (1.00° × 0.10° or 1.00° × 0.05°) and spectral resolutions between 0.5 and 4 nm. Image planes of the spectrographic imager have a programmable spectral dimension with 68, 136, or 272 pixels across each individual spectral band, and a programmable spatial dimension with 5, 10, 20, or 40 pixels across the 1° slit length. A scan mirror sweeps the slit through a second spatial dimension to generate a 1° × 1° spectrographic image once every 5, 10, or 20 s, depending on the scan rate. The four imagers provide narrow-field (1.28° × 1.59°) and wide-field (10.5° × 13.1°) viewing. Each imager has a six-position filter wheel that selects various spectral regimes and neutral densities. The nine sensors ut lize intensified CCD detectors that have an intrascene dynamic range of ~ 10(3) and an interscene dynamic range of ~ 10(5); neutral-density filters provide an additional dynamic range of ~ 10(2-3). The detector uses an automatic gain control that permits the sensors to adjust to scenes of varying intensity. The sensors have common boresights and can operate separately, simultaneously, or synchronously. To be launched aboard the Midcourse Space Experiment spacecraft in the mid-1990's, the ultraviolet and visible imaging and spectrographic imaging instrument will investigate a multitude of celestial, atmospheric, and point sources during its planned 4-yr life.

Photon counting detectors for Fabry-Perot interferometers.

Sealed channel plate photomultipliers with multiple discrete anodes for use as photon counting detectors in the image plane of Fabry-Perot interferometers are described. The influence of design and construction on performance of completed devices is discussed. Effects on spatial resolution, lifetime, and counting efficiency are described. It is shown that devices can be optimized for particular applications. The results should be generally applicable to resistive anode and wedge and strip anode types of sealed detectors.