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Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses
No full textHead and neck squamous cell carcinoma (HNSCC) is a prevalent and often fatal malignancy associated with significant treatment-related toxicity. There is an urgent need for a preclinical model to assess therapeutic options and guide clinical decision-making. To define conditions for establishing patient-derived organoid (PDO) models that faithfully recapitulate morphological, histopathological, and genomic characteristics of HNSCC patients and can predict radiation and chemotherapy responses in patients, PDOs were generated from a group of HNSCC patients. The morphological, histological, mutational, and biological characteristics and treatment responses were evaluated. We demonstrate that the PDOs closely resemble resected tumors from which they were derived with respect to histopathology, differentiation state markers, p16 status, and mutation profiling. We observe patient-to-patient variation in cell proliferation rates. Additionally, they exhibit differential responses to radiotherapy and chemotherapy, which were examined using a cell viability assay. This methodology offers potential for drug screening in a pre-clinical context with the potential to mirror clinical outcomes. Our WNT-free growth conditions maintained the differentiation status of PDOs and enabled rapid assessment of drug response and the development of new models to identify new treatment options for head and neck cancer patients
Perceptions of consent for a paediatric telehealth trial during emergency transport in Pakistan
No full textIntroduction: Childhood mortality in the emergency setting is disproportionately high in low-income and middle-income countries (LMIC), with limited research dedicated to improving timely interventions, especially for critically ill children during transport. To perform essential prehospital paediatric research, there is a need for a tailored consent process, which reflects the specific needs and concerns of participants in this challenging research context.Objective: The objective is to prospectively investigate stakeholder perceptions and preferences regarding consent processes for a specific paediatric ambulance-based telemedicine trial.Methods: Exploratory qualitative study design using face-to-face semistructured interviews and focus group discussions. Data were analysed using thematic analysis. Participants included healthcare providers (paediatric telemedicine physicians and emergency medical technicians) and parents of children who required emergency transportation in Karachi, Pakistan.Results: 47 participants, ranging from 19 to 47 years old, were involved in in-depth interviews or focus group discussions. The participants comprised 29 healthcare workers and 18 parents. Among them, 9 were women and 38 were men. Expressing diverse attitudes towards different consent methods, the majority recommended a prospective written informed consent approach to build trust and provide legal protection. Participants understood the situational incapacity that occurs in emergency settings, emphasised the importance of keeping the consent brief and recommended a subsequent contact in 2-3 days after the emergency transport to reconfirm consent and answer any questions.Conclusion: Our interpretation of the findings revealed that participants preferred a staged consent process for telemedicine trials in LMIC paediatric emergency settings
Atypical electrical injury leading to chest wall necrosis, multi-organ failure and terminal gastrointestinal bleed: A case report
No full textIntroduction: High-voltage electrical injuries (HVI) are usually life-threatening and are commonly caused by contact with high voltage power lines. They can lead to deep burns and multi-system trauma.Case presentation: This report presents an atypical case of a 21-year-old male who had an accidental electrocution with high voltage power lines during a religious event, leading to a 4th-degree burn of the chest wall, right neck, pelvis, bilateral anterior thighs, perineum and both arms; the total body surface area (TBSA) was approximately 37 %. Deep chest wounds exposed the ribs, muscles and fascia. During his hospital stay, he developed several complications. The management of the wound included multiple debridements, reconstruction of the chest wall using a latissimus dorsi muscle flap, and split-thickness skin grafting from the left thigh. Initially the patient recovered but later developed lower gastrointestinal (GI) bleeding and expired due to hypovolemic shock.Discussion: This case highlights the complex management of HVIs involving extensive TBSA. Prompt surgical intervention is essential and includes coverage of deep wounds using a muscle flap, along with skin grafting for protection of the underlying structures. Due to the risk of systemic complications with such injuries, multidisciplinary care is required. In this case, the sudden onset of GI bleeding shows the unpredictable trajectory of such injuries.Conclusion: HVIs involving extensive TBSA can result in rare but fatal complications. Prompt multidisciplinary management is crucial, and there is need for further research to improve outcomes and prevent complications in such complex cases
A systems-change approach to addressing the mortality surveillance gap in Pakistan
No full textWith a lack of cause of death estimation and an inadequate and fragmented Civil Registration and Vital Statistics system, Pakistan faces a significant gap in data on mortality. This poses significant challenges for health policy planning and monitoring. In this viewpoint, we draw on systems-change frameworks to examine and provide recommendations to improve mortality surveillance in Pakistan. We use the multiple cause diagram framework to understand the challenges and barriers to instituting a robust mortality surveillance system in Pakistan. We also examine current and future scenarios and what it will take to get to best future scenarios using the Theory of Change model. Through the multiple cause diagram mapping, we show that the poorly functioning mortality surveillance system in Pakistan is underlain by multiple complex and interrelated multisectoral challenges. However, a cost-effective, agile, and data-lean system of mortality surveillance can exist through strengthening already existing systems. This could be accompanied with context- and resource-sensitive use of different types of surveillance methods such as verbal autopsy tools implemented in the community and integrated into sample registration systems, as well as hospital-based surveillance in urban areas with government coordination. This can be achieved with cross-sectoral, cross-agency collaboration, capacity strengthening, and local stakeholder involvement
Fifth edition WHO classification: mature B-cell neoplasms
No full textWe present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into ‘essential’ and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma classification, providing guidance on how to apply the WHO classification in resource-limited settings
Neuropsychiatric side effects of semaglutide in patients with dementia
No full textAn older woman with dementia and type 2 diabetes was started on semaglutide and subsequently developed severe psychological and physical symptoms, including apathy, significant weight loss and decreased appetite. These symptoms markedly improved after the medication was discontinued. This case underscores the importance of recognising potential psychiatric side effects of semaglutide, especially in older adults with cognitive impairment. The experience highlights the need for careful monitoring when prescribing semaglutide in this population and suggests that discontinuation should be considered if adverse symptoms arise. It also raises awareness about the limited safety data on semaglutide in older patients, emphasising the necessity of further research to understand its effects on this vulnerable group
Micronutrients associated with anemia in school-age children and adolescents 2005-2018: Biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project
No full textBackground: School-age children and adolescents may be at risk of anemia through demands on micronutrients required for growth and maturation.Objectives: This multicountry analysis examined the burden of anemia in children aged 5-19 y by sex and age category and associations with micronutrient deficiencies, inflammation, and BMI.Methods: Children aged 5-19 y from surveys in the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project were included with hemoglobin, ≥1 micronutrient (iron, vitamin A, folate, vitamin B12, or zinc) and inflammation biomarker, and n \u3e 100 per survey. Factors with bivariate relationships with anemia (P \u3c 0.1) were included in multivariable modified Poisson regression models to examine the attributable burden of anemia.Results: This analysis included 54,534 children from 17 surveys in 16 countries (16 surveys for 15-19 y; 9 surveys for 10-14 y; 8 surveys for 5-9 y). Median overall anemia prevalence was 16% (range: 5% in Ecuador, United Kingdom, and United States to 59% in Côte d\u27Ivoire) with the highest burden in 15-19-y-old females (24%). In most surveys, anemia prevalence did not differ by sex for children aged 5-14 y, and median anemia prevalence was lower in children aged 10-14 y (7%) than in those aged 5-9 y (9%) or 15-19 y (22%). In most surveys, higher anemia prevalence was associated (P \u3c 0.05) with iron deficiency (15%) [prevalence ratio (PR): 1.6-14.2; 5-9 y, 4/7 surveys; 10-14 y, 6/6 surveys; 15-19 y, 13/14 surveys), vitamin A deficiency (2%) (PR: 1.8-3.0; 5-9 y, 2/2 surveys; 10-14 y, 2/3 surveys; 15-19 y, 2/3 surveys), and inflammation (13%) (PR: 1.4-2.4: 5-9 y, 4/4 surveys; 10-14 y, 2/4 surveys; 15-19 y, 6/8 surveys). Folate, vitamin B12, zinc, and BMI had weak, variable associations with anemia.Conclusions: Iron deficiency and vitamin A deficiency are consistently associated with anemia in school-age children and adolescents, whereas inflammation and other micronutrients had context-dependent associations. This research underscores the importance of examining multiple micronutrients associated with anemia in the context of factors such as country, age, and sex
Navigating childhood asthma care in Kenya: barriers identified by children and their caregivers
Full text linkBackground: Asthma is one of the most common chronic conditions in children, with significant morbidity and mortality, especially in Africa. Achieving adequate asthma control in children remains challenging because of gaps between standard recommended management strategies and actual treatment practices. This study explored barriers to asthma management as perceived by children and their caregivers in a private tertiary care setting in Kenya.
Methods: An exploratory phenomenological qualitative study was conducted at Aga Khan University Hospital (AKUH), Nairobi. Children aged 6–18 years with a confirmed diagnosis of asthma and their caregivers were recruited. The participants had been receiving treatment for at least one year but had partly controlled or uncontrolled asthma. Purposive sampling was used, and in-depth interviews were conducted with 14 child-caregiver pairs until data saturation. The data were analysed via NVivo software version 12.
Results: Three predetermined themes were highlighted and explored in this study. These were barriers to medication use, barriers to treating modifiable risk factors, and barriers to nonpharmacological interventions. One emerging theme was identified: loss of trust in the health care system. Barriers to medication use were most frequently reported and included challenges with drug administration, forgetfulness, lack of support from schools and extended families, stigma, and monotony in treatment regimens. Modifiable risk factor barriers focused on difficulties attending clinic appointments, whereas nonpharmacological intervention barriers included the high costs of implementing recommended adjustments and ineffective environmental control.
Conclusions: Despite access to specialist-led care and good caregiver knowledge, children with asthma faced barriers such as poor medication adherence, environmental triggers, limited drug access, and inadequate school support. This suggests that expert care alone is insufficient, and a broader, system-wide approach is needed to improve asthma outcomes in Africa
