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Antenatal Corticosteroid in Twin-Pregnant Women at Risk of Late Preterm Delivery: A Randomized Clinical Trial.
No full textIMPORTANCE: Recent guidelines have recommended corticosteroid injection in women with singleton pregnancies at risk of late preterm delivery. However, the effectiveness of antenatal corticosteroid administration in women with twin pregnancies at risk of late preterm delivery has not been evaluated, and studies on this population are lacking.
OBJECTIVE: To evaluate whether antenatal betamethasone administration reduces the risk of neonatal respiratory morbidity in late preterm twin neonates.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter randomized trial, twin-pregnant women at 34 weeks 0 days to 36 weeks 5 days of gestation at risk of late preterm delivery were enrolled across 8 university-based clinical centers in Korea. Data were collected between May 2018 and July 2024. Intention-to-treat analysis was performed.
INTERVENTION: The participants received 2 injections of betamethasone or placebo after randomization (1:1).
MAIN OUTCOMES AND MEASURES: The primary outcome was perinatal death within 72 hours after birth or severe neonatal respiratory morbidity. The exploratory outcomes were mild neonatal respiratory morbidities, other neonatal respiratory morbidities, other neonatal complications, or maternal complications.
RESULTS: A total of 812 participants were randomized and analyzed, with 410 in the intervention group (median [IQR] age, 35 [33-37] years) and 402 in the placebo group (median [IQR] age, 35 [32-38] years). Among 1620 neonates (818 in the intervention group and 802 in the placebo group), there were no perinatal deaths in either group, and severe neonatal respiratory morbidity occurred in 99 neonates (6.1%), with lower risk in the betamethasone group than in the placebo group (39 [4.8%] vs 60 [7.5%]; relative risk [RR], 0.64 [95% CI, 0.42-0.98]). For the exploratory outcomes, continuous positive airway pressure use for 2 hours or more (RR, 0.58 [95% CI, 0.35-0.95]) and transient tachypnea of the newborn (RR, 0.47 [95% CI, 0.25-0.89]) were lower in the betamethasone group. The risk of primary outcome and mild respiratory morbidities was reduced only in neonates delivered between 12 hours or more and less than 7 days after the first betamethasone administration. The risk of neonatal hypoglycemia was increased in the betamethasone group (128 [15.6%] vs 94 [11.7%]; RR, 1.33 [95% CI, 1.01-1.75]), but the risk of neonatal sepsis or maternal chorioamnionitis did not differ between the 2 groups.
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, antenatal betamethasone administration in women with twin pregnancies at risk of late preterm delivery significantly reduced the risk of neonatal respiratory morbidity. The outcomes from this study could serve as a valuable reference in clinical management of twin pregnancies at risk of late preterm delivery.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03547791
A fibroblast-centric network drives cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma.
No full textThe tumor microenvironment (TME) of chronic inflammation-associated cancers (CIACs) is shaped by cycles of injury and maladaptive repair, yet the principles organizing fibrotic stroma in these tumors remain unclear. Here, we applied the concept of hot versus cold fibrosis, originally credentialed in non-cancerous fibrosis of heart and kidney, to lung squamous cell carcinoma (LUSC), a prototypical CIAC. Single-cell transcriptomics of matched tumor and adjacent-normal tissue from 16 treatment-naive LUSC patients identified a cold fibrotic architecture in the LUSC TME: cancer-associated fibroblasts (CAFs) expanded and adopted myofibroblast and stress-response states, while macrophages were depleted. This macrophage-poor, CAF-rich stroma was maintained by CAF autocrine growth factor loops, including TIMP1, INHBA, TGFB1, and GMFB. In parallel, the immune compartment exhibited a hot tumor phenotype with abundant T and B cells, forming spatially distinct but molecularly engaged networks with CAFs. CAF gene programs typifying cold fibrosis in LUSC were conserved in other CIACs, including esophageal and gastric adenocarcinomas. These results redefine desmoplastic regions of tumors through the lens of a non-cancer fibrosis model, demonstrating that conserved stromal circuits constitute therapeutic vulnerabilities in CIACs
Systematic review and meta-analysis of the impact of loss of consciousness on clinical outcomes in mild traumatic brain injury.
No full textWhile loss of consciousness (LOC) is a key factor in assessing head injuries, its impact on clinical outcomes, including persistent post-concussive symptoms, mental health disorders, quality of life, and neurodegeneration, remains unclear. This systematic review explores the association of LOC in Mild Traumatic Brain Injury (mTBI) with clinical outcomes such as mental health, quality of life, and risk of neurodegenerative diseases. Comprehensive systematic review methodology; two electronic databases (PubMed, Embase) were systematically searched from January 1990 to December 2024. Pooled odds ratios (OR) were obtained using a random effects model. A total of 595 studies were assessed with 30 trials meeting inclusion criteria. The presence of LOC is associated with worsened clinical outcomes including persistent post-concussive symptoms (OR 1.89, 95% CI: 1.59-2.25), post-traumatic stress disorder (OR 1.81, 95% CI: 1.54-2.12), depression (OR 2.69, 95% CI: 2.10-3.43), and overall health-related quality of life (OR 1.84, 95% CI: 1.49-2.26). These findings suggest that the role of LOC in the outcomes of mTBI supports a higher risk of poorer short and long-term outcomes. Future studies may investigate variation in post-mTBI sequelae among those with similar LOC timelines
Pemigatinib for Previously Treated Metastatic or Unresectable Central Nervous System Tumors with FGFR Mutations or Rearrangements: FIGHT-207 Results.
No full textCentral nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here we report the efficacy and safety of treatment with pemigatinib, an oral, potent, selective FGFR1-3 inhibitor, in patients with advanced FGFR-altered CNS tumors. FIGHT-207 was a single-arm, open-label, phase 2 study of pemigatinib in patients with advanced solid tumors harboring FGFR fusions/rearrangements or other mutations. Patients received pemigatinib 13.5 mg once daily until disease progression or unacceptable toxicity. Endpoints included tumor response and safety. Of the 13 patients with CNS tumors in FIGHT-207, 10 had glioblastoma. FGFR alterations were FGFR3-TACC3 fusions (n = 9), FGFR1 K656E mutations (n = 2), FGFR1 N546K mutation (n = 1), and FGFR1-MITF fusion (n = 1). Three patients (23%) displayed objective responses (1 complete, 2 partial). Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors
Laser in situ fenestrated endograft (LIFE) repair of complex aortic arch pathology: Early outcomes from the multicenter LIFE registry.
No full textOBJECTIVE: Endovascular repair of aortic arch pathologies is limited by currently available device configurations, variation in aortic arch anatomy, access challenges, and frequent nonelective surgical acuity. The present study aims to assess the feasibility and midterm outcomes of laser in situ fenestrated endograft (LIFE) repair for supra-aortic arch branches during thoracic endovascular repair (TEVAR).
METHODS: Patients who underwent LIFE during TEVAR for aortic arch pathologies (2017-2022) were retrospectively identified at six high-volume centers, and data were collected in the multicenter LIFE registry. Descriptive statistics and Kaplan-Meier analysis were used. Primary outcomes were technical success, stroke, and target vessel instability. Secondary outcomes included 30-day mortality, spinal cord ischemia, and reinterventions.
RESULTS: A total of 82 patients who underwent LIFE with supra-aortic arch involvement were included. The mean age was 62.4 years (29.3% female and 78.0% White). Select demographics of the cohort featured previous stroke in 17.1% of cases, chronic lung disease in 12.2%, and renal insufficiency in 30.5%. Indication(s) for TEVAR included type B aortic dissection in 70.7% of cases, aneurysm in 11.0%, and penetrating atherosclerotic ulcer/intramural hematoma in 4.9%. Repair was performed for nonelective pathologies in 47.9% of cases. Eighty-nine supra-aortic arch branch vessels (innominate, n = 6; left common carotid artery, n = 9; and left subclavian artery, n = 74) were incorporated via LIFE to achieve proximal seal in zone 0 (19%), zone 1 (5%), and zone 2 (75%). LIFE repair was performed for a single-branch vessel in 90% of cases and a double-branch vessel in 10%. Ten patients underwent adjunctive extra-anatomic bypass. Technical success was achieved in 95.1% of cases. Thirty-day mortality was 2.4% (n = 2). Early (\u3c 30 days) neurologic outcomes included a stroke and spinal cord ischemia rate of 7.4% and 0%, respectively. At a mean follow-up of 15 months (range, 1-81 months), there were 5 additional late deaths (6.1%). A total of 8 patients (9.8%) required 11 unplanned reinterventions at a mean of 423 ± 555 days (range, 17-1479 days) postoperatively. Kaplan-Meier estimated survival was 94.5% at 36 months, and reintervention-free survival was 78.0% at 36 months.
CONCLUSIONS: Results from the multicenter LIFE registry demonstrate laser in situ fenestration of complex aortic arch anatomy to be technically feasible with a perioperative mortality and neurologic risk profile that is comparable to standard techniques. Despite a modest reintervention rate in this early experience, midterm survival is excellent, particularly given the high-risk aortic pathologies and patient demographics featured in this cohort. Although perioperative results and midterm outcomes remain promising, longitudinal data are needed to confirm durability of this technique
Addressing unmet needs for chronic kidney disease treatment in type 1 diabetes: A review.
No full textChronic kidney disease (CKD) is a serious complication occurring in nearly one of three people with type 1 diabetes (T1D). Major therapeutic advances have been made in the management of CKD for people with type 2 diabetes (T2D), thereby improving their kidney, cardiovascular, and survival outcomes. However, people with T1D were largely excluded from these CKD therapeutic development programmes. Recent treatment advancements for people with T2D include the introduction of sodium-glucose cotransporter 2 inhibitors, a nonsteroidal mineralocorticoid antagonist, and glucagon-like peptide-1 receptor agonists. The development and progression of CKD in people with T1D are driven by a constellation of risk factors such as hyperglycemia, hypertension, obesity, and others that share common mechanistic links with T2D. As such, a compelling rationale exists for focused studies of these therapeutic classes for the treatment of CKD in T1D. Additionally, care provided by a coordinated team of primary care clinicians, endocrinologists, nephrologists, and cardiologists is central to therapeutic implementation. There is a major unmet need for improved treatments for CKD in people with T1D. Ongoing and future studies will help to establish whether proven therapies for CKD in T2D are also safe and efficacious in people with T1D. Coordinated, cross-specialty approaches to awareness, detection, and intervention for CKD are also needed to improve kidney, cardiovascular, and survival outcomes in people with T1D
A Longitudinal Assessment of Greenhouse Gas Emissions From Inhaler Devices in a National Health System.
No full textNurse practitioner and physician associate mentorship: Improving retention and employment experiences.
No full textBACKGROUND: Clinician turnover is costly for health care organizations.
LOCAL PROBLEM: A retention strategy for newly hired nurse practitioners (NPs) and physician associates (PAs) was needed at our organization.
METHODS: A quality improvement project was conducted to determine whether a mentorship program could improve retention and employment experiences of newly hired NPs and PAs.
INTERVENTIONS: A one-to-one mentorship program was implemented for newly hired NPs and PAs. (a) Retention and productivity data were compared for mentee participants vs. nonparticipants. (b) Mentee and mentor participants completed two program evaluation surveys to examine the program\u27s impact on their employment experiences.
RESULTS: Sixty-eight mentee-mentor pairs completed their mentoring relationship during the first 3 years of the program. Retention was higher among mentee participants vs. nonparticipants during their first (96% vs. 85%, p = .0332) and second year of employment (83% vs. 65%, p = .0480). Productivity during the first year was similar for mentee participants and nonparticipants (38th percentile vs. 37th percentile, p = .84). Most participants (≥69%) believed the program improved onboarding, personal and professional growth, work environment, and NP and PA community connection.
CONCLUSIONS: The mentorship program improved first- and second-year retention of newly hired NPs and PAs and employment experiences of program participants. By our estimates, the program helped retain 15 NPs and PAs who would have otherwise left the organization, yielding potential organizational savings of 1.72M. A mentorship program can be an effective retention strategy for reducing health care turnover and related costs