ウィリアムズ症候群

BACKGROUND: A prospective randomized controlled trial of exclusive human milk nutrition (EHM) in infants with single-ventricle physiology (SVP) was previously published. This study evaluates growth and health outcomes at 3-6 months. METHODS: Demographics, anthropometrics, and clinical outcomes were collected prospectively. Anthropometric z-scores were calculated using WHO standards. RESULTS: One hundred seven infants were randomized to EHM or control diet, with 23 infants meeting predefined exclusion criteria, 8 infants withdrawn/died, leaving 76 infants at discharge. At 3-6 months, 74 infants completed follow-up. Infants with hypoplastic left heart syndrome (HLHS) were similar (control 73%, EHM 86.5%; p = 0.24). Growth, z-scores, and hospitalization did not differ between groups up to 6 months. Median growth velocity was 25 (IQR: 20.24-30.99) and 22 (IQR: 18.76-23.94) g/day from birth to 3-6 months. Overall, 50-60% of infants achieved 100% PO intake by 3-6 months of age. CONCLUSIONS: Neonates with SVP receiving an EHM diet from birth to 30 days post-surgery had similar growth at 3-6 months of age compared to the control diet. Infants with SVP benefit from a protocolized nutritional approach, as evidenced by normal growth velocities in infancy. Centers may consider delaying gastrostomy tube placement until after the Glenn operation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov ( www. CLINICALTRIALS: gov , Trial ID: NCT02860702). IRB APPROVAL: This trial was approved by the Institutional Review Board of the University of Texas Health Sciences Center at San Antonio (ID: HSC20150779H). IMPACT: This multicenter RCT demonstrates the long-term benefits of exclusive human milk nutrition in infants with SVP, with improved growth and reduced necrotizing enterocolitis. A multidisciplinary approach and a well-thought-out nutritional algorithm can optimize growth in infants with complex congenital heart disease, similar to healthy term infants up to 6 months of age. The majority of infants with SVP requiring an operation within the first month of life are able to achieve 100% of their intake via PO by 6 months of age; therefore, delaying gastrostomy tube placement until after the Glenn operation may be considered.

PURPOSE: IMC-C103C is an ImmTAC bispecific (MAGE-A4×CD3) T cell engager targeting a peptide from the cancer-testis antigen MAGE-A4 presented by HLA-A*02:01. This phase 1/2 study in advanced solid tumors (IMC-C103C-101; NCT03973333) investigated the safety and preliminary anti-tumor activity of IMC-C103C. METHODS: HLA-A*02:01+ patients with previously treated advanced solid tumors received IMC-C103C by weekly intravenous infusion, with step-up dosing introduced at higher dose levels. Dose-escalation decisions were guided by the mTPI-2 method. Key objectives included evaluating safety and preliminary anti-tumor activity; pharmacokinetics, pharmacodynamics, and biomarkers were also assessed. RESULTS: 68 patients were enrolled in 10 dose-escalation cohorts (n=56; 64% ovarian carcinoma (OC)) and one OC expansion cohort (n=12). In dose escalation, patients received doses ranging from 0.5 to 240 µg. The dose-limiting toxicity rate at the two highest dose levels (1/6 and 2/10) did not exceed the maximum tolerated dose. A lower-dose regimen of 15-45-140 µg, with clinical activity, and a more favorable tolerability profile, was selected as the expansion dose. There were no treatment-related discontinuations or deaths. The most common treatment-related adverse events were cytokine-mediated, including grade 1/2 cytokine release syndrome and associated symptoms. While MAGE-A4 expression was observed in most patient's tumors (71% positive), the level of expression was low (median H-score=16). Initial clinical and pharmacodynamic activity was observed at doses of 15 µg, with more consistent activity observed at doses ≥90 µg. At doses ≥90 µg, patients with MAGE-A4+ OC had deeper reductions in tumor size and circulating tumor DNA and trended to have longer overall survival than patients with MAGE-A4- OC. CONCLUSIONS: IMC-C103C was well tolerated at doses up to 140 µg, induced dose-dependent pharmacodynamic changes, and demonstrated clinical activity in multiple patients with MAGE-A4+ solid tumors. Clinical activity was dependent on MAGE-A4 expression; however, expression was especially low in the higher dosing cohorts, limiting adequate efficacy assessment. TRIAL REGISTRATION NUMBER: NCT03973333.

Accurate detection of respiratory viruses is essential for infection control, patient management and public health response. Nasopharyngeal swabs (NPS), collected by healthcare workers (HWC-NPS), remain the gold standard for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) detection but require trained personnel and can be uncomfortable for patients. Self-collected swabs, such as oral-nasal swabs (SC-ONS) and mid-turbinate swabs, offer scalable alternatives suitable for mass testing. Previous mid-turbinate swab designs included a plastic stopper and were not compatible with automated laboratory testing. This study compared the performance of (i) SC-ONS, (ii) an automation-friendly, redesigned version of mid-turbinate swab (SC-MTS) and (iii) HWC-NPS in detecting SARS-CoV-2. Between April and June 2022, paired NPS, ONS and MTS samples were collected from 100 participants at a Coronavirus disease 2019 (COVID-19) assessment centre in Hamilton, Ontario. Samples were tested for SARS-CoV-2 by reverse-transcriptase PCR. Compared to HWC-NPS, SC-ONS demonstrated 82.1% sensitivity and 100% specificity, while SC-MTS showed 75.0% sensitivity and 100% specificity. Agreement with HWC-NPS was strong for both SC-ONS (κ=0.863) and SC-MTS (κ=0.804). Agreement between SC-ONS and SC-MTS was nearly perfect (κ=0.944). Cellular material yields as well as SARS-CoV-2 viral loads were lower for self-collected swabs than HWC-NPS, while viral load comparisons revealed no significant difference between SC-ONS and SC-MTS. Our study aligns with previous work demonstrating the use of self-collected mid-turbinate swabs for the detection of respiratory viruses, while also demonstrating the compatibility of the newly designed swabs with automated laboratory instruments. Our results, while conducted in a relatively small sample, suggest that self-collected ONS and MTS are reliable alternatives to HWC-NPS, offering practical, less invasive, automation-friendly options for large-scale respiratory virus surveillance and pandemic preparedness.

Prion diseases, of which Creutzfeldt-Jakob disease is the most common, are fatal neurodegenerative disorders and are often rapidly progressive. They are associated with a significant palliative care burden for patients and families, ranging from prognostic uncertainty to complex symptom management to caregiver distress. Healthcare professionals face unique pressures when caring for these patients, which can include a lack of familiarity with this rare diagnosis and rapidly evolving symptom needs due to accelerated clinical deterioration. We convened a multidisciplinary panel of experts from around the UK, including palliative care doctors, general practitioners, physician and nurse specialists in prion diseases, and a lived experience representative to compile practical, consensus-based recommendations for managing prion diseases, much of which can also be applied to other rapidly progressive dementias. In this article, we examine the available evidence base for managing various aspects of prion diseases. Where evidence is limited, we suggest best practices informed by decades of our collective experiences.

Mechanisms underlying feedback learning in intellectual disability (ID) remain poorly understood. Down syndrome (DS), Fragile X syndrome (FXS), and Williams syndrome (WS) are genetic syndromes associated with ID, with distinct attention and arousal regulation profiles. Pupil dilation is a well-established index of feedback processing in typical development; little is known about these processes in non-social learning in these syndromes. Participants with DS (n = 13), FXS (n = 13), WS (n = 27), and typically developing (TD) individuals (n = 56) aged 6-60 years completed a reward contingency reversal task while eye-tracking recorded pupil dilation and gaze allocation. Data were analyzed using Bayesian mixed-effects models. All groups effectively learned from feedback, staying with rewarded options and switching after losses. WS participants performed similarly to TD participants. DS and FXS individuals showed more variable behavioral performance, indicating potential individual differences in feedback processing that warrant further investigation. Physiologically, TD individuals showed greater pupil dilation following losses than wins, whereas WS individuals showed no difference, suggesting attenuated physiological sensitivity to feedback valence. All groups tended to fixate on the previously rewarded options. This research highlights the value of combining behavioral and physiological approaches in ID research.