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Exploratory outcomes of the DHA WIN randomized controlled trial: Supplementing women with docosahexaenoic acid did not reduce the impact of neoadjuvant breast cancer chemotherapy on quality of life or exercise behaviour
No full textSupplementation of omega-3 (n-3) polyunsaturated fatty acids has been associated with reduced side effects and improved quality of life (QoL) in breast cancer patients receiving chemotherapy. The current study reports secondary outcomes from the DHA WIN randomized controlled trial which was designed to evaluate docosahexaenoic acid (DHA) supplementation (4.4 g/day) in conjunction with six cycles of neoadjuvant chemotherapy (NAC) (3 weeks/cycle) in women with non-metastatic breast cancer (n = 49). The objective of the current study was to assess the effects of DHA supplementation on QoL and exercise behaviour in women undergoing NAC for breast cancer. Self-administered questionnaires were used to measure QoL and exercise behaviour before starting chemotherapy (baseline), before each chemotherapy cycle (exercise), and after completing chemotherapy. DHA supplementation did not significantly affect QoL, aerobic exercise volume or resistance training frequency during treatment. However, mean aerobic exercise volume was significantly lower at week 12 (-53.5 minutes/week; 95% CI, -100.5 to -6.3; p = 0.02) and week 18 (-70.8 minutes/week; 95% CI, -123.0 to -18.6; p = 0.01) compared to baseline. Mean resistance training frequency was lower at week 12 (-0.57 times/week; 95% CI, -1.0 to -0.13; p = 0.02) compared to baseline. Meeting exercise guidelines during chemotherapy was not associated with better QoL. In the current exploratory study, QoL and exercise decreased during treatment regardless of DHA supplementation, highlighting the need for supportive care and potential therapies that may mitigate these declines in breast cancer patients receiving NAC. Adequately powered studies are needed to determine if DHA supplementation improves these two indices of health. The trial is registered at ClinicalTrials.gov (NCT03831178)
Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland
No full textOBJECTIVES: Sjögren\u27s disease (SjD) and systemic lupus erythematosus (SLE) share genetic risk at the DDX6-CXCR5 locus (11q23.3). Identifying and functionally characterising shared SNPs spanning this locus can provide new insights into common genetic mechanisms of autoimmunity.
METHODS: Transdisease meta-analyses, fine-mapping, and bioinformatic analyses prioritised shared likely functional single nucleotide polymorphisms (SNPs) for allele-specific and cell type-specific functional interrogation using electromobility shift, luciferase reporter, and quantitative chromatin conformation capture assays and clustered regularly interspaced short palindromic repeat (CRISPR) gene regulation.
RESULTS: Five shared SNPs were identified as likely functional in primary human immune cells, salivary gland and kidney tissues: rs57494551, rs4936443, rs4938572, rs7117261, and rs4938573. All 5 SNPs exhibited cell type-specific and allele-specific effects on nuclear protein binding affinity and enhancer/promoter regulatory activity in immune, salivary gland epithelial, and kidney epithelial cell models. Mapping of chromatin-chromatin interactions revealed a chromatin regulatory network that expanded beyond DDX6 and CXCR5 to include PHLDB1, lnc-PHLDB1-1, BCL9L, TRAPPC4, among others. Coalescence of functional assays and multiomic data analyses indicated that these SNPs likely modulate the activity of 3 regulatory regions: intronic rs57494551 regulatory region, intergenic SNP haplotype (rs4938572, rs4936443, and rs7117261) regulatory region, and rs4938573 regulatory region upstream of the CXCR5 promoter.
CONCLUSIONS: Shared genetic susceptibly at the DDX6-CXCR5 locus in SjD and SLE likely alters common mechanisms of autoimmunity, including interferon signalling (DDX6), autophagy (TRAPPC4), and lymphocytic infiltration of disease-target tissues (CXCR5). Further, using multiomic data from patients with SjD, combined with bioinformatic and in vitro functional studies, can provide mechanistic insights into how genetic risk influences the biological pathways that drive complex autoimmunity
The Role of Bronchoscopy in the Diagnosis of Interstitial Lung Disease: A State-of-the-Art Review
No full textThe diagnostic evaluation of interstitial lung diseases (ILDs) remains challenging due to their heterogeneous etiologies and overlapping clinical and radiographic patterns. A confident diagnosis often necessitates histopathological sampling, particularly when high-resolution computed tomography and serologic assessments are inconclusive. While surgical lung biopsy (SLB) has long been considered the diagnostic gold standard, its invasiveness, associated morbidity, and limited feasibility in high-risk patients have driven the pursuit of less invasive alternatives. Here, we review the current applications, diagnostic yield, procedural techniques, and complications of several bronchoscopic modalities. Bronchoalveolar lavage (BAL) aids in characterizing inflammatory profiles and differentiating among conditions such as hypersensitivity pneumonitis, sarcoidosis, and eosinophilic pneumonia. Endobronchial biopsies (EBBs) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) are valuable in diagnosing granulomatous diseases with lymphadenopathy. Transbronchial lung biopsy (TBLB) is effective for peribronchial and centrilobular diseases but is limited by small sample size and tissue distortion. Transbronchial lung cryobiopsy (TBC) enables acquisition of larger, well-preserved parenchymal tissue samples from the peripheral lung. Over recent years, studies have demonstrated that TBC, when interpreted within a multidisciplinary discussion (MDD), achieves diagnostic concordance rates with SLB exceeding 75%, and up to 95% in cases where high diagnostic confidence is reached. When performed in experienced centers using standardized protocols, TBC is considered a viable first-line histopathologic tool in the diagnostic evaluation of ILD. Adequate training and standardization of the TBC procedure are needed to ensure low complication rates and a high yield
Socioeconomic disparities and bladder cancer stage at diagnosis: a statewide cohort analysis
No full textBACKGROUND: Bladder cancer is the ninth most common cancer worldwide. Despite its prevalence, large-scale studies on the relationship between socioeconomic disparities and disease stage at presentation are lacking. This study examines the association between the Area Deprivation Index (ADI), a robust measure of socioeconomic status, and stage at diagnosis among bladder cancer patients.
METHODS: Patients diagnosed with bladder cancer (any TNM stage) from the Michigan Department of Health and Human Services (2004-2019) were retrospectively analyzed. ADI was assigned based on patients\u27 residential census-block group and stratified into quartiles, with the fourth quartile (ADI 75-100) representing the most deprived. Multivariable logistic regression tested the impact of ADI on advanced disease stages (muscle invasive disease [≥T2], positive nodal status [cN+], metastatic disease [cM+]).
RESULTS: Among 29 010 patients, the majority were non-Hispanic White (92%), males (75%), and residents in metropolitan areas (81%). Patients in the third and fourth ADI quartiles had higher rates of ≥T2 (22%, 24.5%) compared with the first and second quartiles (18%, 19.5%) (P \u3c .001), as well as increased rates of cN+ (3.4%, 3.7%) and cM+ (2.8%, 3.2%) (P \u3c .001). Multivariable regression showed that each 10-unit rise in ADI increased odds of T2 by 4% (95% CI = 1.03 to 1.06, P \u3c .001), cN+ by 4% (95% CI = 1.01 to 1.07, P = .038), and cM+ by 6% (95% CI = 1.02 to 1.09, P = .003).
CONCLUSION: Higher ADI correlates with advanced bladder cancer stages at diagnosis. Addressing these disparities is essential to improve outcomes in bladder cancer care
Economic and geographical disparities in global contribution to open access publishing in anaesthesiology: A bibliometric analysis
No full textBACKGROUND AND AIMS: Open access (OA) publishing improved the reach of scientific discoveries, particularly among researchers in lower-income countries. However, OA publishing still has a global imbalance. This bibliometric analysis evaluates anaesthesia OA journals to explore geographical and economic disparities in publication volume.
METHODS: We queried the Directory of Open Access Journals for OA anaesthesia-related journals between 2014 and 2024. Data from the included journals were analysed using Scopus, from which we extracted the year of publication and the corresponding author\u27s affiliation. Additional metrics were obtained from each journal website. Countries were then categorised by income level and geographical region.
RESULTS: Thirty-four anaesthesiology OA journals were analysed, encompassing 27,634 publications from 120 countries. The leading contributors were India (23.96%), the USA (14.98%) and China (6.54%). Low-income countries accounted for 0.37% of total publications, followed by upper-middle-income (17.97%), lower-middle-income (29.07%), and high-income (52.54%) countries. The geographical distribution of publication volume was as follows: Southeast Asia (25.38%), Europe (23.18%), Western Pacific (18.92%), Americas (23.91%), Eastern Mediterranean (8.03%) and Africa (0.59%). Nineteen journals required a mean article processing charge (APC) of US $2,164.89, accounting for 51.89% of the total publications. India ranked first in non-APC journals, while the USA led in APC journals.
CONCLUSION: While OA publishing enhances accessibility for readers, it still presents challenges for authors, particularly in economically disadvantaged countries. Significant geographical and economic disparities exist in OA publication volume, likely due to limited investment and structural barriers in lower-income countries
Aortic Valve Stenosis and Calcified Abdominal Aortic Stenosis Treated With Lithotripsy-Facilitated TAVR and Aortic Stenting
No full textThe Use of Multimodality Images in The Diagnosis of Unroofed Coronary Sinus Syndrome
No full textUnroofed coronary sinus syndrome is a very rare entity that accounts for only ∼1% of atrial septal defects. Here, we present a case series of patients with unroofed coronary sinus syndrome and discuss its clinical presentation, imaging diagnostics, and management options
Pigmented Rings With Central Clearing: A Dermoscopic Feature of Melasma
No full textMelasma, a challenging pigmentary disorder affecting the face, often poses diagnostic difficulties due to its similarity to numerous other conditions. This study aimed to introduce and evaluate a novel dermoscopic feature, pigmented rings with central clearing (PRCC), in aiding the diagnosis of melasma and distinguishing it from similar conditions
A case report of an interventricular septal hematoma presenting as a STEMI post-pacemaker implantation
No full textKey Teaching Points: Septal hematoma should be recognized as a potential complication of pacemaker implantation. It should be suspected in patients who present with chest pain, electrocardiogram changes, or hemodynamic instability following the procedure. Echocardiography and cardiac catheterization are valuable tools for diagnosing and assessing the condition. Management ranges from conservative observation to interventional procedures, depending on the severity of the hematoma and the patient\u27s stability. Close follow-up with echocardiography is essential to monitor for potential complications
Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series
No full textBACKGROUND: Pathogenic variants of fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (FUS-ALS), with evidence of gain of function. Jacifusen is an antisense oligonucleotide targeting FUS pre-mRNA, previously shown to delay neurodegeneration in a mouse model and potentially slow functional decline in a first-in-human study. Here, we sought to further evaluate use of jacifusen as a treatment for FUS-ALS.
METHODS: This expanded access programme was conducted through a series of single-patient investigational new drug applications at five sites (four hospitals in the USA and one in Switzerland). Participants carried a FUS variant and had clinical evidence of motor neuron disease onset or electrophysiological abnormalities, if not a diagnosis of ALS. Participants were ineligible if chronically ventilated with tracheostomy. Enrolled sequentially, participants received serial intrathecal injections of jacifusen over 2·8-33·9 months. Based on multiple ascending doses of jacifusen (from 20 mg to 120 mg), successive protocols were modified as safety and other data were acquired, with the last participants enrolled receiving 120 mg doses monthly from the start of their treatment. Safety was assessed using the Common Terminology Criteria for Adverse Events version 4.0 and standard cerebrospinal fluid (CSF) metrics. Concentration of neurofilament light chain (NfL) in CSF was used as a biomarker of axonal injury and neurodegeneration, and the ALS Functional Rating Scale-Revised (ALSFRS-R) score was used as an overall measure of motor function. Biochemical analysis and immunohistochemical staining were done on post-mortem CNS tissues to quantify FUS protein expression and assess the burden of FUS pathology.
FINDINGS: Between June 11, 2019, and June 2, 2023, we recruited 12 participants (median age 26 years [range 16-45]; seven [58%] were female and five [42%] were male) into the expanded access programme. Transient elevations in cell counts or total protein concentration in CSF (six [50%] participants) were unrelated to treatment duration. The most common adverse events were back pain (six [50%]), headache (four [33%]), nausea (three [25%]), and post-lumbar puncture headache (three [25%]). Two participant deaths were recorded during the programme, both thought to be unrelated to the investigational drug. The concentration of NfL in CSF was reduced by up to 82·8% after 6 months of treatment. Although most participants had continued functional decline (as measured by ALSFRS-R) after starting treatment with jacifusen, one showed unprecedented, objective functional recovery after 10 months, and another remained asymptomatic, with documented improvement in electromyographic abnormalities. Biochemical and immunohistochemical analysis of CNS tissue samples from four participants showed reduced FUS protein levels and an apparent decrease in the burden of FUS pathology.
INTERPRETATION: The findings suggest the safety and possible efficacy of jacifusen for treating FUS-ALS. The efficacy of jacifusen is being further evaluated in an ongoing clinical trial.
FUNDING: ALS Association, Project ALS, Ionis Pharmaceuticals, Tow Foundation, Nancy D Perlman and Thomas D Klingenstein Innovation Fund for Neurodegenerative Disease, National Institutes of Health, Angel Fund for ALS Research, Cellucci Fund for ALS Research, Max Rosenfeld ALS Fund, University of Minnesota, and the Muscular Dystrophy Association