• Differences in tumor-associated cytokine production and immune mechanisms between myofibroblastic cancer associated fibroblasts and myofibroblasts.
    3 weeks ago
    Despite advances in oral cancer treatment, therapeutic resistance remains a major challenge. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment. Building on our previous findings on immune responses in gingival fibroblasts, we investigated the immune characteristics of CAFs. Myofibroblast CAF-like cells (myCAF-like) were established using a co-culture system and compared with gingival fibroblast-derived myofibroblasts. MyCAF-like cells exhibited markedly reduced expression of TLR3 and TLR4, whereas RIG-I, COX-2, IL-1β, IL-6, and IL-8 were significantly upregulated. Activation of p38 MAPK signaling contributed to the increased expression of COX-2 and pro-inflammatory cytokines, and TGF-β was involved in the phenotypic transformation of gingival fibroblasts into myCAF-like cells. Microarray analysis revealed upregulation of IL-1α, IL-1β, CXCL8, PTGS2, and CXCL5, alongside downregulation of OMD, COL15A1, and ASPN in myCAF-like cells. Collectively, these findings demonstrate that CAFs acquire a distinct inflammatory signature that differs from gingival fibroblasts and promotes tumor invasion and progression. Targeting CAF-associated inflammatory and signaling pathways may represent a promising strategy to overcome tumor infiltration and treatment resistance in oral cancer.
    Cancer
    Policy
  • Role of the H19/miR-423-5p/DTX3L Axis in Enhancing the Malignant Phenotype of Nasopharyngeal Carcinoma Cells.
    3 weeks ago
    Deltex E3 ubiquitin ligase 3L (DTX3L) is a well-established ubiquitin ligase implicated in various cancers, but its role in nasopharyngeal carcinoma (NPC) progression remains elusive. In this study, we confirmed for the first time that DTX3L was highly expressed in C666-1 and NPC/HK1 NPC cells. DTX3L overexpression promoted NPC cell proliferation, invasion, and migration. Conversely, DTX3L knockdown suppressed these malignant phenotypes. Notably, DTX3L activated the β-catenin pathway, as evidenced by increased β-catenin nuclear translocation, increased transcriptional activity, and elevated expression of its downstream target c-Myc. Mechanistically, we identified an upstream regulatory axis in which the oncogenic long noncoding RNA H19 acted as a molecular sponge for miR-423-5p, thereby alleviating the miR-423-5p-mediated repression of DTX3L. Dual-luciferase reporter assays confirmed that miR-423-5p directly targeted both DTX3L and H19, supporting the presence of a competitive endogenous RNA (ceRNA) network. Furthermore, rescue experiments demonstrated that DTX3L knockdown largely abolished the proliferative advantage conferred by H19 overexpression. Collectively, the results of our study revealed that the H19/miR-423-5p/DTX3L axis is a novel ceRNA-driven mechanism that promotes NPC progression via activation of β-catenin signaling.
    Cancer
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  • Prevalence and Survival Outcomes of L1 Cell Adhesion Molecule-Positive in Endometrial Cancer Across Molecular Subtypes: A Systematic Review and Meta-Analysis.
    3 weeks ago
    L1 cell adhesion molecule (L1CAM) has emerged as a potential prognostic biomarker in endometrial cancer. This systematic review and meta-analysis aimed to comprehensively evaluate the prevalence of L1CAM expression across molecular subtypes of endometrial cancer and its prognostic significance for survival outcomes.

    A systematic literature search of PubMed, Embase, and Cochrane Library was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies reporting L1CAM expression in endometrial cancer, stratified by molecular subtypes (polymerase epsilon [POLE], mismatch repair deficiency [MMR-D], no specific molecular profile [NSMP], p53 wild type [p53wt], p53 abnormal [p53abn]), and their association with survival outcomes were included. Pooled prevalence and hazard ratios with 95% CIs were calculated using random-effects models.

    Twenty-one retrospective studies met the inclusion criteria. The overall pooled prevalence of L1CAM positivity was 15%. Stratified by molecular subtype, prevalence was the lowest in POLE-mutated tumors (4.87%), followed by p53abn tumors (52.86%), MMR-D tumors (52.16%), NSMP (30.88%), and p53wt (25.99%). L1CAM positivity was significantly associated with worse disease-specific survival (hazard ratio [HR], 2.49 [95% CI, 1.75 to 3.55]) and progression-free survival (HR, 2.50 [95% CI, 1.56 to 4.01]). Subgroup analyses revealed significant associations in MMR-D tumors (HR, 1.75 [95% CI, 1.06 to 2.89]), NSMP tumors (HR, 5.41 [95% CI, 2.92 to 10.03]), and a borderline effect in p53abn tumors (HR, 1.69 [95% CI, 1.00 to 2.85]).

    The highest prevalence of L1CAM was found in p53abn endometrial tumors. L1CAM positivity is associated with poor survival outcomes, particularly in MMR-D and NSMP subgroups. These findings highlight the potential of L1CAM as a prognostic biomarker that could refine risk stratification and guide adjuvant management more accurately in endometrial cancer, warranting validation in prospective studies.
    Cancer
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  • [Why has bladder cancer incidence not decreased like in lung cancer?].
    3 weeks ago
    Compared with lung cancer (excluding lung adenocarcinoma), where a decreased incidence has been reported in Sweden following a decline in the prevalence of daily smokers, we observed an increased incidence of bladder cancer, especially in older men. Given that approximately half of the individuals diagnosed with either malignancy are current or former smokers, the reasons for this paradoxical shift in incidences between the diseases remain unclear. However, it is noteworthy that bladder cancer mortality did not rise in parallel with the increased incidence, and even decreased among men.
    Cancer
    Chronic respiratory disease
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  • New Zealand paediatric respiratory stock-take survey.
    3 weeks ago
    Tamariki (children) in Aotearoa New Zealand suffer high rates of respiratory morbidity. There are also geographic, socio-economic and ethnicity inequities, with tamariki Māori and Pacific children, experiencing the highest rates. Our aim was to survey New Zealand respiratory health services and identify gaps in delivery.

    We invited health practitioners from all districts to respond to an online survey and separately contacted individuals known to deliver paediatric respiratory care. We included medical, nursing and allied health staff and collated responses.

    There were 23 responses from 17 hospitals. Respiratory- and sleep-specialist senior medical officers (SMOs) were employed in only three major centres. Full time equivalent (FTE) for paediatricians with an interest (PWI) in respiratory care was evenly distributed with low numbers reported in the Northern region, Wellington and Canterbury. Senior nurse FTE was fairly constant across the country, except in the Northern region. Allied health staffing was inconsistent across the country with many districts in the Te Manawa Taki region reporting little or no respiratory physiotherapy staffing. More than half of districts reported limited or no access to videofluoroscopic swallow studies. There is poor access to chest computed tomography (CT) scanning under general anaesthetic in more than half of centres.

    Despite high levels of respiratory disease and morbidity, with serious disparities, there is inadequate staffing and provision of services. There is an urgent need for better co-ordination of care but a lack of both national and regional frameworks despite respiratory health being a current health target.
    Chronic respiratory disease
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  • Nursing Home Administrator Perspectives on the Role of State Guidance and Assistance in COVID-19 Response: A Rhode Island Case Study.
    3 weeks ago
    The COVID-19 pandemic significantly impacted nursing homes in the United States. The Departments of Health within each state played a substantial role in providing guidance, issuing regulations, and supplying resources to help organizations respond to this health emergency. This research characterizes nursing home administrator perspectives on the role of Rhode Island's state agencies during the COVID-19 pandemic.

    This qualitative case study includes data from 19 repeated interviews with administrators of six nursing homes, conducted from July 2020-December 2021. In-depth, semi-structured interviews focused on their COVID-19 response, including infection control, vaccination, and interactions with state agencies, among other topics. Interview transcripts were qualitatively analyzed to determine overarching themes.

    Three themes emerged from analysis of interview transcripts: 1. Nursing home administrators described the regulatory guidance and communications from Rhode Island's Department of Health, which shaped their COVID-19 response. 2. Administrators discussed the tangible resources and support, such as personal protective equipment and staffing support, they received from the state. 3. Administrators identified the strengths and challenges in collaborating with state agencies and noted areas for improvement.

    Study findings have implications for how states help nursing homes respond during emergencies. While the vaccine has reduced the impact of COVID-19 on nursing home residents and staff, insights provided by administrators in this case study suggest best practices for improving future health emergency communications around guidance and regulations, and suggestions for necessary resources.
    Chronic respiratory disease
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  • A comparative study of incidence rate and severity of influenza virus and respiratory syncytial virus associated hospitalisation in older adults in Jiangsu Province, China: a retrospective analysis of a regional medical database.
    3 weeks ago
    Few studies have compared the disease burden between influenza virus (IFV) and respiratory syncytial virus (RSV) in older adults, particularly outside high-income countries. We aimed to compare IFV- and RSV-associated hospitalisation burden and severity in older adults in Jiangsu Province, China.

    Drawing on a medical database from Jiangsu Province, an economically-developed province in eastern China, we included acute respiratory infections (ARI) admission records in adults aged ≥60 years during 2020 to 2023, linked with viral testing data, where available. We applied a time-series regression model for estimating RSV- and IFV-associated hospitalisation rates by year, age group, and sex. We compared disease severity, defined as a composite of mechanical ventilation use, intensive care unit (ICU) admission, or in-hospital mortality, between RSV- and IFV-positive cases using multivariable logistic regression, with adjustments for age, sex, year, region, and laboratory method.

    We included 188 529 ARI hospitalisation episodes during the study period. RSV and IFV had comparable hospitalisation rates, peaking in 2023 at 98 per 100 000 person-years (95% confidence interval (CI) = 81-115) for RSV and 116 per 100 000 person-years (95 CI = 100-133) for IFV. Hospitalisation rates increased with older age and were marginally higher in males. The risk for severe cases was 1.47 (95% CI = 1.086-1.997, P = 0.013) times higher in RSV than in IFV. Older age and being males were independent risk factors for severe cases.

    We found the RSV hospitalisation burden to be comparable to that of IFV in older adults, albeit with higher severity. The findings contribute to the evidence base for recommendation of RSV and IFV vaccination in older adults in China.
    Chronic respiratory disease
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  • Asthma patients are at increased risk for adverse events and reoperation following posterior lumbar fusion.
    3 weeks ago
    Posterior lumbar fusion (PLF) is a common procedure for which patient factors are known to influence outcomes. Although asthma is comorbid for many PLF patients, it has not been assessed for correlation to adverse events following PLF. We used a national administrative database to evaluate the relative odds of adverse events following PLF in patients with versus without asthma.

    Adult patients undergoing primary one- or two-level PLF with or without interbody fusion were identified from 2015 - 2023Q1 PearlDiver datasets. Asthma patients were matched 1:4 based on age, sex, and Elixhauser Comorbidity Index (ECI). The incidence of 90-day adverse events were compared using multivariable logistic regression. Five-year reoperations were compared with Cox proportional hazards modeling. The matched asthma group was then stratified by disease severity for multivariable analysis of 90-day aggregated adverse events.

    After matching, 19,078 asthma patients undergoing PLF were compared to 75,838 patients without asthma. Asthma patients were at increased odds of 90-day pulmonary adverse events, (p < 0.0001 for each) as well as non-pulmonary adverse events (p < 0.0001 for each). These associations increased in odds with increasing severity of asthma. Further, asthma patients had significantly higher rates of five-year revision, reflected by lower reoperation free survival compared with non-asthma patients (89.2% versus 92.6%, p < 0.0001).

    Over a tenth of patients undergoing PLF were identified as having asthma and were found to be of greater odds of pulmonary and non-pulmonary adverse events (a trend that increased with asthma severity), as well as five-year revisions. Stringent pre-operative optimization and postoperative management strategies should be employed for asthma patients undergoing PLF.
    Chronic respiratory disease
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  • Comparison of post-discharge mortality and medical expenditures in COVID-19 patients according to mechanical ventilation and extracorporeal membrane oxygenation use: The LIFE study.
    3 weeks ago
    Outcomes related to health status and economic burden among patients who experienced critical COVID-19 remain insufficiently studied. We examined 180-day post-discharge mortality and total medical expenditures in COVID-19 patients according to their use of mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) during hospitalization. Using medical claims data from a Japanese municipality, this retrospective cohort study analyzed hospitalized COVID-19 patients who were discharged between April 1, 2020 and September 30, 2021. Patients were categorized into an MV/ECMO group (indicating severe disease) or a non-MV/ECMO group. Their differences in mortality and expenditures were compared using the χ2 test and Mann-Whitney U test, respectively. A Cox regression analysis was performed to calculate the hazard ratios of MV/ECMO use for mortality, and a generalized linear model with gamma distribution was constructed to examine the association between MV/ECMO use and expenditures. The covariates included age, sex, comorbidities, and length of stay. The MV/ECMO group had significantly higher mortality (16.0% vs. 11.1%, p = 0.002) and expenditures ($8,732 vs. $3,460, p < 0.001) than the non-MV/ECMO group. MV/ECMO use was significantly associated with higher mortality (hazard ratio: 1.66, 95% confidence interval: 1.27-2.15); other risk factors included age (1.06, 1.05-1.07), dementia (1.48, 1.10-1.99), and cancer (1.92, 1.56-2.36). MV/ECMO use was also significantly associated with higher expenditures (Exp[β]: 1.49, 95% confidence interval: 1.29-1.73); other risk factors included kidney disease (1.60, 1.29-2.01), cerebrovascular disease (1.74, 1.56-1.94), and cancer (1.28, 1.14-1.44). Survivors of severe COVID-19 who required MV or ECMO during hospitalization were associated with higher post-discharge mortality and expenditures, suggesting a need for targeted care to reduce their clinical and economic burden.
    Chronic respiratory disease
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  • Clinical presentation and management outcomes of pediatric lung abscess: A retrospective cohort study.
    3 weeks ago
    Pediatric lung abscess is an uncommon but potentially serious complication of pneumonia. Limited data exists on its clinical features, diagnostic workup, and outcomes in otherwise healthy children.

    To describe the clinical characteristics, management strategies, and outcomes of children diagnosed and treated for lung abscess in Jordan.

    We conducted a retrospective descriptive study of 23 pediatric patients diagnosed with and managed for lung abscess in Jordan. Data collected included demographic characteristics, clinical presentation, laboratory findings, treatment regimens, and outcomes.

    The mean age was 7.2 years (SD 3.1), with 60.9% male and no underlying chronic diseases in any patient. Systemic symptoms such as fever (91%) and hypoactivity (91%) were common. Cough was reported in 87% of cases, with varying patterns (dry, wet, or both). Imaging confirmed that 56.5% of abscesses were located in the left lung and 43.5% in the right lung. TB was systematically excluded using PPD and PCR testing. All patients received initial broad-spectrum antibiotics; 87% required escalation to include piperacillin-tazobactam combined with aminoglycoside (either amikacin or gentamicin). The mean duration of antibiotic use was 4.8 weeks. Only one patient (4.3%) underwent surgical intervention, and two patients (8.7%) required ICU care. Follow-up imaging 1-2 weeks after completion of therapy showed full resolution in 91% of cases.

    Pediatric lung abscess in otherwise healthy children presents with significant systemic and respiratory symptoms but responds well to prolonged, escalated antibiotic therapy. Conservative management is effective in the majority of cases, with excellent clinical and radiological outcomes and low surgical intervention rates.
    Chronic respiratory disease
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