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[Expert consensus on the clinical application of PARP inhibitors in breast cancer (2025 edition)].2 weeks agoBreast cancer poses a major threat to women's health in China, with its incidence rate continuously rising, leading to an increasing disease burden and an urgent need for novel and effective treatment strategies. In recent years, poly ADP-ribose polymerase (PARP) inhibitors, as a new class of anti-tumor drugs targeting the DNA damage repair pathway, have demonstrated significant efficacy in the treatment of breast cancer with BRCA1/2 mutations. These agents induce a "synthetic lethality" effect by specifically inhibiting DNA repair in tumor cells, offering a new option for precision therapy. Currently, PARP inhibitors such as olaparib and fluzoparib have been approved for clinical use. Based on the latest evidence-based medical data, the Professional Committee on Clinical Research of Oncology Drugs, China Anti-Cancer Association, Expert Committee for Monitoring the Clinical Application of Antitumor Drugs and Breast Cancer Expert Committee of National Cancer Quality Control Center, Cancer Chemotherapy Quality Control Expert Committee of Beijing Cancer Treatment Quality Control and Improvement Center have jointly organized and invited domestic oncology experts with rich diagnosis and treatment experience as well as relevant interdisciplinary experts to compile the "Expert consensus on the clinical application of PARP inhibitors in breast cancer (2025 edition)". This consensus aims to provide guidance on the standardized application and safety management of PARP inhibitors in breast cancer treatment, with the goal of supporting clinical practice.Non-Communicable DiseasesCancerCare/Management
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Single-cell multiomic and spatial landscape of the primate pineal gland reveals circadian and melatonin regulatory architecture.2 weeks agoThe mammalian pineal gland maintains normal circadian rhythms and homeostasis by secreting melatonin. However, the lack of a single-cell-resolved regulatory map limits our understanding of how these neuroendocrine functions are orchestrated. Here, we constructed a multiomics atlas of the pineal gland from Macaca fascicularis by integrating snRNA-seq, snATAC-seq, and spatial transcriptomics. We identified pinealocytes as the predominant cell type, alongside six glial and vascular lineages. Chromatin accessibility analysis delineated cell-type-specific regions enriched for melatonin synthesis and phototransduction genes. Notably, we resolved a dual-layer regulatory architecture: While melatonin synthesis programs are robustly organized, circadian clock regulators exhibit a distinct, sparse spatial pattern. Coexpression networks further identified core modules and regulatory hubs-including CRX/OTX2, LHX4, and RORA-that integrate these circadian and light-responsive signals. Cell-cell communication analysis identified signaling axes, such as PTN-ALK/SDC2, RA-RORB, and NRG1-ERBB4, that potentially coordinate this spatial functional organization. Integrating genetic traits showed that sleep and neuropsychiatric risk variants preferentially map to these pineal regulatory modules. Specifically, sleep-associated loci converged on MEIS1-linked elements, while bipolar disorder-associated loci highlighted candidate genes of RDH12 and SDK2. Overall, this study reveals the cellular diversity and spatial regulatory logic of the primate pineal gland, providing a physiological foundation for investigating circadian and neuroendocrine regulation in healthy and disease models.Non-Communicable DiseasesPolicy
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Risk factors for post-renal transplant ureteral stenosis: a survival analysis in a contemporary cohort.2 weeks agoUreteral stenosis remains a significant urological complication after kidney transplantation. This study aimed to identify independent risk factors for the development of post-transplant ureteral stenosis and to evaluate their temporal impact using survival analysis in a contemporary cohort.
A retrospective single-center cohort study was conducted, including 342 deceased donor kidney transplant recipients between 2014 and 2024. The primary endpoint was the time to radiologically confirmed ureteral stenosis within the first post-transplant year. Univariate analysis and Kaplan-Meier survival curves were used to identify associated factors. A multivariable Cox proportional hazards model was constructed to determine independent predictors, adjusting for clinically relevant variables.
The incidence of ureteral stenosis was 11.1% (n = 38). Multivariable Cox regression identified urinary fistula as the strongest associated factor (Hazard Ratio [HR]: 8.28; 95% CI: 3.87-17.72; p < 0.001), drastically reducing median stenosis-free survival to 188.9 days. Diabetes mellitus showed a borderline association with stenosis (HR: 2.41; 95% CI: 1.02-5.72; p = 0.046). Conversely, the prophylactic use of a double-J stent was an independent protective factor, reducing the risk of stenosis by 72% (HR: 0.28; 95% CI: 0.11-0.73; p = 0.009). Postoperative urinary tract infection showed a non-significant trend (HR: 1.89; p = 0.079).
Urinary fistula was the strongest predictor of ureteral stenosis, underscoring the importance of its prevention. Routine prophylactic double-J stenting appeared to be an effective protective strategy. Diabetes mellitus showed a borderline association with stenosis and may identify a subgroup requiring closer postoperative urological surveillance; this finding should be interpreted cautiously and confirmed in larger studies.DiabetesAccessCare/ManagementAdvocacy -
Living with diabetes: quality of life and functional impairment among adults with type 2 diabetes in Northern Brazil.2 weeks agoType 2 diabetes mellitus (T2DM) is a growing public health concern in Brazil, especially in underserved regions where social and geographic barriers may affect disease management and quality of life. Functional capacity and health-related quality of life (HRQoL) are critical dimensions often overlooked in primary care approaches. To assess the functional capacity and HRQoL of individuals with T2DM receiving care in primary health units in Tocantinópolis, Northern Brazil, and to explore associations with sociodemographic and clinical variables. This is a cross-sectional, descriptive, and analytical study involving 99 adults diagnosed with T2DM. Functional capacity was assessed through validated protocols measuring upper and lower limb muscle strength, hamstring flexibility, mobility and cardiorrespiratry fitness. Physical activity was analyzed using the International Physical Activity Questionnaire (IPAQ) and HRQoL was assessed through Diabetes Quality of Life (DQOL). Sociodemographic and clinical data were also collected. Statistical analysis included descriptive statistics and linear regression models. Most participants were women (71%), with a mean age of 58.7 years. The physical and psychological domains of DQOL presented the lowest scores, while the social domain had the highest. Functional capacity was low for most participants. There were significant associations between low physical activity levels and poorer HRQoL scores in the physical and psychological domains. Individuals with T2DM in this sample presented reduced functional capacity and compromised HRQoL, particularly in domains related to physical and psychological well-being. These findings highlight the urgent need for integrated health strategies in primary care that address physical activity and emotional support for people living with diabetes in remote and low-resource settings.DiabetesDiabetes type 2AccessCare/Management
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Optimising care for uncomplicated type 2 diabetes mellitus in Lagos, Nigeria: cost and benefit estimates using real-world data.2 weeks agoDiabetes mellitus accounts for a significant share of morbidity and mortality in ages 30-70 years worldwide. In sub-Saharan Africa, diabetes care is often suboptimal for reasons ranging from health system weaknesses to patient illiteracy and non-compliance with recommendations. This study explores the potential costs and health benefits of optimising care for uncomplicated type 2 diabetes in Lagos State, Nigeria.
Longitudinal data on medical care patterns and resource use (consultations, medications, diagnostics and lifestyle counselling) over a 1-year period were collected retrospectively from 84 health facilities in Lagos. Medical resource prices were obtained from a subsample of 26 facilities. Patient care gaps were assessed by comparing actual journeys to official diabetes management guidelines. Mixed-effect regression analyses were employed to explore the impact of care elements on blood glucose control and model the potential complications averted if all patients received recommended care, with extrapolation to the entire Lagos population.
Data from 642 patients with uncomplicated type 2 diabetes were analysed. A one-unit increase in consultation score (a measure of the adequacy of consultation visits) and having health insurance coverage were linked to 47-unit and 29-unit lower blood glucose levels, respectively. Optimising diabetes care requires US$3716 per patient annually, totalling US$2.1 billion statewide, with medications comprising 97% of costs. Enhanced care could reduce stroke and myocardial infarction by 2% (12 675 cases) and 4% (22 282 cases) over 7 years, respectively, at a cost of US$61 492 per complication averted.
The investment required to optimise diabetes care in Lagos is currently unfeasible in the existing approaches. There is a need to explore innovative financing and delivery options, including digital value-based care interventions and cost-saving care approaches such as pooled medication procurement, while also investing in local medicines production capacity and expansion of the health insurance coverage.DiabetesDiabetes type 2AccessAdvocacy -
Using the enhanced liver fibrosis test to identify disease in at-risk populations.2 weeks agoSteatotic liver disease is common and has increased prevalence among those with type II diabetes mellitus or hazardous alcohol use. Identifying individuals with advanced liver disease early through screening may afford timely opportunities to reduce disease progression. This study assesses the application of non-invasive tests in at-risk populations to identify clinically important disease.
The enhanced liver fibrosis (ELF) test and liver stiffness measurement (LSM) were used as non-invasive means to assess risk of fibrosis in two at-risk populations in Leeds, UK. Patients in a community diabetes clinic and patients with hazardous alcohol use attending alcohol treatment services between March 2019 and March 2020 were offered ELF testing alongside routine review. Those with ELF ≥9.5 were offered LSM.
In total, 972 patients were assessed, of whom 325 underwent both ELF and LSM. Patients referred from the diabetes clinic were typically older and had higher body mass index values, while alanine aminotransferase and serum bilirubin values were higher in those referred from alcohol services. Forty-five per cent of patients referred from the diabetes service had an ELF score below 9.5, and only 7.9% undergoing LSM had readings ≥15 kPa. Seventy-two per cent of patients referred from the alcohol service had ELF scores below 9.5, with 31% subsequently having LSM values ≥15 kPa.
Steatotic liver disease is relatively common in those with risk factors and particularly those drinking excess alcohol. Strategies for identifying at-risk individuals may help to increase early diagnosis, though care must be taken when selecting appropriate tests.DiabetesDiabetes type 2AccessCare/ManagementAdvocacyEducation -
Community insights into type 1 diabetes care in Armenia: a qualitative study informing health policy reform.2 weeks agoTo explore the lived experiences of children with type 1 diabetes (T1D) and their caregivers in Armenia, a post-Soviet country, and to identify system-level barriers to care from the community perspective.
Qualitative study using a phenomenological design with inductive thematic analysis.
Muratsan Hospital Complex, the primary national referral centre for paediatric endocrinology, Yerevan, Armenia.
12 children aged 13-17 years with T1D and their caregivers, recruited through purposive sampling across 7 of Armenia's 10 administrative regions.
Five themes emerged from the data: (1) barriers to care, (2) quality of care, (3) perceived control of T1D, (4) knowledge of T1D and (5) government and non-governmental organisation (NGO) support. Participants described unreliable government-supplied glucose strips, geographical barriers rooted in the centralisation of specialist care in the capital, abrupt withdrawal of state support at age 18, reliance on the KATIL NGO to fill gaps in both clinical and psychosocial support and pervasive stigma encountered across family, school and clinical settings.
Children with T1D in Armenia navigate a post-Soviet health system where provisions exist but remain fragmented, limited by centralised care, geographical barriers and variable support. This unique context shapes the relationship and expectations patients have of the healthcare system. Community perspectives are indispensable in these settings, surfacing system-level gaps that conventional data cannot capture. These findings have relevance for other health systems navigating similar structural transitions.DiabetesDiabetes type 1AccessCare/ManagementPolicy -
It's Best to Test in Hospital: Improved Testing Rates with Immediate Postpartum Diabetes Testing in Patients with Gestational Diabetes in a Community-Academic Medical Center.2 weeks agoImmediate postpartum diabetes (IPD) testing on day 1 or 2 shows similar diagnostic value to testing at 4 to 12 weeks' postpartum and achieves higher completion rates. Our institution implemented IPD testing on December 1, 2023, before the American College of Obstetricians and Gynecologists' endorsement, to compare pre and postimplementation testing rates and to assess associated maternal and neonatal outcomes.
We conducted a retrospective cohort study of patients with gestational diabetes mellitus (GDM) who delivered at our community-academic medical center before (September 1, 2022-November 15, 2023) and after (December 1, 2023-October 31, 2024) IPD implementation. The preimplementation group underwent outpatient testing 4 to 12 weeks' postpartum. The postimplementation group was tested in-hospital 1 or 2 days' postpartum. Both groups received a 2-h our glucose challenge test. Electronic medical records were queried for demographics, medical and obstetric history, GDM information, and postpartum diabetes testing results. Completion rates, maternal, and neonatal factors were compared across and within cohorts using chi-square tests and t-tests.
Across 155 patients (63 preimplementation, 92 postimplementation), baseline characteristics were similar, excluding age. Testing completion increased nearly 5-fold postimplementation (14.3% [9/63] vs. 68.5% [63/92], p < 0.01). In the postimplementation group, 49% of tested patients had abnormal results (43% impaired glucose metabolism, 6% overt diabetes). Non-English speakers and those with a postpartum length of stay > 1 day were more likely to be tested (22.2 vs. 3.45%, p = 0.02; 98.4 vs. 48.3%, p < 0.01). Neonates in the tested group had a lower mean birth weight (3,137.1 ± 665.1 vs. 3,374.4 ± 484.7 g; p = 0.05), longer nursery stay (2.55 ± 2.2 vs. 1.83 ± 0.69 days; p = 0.03), and more neonatal intensive care unit admissions (20.63 vs. 0%; p = 0.01).
IPD testing dramatically improved testing and identified a high prevalence of persistent dysglycemia immediately postpartum. Hospital systems should consider implementing this practice change to improve testing rates and early intervention in postpartum care of patients with GDM.
· IPD testing is a feasible and replicable practice.. · IPD testing increased rates nearly 5-fold compared with traditional timing.. · Persistent dysglycemia was identifiable immediately postpartum.. · Longer hospital stays increased the likelihood of testing.. · In-hospital testing may reduce language barriers..DiabetesAccess -
Outcomes and factors associated with medical treatment failure in patients with spinal epidural abscess: A 14-year experience.2 weeks agoThe optimal therapeutic approach for treating spinal epidural abscesses (SEAs) is not well defined. This study aimed to describe the failure rate of medical management and identify factors associated with failure.
We conducted a single-centre retrospective cohort including all adult patients diagnosed with SEA between 2009 and 2022. The primary endpoint was a composite of in-hospital mortality and motor neurological sequelae at discharge.
Among 76 patients, 22.4% (n = 17) received initial intervention, while 77.6% (n = 59) received medical management. Among medically managed patients, 42.5% (n = 25) experienced treatment failure, and 27.1% (n = 16) required salvage surgery. Factors associated with treatment failure included diabetes mellitus (32.0% vs 8.8%, p = 0.040), an erythrocyte sedimentation rate (ESR) greater than 75 mm/h (66.7% vs 31.0%, p = 0.021), methicillin-resistant Staphylococcus aureus (MRSA) (28.0% vs 0%, p < 0.001) and anterior epidural involvement (91.3% vs 60.6%, p = 0.014). Although patients initially treated surgically had significant worse neurological motor situation at presentation than those managed medically (ASIA A or B 20.0% vs 3.4%), the primary endpoint occurred more frequently in patients with failure of initial medical treatment than in those initially operated (65.0% vs 35.3%, p = 0.035). SEA-related mortality was also higher among those with medical treatment failure (16.0% vs 0%, p = 0.038).
Failure of medical management of SEA was common and could lead to worse outcomes. Diabetes mellitus, ESR greater than 75 mm/h, MRSA, and ventral epidural involvement were associated with failure. Initial surgery might be considered for low operative risk patients in the presence of these factors. Prospective trials are needed to better guide initial management strategies.DiabetesAccessCare/ManagementAdvocacy -
Association between coronavirus disease 2019 and new-onset autoimmune diseases during the early phase of the pandemic.2 weeks agoEmerging evidence suggests that viral infections, including SARS-CoV-2, may trigger autoimmunity. This study investigated the risk of developing autoimmune diseases following coronavirus disease 2019 (COVID-19) using sequence symmetry analysis. We utilized nationwide population-based data from South Korea by linking the National Health Insurance Service database with the Korea Centers for Disease Control and Prevention Agency COVID-19 registry. This study included 2,678 patients with COVID-19 and 92,725 patients without COVID-19 identified between 01/10/2020 and 30/06/2021, during the early phase of the pandemic. Both groups consisted of individuals who were diagnosed with autoimmune diseases within 180 days before or after the index date. We calculated the adjusted sequence ratio (aSR) to compare the incidence of autoimmune diseases within 180 days before and from 14 to 180 days after the index date (the COVID-19 diagnosis date for the COVID-19 group and the first medical visit for the non-COVID-19 group). The differences in autoimmune disease incidence between the groups were evaluated using the ratio of aSR (RaSR). The incidence of newly diagnosed autoimmune diseases-Behcet's disease (RaSR, 2.03), ankylosing spondylitis (2.04), ulcerative colitis (1.15), Crohn's disease (2.22), psoriasis (1.27), type 1 diabetes mellitus (1.61), and Graves' disease (1.14)-was significantly higher in the COVID-19 group than in the non-COVID-19 group after the index date. Subgroup analysis comparing patients with non-severe COVID-19 with those without COVID-19 yielded consistent findings. Furthermore, the incidence of inflammatory bowel diseases was higher in the non-severe COVID-19 group after the index date (RaSR, 1.29). These findings reinforce growing evidence that COVID-19 could induce autoimmunity and increase the risk of developing autoimmune diseases. Therefore, clinicians should remain vigilant for potential autoimmune complications in patients with a history of COVID-19 when clinically indicated.DiabetesChronic respiratory diseaseDiabetes type 1AccessAdvocacy