Citations

Abstract Background and Aims The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. Methods The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan–Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. Results One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (−11.6, 11.9), massive/torrential −5.8% (−17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (−3.0, 22.7), massive/torrential -15.2% (−28.9, −1.5)]. Conclusions Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.

BACKGROUND: Patients with functioning pituitary adenomas (FPA) require a multidisciplinary team-based approach to select best medical, surgical, and radiation treatments, including stereotactic radiosurgery (SRS). OBJECTIVE: The aim of this study was to provide evidence-based recommendations on the use of SRS for adult patients with FPA. METHODS: PubMed and Embase were searched from data base inception to June 8, 2021. Full-text articles were then screened using published exclusion/inclusion criteria. Evidence tables were developing based on data extraction from the full-text reviews, and evidence-based recommendations were finalized. RESULTS: Of the total 1842 abstracts pertinent to this topic, 343 full articles met eligibility. Of these, 21 met entry criteria and were included in the evidence tables. The provided Class III evidence supported 2 Level III recommendations: 1. SRS, hypofractionated SRS, fractionated (>5 fractions) radiotherapy, and conventional radiation therapy provide excellent radiographic control with variable hormonal reduction and endocrine remission rates. For SRS and fractionated radiotherapy hormonal reduction may continue for up to 10 years after treatment. 2. Clinicians may continue to administer endocrine suppressive medical treatment before SRS as this may not affect radiographic control. CONCLUSION: This systematic review provides evidence-based recommendations to guide providers caring for adult patients with FPA when making decisions pertinent to radiosurgery. The CNS Guidelines Committee will continue to pursue timely updates to further improve the care of patients with this diagnosis.

Background Dementia with Lewy bodies (DLB) is a common degenerative dementia, but no studies investigate bereaved caregiver experiences. Objective To investigate the experiences of caregivers three months after the death of persons with DLB using a mixed-methods approach. Methods Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were followed prospectively every 6 months until the person with DLB died. Caregivers completed a study visit with questionnaires and a semi-structured interview ∼3 months later. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of post-death measures with pre-death patient and caregiver variables. Thematic analysis was used to analyze the interviews. Results Seventy-three caregivers completed visits (mean 3.5 months post-death). Most of the caregivers were women (82.2%) and spouses (76.7%) or adult children (17.8%). Over 40% had scores indicating risk for clinical depression. Post-death caregiver experiences (depression, quality of life, grief, resilience) correlated with pre-death caregiver experiences. Post-death experiences did not associate with patient characteristics, disease-related symptoms, or healthcare services used in the last 6 months of life. Trajectories for caregiver measures from pre- to post-death visits varied widely. Interview themes included grief and sadness, anger, guilt and regret, relief, appreciation/gratitude, and adjusting to a new normal. Conclusions The finding that pre-death caregiving experiences have the strongest association with post-death experiences emphasizes the critical importance of accessible and evidence-based caregiver support before and after the death of a person with DLB. Research is needed to develop interventions for current and bereaved caregivers of individuals with DLB. Trial registration information NCT04829656 (submitted 2021-03-22).

ABSTRACT Post‐translational modifications, such as glycosylation and phosphorylation, play a critical role in protein trafficking, interactions, and stability. Disruptions in these pathways can lead to glycosylphosphatidylinositol (GPI) deficiencies, which present with a spectrum of clinical features, including congenital anomalies, dysmorphic features, developmental delay, hypotonia, and epilepsy. Biallelic variants in PIGV , a key mannosyltransferase in GPI biosynthesis, cause Hyperphosphatasia with Impaired Intellectual Development Syndrome 1 (HPMRS1), a rare disorder characterized by hyperphosphatasia, seizures, developmental delay, hypotonia, abnormal MRI findings, and distinct facial dysmorphisms. Fewer than 30 cases have been reported to date. We conducted a case study and literature review; with clinical data obtained from medical records. A 2‐year‐old female presented with developmental delay, myoclonic epilepsy, hypotonia, and mild facial dysmorphism. Laboratory results showed elevated alkaline phosphatase (899 U/L) and low pyridoxal 5′‐phosphate levels in cerebrospinal fluid (CSF). Brain MRI revealed diffuse cerebral volume loss and ventriculomegaly. Trio genome sequencing identified two PIGV variants: c.1415T>C‐p.(Leu472Pro) and c.524T>C‐p.(Leu175Pro). Functional studies using PIGV ‐knockout HEK293 cells transfected with wild‐type or mutant PIGV constructs demonstrated reduced GPI‐anchored protein (GPI‐AP) expression under weaker promoters, indicating impaired enzymatic activity. We report two novel PIGV variants associated with HPMRS1, emphasizing the value of functional assays in variant interpretation. Our findings also highlight the diagnostic relevance of alkaline phosphatase measurement in patients with refractory seizures.

Background: Transfusion has a persistent low risk of transfusion-transmitted infection and transfusion-associated graft- versus -host disease that may be addressed using pathogen reduction. The Red Cell Pathogen Inactivation (ReCePI) trial tested whether amustaline/glutathione pathogen-reduced red cells are noninferior to conventional transfusions for support of acute surgical blood loss. Methods: A phase 3, double-blinded, noninferiority trial randomized cardiac or thoracic–aorta surgery patients with increased risk of red cell transfusion to receive pathogen-reduced or conventional red cells during and for 7 days postsurgery. The primary endpoint was the proportion of patients with acute kidney injury (AKI), which is defined as an increase from baseline of greater than or equal to 0.3 mg/dl serum creatinine within 48 h of surgery. Noninferiority was claimed if the upper bound 95% CI of the treatment difference was less than half (50%) of the observed conventional arm incidence. Adverse events and treatment-emergent red cell antibodies were assessed for 28 and 75 days, respectively. Results: A total of 581 subjects were randomized, and 321 (55%) were transfused with study red cells. Transfused subjects in both arms had similar baseline demographics, medical histories, hemoglobin levels, and surgical procedures. Hemoglobin day 3 nadir levels (8.6 g/dl [7.8 to 9.2] in the pathogen-reduced arm; 8.4 g/dl [7.8 to 9.3] in the conventional arm; P = 0.52) were comparable. Incidence of AKI by 48 h was 46 of 157 (29.3%) in the pathogen-reduced arm and 45 of 161 (28.0%) in the conventional arm (treatment difference, 0.7%; 95% CI, −8.9 to 10.4%; noninferiority margin, 14.0%; P = 0.001 for noninferiority). AKI within 7 days by Kidney Disease Improving Global Outcomes staging criteria was not different (59 of 159 [37.1%] in the pathogen-reduced arm; 55 of 162 [34.0%] in the conventional arm; P = 0.53), but stage III was more common in the pathogen-reduced arm (pathogen-reduced arm, 15 of 159 [9.4%]; conventional arm, 7 of 162 [4.3%]; P = 0.075). Of 159 pathogen-reduced red cell recipients, 5 (3.1%) developed specific, low-titer antibodies without evidence of hemolysis. Conclusions: The incidence of AKI in recipients of pathogen-reduced red cells was noninferior to conventional red cell transfusion. Treatment-emergent antibodies were uncommon and not clinically significant.

BACKGROUND AND OBJECTIVES: Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited. METHODS: This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus. We report favorable outcome, obliteration, hemorrhage, and permanent symptomatic adverse radiation effect rates. RESULTS: The median age was 31 years (IQR: 19-44) at the first volume stage, with patients treated in 2–4 stages. The median total nidus volume was 21 cm 3 (IQR: 13.9-30.1 cm 3 ), and a median prescription dose of 17 Gy (IQR: 16-18 Gy) was used. The median radiographic and clinical follow-up were 48 and 55 months, respectively. Seventy-seven patients (20.4%) had a favorable outcome, with the 3-year and 5-year rates being 3.9% and 18%, respectively. 127 patients (33.6%) achieved obliteration, with the 3-year and 5-year rates being 6.8% and 26%, respectively. Obliteration rates of AVMs <15 cm 3 were 81% and 31%, respectively. The latency period hemorrhage incidence rate was 3.02 cases per 100 patient-years; 52 patients (13.8%) had a bleed. Seventy-two patients (19%) had symptomatic adverse radiation effect; in 38 patients (10.1%), these were permanent. Total nidus volume, prescription dose at first stage, diffuse nidus, and prior hemorrhage were all independent affecting outcome rates. CONCLUSION: VS-SRS can be used to treat large AVMs as a standalone treatment. Obliteration rates and favorable outcomes are lower than that with smaller AVMs, and repeat treatment is often required. Optimizing treatment plans, by increasing prescription doses, reducing treatment volume at each stage, and increasing the number of stages, may lead to better outcomes.

Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

Abstract Background Patients with short bowel syndrome–associated intestinal failure (SBS‐IF) require complex, personalized, and multidisciplinary care; however, there are disparities in access. This study measured the impact of unmet needs and treatment burden among patients and their caregivers. Methods This cross‐sectional, mixed‐method study included US adults self‐reporting SBS‐IF and receiving home parenteral nutrition for ≥6 months and their caregivers. One‐hour interviews informed the development of a 30‐min survey administered to participants from an online health community. Results Among 68 patients, the mean age was 42 years, 79% were female, and 88% were White. Most of the 16 caregivers were female (69%), and younger than 45 years (69%). Of 32 patients (47%) receiving care from an SBS specialist, only 19 (59%) were referred after diagnosis; in 58% of these, referral occurred >6 months after diagnosis. Depression was reported in 44 patients (65%), with 54% not receiving professional mental health care. Financial concerns were common, with 44 patients (65%) unable to work and 40 patients (59%) reporting annual household income of <$50,000. Of 32 patients reporting difficulty paying medical bills, 22 (32%) could not fill prescriptions and 19 (28%) canceled/delayed healthcare provider visits. Social determinant of health challenges were reported by 44 patients (65%). Caregivers' responsibilities impacted their ability to work (50%) and future outlook (63%). Conclusion Patients with SBS‐IF face difficulties accessing specialized healthcare, and are at risk of adverse healthcare outcomes, financial hardships, and poor quality of life. Mental health and work/financial issues were common among both patients and caregivers.

Gastrointestinal (GI) defects pose a significant clinical challenge, impacting patient outcomes and healthcare costs. Endoscopic closure techniques have emerged as effective and minimally invasive approaches to manage these defects. This review explores the various endoscopic techniques, including over-the-scope clips (OTSC), endo suturing systems, through-the-scope (TTS) clips, and the X-Tack system. Each technique offers distinct advantages and limitations, making it suitable for specific clinical scenarios. While these devices have demonstrated promising results in clinical practice, further research is needed to optimize their use and address knowledge gaps. Large-scale randomized controlled trials are essential to establish evidence-based guidelines for device selection and procedural techniques. By embracing technological advancements and addressing research limitations, the field of endoscopic closure devices has the potential to revolutionize GI care, leading to improved patient outcomes and expanded therapeutic possibilities.