Bartter syndrome (BS) is a rare inherited renal tubular disorder characterized by hypokalemia, metabolic alkalosis, renal salt wasting, and secondary hyperreninemic hyperaldosteronism with normal or low blood pressure. The classical form (type III) is commonly present in infancy or early childhood but may demonstrate variable clinical features, leading to delayed diagnosis. A 9-month-old male infant was admitted with severe pneumonia and septic shock requiring mechanical ventilation. The child developed persistent hypokalemia, hyponatremia, and metabolic alkalosis despite appropriate correction, resulting in four episodes of extubation failure. Persistent dyselectrolytemia in the presence of normotension and inappropriate renal electrolyte losses raised suspicion of an underlying renal tubular disorder. Elevated plasma renin and aldosterone levels supported the diagnosis of classical BS. Stabilization of serum electrolytes resulted in successful extubation and clinical improvement. This case highlights the importance of considering BS in infants with refractory electrolyte imbalance and unexplained ventilator dependence, particularly when renal salt wasting is evident.

Nitric oxide (NO) is an important signaling molecule in maintaining normal physiological processes like blood flow, neurotransmission and immune regulation. In cancer, it exhibits a dual role in context-dependent mechanism. At low levels, it activates angiogenesis, migration and tumor promotion; on the other hand, with an increase in concentration, it promotes apoptosis and has an anti-metastatic effect. Hence, regulated levels of NO are required to maintain normal hemostasis. NO has temporal and spatial regulation as its pro- and anti-metastatic effects are decided by the tumor stage, tumor microenvironment, and nitric oxide synthase isoforms expression. NO regulates EMT markers like upregulation of Snail, Twist, and ZEB1 (pro-EMT factors and downregulation of E-cadherin. NO also regulates the crosstalk between signaling factors, such as TGF-β, Wnt/β-catenin and NF-κB; during EMT and hypoxia-induced angiogenesis. NO promotes immunosuppression and metastasis by interacting with tumor-associated macrophages and myeloid-derived suppressor cells, which express iNOS. NO activates cancer promotion pathways like NF-κB, upregulates pro-metastatic genes (MMPs, cytokines), PI3K/Akt/mTOR and p53/Nrf2, along with regulating non-coding RNAs. Thus, NO is a potential target in cancer therapeutics and reviews focus on the new advancements using NO as a potential biomarker and therapeutic agent.

Multistep molecular trajectory of monocytic myeloid-derived suppressor cell induction by diffuse large B-cell lymphoma cells.

We present a case of concomitant splenic artery aneurysmal rupture with uterine rupture in a 32 year-old pregnant woman at 34 weeks of gestation with a history of one previous Cesarean section. The patient presented to the Emergency Department (ED) due to a sudden abdominal pain, which resolved spontaneously. In the ED, she displayed tachycardia, sweating, and lethargy, with no detectable fetal heart rate, raising suspicion of uterine rupture. Surgical exploration revealed significant intra-abdominal hemorrhage from a prior uterine incision, resulting in intrauterine fetal demise (IUFD) and placental abruption. The uterine rupture was promptly repaired, and the uterus remained stable. Subsequently, substantial bleeding and a massive hematoma were discovered. The patient received blood transfusions and underwent surgery to address the source of bleeding, identified as a ruptured splenic artery aneurysm, and successfully managed with packing and ligation. She recovered in the Intensive Care Unit (ICU). This case highlights the rare co-occurrence of uterine rupture and splenic artery aneurysm without apparent changes in vital signs or abdominal findings. In spite of the IUFD and massive hemorrhage, the patient ultimately maintained normal blood pressure.

Cardiovascular phenotype in women 1-3years after hypertensive pregnancy disorders: Impact of sex-independent and pregnancy-specific risk factors.

Usefulness of T1 volumetric isotropic turbo spin-echo acquisition black-blood magnetic resonance imaging for follow-up evaluation after flow diverter implantation.

Cardiovascular diseases include various heart and blood vessel disorders. Arterial stenosis, caused by the buildup of fatty deposits and other materials, narrows arteries and disrupts normal blood flow, leading to increased wall shear stress and flow disturbances. In this study, the Caputo-Fabrizio fractional derivative is applied to analyze blood flow with copper nanoparticles in an inclined stenosed artery. Blood is modeled as a non-Newtonian Casson fluid under a uniform magnetic field and pressure gradient. Using the Laplace and Hankel transform techniques, analytical solutions for blood and magnetic particle velocities are obtained, and the effects of flow parameters, Hartmann number, time, Casson fluid parameter, and fractional order are presented graphically. Validation against limiting cases shows good agreement with previous studies. The results demonstrate that blood and particle velocities increase with fractional order, time, and Casson fluid parameter, but decrease with higher Hartmann number, with blood velocity generally exceeding particle velocity. These findings are useful for designing targeted drug delivery systems by understanding the behavior of non-Newtonian nanofluids in stenosed arteries under magnetic fields.

Hypertensive disorders of pregnancy (HDP) cause adverse maternal and fetal outcomes, and establishing an early prediction method for HDP is needed. Existing methods based on serum markers require blood sampling. Therefore, we aimed to develop and validate a noninvasive HDP prediction model based on home blood pressure monitoring. In a development cohort, home blood pressure monitoring data from 443 pregnant women including 65 HDPs were divided into training data (n=365) and test data (n=78) to develop a logistic regression-based prediction model. Normal blood pressure variations depending on season and gestational age were subtracted. At each time point, 4 features were calculated for the last 4 weeks of data: average systolic blood pressure, average diastolic blood pressure, correlation coefficient between systolic blood pressure and diastolic blood pressure, and upward trend of systolic blood pressure against day. In a validation cohort, HBPM data from 264 pregnant women including 33 HDPs were collected prospectively and used to validate the model. The area under the receiver operating characteristic curve was 0.949 (95% CI, 0.890-1.000), 0.884 (95% CI, 0.807-0.961), and 0.845 (95% CI, 0.759-0.930) for the training, test, and validation data, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value were 0.923, 0.888, 0.387, and 0.993 for the training data; 0.667, 0.897, 0.867, and 0.729 for the test data; 0.758, 0.766, 0.316, and 0.957 for the validation data. Our HDP prediction model based on home blood pressure monitoring showed high negative predictive values and may contribute to reducing medical consultations.

Hypertension is a significant global public health issue and its pathogenesis is strongly associated with visceral obesity. The Chinese Visceral Adiposity Index (CVAI), a well-established indicator based on the metabolic profile of Asian populations, has been linked to an increased risk of hypertension. However, there is a lack of comprehensive evidence regarding the differential relationship between the CVAI and the incidence of hypertension in participants with normal vs. elevated blood pressure (BP). This study aimed to utilize longitudinal data to examine the association between the CVAI and the incidence of hypertension across populations with different baseline BP levels. Data from the China Health and Retirement Longitudinal Study (CHARLS) database were used for this retrospective cohort analysis. Participants aged ≥45 years without hypertension at baseline (2011) were included and followed up until 2020 to assess the incidence of hypertension. The CVAI was calculated using a sex-specific formula incorporating age, waist circumference (WC), body mass index (BMI), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). Multivariate logistic regression and restricted cubic spline (RCS) models were used to evaluate the nonlinear association between CVAI and hypertension risk. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive ability of CVAI. For the sensitivity analyses, univariate RCS models were employed to assess the robustness of the findings. Among 5311 participants, 1,819 (34.25%) developed hypertension during the 9-year follow-up period. CVAI emerged as an independent risk factor for incident hypertension. Comparing the highest to the lowest quartile of CVAI, the adjusted odds ratio (OR) was 1.77 (95% CI: 1.32-2.38) in the normal BP group and 3.21 (95% CI: 2.26-4.61) in the elevated BP group. A linear dose-response relationship was observed between CVAI and hypertension risk in both groups. These associations remained robust and linear in sensitivity analyses after excluding participants with diabetes, heart disease, or stroke. Clinically, CVAI offers a simple, low-cost tool to improve hypertension risk stratification and enable earlier targeted prevention, particularly among individuals with elevated BP.

Abstract Background: One of the recognized hallmarks of cancer cells is deregulated cellular metabolism, characterized by enhanced metabolic autonomy compared with non-transformed cells. Tumor cells display an overall increase in glucose metabolism, enhanced aerobic glycolysis and decreased oxidative phosphorylation, accompanied by a requirement for a high rate of protein, nucleotide, and fatty acid synthesis to provide the raw materials for cell division. Approximately 70-80% of all breast cancers (BC) are hormone receptor positive (HR+), and most HR+ breast cancers are HER2-negative (Her2-). The metabolic dependencies of HR+/Her2- BC and in particular, high-risk HR+ BC, are poorly understood. In depth analyses of in vivo metabolic processes by HR+ BC using carbon-13 labeled glucose (13C-glucose) infusions have never been done in humans. 13C-glucose is a stable isotope tracer that has been widely used in vitro, in vivo, and in patients in a variety of disease settings to study glucose, amino acid, and lipid metabolism. We hypothesize that HR+ breast cancers in vivo have altered use of metabolic pathways that can be determined by in vivo 13C isotope glucose labelling. The primary objective is to describe and discover new insights into the glucose, TCA cycle, amino acid, and lipid metabolic dependencies of HR+/Her2- BC, via liquid chromatography-mass spectrometry (LC-MS) and matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry analysis of in vivo U-13C-glucose-labeled biopsy of tumor and benign adjacent tissue. Methods: This is an ongoing pilot study that will enroll 16 patients with early stage I, II or III HR+/Her2- breast cancer who do not require neoadjuvant therapy and have planned curative primary resection. They will receive intraoperative 13C-glucose intravenous infusions followed by core biopsies of tumor and normal breast tissue and blood will be collected at time of resection. Tumor samples will be analyzed for metabolite labeling by LC-MS and spatial distribution of metabolite levels and labeling patterns by MALDI-MS. Genomic and proteomic analyses will be performed and related to observed metabolic fluxes. Demographic and clinicopathological information will be collected. ClinicalTrials.gov ID NCT05736367. Results: Preliminary results from LC-MS of tumors from the first four patients show avid glucose metabolism in HR+/Her2- BC. These tumors locally produce lactate from glucose, with higher 13C-lactate labeling observed in the tumor than in circulation. The contribution of glucose-derived lactate to the TCA cycle is approximately 30%, which is similar to what has previously been observed in hormone receptor-negative (HR-) BC. Interestingly, there was little to no labeling of the amino acid serine, demonstrating minimal activity of the de novo serine synthesis pathway in these tumors. This contrasts with previous results demonstrating extensive serine synthesis in HR-/Her2- BC and a common genomic amplification of the rate-limiting enzyme PHGDH in HR-/Her2- BC. This trial is ongoing, and further results will be presented at a future date. Conclusion: This study has the potential to discover new insights into the glucose, TCA cycle, amino acid, and lipid metabolic dependencies of HR+/Her2- breast cancer and will allow these critical pathways to be resolved spatially within the tumor, allowing analysis such as the effects of distance from blood vessels and of specific cell subpopulations. Grant Support: Ludwig Institute for Cancer Research, Ludwig Princeton Branch. Citation Format: C. Omene, S. Kumar, M. George, L. Potdevin, J. Smith, A. Shah, K. Matsuda, D. Toppmeyer, M. Gupta, K. Olszewski, E. White, J. Rabinowitz. Clinical investigations into the metabolic pathways of early stage hormone receptor positive/HER2 negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-09-28.

Mosaicism refers to the presence of multiple cell clones with distinct genotypes arising from a single zygote. The phenotype of mosaic individuals depends on the extent of mosaicism, ranging from localised to almost generalised. We report three diagnostically challenging cases with previously unrecognised mosaicism in the tumour predisposition syndromes (TPS) von Hippel-Lindau syndrome, neurofibromatosis type 1 and neurofibromatosis type 2. In all three patients there was a strong clinical suspicion for a TPS; however, no pathogenic variant (PV) was detected in these patients in DNA extracted from blood. With next generation sequencing (NGS) analysis of multiple affected tissue samples of these patients we were able to detect a recurrent PV at varying variant allele fractions. In all three patients, low-grade mosaicism was in retrospect confirmed in normal tissue and blood (variant allele frequency: 1%-7%). Therefore, we conclude that NGS on multiple affected tissues is an effective strategy to detect low-level mosaicism. Identification of previously unrecognised low-grade mosaic cases not only allows for more precise diagnosis and management advice for the index patient, but also accurate genetic counselling for family members.

Hypertension and diabetes mellitus are both known risk factors for atrial fibrillation (AF). Whether coexisting hypertension exacerbates AF risk among individuals with diabetes remains unclear. This study aims to investigate the association between hypertension and incident AF in this population. We studied participants in the prospective Kailuan Study, including 18,084 adults diagnosed with diabetes between 2006 and 2011 and free of AF at baseline. Hypertension was defined by a previous diagnosis, use of antihypertensive medications, or systolic/diastolic blood pressure ≥140/90 mmHg. Incident AF was identified via biennial ECGs and hospital records. Cox proportional hazards models adjusted for demographic, lifestyle, metabolic, and clinical covariates were used to estimate hazard ratios (HRs). Over a median follow-up of 14.8 years (IQR 12.7-16.8), 275 participants with diabetes developed AF, and 5,265 died from any cause. Hypertension was associated with a higher risk of AF (adjusted HR, 1.48; 95% confidence interval [CI], 1.05-2.07) compared to those without hypertension. Compared to participants with normal blood pressure, the adjusted HRs for AF were 1.54 (95% CI, 1.11-2.13) for grade 1 hypertension and 1.61 (95% CI, 1.06-2.44) for grade 2 hypertension. Among those with hypertension, target organ damage-particularly prior myocardial infarction or ischemic stroke-further elevated AF risk (HR, 2.66; 95% CI, 1.26-5.60). Hypertension independently increases AF risk in individuals with diabetes, especially with higher blood pressure levels and target organ damage. Early hypertension control is crucial for the prevention of AF in this high-risk population.

Donor-derived cytogenetic abnormalities are a rare finding following allogeneic hematopoietic cell transplantation. Deletion of the long arm of chromosome 20 [del(20q)] is one of the more frequently observed structural abnormalities, but its significance in the post-transplant setting remains unclear. We describe a unique case of donor-derived del(20q) with 26 years of post-transplant follow-up, the longest reported to date. The recipient remains well with normal blood counts despite persistent del(20q) in both myeloid and lymphoid lineages and the presence of coexisting somatic mutations in DNMT3A and TP53. Retrospective analysis of the donor's marrow confirmed del(20q) and low-level DNMT3A and TP53 mutations at the time of transplant; the donor later developed therapy-related MDS after radiation therapy for thyroid cancer. To contextualize this case, we reviewed 20 published reports of donor-derived del(20q) post-transplant. The median time to detection was 16 months post-transplant, and 35% of cases progressed to donor-derived malignancy. Among those who progressed, the median time to malignancy diagnosis was 22 months post-transplant. Clinical outcomes across cases ranged from asymptomatic persistence and cytopenias to donor-derived myeloid malignancies, highlighting the need for long-term follow-up and potential use of molecular profiling to better define the neoplastic potential of donor-derived del(20q) after transplantation.

Single-cell transcriptomics reveals targeted modulation of inflammatory repertoire by SOCE blockers.

Tumor-infiltrating B lymphocytes (TIL-Bs) are increasingly recognized as favorable prognostic markers in multiple cancer types and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic data for 15 distinct tumors using 8,720 samples of treatment naïve patients from The Cancer Genome Atlas and normal tissues from Gene Tissue Expression. B-lymphocyte infiltration correlated with survival for some but not all tumors. In lung adenocarcinoma (LUAD), CD79A levels were strongly predictive of overall survival, while CD8A transcripts were not, indicating that leukocytic infiltration per se does not explain the B-cell's impact. Single-cell RNA sequencing and flow cytometry identified increased relative numbers of CD11c+ B cells in treatment-naïve LUAD patients compared to normal tissue and blood. In LUAD, CD11c+ TIL-Bs were localized near CD4+ T cells and in vitro stimulation with anti-IgG with/without CD40 agonist resulted in expansion and rapid differentiation. Stimulation also induced IL-12, IL-21, and TNF-α secretion, which are cytokines known to enhance antitumor immunity. Overall, the data indicte that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.

Purpose This study aimed to establish an experimental rat model of Terson syndrome and explore occludin’s role in blood-retinal barrier disruption. Methods We induced acute intracranial pressure elevation in rats via cisterna magna normal saline or autologous blood injections (0.25–0.75 mL over 30–60 s) and monitored intraocular hemorrhage over 7 days. Retinal leakage was assessed via fluorescein flat-mounts, vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) via enzyme-linked immunosorbent assay (ELISA), and occludin via immunofluorescence. Results Both injections into the cisterna magna effectively induced Terson syndrome manifestations. All experimental groups demonstrated significant fluorescein leakage from posterior pole vessels within 1 min post-injection, with predominant extravasation observed along superficial retinal veins. While venous leakage progressively diminished after 30 min, peripheral capillary leakage emerged. Retinal VEGF levels significantly increased at 30 and 60 min post-intracranial pressure elevation, while IL-6 levels rose at 30 min. Quantitative analysis demonstrated no significant alterations in total retinal occludin levels. Additionally, stratified analysis revealed unchanged occludin levels in both the intermediate capillary plexus (ICP) and the deep capillary plexus (DCP). The superficial vascular complex (SVC) exhibited significant occludin reduction at 1, 30, and 60 min post-induction and the retinal pigment epithelium (RPE) showed delayed occludin downregulation at day 5. Conclusions This study established a preliminary experimental rat model of Terson syndrome. The model suggests Terson syndrome results from intracranial hypertension compressing the central retinal vein, disrupting tight junctions, and causing blood-retinal barrier failure, leading to hemorrhage.

Mammae aberrans in the axilla is a developmental abnormality caused by the persistence of breast tissue along the milk line and can cause fluctuating axillary masses due to hormonal stimulation, with a reported prevalence of approximately 0.4–6%. Methods: This article is presented as a descriptive case report based on data from the Department of Surgery at Cut Meutia Regional General Hospital, North Aceh, including medical history, physical examination, routine blood tests, fine needle aspiration biopsy (FNAB), excision, histopathological examination, and follow-up. Results: A 16-year-old female patient complained of a lump in her right axilla for approximately two years, which had enlarged in the last month and caused severe pain before menstruation. Examination revealed a mass measuring approximately 3×3×2 cm, without lymph node enlargement, and normal routine blood tests. Two FNAB punctures showed fat droplets/matrix without epithelial proliferation or malignant cells (benign smear) with the impression of aberrant mammary glands. The patient underwent mass excision; histopathology showed mature fatty tissue and fibrocollagen accompanied by ductular proliferation without signs of malignancy, and at the 1-week follow-up, the pain had disappeared and the lump was no longer visible. Discussion: The cyclic pain pattern associated with menstruation is an important clue for distinguishing aberrant mammary glands from differential diagnoses of axillary masses in adolescents, while excision provides diagnostic certainty and symptom improvement. Conclusion: Mammae aberrans should be considered in adolescents with axillary masses affected by the menstrual cycle, and excision is recommended in symptomatic cases for histopathological confirmation and resolution of complaints.

Primary aldosteronism, an overt form of renin-independent aldosterone production, leads to steeper eGFR decline compared to primary hypertension. Mounting evidence suggests that milder forms of renin-independent aldosterone production ("subclinical primary aldosteronism") are highly prevalent; however, the link between subclinical primary aldosteronism and eGFR decline remains unknown. This prospective cohort study included 976 Canadian adults aged 40-69 years, with predominantly normal blood pressure or mild untreated hypertension, from the randomly sampled, population-based CARTaGENE cohort. Aldosterone and renin concentrations were measured at enrollment (2009-2010). Creatinine and cystatin C were measured at enrollment and 5-7 years post-enrollment. Multivariable linear mixed regression models were used to measure the associations of aldosterone, renin, and the aldosterone-to-renin ratio (ARR) with eGFR decline over time. The mean (SD) age of participants was 53 (7) years; 51% were female. Mean blood pressure was 121 (15)/72 (10) mmHg, and 11% had blood pressure ≥140/90 mmHg. Mean eGFRCrCysC was 109 (16) mL/min/1.73m2. At higher ARR levels, there was steeper mean eGFR decline over time [Tertile 1 (ARR ≤0.49 ng/dL per mU/L): -1.40 (1.77) mL/min/1.73m2/year, Tertile 2 (ARR 0.50-0.87 ng/dL per mU/L): -1.48 (1.75) mL/min/1.73m2/year, Tertile 3 (ARR >0.87 ng/dL per mU/L): -1.57 (1.79) mL/min/1.73m2/year; p=0.01], representing 11% steeper decline in the highest versus lowest ARR tertile. At lower renin levels, there was steeper mean eGFR decline over time [Tertile 1 (renin ≤9.2 mU/L): -1.59 (1.80) mL/min/1.73m2/year, Tertile 2 (renin 9.3-15.9 mU/L): -1.53 (1.77) mL/min/1.73m2/year, Tertile 3 (renin >15.9 mU/L): -1.33 (1.72) mL/min/1.73m2/year; p=0.04], representing 16% steeper eGFR decline in the lowest versus highest renin tertile. There was no significant association between aldosterone and eGFR change over time (p=0.50). All aforementioned associations were independent of blood pressure and were consistent among participants with normal blood pressure in isolation. Independent of blood pressure, elevated ARR and suppressed renin were associated with steeper eGFR decline over time.

Kidney scarring (KS) secondary to urinary tract infections is a common cause of secondary hypertension in children. We investigated the association between serum cystatin C and hypertension in children with KS using 24-h ABPM. One hundred eleven children (aged 6-18 years) with DMSA-confirmed KS were included. All patients underwent 24-h ABPM, and serum cystatin C, creatinine, creatinine-based eGFR, and cystatin C-based eGFR were calculated. Hypertension was defined according to current AAP and ESH recommendations, using age and gender/height-specific threshold values in ABPM. The relationships between hypertension, biochemical parameters, and scar severity were assessed using multivariate analysis. No participant was taking antihypertensive medication at the time of ABPM. Hypertension was detected in 36.9% (n = 41) of patients. Serum cystatin C levels were significantly higher in the hypertensive group (1.06 mg/L vs. 0.94 mg/L, p = 0.004). When assessed for kidney function, both creatinine-based eGFR (p = 0.044) and cystatin C-based eGFR (67 [42-183] vs. 74.9 [30.9-183] mL/min/1.73 m2, p = 0.004) were significantly lower in the hypertensive group than in the normotensive group. Mean systolic nocturnal dip was < 10% (non-dipper) in both groups. In multivariate logistic regression, only high-grade scarring (Grades 3-4) remained an independent risk factor, increasing the risk of hypertension by 3.44-fold (95% CI: 1.45-8.16, p = 0.005). High-grade scarring is a significant independent risk factor for hypertension. Although cystatin C reflects the severity of kidney damage, its association with hypertension depends on the scar burden. Since circadian rhythm disturbances (non-dipping) are common, even in children with normal office blood pressure, ABPM may be necessary for monitoring those with KS.

Background: Glycogen storage disease type Ia (GSDIa) is a rare, inherited, autosomal recessive deficiency of glucose-6-phosphatase (G6Pase), an enzyme necessary in glycogenolysis and gluconeogenesis. To maintain normal blood glucose levels and ensure survival, individuals living with GSDIa must frequently consume complex carbohydrates (eg, uncooked cornstarch). Dietary management can result in chronic complications and significant patient burden. DTX401 (pariglasgene brecaparvovec) is an investigational adeno-associated virus serotype 8 vector (AAV8)–based gene therapy designed to restore endogenous glucose production. Objectives: Patient experience interviews were conducted as part of an open-label, phase 1/2 dose-escalation trial (NCT03517085) evaluating the safety and efficacy of DTX401 in adults ≥18 years with GSDIa. Methods: Telephone interviews were conducted at Weeks 24, 52, and 104, using a semistructured interview guide. Qualitative interview data were audio recorded, transcribed, coded, and analyzed. Results: Most (86%; n = 6/7) reported overall symptom improvement and reduced burden following DTX401 treatment. Three (43%) reported no negative outcomes following gene therapy; 4 (57%) mentioned at least one negative change attributed to instances of blood sugar instability, lifestyle, or diet adjustments. Satisfaction fluctuated across timepoints; however, most were somewhat satisfied/very satisfied with gene therapy at Weeks 24 (80%), 52 (86%), and 104 (86%). No participants reported being very dissatisfied. Discussion: Following DTX401 treatment, most participants reported substantial reduction in cornstarch intake and corresponding improvements in symptoms, physical function, diet management, emotional function, self-perception, social function, sleep quality, work performance, and overall health. Few negative changes were reported. While some results regarding met expectations were mixed, most indicated they would still want gene therapy even if they had to continue cornstarch and if they had continued diet restrictions, and most reported satisfaction with treatment. While the study had limitations, interview results suggest that DTX401 helps to address aspects of the condition and treatment that patients have identified as burdensome. Conclusions: Most interviewees in this open-label trial of investigational DTX401 described positive experiences, including substantial reduction in burden and improved health-related quality of life following treatment throughout the trial. To optimize patient outcomes and experience with gene therapy, guidance on and close monitoring of dietary changes during implementation should be provided.