Citations

ABSTRACTBackground and ObjectiveThe diagnosis of interstitial lung diseases (ILDs) often relies on the integration of various clinical, radiological, and histopathological data. Achieving high diagnostic accuracy in ILDs, particularly for distinguishing usual interstitial pneumonia (UIP), is challenging and requires a multidisciplinary approach. Therefore, this study aimed to develop a multimodal artificial intelligence (AI) algorithm that combines computed tomography (CT) and histopathological images to improve the accuracy and consistency of UIP diagnosis.MethodsA dataset of CT and pathological images from 324 patients with ILD between 2009 and 2021 was collected. The CT component of the model was trained to identify 28 different radiological features. The pathological counterpart was developed in our previous study. A total of 114 samples were selected and used for testing the multimodal AI model. The performance of the multimodal AI was assessed through comparisons with expert pathologists and general pathologists.ResultsThe developed multimodal AI demonstrated a substantial improvement in distinguishing UIP from non‐UIP, achieving an AUC of 0.92. When applied by general pathologists, the diagnostic agreement rate improved significantly, with a post‐model κ score of 0.737 compared to 0.273 pre‐model integration. Additionally, the diagnostic consensus rate with expert pulmonary pathologists increased from κ scores of 0.278–0.53 to 0.474–0.602 post‐model integration. The model also increased diagnostic confidence among general pathologists.ConclusionCombining CT and histopathological images, the multimodal AI algorithm enhances pathologists' diagnostic accuracy, consistency, and confidence in identifying UIP, even in cases where specialised expertise is limited. image

Abstract Oligodendrogliomas are initially slow-growing brain tumors that are prone to malignant transformation despite surgery and cytotoxic therapy. Understanding of oligodendroglioma evolution and new treatments for patients have been encumbered by a paucity of patient-matched newly diagnosed and recurrent tumor samples for multiplatform analyses, and by a lack of preclinical models for interrogation of therapeutic vulnerabilities that drive oligodendroglioma growth. Here we integrate spatial and functional analyses of tumor samples and patient-derived organoid co-cultures to show that synaptic connectivity is a hallmark of oligodendroglioma evolution and recurrence. We find that patient-matched recurrent oligodendrogliomas are enriched in synaptic gene expression programs irrespective of previous therapy or histologic grade. Analyses of spatial, single-cell, and clinical data reveal epigenetic misactivation of synaptic genes that are concentrated in regions of cortical infiltration and can be used to predict eventual oligodendroglioma recurrence. To translate these findings to patients, we show that local field potentials from tumor-infiltrated cortex at the time of resection and neuronal hyperexcitability and synchrony in patient-derived organoid co-cultures are associated with oligodendroglioma proliferation and recurrence. In preclinical models, we find that neurophysiologic drugs block oligodendroglioma growth and pathologic electrophysiology. These results elucidate mechanisms underlying oligodendroglioma evolution from an indolent tumor to a fatal disease and shed light on new biomarkers and new treatments for patients.

Supplemental O 2 (hyperoxia) in premature infants detrimentally affects bronchial airways leading to increased senescence. Understanding the mechanisms by which hyperoxia initiates senescence in developing airways is critical for future therapeutic strategies. The current study showed that hyperoxia-induced senescence is mediated through increased mitochondrial reactive oxygen species and endoplasmic reticulum (ER) stress. ER stress inhibitors or mitochondria-targeted antioxidants may represent future therapies to blunt detrimental effects of supplemental oxygen in developing lungs.

Ultrasound-guided peripheral vascular access was rarely used by Certified Registered Nurse Anesthetists (CRNA) within a large academic hospital since the use of ultrasound had not been common practice among CRNAs. The purpose of this quality improvement project was to develop an educational intervention to increase the use of ultrasound for peripheral vascular access among CRNAs by 20% while also improving their knowledge, comfort, and confidence in using the technology. A pre-intervention survey revealed limited use of ultrasound for peripheral vascular access by practicing CRNAs, despite benefits of enhanced patient care demonstrated in the literature. The educational intervention included a virtual learning module, hands-on simulated training, and pre- and post-intervention knowledge assessments to measure CRNAs’ skills in ultrasound-guided techniques. Post-intervention results demonstrated a 64% increase in ultrasound use, with the average monthly rate of individual usage rising from 2.1 to 3.4 times. Additionally, participants’ knowledge scores improved from 52% to 82%, and they reported increased confidence with performing ultrasound-guided vascular access procedures. While certain barriers, like lack of access to ultrasound machines and time constraints persisted after the intervention, this education effectively addressed individual knowledge and skill gaps. This quality improvement project underscores the value of structured educational programs in advancing the use of ultrasound technology in healthcare. This highlights the importance of ongoing training and education to sustain and improve CRNAs’ knowledge and skills.

AbstractChronic pelvic pain (CPP), a debilitating condition affecting an estimated 25% of women worldwide, represents a significant yet understudied global health crisis. Existing research is limited and likely fails to capture the true impact of CPP on global health. What is known is that CPP results in a profound health, societal, and economic burden on women. Our inability to fully understand this burden is a critical gap in women's healthcare. To address this urgent need, the International Federation of Gynecology and Obstetrics (FIGO) and the International Pelvic Pain Society (IPPS) have partnered to develop this consensus statement where we examine the key challenges to accessing CPP care and propose a framework for overcoming these barriers. We emphasize that effective global strategies for addressing the negative health consequences of living with CPP must prioritize the lived experiences of patients, empower healthcare professionals with the necessary tools and training, and drive meaningful policy change. This call to action is grounded in a comprehensive vision of women's health and rights to address the full spectrum of conditions women experience throughout their lives. Given its high prevalence, CPP must be a central focus of this expanded vision.

Abstract Aims To investigate the cost‐effectiveness of early initiation of metformin and usual care for gestational diabetes mellitus (GDM). Methods Economic evaluation from a healthcare perspective, based on the EMERGE randomised controlled trial. In total, 535 women with GDM were randomised to placebo in addition to usual care or metformin in addition to usual care. Economic outcomes included incremental healthcare costs and quality adjusted life years ( QALYs ) and expected cost‐effectiveness at cost‐effectiveness threshold values of €20,000, €45,000 and €100,000 per QALY gained. Uncertainty was explored using parametric, non‐parametric, deterministic and probabilistic methods and heterogeneity using subgroup analysis. Results On average, relative to the placebo arm, the early metformin arm was associated with non‐statistically significant mean increases of €193.07 (95% CI : −€789.88, €1176.01; p = 0.700) and 0.002 QALYs (95% CI : −0.009, 0.013; p = 0.771). In terms of expected cost‐effectiveness at threshold values of €20,000, €45,000 and €100,000 per QALY gained, the probability of the early metformin arm being more cost‐effective was estimated at 0.423, 0.452 and 0.524. Exploratory subgroup analyses provided more favourable but not definitive evidence in favour of the early metformin arm for cohorts with previous GDM and previous caesarean section. Conclusions We do not find definitive evidence that early initiation of metformin in addition to usual care for GDM was more cost‐effective than usual care alone. The clinical and economic evidence may be considered equivocal, but worthy of further examination.

Despite ongoing efforts to employ structure-based methods to discover targeted protein degraders (TPD), the prevailing strategy remains synthesizing a focused set of heterobifunctional compounds and screening them for target protein degradation.

Abstract Background: There is a need for effective and affordable nondrug therapies for the acute treatment of migraine. Transnasal neuromodulation via evaporative cooling may modulate the sphenopalatine ganglion, which is implicated in migraine. The study aimed to evaluate the safety, tolerability, and optimal dose of this method for acute migraine treatment. Methods: A prospective, randomized, double-blind, multicenter study was conducted at 3 US sites. Subjects received 15 minutes of in-clinic treatment during a migraine attack. Twenty-four subjects were randomized into three groups: 24 liters per minute (LPM), 18 LPM, and 6 LPM. Pain and Most Bothersome Symptom (MBS) were recorded at baseline 2 and 24 hours post treatment. The primary endpoint was pain relief (PR) at 2 hours. Secondaryendpoints included tolerability, MBS relief and pain freedom (PF) at 2 hours and 24 hours Results: Eighty-seven adults with episodic migraine with or without aura were enrolled. PR at 2 hours without rescue medication (woRM) was reported by 89% (8/9) of the participants who received 6LPM. PR at 2 hwoRM was reported to be 56% (5/9) and 50% (3/6) in the 18LPM and 24LPM groups, respectively. PF at 2 hours woRM was reported by 44% (4/9) of participants in the 6LPM group, and no participants in the 18LPM or 24LPM group reported PF at 2 hours. MBS relief at 2 hwas 78% (7/9), 67% (6/9) and 50% (3/6) in the 16, 18 & 24LPM groups, respectively. No adverse events occurred in the 6LPM group,and none were serious or severe in any group. Moderate discomfort was reported by 11% (1/9) of the participants in the 6LPM group. In contrast, 33% (3/9) and 83% ofthe 18LPM and 24LPM groups reported moderate or severe discomfort, respectively. Zero, one, and two subjects discontinued the 15-minute session in the 6LPM, 18LPM, and 24LPM groups, respectively. The study was terminated early because of slow subject accrual. Conclusions: Lower flow rates during transnasal cooling were both effective and tolerable for acute migraine treatment. The study became a dose-ranging trial, with lower flow rates,showing greater efficacy. A future at-home study is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT04936061; Registration date: June 15, 2021. The full study protocol can be accessed at https://clinicaltrials.gov/study/NCT04936061.