Giant cell tumor of bone (GCTB) is an intermediate bone neoplasm defined by recurrent H3F3A mutations and limited systemic treatment options beyond denosumab. Patient-derived cancer cell lines (PDCs) offer a scalable platform for mechanistic studies and therapeutic discovery, yet the extent to which culture dimensionality alters baseline molecular states and drug response in GCTB remains unclear. Here, we performed integrated transcriptomic, proteomic, and pharmacologic profiling of thirteen patient-derived GCTB cell lines cultured under two-dimensional (2D) monolayer and three-dimensional (3D) spheroid conditions. RNA sequencing and data-independent acquisition (DIA)-based quantitative proteomics were conducted on paired cultures, and drug sensitivity was assessed using a panel of 221 anticancer agents. 3D culture reproducibly induced compact spheroid formation across all cell lines and was accompanied by broad remodeling of gene expression, protein abundance, and drug-response profiles. Unsupervised analyses consistently demonstrated that samples clustered primarily by culture condition rather than by cell-line identity at both the transcriptome and proteome levels. Although global trends were shared, a substantial fraction of molecules showed RNA-protein discordance, indicating that transcriptomic changes alone do not fully explain culture-dependent functional remodeling. Pathway analyses highlighted enrichment of extracellular matrix-related processes, stress-response programs, and metabolic regulation in 3D cultures, with several features more prominent at the protein level. Functionally, 3D culture generally reduced sensitivity to many agents while preserving compound-dependent vulnerabilities. These results establish culture dimensionality as a key determinant of therapeutic susceptibility in GCTB PDCs and support incorporating proteome-informed 3D models into translational pipelines to prioritize clinically relevant drug candidates and biomarkers.

Chronic stress resulted in poor prognosis of cancer patients in the clinic. This study aimed to explore the mechanism by which chronic stress promotes the progression of lung adenocarcinoma (LUAD) through circ_RPPH1/miR-326 axis. Chronic stress-induced LUAD in vitro and in vivo models were established in A549 cells and C57BL/6 male mice. Sucrose preference test (SPT) and forced-swimming test (FST) were used for in vivo model evaluation. qRT-PCR and western blot were used to detect mRNA and protein levels. Cell proliferation, migration and invasion were also evaluated. Luciferase reporter assay was for target gene verification. In A549 cells, acetylcholine (ACh)-induced chronic stress contributed to the upregulation of circ_RPPH1. circ_RPPH1 knockdown remitted the carcinogenic effect of chronic stress on A549 cells. circ_RPPH1 serves as a sponger of miR-326, and miR-326 downregulation neutralized the beneficial role against tumor cell function and EMT in vitro. In vivo, circ_RPPH1 knockdown reduced the tumor volume and EMT-related protein levels of tumor-bearing mice under chronic stress treatment, while miR-326 antagomir co-transfection neutralized the effect. LARP1 might be the target gene of circ_RPPH1/miR-326 axis in CUMS mice. circ_RPPH1/miR-326 axis was involved in chronic stress-promoted progression and metastasis of LUAD.

To provide an overview of the current state of international research on technology-based applications for informal caregivers of people with advanced cancer, with a particular focus on advanced breast cancer.

This scoping review was conducted in accordance with the Joanna Briggs Institute methodology and reported in line with the PRISMA-ScR guideline. The PCC framework was used to define the search terms, and develop the search strategy for the databases PubMed, CINAHL, and Web of Science. The systematic search identified 13 relevant articles describing ten different technology-based applications. One additional article was identified through a manual search.

In total, 14 studies covering ten distinct interventions were included. Some interventions were adapted from face-to-face programmes for digital delivery, whereas only a minority were explicitly informed by theoretical models from psychology or health science. The included studies addressed five main areas: informational support, mental and psychosocial support and enhancement of quality of life, physical and practical support, communication support, and preparation for caregiving and death. Evaluations reported predominantly positive findings, particularly with regard to quality of life, anxiety, depressive symptoms, and coping. However, most studies focused on advanced cancer more broadly rather than on advanced breast cancer specifically.

The reviewed literature suggests that technology-based interventions for informal caregivers of people with advanced cancer are available in several countries and address a range of support needs. However, no intervention tailored to relatives of patients with advanced breast cancer was identified as having been fully developed and evaluated. The findings highlight the need for future research on targeted, sustainable digital support for this group. The development of the Gesi-BK platform is based on the results of this scoping review.

Advances in cystic fibrosis (CF) treatment have seen more people with CF starting a family. Females with CF (FwCF) have expressed a need for improved reproductive health-related shared decision-making (SDM) with health care providers. This study explored perspectives of FwCF and clinicians on the role and implementation of SDM tools in CF reproductive health care.

We conducted qualitative semi-structured interviews with FwCF and clinicians. We recruited clinicians through professional networks and FwCF via a previous study and social media. Interviews explored experiences of SDM related to reproductive health. Participants were given examples of SDM tools and asked to consider their utility within CF care. We analyzed interview transcripts using an inductive approach, identifying key themes.

Six FwCF and 23 clinicians participated. Four themes were identified: Perceived usefulness of an SDM approach for CF reproductive health, Role of tools in facilitating SDM, Considerations for SDM tool development, and Implementation of SDM in routine CF care. Participants saw information provision as key to SDM, enhancing patient confidence to initiate and engage in conversations. Participants considered SDM tools helpful at three stages: preparing for consultations, facilitating in-consultation communication, and supporting post-consultation reflection and discussion. Trustworthy content was key to engagement. Participants felt reproductive health conversations should start in adolescence and recur throughout the life course. Clinicians highlighted the need for a service-wide culture supporting SDM.

Both groups supported early and ongoing reproductive health-related SDM. Further research should evaluate CF-specific reproductive health SDM interventions that build confidence, skills, and foster a health-service culture supportive of SDM.

Children with medical complexity are at risk of pulmonary injury due to chronic pulmonary aspiration. Our study aimed to determine the effect of multidisciplinary evaluation and periodic follow-up of aerodigestive disorders on the final status of the respiratory conditions.

Children followed for at least 1 year by the Medipol University Aerodigestive Clinic between March 2019 and August 2024 were included. Demographic data, underlying diagnoses, respiratory and nutritional status at admission, hospitalization frequency and duration, and home ventilation requirements were analyzed. Swallowing dysfunction and/or aspiration were assessed using clinical and instrumental methods. All children received tailored swallowing and nutritional therapy.

Of 89 children, 72 of them were followed for at least 1 year (12 died, 5 lost follow-up). The median follow-up period was 30 months (18-46 months). The median age during that time of admission was 30 months (11-62 months). The most common underlying conditions were neuromuscular disorders (43%), bronchopulmonary dysplasia (14%), and congenital heart disease (13%). Dysphagia was confirmed instrumentally in 61% of patients. Among tracheostomized children, 13 of 22 (60%) were successfully decannulated. Respiratory support was reduced or discontinued in 14 of 31 (45%) children. Oral feeding was achieved in 21 (29%) previously tube-fed children. Hospitalizations decreased in all but one child, and 45 (62.5%) required no hospitalization in the year following aerodigestive clinic evaluation.

A multidisciplinary aerodigestive approach improves respiratory outcomes in children with medical complexity by reducing the need for respiratory support, facilitating decannulation, and decreasing hospitalizations.

Patients with severe pulmonary embolism (PE) may experience hemodynamic instability with intubation and mechanical ventilation. However, the characteristics and outcomes of intubated PE patients have not been previously described in the literature.

We conducted a retrospective cohort study of patients requiring activation of our hospital's Pulmonary Embolism Response Team (PERT) from 2012 to 2021 who were intubated within 24 h of their acute PE diagnosis. Our primary outcome was peri-intubation hemodynamic instability and death occurring within 30 min. Our secondary outcome was peri-intubation hemodynamic instability and death within 3 h of intubation.

We included 51 patients. Within 30 min of intubation, seven (14%) patients had a new or increased vasopressor requirement, four (8%) suffered cardiac arrest, and 1 (2%) required ECMO. Within 3 h, 26 (51%) patients had a new or increased vasopressor requirement, six (12%) suffered cardiac arrest, and five (10%) required ECMO. Patients with a central PE (n = 29, 57%) were more likely to experience peri-intubation hemodynamic instability (OR 3.4, 95% CI [0.95, 13], p = 0.048). Patients who had right ventricular strain on CT (OR 3.7, 95% CI [1.01, 15], p = 0.043) or echocardiogram (OR 8.0, 95% CI [1.9, 42], p = 0.0014) were also more likely to experience hemodynamic instability.

Peri-intubation hemodynamic deterioration occurs in more than half of patients with acute PE, and severe events, like cardiac arrest, are common. Physicians should be cautious when intubating PE patients. Further research is needed to identify optimal strategies to treat PE patients who require intubation.

Introduction: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, first emerged in Wuhan, China, in late 2019. Besides respiratory involvement, COVID-19 may cause coagulation abnormalities, leading to thromboembolic events. Mild forms of acute pancreatitis have also been reported in patients with COVID-19 pneumonia. The aim of this case report is to highlight rare extrapulmonary manifestations of SARS-CoV-2 infection, with emphasis on pancreatic involvement. Case Report: A male patient was admitted with sore throat, dry cough, and fever up to 38.0°C. He had received the first dose of the Sinopharm COVID-19 vaccine three weeks prior and was obese (BMI 44.7 kg/m²). On admission, he developed pulmonary thromboembolism. Color Doppler ultrasonography of the lower extremities showed no signs of superficial or deep vein thrombosis. On the eleventh day of treatment, laboratory tests revealed elevated serum amylase, lipase, and leukocyte count. Abdominal ultrasonography demonstrated a hyperechoic, non-enlarged pancreas, consistent with mild acute pancreatitis. Given the widespread presence of endothelial cells, SARS-CoV-2 infection may affect multiple extrapulmonary organs, including the CNS, cardiovascular system, kidneys, pancreas, liver, and gastrointestinal tract. Conclusion: SARS-CoV-2 infection may lead not only to pneumonia but also to thromboembolic complications and mild acute pancreatitis. Awareness of such rare extrapulmonary manifestations is important for timely diagnosis and management.

Pneumocystis jirovecii pneumonia (PCP) can cause severe hypoxemic respiratory failure in immunocompromised patients. Contemporary outcomes of venovenous extracorporeal membrane oxygenation (VV ECMO) support for PCP are poorly characterized, and existing reports are limited to small case series.

Retrospective cohort study.

International registry study using the Extracorporeal Life Support Organization (ELSO) registry.

Adults with PCP-associated hypoxemic respiratory failure supported with VV ECMO between 2011 and 2024.

VV ECMO.

A total of 209 patients with PCP-associated respiratory failure supported with VV ECMO were identified. The overall in-hospital mortality was 60.8%. Survivors were younger than nonsurvivors (median age 41.9 vs. 46.8 yr; p = 0.047). Duration of mechanical ventilation before VV ECMO was longer among nonsurvivors (median 4.7 vs. 1.6 d; p = 0.019). The proportion of patients with HIV infection was similar among survivors and nonsurvivors (19.5% vs. 22.1%; p = 0.73). Pre-ECMO vasopressor use, prone positioning, and renal replacement therapy were common and did not differ between groups. Clinical course was characterized by prolonged VV ECMO support (median 18.6 d) and frequent complications, including pneumothorax (21.1%), renal replacement therapy during VV ECMO (31.6%), intracranial hemorrhage or stroke (7.7%), and major pulmonary or gastrointestinal hemorrhage (16.8%). PCP accounted for a small proportion of VV ECMO runs reported to the ELSO registry throughout the study period at 0.36% of reported cases. No significant temporal trend in mortality was observed.

PCP-associated respiratory failure supported with VV ECMO is associated with substantial mortality and prolonged VV ECMO support. These findings provide contemporary benchmarks that may inform VV ECMO candidacy discussions and expectations in this challenging patient population.

 The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented strain on healthcare systems worldwide, potentially exacerbating existing vulnerabilities in maternal healthcare. This study examines the pandemic's impact on obstetric haemorrhage-related mortality in South Africa using the data from the Confidential Enquiry into Maternal Deaths (CEMD).

 We conducted a retrospective analysis of maternal mortality data from 2017-2023, focusing on obstetric haemorrhage mortality trends before, during and after the COVID-19 pandemic. Data were extracted from national confidential enquiries, including institutional maternal mortality ratios (iMMR) and absolute death numbers.

 The analysis revealed a significant increase in obstetric haemorrhage mortality during the peak pandemic years (2020-2021), with deaths rising from 179 in 2019 to 237 in 2021, and iMMR increasing from 18.1 to 23.3 per 100 000 live births. This was followed by a substantial decline in subsequent years (2022-2023). The findings suggest that initial pandemic disruptions severely impacted maternity care services, while subsequent recovery reflects adaptive strategies and resource reallocation.

 The COVID-19 pandemic exposed critical vulnerabilities in South Africa's ability to maintain essential maternity services during health system shocks.Contribution: The confidential enquiry process provides invaluable insights for strengthening health system resilience and preparing for future emergencies.

 Maternal mortality highlights health system effectiveness and social fairness. South Africa's Confidential Enquiry into Maternal Deaths (CEMD) monitors and improves maternal healthcare. While initial decreases in maternal mortality were positive, the COVID-19 pandemic and ongoing provincial inequalities jeopardise reaching the Sustainable Development Goal (SDG) target.

 This analysis evaluated South Africa's maternal mortality reduction path by examining CEMD data trends, the pandemic's effect and provincial disparities to gauge progress towards its SDG commitments.

 A longitudinal trend analysis was conducted using secondary data from CEMD reports (2017-2022). The analysis focused on national and provincial institutional Maternal Mortality Ratio (iMMR) trends. Comparative analysis quantified changes and identified patterns of disparity.

 Pre-pandemic improvement was abruptly reversed by a significant 42% surge in the national iMMR during the pandemic, underscoring the fragility of previous gains. Although a decrease was observed in 2022, the rate remained above the 2019 baseline, indicating an incomplete recovery. Furthermore, profound inter-provincial disparities were evident, with only two provinces sustaining a downward trend, the majority showing no clear improvement and three provinces consistently exhibiting exceptionally high and volatile iMMRs.

 South Africa is not yet on track to meet its SDG target for maternal mortality. The pandemic exposed and exacerbated systemic weaknesses, while deep-rooted provincial inequities persist. Achieving sustainable progress requires a dual strategy: building a more resilient health system capable of withstanding future shocks and implementing targeted, equity-focused interventions in underperforming regions to ensure that maternal healthcare is accessible and effective for all.