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Dessicating Stress Triggers and Exacerbates Experimental Ocular Graft-Versus-Host-Disease
No full textIntroduction: Chronic ocular graft-versus-host disease (oGVHD) is one of the most common complications after allogeneic hematopoietic stem cell transplantation (aHSCT). Recent studies indicate that desiccating stress by air-conditioning in transplantation wards increases the incidence of oGVHD. To test the hypothesis that experimental desiccating stress is a risk factor for oGVHD a mouse model of oGVHD was subjected to experimental desiccating stress.
Materials/methods: A previously established chemo-induced minor-mismatch mouse model of oGVHD was used. One group was challenged with desiccating stress for 18 days and compared to non-desiccated GVHD animals. Clinical phenotyping was performed weekly and ocular tissue and regional lymph nodes were collected on days 7 and 28 for flow-cytometry, tear film cytokine analysis, histology for corneal lymphatics and dendritic cell counts, and corneal gene expression.
Results: Desiccating stress leads to significant earlier and more severe systemic and oGVHD accompanied by higher numbers of activated corneal dendritic cells, higher expression of TNF in tear film and earlier corneal lymphangiogenesis. Gene expression analysis suggests that systemic GVHD severity may influence oGVHD. Different inflammatory pathways are upregulated at d28 following desiccating stress in contrast to non-desiccated GVHD.
Conclusions: The data presented strengthens the hypothesis, that desiccating stress during aHSCT is a risk factor for oGVHD. Together with already published clinical data, there is increasing evidence that implicates protecting patients from desiccation during the engraftment of allogeneic hematopoietic stem cells. Furthermore, specific prophylactic therapies should be developed and tested to reduce the incidence and severity of oGVHD
On the Nose: Nasal Neurostimulation as a Technology Countermeasure for Sinonasal Congestion in Astronauts
No full textHuman spaceflight subjects the body to numerous and unique challenges. Astronauts frequently report a sense of sinonasal congestion upon entering microgravity for which the exact pathomechanisms are unknown. However, cephalad fluid shift seems to be its primary cause, with CO2 levels and environmental irritants playing ancillary roles. Current management focuses on pharmacotherapy comprising oral and nasal decongestants and antihistamines. These are among the most commonly used treatments in astronauts. With longer and more distant space missions on the horizon, there is a need for efficacious and payload-sparing non-pharmacological interventions. Neurostimulation is a promising countermeasure technology for many ailments on Earth. In this paper, we explore the risk factors and current treatment modalities for sinonasal congestion in astronauts, highlight the limitations of existing approaches, and argue for why neurostimulation should be considered
Improving Pediatric Heart Failure Outcomes Through Collaboration and Innovation: The Current Status of the Advanced Cardiac Therapies Improving Outcomes Network (Action)
No full textThe Advanced Cardiac Therapies Improving Outcomes Network (ACTION) was founded in 2017 as a learning health care system to bring together all stakeholders with the aim of improving outcomes for pediatric and congenital heart disease patients with heart failure. From an initial focus on the ventricular assist device (VAD) population, work in the network has expanded to encompass the scope of heart failure in these patients. Through the collection and use of real-world data, the field has gained greater understanding of best practices in care of these patients, as well as improved access to devices with pediatric labeling of devices previously approved only for adults. Recent and current work across the network\u27s major focus areas (VAD, heart failure, muscular dystrophy, and Fontan) are highlighted
Unmet Supportive Care Needs in Patients With Advanced Cancer and Its Impact on Distress
No full textPurpose: Patients with advanced cancer endure considerable physical and emotional distress without sufficient supportive care. This cross-sectional study examined the relationship between cancer-related symptoms, supportive care needs, and distress levels in patients with advanced lung, head and neck, or gastrointestinal cancers.
Methods: 158 patients were assessed for symptom burden and distress levels using the M.D. Anderson Symptom Inventory (MDASI) and unmet needs using the Supportive Care Needs Survey (SCNS-34) within one month of treatment initiation. Pearson correlations and multiple regression analyses were used to explore associations between supportive care needs and distress.
Results: Distress levels were moderate across the study population, with fatigue, pain, and disturbed sleep being the most reported symptoms. Patients who lived with their caregivers reported significantly lower needs in four out of five domains. Positive correlations were found between distress levels and supportive care needs in the psychological (r = 0.342, p \u3c 0.001), health system (r = 0.253, p = 0.001), patient care and support (r = 0.237, p = 0.003), and physical and daily living domains (r = 0.378, p \u3c 0.001). Multiple regression analysis showed that these domains collectively explained a significant portion of the variance in distress levels (R2 = 0.169, p \u3c 0.001).
Conclusion: Independent of demographic or clinic characteristics, patients with advanced cancer experience moderate distress and unmet supportive care needs, particularly in psychological and health system domains. The association between living with caregivers and lower reported needs suggests that caregiver support may play a crucial role in meeting these needs. Therefore, integrating strategies that involve and support caregivers could potentially reduce distress and improve the quality of life for patients with advanced cancer
Hemophagocytic Lymphohistiocytosis in a Pediatric Lung Transplant Recipient
No full textBackground: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication of solid organ transplantation and is a syndrome of systemic hyperinflammation secondary to dysregulation of the inflammatory response, primarily involving lymphocytes and macrophages. It is often fatal and therefore early recognition and treatment are crucial. Among 11 adult cases of HLH in post-lung transplant cases found in the literature, only one patient survived.
Case: We report the first known pediatric case of HLH following lung transplantation. The patient, a previously healthy adolescent, developed end-stage bullous lung disease secondary to acute respiratory distress syndrome (ARDS) and underwent bilateral lung transplantation. Two months posttransplant, he was admitted with an asymptomatic febrile illness of unclear etiology. By day four, evolving multiorgan dysfunction raised concern for HLH. Despite extensive infectious, autoimmune, and malignancy workups, no definitive trigger was identified. Treatment was initiated with dexamethasone monotherapy with subsequent clinical improvement and discharge 1 month later.
Conclusion: Solid organ transplantation appears to raise a patient\u27s risk of developing HLH, although the underlying mechanisms are unclear. Literature review suggests patients are most likely to develop this complication within the first few months of transplantation, and a high index of suspicion must be maintained in those who present with a febrile illness of unclear etiology. Standard HLH treatment protocols may not be applicable to this patient population, and further studies are needed
Neutralizing Antibody Immune Correlates in Covail Trial Recipients of an Mrna Second COVID-19 Vaccine Boost
No full textNeutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic\u27s evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate\u27s contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ( COVID-19 ) and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ( predicted-at-exposure ) titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate
Acute Loss of Tactile Input Leads to General Compensatory Changes in Eye-Hand Coordination during Object Manipulation
No full textCurrent models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants of either sex on a manual dexterity task requiring the movement of small metal pegs, both before and after the administration of digital anesthesia, which selectively abolished cutaneous sensations in the fingertips while preserving motor function. We recorded participants\u27 gaze and hand positions. Despite loss of cutaneous feedback, participants successfully completed the pegboard task. However, they exhibited significantly longer trial times and altered force profiles. Notably, acute somatosensory loss triggered a rapid shift in visual behavior, characterized by a tighter coupling between gaze and hand positions across all task actions, even those not directly involving object manipulation. These changes, which occurred with anesthesia of the dominant and nondominant hands, were not evident with sham (saline) injections. Our findings underscore the contributions of sensory feedback to force control in service of dexterous object manipulation and reveal the nonselective nature of compensatory gaze-hand coordination processes
Two-Dimensional Speckle Tracking of the Ascending Aorta: A Novel Approach to Evaluate Arterial Stiffness in Pediatric Patients With Repaired Conotruncal Anomalies Using Echocardiography
No full textBackground: Children with repaired conotruncal abnormalities (CTA) are at risk of progressive aortic dilation and deteriorating aortic elasticity even after surgical correction. Strain imaging, using a 2-dimensional speckle tracking echocardiography (2D-STE), has been used for arterial stiffness assessment, but pediatric data are still lacking. We investigated the feasibility, reproducibility, and clinical value of 2D-STE derived ascending aorta (AAo) stiffness in children with repaired CTA.
Methods: 22 pediatric patients with repaired CTA were included along with 25 age- and sex- matched healthy controls (mean age 10.2 ± 4.5 years). Conventional 2D echocardiographic and 2D-STE assessment of AAo mechanics was performed. M-mode AAo strain, aortic distensibility and aortic stiffness index as well as 2D-STE derived AAo global circumferential strain (GCS) were calculated and compared between groups.
Results: 2D-STE was successfully performed and analyzed in the entire, prospectively enrolled cohort. Patients with repaired CTA had significantly lower 2D-STE derived AAo GCS compared to controls (9.4 ± 1.3 vs. 15.2 ± 1.7, P-value \u3c 0.001). AAo GCS in repaired CTA patients had strong negative correlation with age (r = -0.76, CI -0.9 to -0.51) and a moderate negative correlation with the absolute aortic valve annulus (r = -0.55), absolute aortic root (r = -0.67), absolute sino-tubular junction (r = -0.67) and absolute AAo dimension (r = -0.71). On multivariate analysis, absolute aortic root and ascending aorta dimension were significantly associated with AAo GCS independent of other variables. Intra-observer reproducibility was good to excellent for the CTA and entire cohort (ICC = 0.87 and 0.96 respectively), while inter-observer reproducibility was moderate for the CTA cohort 0.71 vs. 0.92 for the entire cohort.
Conclusion: AAo GCS using 2D STE is highly feasible and reproducible as well as provides novel insights into the aortic deformation mechanics in pediatric patients with repaired CTA, thus holds promise in longitudinal assessment and risk stratification of aortopathy-associated congenital heart disease patients
All Roads That Lead to the Myocardium: Assessment of Anomalies of Coronary Artery Course
No full textNutrition Provision in Pediatric Extracorporeal Membrane Oxygenation: Evidence, Challenges, and Clinical Considerations
No full textBackground/objectives: Nutritional support is a critical yet challenging aspect of care for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). Malnutrition is prevalent in this population and is associated with worse clinical outcomes. This review synthesizes current evidence on nutritional strategies for pediatric ECMO patients, emphasizing assessment methods, feeding routes, challenges, and clinical outcomes.
Methods: A literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published between January 2010 and 2025. Keywords included pediatric ECMO , nutrition , enteral feeding , and parenteral nutrition . Studies addressing nutritional assessment, enteral and parenteral feeding practices, and their impact on clinical outcomes were included.
Results: Malnutrition is a significant risk factor for morbidity and mortality in ECMO patients, yet nutritional support remains highly variable. While enteral nutrition (EN) is preferred, feeding intolerance and gastrointestinal dysfunction often necessitate parenteral nutrition (PN). Early EN initiation, even at trophic levels, is associated with improved gut integrity and outcomes. However, achieving full nutritional goals enterally remains a challenge, particularly in neonates. PN remains essential in cases of feeding intolerance but is linked to hepatic dysfunction and metabolic imbalances.
Conclusions: Optimizing nutritional support in pediatric ECMO patients requires individualized assessment and a structured approach to enteral and parenteral feeding. Further research is needed to establish standardized feeding protocols and determine the optimal timing and composition of nutritional support to improve outcomes