Breastfeeding Characteristics and Duration of Feeding Human Milk in Infants With Congenital Heart Disease
Future efforts to support feeding human milk in infants with CHD should emphasize practices that support maximal human milk production.
KEY FINDINGS: Future efforts to support feeding human milk in infants with CHD should emphasize practices that support maximal human milk production.
BACKGROUND: Although infants with congenital heart disease (CHD) are able to breastfeed successfully, the factors that affect feeding human milk across the first year are not well established. The aim of this study was to examine breastfeeding characteristics and their relationships to the exclusivity and duration of feeding human milk among infants with CHD.
DETAILS: Breastfeeding characteristics data from a cohort of 75 infants with CHD enrolled in a study that examined relationships among milk type and infant growth in the first year of life were analyzed. Infants whose mothers reported not having enough milk were exclusively fed human milk for a shorter duration than those who did not have this challenge ( P = .04); however, the duration of feeding any human milk did not differ ( P = .18). Average daily volume expressed at 1 month was positively related to the duration of exclusive human milk (ß = .07, P = .04) and any human milk (ß = .07, P = .04) feeding.
Our Most Popular Resources
Copyright © Wolters Kluwer Health, Inc. All rights reserved.
Source: Russel, S. M., Lessen, R., Rovner, A. J., et al. (2024). Breastfeeding Characteristics and Duration of Feeding Human Milk in Infants With Congenital Heart Disease. The Journal of Perinatal & Neonatal Nursing. 2024; 38(1): 46-53. Published: January/March, 2024. DOI: 10.1097/JPN.0000000000000740.
Formononetin May Protect Against Anthracycline Cardiotoxicity Through Cardiac Metabolic Improvement
A preclinical study identified ERRa as an early metabolic regulator of anthracycline-induced cardiotoxicity, with its reduction occurring before overt cardiac dysfunction. Formononetin, an ERRa activator, improved cardiac metabolism and function in mouse and pig models while also enhancing doxorubicin's anticancer activity in breast cancer organoids. The findings suggest a potential dual-action strategy for protecting the heart during anthracycline therapy, but clinical studies are still needed.
KEY FINDINGS: The findings identify ERRα downregulation as an early and potentially causal component of anthracycline-induced cardiac injury. Formononetin improved cardiac energy metabolism and function in experimental models while retaining, and potentially enhancing, doxorubicin's anticancer activity in breast cancer organoids. The study therefore suggests that pharmacologic activation of ERRα could represent a future strategy for simultaneously addressing anthracycline cardiotoxicity and cancer treatment. However, the evidence remains preclinical, and clinical studies are required to determine whether these findings translate into cardioprotection in patients receiving anthracycline chemotherapy.
BACKGROUND: Anthracyclines such as doxorubicin are effective anticancer agents, but their use can be limited by anthracycline-induced cardiotoxicity (AIC). Early metabolic disturbances in cardiac muscle may contribute to the development of cardiac dysfunction. This study investigated the role of estrogen-related receptor α (ERRα), a regulator of cardiac energy metabolism, in AIC and evaluated whether pharmacologic activation of ERRα with formononetin could provide cardiac protection while maintaining anticancer activity.
DETAILS: The investigators used a porcine model of anthracycline cardiotoxicity to examine changes in ERRα over time and cardiomyocyte-specific gain- and loss-of-function mouse models to assess its functional role. Mechanistic experiments, including ChIP-qPCR, reporter assays, and microscale thermophoresis, were used to investigate how formononetin interacts with the ERRα pathway. Cardiac tissue from patients who had received chemotherapy was also examined, while human breast cancer patient-derived organoids were used to evaluate potential effects on tumor activity. ERRα expression was reduced in hearts from the porcine AIC model and in cardiac tissue from patients treated with chemotherapy. In pigs, the reduction occurred at the 6-week subclinical stage, before overt cardiac dysfunction developed. Increasing ERRα expression specifically in cardiomyocytes enhanced mitochondrial metabolic programs and fatty-acid oxidation and preserved systolic function after doxorubicin exposure, whereas ERRα reduction worsened metabolic dysfunction and cardiac impairment.
Our Most Popular Resources
Drug screening identified formononetin as a selective ERRα activator. In mouse and pig models, formononetin increased ERRα activity, improved cardiac mitochondrial metabolism, and reduced anthracycline-associated cardiac injury. Mechanistic experiments indicated that formononetin interacts with the ERRα/PGC-1α complex and promotes its stability, supporting activation of downstream metabolic pathways.
Importantly, formononetin also demonstrated anticancer activity in human breast cancer patient-derived organoids. Treatment with formononetin alone reduced organoid viability and proliferation, while combining formononetin with doxorubicin produced greater antitumor effects.
Copyright © Skyscape. All rights reserved.
Source: Wang, X., Ling, G., Wei, Y., et al. Natural ERRα Activator Formononetin Ameliorates Anthracycline Cardiotoxicity via Metabolic Improvement. Circulation Research. 2026; 139(7): e329042. Published: September 11, 2026. DOI: 10.1161/CIRCRESAHA.126.329042.
Self-Sampling HPV Testing Increases Cervical Cancer Screening Uptake in Primary Care
A Singapore randomized trial found that offering HPV self-sampling increased cervical cancer screening uptake from 42.8% to 56.6%. More than half of screened women chose self-sampling, suggesting that flexible screening options may help reach women who otherwise remain unscreened.
KEY FINDINGS: Offering HPV self-sampling as an additional screening option substantially increased cervical cancer screening participation and high-risk HPV detection compared with clinician sampling alone in this Singapore primary care population. The benefit was particularly relevant to women who had never previously undergone screening, suggesting that providing greater choice and convenience may help reach populations that are otherwise difficult to engage. More than half of screened women in the intervention group selected self-sampling, indicating substantial acceptance of this approach. However, lower uptake among women with less educational attainment highlights the need for targeted education and engagement strategies when implementing self-sampling programs.
BACKGROUND: Cervical cancer screening remains suboptimal in Singapore, where clinician-collected HPV testing has been the standard approach. Concerns related to discomfort, privacy, embarrassment, or the clinical setting may discourage some women from participating in screening. This pragmatic randomized controlled trial evaluated whether offering self-sampling for HPV DNA testing alongside clinician sampling could increase cervical cancer screening uptake and detection of high-risk human papillomavirus (HPV) compared with clinician sampling alone.
DETAILS: The open-label, 2-arm randomized controlled trial used a Zelen design and was conducted across National Healthcare Group Polyclinics in Singapore. Women aged 30-69 years who were due for cervical cancer screening were randomly assigned 1:1 to an intervention group or usual care. Women in the intervention group were offered clinician sampling followed by self-sampling if they did not choose clinician sampling, whereas women receiving usual care were offered clinician sampling alone. The primary outcome was detection of high-risk HPV DNA, with screening uptake as the secondary outcome.
Our Most Popular Resources
Between August 2024 and February 2025, 650 women were randomized, with 640 participants included in the final analysis, 320 in each group. Subgroup analyses evaluated outcomes according to previous screening history, while multivariable analyses examined factors associated with screening choices.
High-risk HPV detection was significantly greater when self-sampling was offered alongside clinician sampling than with clinician sampling alone: 3.1% versus 0.3%, respectively, representing an absolute difference of 2.8% (95% CI, 0.8-4.8; P<.001). The higher detection rate was driven by greater screening participation, with screening uptake reaching 56.6% in the intervention group compared with 42.8% with usual care, an absolute difference of 13.8% (95% CI, 6.0-21.4; P<.001).
The increase in screening uptake was particularly evident among women who had no previous screening and those with a regular screening history. Among women who underwent screening in the intervention group, 56.4% selected self-sampling. Lower educational attainment was associated with lower odds of choosing self-sampling rather than declining screening altogether.
Copyright © Skyscape. All rights reserved.
Source: Ng, X. R., Quek, I. P., Pereira, M. J., et al. Effect of Self-Sampling HPV DNA Testing on Cervical Cancer Screening in Singapore's Primary Care: Pragmatic Randomized Controlled Trial Annals of Family Medicine.. 2026; 24(4): 291-300. Published: July, 2026. DOI: 10.1370/afm.250683.
Biochemical Effects of Oral Contraceptives in Young Women With Classic Congenital Adrenal Hyperplasia
A prospective study found that ethinylestradiol/levonorgestrel reduced key adrenal androgens while increasing cortisol levels. Nearly half of participants had a reduction in hydrocortisone dose following biochemical changes. Larger randomized studies are needed to confirm these findings.
KEY FINDINGS: In adolescent and young women with classic 21OHD, combined OC containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel was associated with broad reductions in circulating and urinary androgen-related steroids and an increase in cortisol levels. Nearly half of the participants who completed the study required a reduction in hydrocortisone dosage during the six-OC-cycle observation period. These findings suggest that combined OCs may provide an adjunctive approach for managing persistent androgen excess in females with classic CAH when conventional glucocorticoid treatment does not provide satisfactory biochemical control. However, the study was small and observational, so the findings do not establish a causal relationship, and randomized studies are needed to determine the longer-term clinical and metabolic effects of OC therapy in this population.
BACKGROUND: Androgen excess remains a therapeutic challenge in adolescent and young women with classic 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH). Combined oral contraceptives (OCs) containing ethinylestradiol and a progestin can influence ovarian and adrenal steroidogenesis, but their effects on the broader steroid profile in women with classic 21OHD have not been systematically characterized. This prospective observational study evaluated changes in circulating and urinary steroid metabolites following initiation of a combined OC in adolescent and young women with classic 21OHD.
DETAILS: The multicenter study enrolled 20 young women with genetically confirmed classic 21OHD between March 2021 and March 2024. Participants were 13-25 years old at baseline sampling, although the recruited cohort had a median age of 16 years and a range of 11-24 years. The participants initiated a combined OC containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel. The study included three assessments: before OC initiation, during the third OC cycle, and during the sixth OC cycle. Blood samples and 24-hour urine collections were obtained at each visit, with plasma steroids measured using liquid chromatography-mass spectrometry and urinary metabolites assessed using gas chromatography-mass spectrometry. Seventeen of the 20 participants completed the study, with a median age of 16.8 years (range, 11-24). The reasons for OC initiation included irregular menses, contraception, amenorrhea, dysmenorrhea, and hyperandrogenemia. Most participants were receiving hydrocortisone and fludrocortisone for CAH management. The prospective design and combined assessment of plasma and urinary steroid profiles allowed detailed characterization of biochemical changes during OC treatment.
Our Most Popular Resources
Combined OC therapy was associated with significant reductions in several circulating androgens and androgen precursors. Compared with baseline, plasma concentrations of 17α-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, and testosterone decreased significantly, with all P values <0.005. Plasma cortisol concentrations increased significantly (P<0.001), while urinary 24-hour excretion of androgen metabolites, including the 11-oxygenated androgen metabolite 11-oxo-etiocholanolone, also declined.
The broader steroid analysis showed reductions in multiple androgen-related metabolites, including androsterone, etiocholanolone, DHEA, testosterone, dihydrotestosterone, 11-oxo-etiocholanolone, and 11β-hydroxyandrosterone. Cortisol concentrations and urinary cortisol excretion increased during OC treatment. These biochemical changes had implications for glucocorticoid management: 8 of 17 participants (47%) who completed the study had at least one reduction in hydrocortisone dose during follow-up in response to laboratory changes.
Copyright © Skyscape. All rights reserved.
Source: Kouri, C., Sommer, G., Cavalieri Costa, F., et al. Biochemical Control in Young Women With Congenital Adrenal Hyperplasia Taking Oral Contraceptives: A Prospective Observational Study. v. 2026; 195(3): 385-395. Published: September, 2026. DOI: 10.1093/ejendo/lvag160.
Next-Generation Phenotyping May Strengthen Variant Interpretation in Mowat-Wilson Syndrome
In a proof-of-concept study, GestaltMatcher ranked Mowat-Wilson syndrome as the leading diagnosis in a 4-year-old child with a de novo ZEB2 variant. Three of 4 facial images met the PP4 moderate threshold and 1 met the supporting threshold. Integration of facial, HPO, and molecular data through PEDIA ranked ZEB2 as the most likely disease-causing gene. The findings suggest that AI-assisted phenotyping may provide quantitative support for variant interpretation while complementing expert clinical genetics assessment.
KEY FINDINGS: Computational facial phenotyping using GestaltMatcher identified MWS as the leading diagnosis in a child with a suspected de novo ZEB2 variant and provided quantitative evidence that supported variant interpretation. Three of 4 facial images reached the PP4 moderate threshold, while 1 reached the supporting threshold. Integration of facial phenotype, HPO information, and molecular data through PEDIA ranked ZEB2 first and contributed to classification of the variant as likely pathogenic. The findings provide a proof of concept for incorporating NGP into rare-disease diagnostic and variant-interpretation workflows, although larger, multicenter studies are needed to establish reproducibility and generalizability.
BACKGROUND: Mowat-Wilson syndrome (MWS) is a rare neurodevelopmental disorder caused by pathogenic variants in the ZEB2 gene and characterized by developmental impairment, epilepsy, congenital anomalies, and distinctive craniofacial features. Although next-generation phenotyping (NGP) tools such as GestaltMatcher can assist in recognizing rare genetic disorders, their use as quantitative evidence for variant interpretation within the American College of Medical Genetics and Genomics (ACMG) framework remains less established. This study evaluated whether computational facial phenotyping and multimodal clinical data could support variant prioritization and the ACMG PP4 phenotype-specificity criterion in MWS.
DETAILS: The investigators applied GestaltMatcher to a 4-year-old child with an undiagnosed neurodevelopmental disorder, suspected MWS, and a de novo ZEB2 variant. Facial photographs were analyzed alongside Human Phenotype Ontology (HPO) terms and simulated exome data using the PEDIA framework. Bayesian likelihood modeling was used to establish Gestalt score thresholds corresponding to supporting, moderate, strong, and very strong PP4 evidence. Brain MRI was also analyzed for structural abnormalities associated with MWS. The GestaltMatcher model had been trained using 9,671 images from 7,294 patients representing 275 disorders. For the MWS analysis, the dataset included 11 individuals with MWS and 14 age-matched controls.
Our Most Popular Resources
GestaltMatcher ranked MWS as the leading diagnosis, while integration through PEDIA also ranked ZEB2 as the most likely disease-causing gene. Across the 4 facial images from the proband, 3 achieved the PP4 moderate threshold and 1 achieved the PP4 supporting threshold. The established Gestalt score thresholds were 0.5111 for supporting, 0.5672 for moderate, 0.6609 for strong, and 0.7632 for very strong evidence.
Using the NGP-derived PP4 moderate evidence together with the original ACMG evidence, the ZEB2 variant was classified as likely pathogenic. Brain MRI demonstrated subtle thinning of the corpus callosum, a finding consistent with previously reported MWS-associated neuroimaging abnormalities. MRI-derived features also differentiated individuals with MWS from age-matched controls in exploratory analysis.
An additional exploratory case involving an infant with molecularly confirmed MWS showed that GestaltMatcher could prioritize MWS based solely on infant facial characteristics. The authors emphasize that NGP is intended to complement, rather than replace, expert clinical genetic assessment.
Copyright © Skyscape. All rights reserved.
Source: Hsieh, T. C., Todd, D., Warner, T., et al. Leveraging Next-Generation Phenotyping in Dysmorphology to Support Variant Interpretation in Mowat-Wilson Syndrome. Neurology Genetics. 2026; 12(4): e200384. Published: July 1, 2026. DOI: 10.1212/NXG.0000000000200384
Broad-Spectrum Antibiotic Use Is Lower Among Hospice Patients With Cancer at the End of Life
In this nationwide Korean cohort, hospice utilization was associated with lower broad-spectrum antibiotic use as death approached, particularly during the final week and final 3 days of life. The findings suggest that hospice involvement may be associated with a transition toward more selective antimicrobial use and less intensive treatment near the end of life. However, the study was observational, and causality cannot be established. Important clinical variables, including infection severity, microbiological findings, functional status, symptom burden, cancer stage, and treatment intent, were unavailable in the claims data.
KEY FINDINGS: Among adults with cancer approaching death, hospice utilization was associated with less frequent and lower-intensity broad-spectrum antibiotic exposure, particularly during the final days of life. The findings are consistent with a transition toward comfort-focused care, although they do not establish that hospice care itself caused the reduction. Hospice initiation occurred relatively close to death, with a mean interval of 39.9 days and a median of 22.0 days, and some antibiotic treatment may have preceded hospice enrollment. In addition, cancer stage, treatment status, infection severity, microbiological findings, functional status, symptom burden, and treatment intent were unavailable in the claims data.
BACKGROUND: Antibiotic treatment remains common during end-of-life care for patients with cancer, despite uncertain benefits for survival and potential burdens including drug toxicity, intravenous administration, adverse effects, and antimicrobial resistance. This retrospective cohort study evaluated whether hospice involvement was associated with differences in broad-spectrum antibiotic use among adults with cancer during the final 3 months of life.
DETAILS: Investigators analyzed Korean National Health Insurance Service claims data for adults aged ≥18 years who died between January 1, 2018, and December 31, 2021, with one of the 10 leading cancer-related causes of death. Hospice users had received inpatient, home-based, or consultation-based hospice care before death. Broad-spectrum antibiotic exposure included anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides. The final 90 days of life were divided into four intervals: 1–3 months before death, 1 week to 1 month before death, the final week, and the final 3 days. Antibiotic exposure was assessed by the proportion of patients receiving antibiotics and by days of therapy (DOT) per 1,000 patient-days. Propensity score matching was performed at a 1:2 ratio.
Our Most Popular Resources
After matching, 38,102 hospice users and 75,736 non-hospice users were analyzed. During the final 3 months of life, 74.6% of hospice users and 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P0.001). Antibiotic use was initially slightly higher among hospice users during the period 1–3 months before death, at 34.0% versus 32.2% (P0.001), but became consistently lower among hospice users thereafter. From 1 week to 1 month before death, use was 31.1% versus 32.8%; during the final week, 11.3% versus 18.5%; and during the final 3 days, 4.8% versus 10.3% among hospice and non-hospice users, respectively (all P0.001).
Days of therapy per 1,000 patient-days were also consistently lower among hospice users, with the greatest differences occurring during the final week and final 3 days of life. Carbapenems and glycopeptides demonstrated particularly pronounced differences between the groups. In cancer-specific analyses, patients with hematologic malignancies had the highest overall antibiotic exposure, followed by those with pancreatobiliary and gastric cancers, while exposure was comparatively lower among patients with breast and liver cancers.
Copyright © Skyscape. All rights reserved.
Source: Jeung, Y. S., Kim, H. J., Yu, J., et al. Comparison of Broad-Spectrum Antibiotic Use According to Hospice Utilization Among Patients with Cancer at the End of Life in South Korea: A Nationwide Analysis. Journal of Hospice and Palliative Care. 2026; 29(2): 41-50. Published: June 1, 2026. DOI: 10.14475/jhpc.2026.29.2.41.
Specialty: