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Estimate the Association of Dexamethasone Prescription with Acute Kidney Injury among...
Yuanhui Hu
Haoxin Song

Yuanhui Hu

and 13 more

June 08, 2025
OBJECTIVE To examine the association of dexamethasone prescription with AKI among hospitalized children in China. METHOD Children aged 1 to 18 years who were hospitalized for at least two days between January 1 and December 31, 2022 were included in this retrospective cohort study. Patients without available serum creatinine (Scr) tests or with severe renal impairment on admission were excluded. Baseline characteristics were balanced using inverse probability weighting (IPW) based on propensity scores. Multifactorial logistic regression was used to assess the association between the use of dexamethasone and the risk of AKI. Subgroup analyses were performed based on all covariates. Sensitivity analyses was performed by propensity score matching. RESULTS A total of 1,978 patients met the inclusion criteria, comprising 685 dexamethasone-exposed patients (96 AKI events, 14.0%) and 1,282 non-exposed patients (84 AKI events, 6.6%), yielding an overall AKI incidence rate of 6.6 events per 1,000 person-days. The IPW-adjusted multivariate logistic regression revealed that dexamethasone was an independent protective factor for AKI ( OR 0.47, 95% CI 0.32–0.69, P<0.01). A decreased risk of AKI was associated with male sex, younger age, low baseline Scr, diuretic use, and absence of comorbid fever or pulmonary infection (P<0.05). Sensitivity analyses suggested that dexamethasone may reduce the risk of AKI (Adjusted OR 0.66, 95% CI 0.37–1.17, P = 0.15). CONCLUSION Dexamethasone may be associated with decreased risk of AKI in hospitalized children. However, large-scale prospective studies are needed to further examine the association between dexamethasone and the risk of AKI in children.
Reinforcement Learning for Dynamic Web Firewall Policy Optimization
Zaynab Sai'd

Zaynab Sai'd

and 1 more

June 09, 2025
The dynamic and ever-evolving nature of cyber threats necessitates adaptive and intelligent security mechanisms for web firewalls. This research investigates the application of Reinforcement Learning (RL) algorithms to optimize web firewall policies in real-time, enabling proactive defense against sophisticated attack patterns. By continuously learning from network traffic and security events, the RL agent adaptively tunes firewall rules to minimize false positives and false negatives, improving both security efficacy and system performance. The study explores various RL techniques, such as Q-learning and deep reinforcement learning, to evaluate their effectiveness in dynamically adjusting firewall configurations under diverse and unpredictable cyber-attack scenarios. Experimental results demonstrate that RL-driven firewall policy optimization significantly enhances the responsiveness and robustness of web security infrastructure compared to static rule sets, paving the way for more autonomous and resilient cyber defense systems.
A cross-sectional virological and sero-epidemiological study of exposures to avian in...
Mahbubur Rahman
Timothy M Uyeki

Mahbubur Rahman

and 16 more

June 08, 2025
Background Avian influenza A viruses (AIVs) are endemic among poultry in Bangladesh sold at live bird markets (LBMs). We assessed virologic and serologic evidence of exposure to AIVs among LBM workers. Methods A cross-sectional study recruited 702 randomly sampled workers from 42 LBMs in Dhaka, Bangladesh during 2017. Nasal and throat swabs collected from workers and air samples from LBMs were tested for influenza A virus by RT-PCR with positives subtyped for A(H5), A(H7) and A(H9). Baseline sera from 695 workers and follow-up sera from 89 workers with influenza A positive respiratory specimens were tested by microneutralization assay for antibodies to A(H5N1) clade 2.3.2.1a and A(H9N2) G1 lineage viruses circulating in poultry. A seropositive result was defined as a neutralizing antibody titer ≥1:40. Results Most LBM workers reported slaughtering (93.3%) and defeathering (84.5%) poultry. Ninety-nine (14.1%) had ≥1 respiratory specimen that tested influenza A positive but negative for A(H1) and A(H3). Of these 99, subtyping identified 28 (28.3%) A(H9); 2 (2%) A(H5); 3 (3%) both A(H5) and A(H9); and 66 (66.7%) A(non-subtypeable). Influenza A viruses were detected in air samples at 25 LBMs (59.5%), including A(H9) only in 10 LBMs (40%), A(H5) only in one (4%), both A(H5) & A(H9) in 13 (52%) and one A(non-subtypeable) (4%). None of the participants were seropositive for AIVs. Conclusion LBM workers had extensive exposure to AIVs, but none had serologic evidence of infection with A(H5N1) or A(H9N2) viruses circulating among poultry in Bangladesh. Ongoing surveillance of AIVs in LBMs and poultry workers is needed.
Investigating the Biochemical Mechanisms and Anticancer Potential of Camel Urine: A C...
Prof Roberto Grobman

Prof Roberto Grobman

and 2 more

June 09, 2025
Camel urine (CU), long utilized in traditional Middle Eastern and North African medicine, is now emerging as a promising subject of modern oncological research. Recent studies have revealed that CU possesses a unique biochemical composition enriched with potentially therapeutic compounds, including the arginine analog canavanine, which disrupts protein synthesis in rapidly proliferating cancer cells (Alhaider et al., 2012), and nanobody-derived antibodies capable of targeting tumor-specific antigens with high precision (Muyldermans, 2013). In vitro and in vivo experiments have consistently demonstrated CU's anticancer potential, showing induction of apoptosis, inhibition of tumor cell proliferation, suppression of angiogenesis, and immune system modulation (Hegazy et al., 2015; Al-Yousef et al., 2012; Mothana et al., 2010). These effects have been observed across various cancer models, including breast, colon, liver, and brain tumors. Although CU's composition varies based on factors such as camel breed and hydration status, advances in bioactive compound isolation and purification offer a viable path toward standardization. While concerns remain-particularly regarding toxicity, microbial content, and the absence of human clinical trials-the body of preclinical evidence supports CU as a compelling candidate for further investigation as an adjunct or source for novel cancer therapeutics. This review highlights CU's mechanisms of action and calls for expanded translational research, including toxicology studies, compound refinement, and eventually, clinical evaluation.
Dynamical Basis Theory: Linear-Algebraic Foundations and Quantum Applications Resolvi...
Parker Emmerson

Parker Emmerson

June 09, 2025
A document by Parker Emmerson. Click on the document to view its contents.
Origins of Dark Matter: The Neutrino-Sourced Recursion Model and the Theory of the C-...
Bruno Wayne Salter

Bruno Wayne Salter

June 09, 2025
Dark matter, constituting 27% of the universe, remains elusive in its composition and formation mechanisms. This paper proposes a neutrino-fractured model of dark matter genesis, where neutrinos undergo mass fragmentation within cosmic voids, interacting with black hydrogen to form stable dark matter particles. This recursive transformation aligns with structured necessity, ensuring a balanced mass-energy exchange with dark energy (68%). The model builds upon neutrino oscillations, cosmic filament replenishment, and intergalactic matter transitions, bridging quantum field fluctuations with large-scale astrophysics.
A variational formulation for modeling a protium hydrogen molecular ionization and a...
Fabio Botelho

Fabio Botelho

June 09, 2025
This article develops a variational formulation for modeling a protium hydrogen molecular ionization obtained through a high temperature scalar field and an appropriate electric one action. The results are based on standard tools of calculus of variations and optimization theory. Finally, we highlight the context here addressed is essentially an Euler-Bernoullian one and includes the establishment of a new approximate Bernoulli-interacting-gas type equation.
Origins of Dark Energy -Theory of C-Universe Part II
Bruno Wayne Salter

Bruno Wayne Salter

June 09, 2025
Cosmic evolution does not unfold randomly-it follows a structured necessity that ensures perpetual refinement and equilibrium across infinite scales. This work explores the origins of dark energy, demonstrating how its emergence is governed by recursive transitions rather than chaotic acceleration. Through neutrino self-regeneration, dark hydrogen catalysis, and void-incubated emergence, dark energy manifests as a structured refinement rather than an uncontrolled force. Neutrinos, acting as agents of cosmic balance, undergo adaptive transformations, shedding mass and synchronizing with cosmic expansion. Their interactions with dark hydrogen containment zones further refine their evolution, ensuring energy transitions unfold within structured frameworks. Meanwhile, cosmic voids, often perceived as mere empty spaces, serve as active incubators, governing acceleration through layered refinement. By linking containment with expansion, this study redefines the role of recursive structuring within cosmic acceleration, illustrating that dark energy emerges not as a force of entropy but as an adaptive necessity. The findings challenge conventional interpretations of chaotic energy dispersal, instead presenting dark energy as a regulated progression aligned with recursive evolution.
Information-Theoretic Obstructions to Embedding Reconstruction: Sharp Constants via A...
Faruk Alpay

Faruk Alpay

June 09, 2025
This article establishes sharp information-theoretic limits on reconstructing high-dimensional embeddings from probabilistic outputs. For a system with embedding dimension d and output entropy H, any reconstruction ê satisfies E[∥ê − e∥ 2 2 ] ≥ 1 2πe • d H 2 , with equality achieved for Gaussian distributions. The proof employs the Alpay ⋆-algebra structure, whose derivation property yields fixed-point theorems via Grothendieck's adjoint functor theorem. It is proved that the Alpay entropic operator Φ creates reconstruction barriers when ∥Φ∥ op > e Hc. Spectral formulas λ 1 = 1 − exp(−H) connecting to optimal transport are derived, and a categorical framework is developed where reconstruction morphisms factor through the initial object φ ∞. The constant 1 2πe emerges from Shannon's entropy power inequality through spectral analysis. Algorithms achieving these bounds are provided along with topological invariants. Permanently archived on Arweave.
Conservative Management of Atrioventricular Groove Hematoma in Mitral Valve Repair Su...
Xia Zhang
Yangzhao Zhou

Xia Zhang

and 4 more

June 07, 2025
Conservative Management of Atrioventricular Groove Hematoma in Mitral Valve Repair Surgery: A Case ReportFirst author’s given name : Xia; Family name: Zhang.Author’s names (given name, family name) : Xia Zhang1 ; Yangzhao Zhou1 ; Zhaoshun Yuan1 ; Jianming Li1 ; Kang Zhou1* .
Management of a Pediatric Oral Hemangioma Using Intralesional Sodium Tetradecyl Sulfa...
Niroj Khanal
Bibek Kattel

Niroj Khanal

and 4 more

June 07, 2025
Management of a Pediatric Oral Hemangioma Using Intralesional Sodium Tetradecyl Sulfate: A Case ReportKey Clinical Message: Benign vascular lesions called oral hemangiomas are frequently seen in young children. In this case study, intralesional sodium tetradecyl sulfate (STS) was used successfully to treat a 10-year-old girl who had an oral hemangioma. The lesion was noted a few weeks after birth, which was located on maxillary labial and vestibular mucosa from teeth 12 to 16 with effacement of right nasolabial fold. Diagnosis was confirmed through ultrasonography and contrast enhanced computer tomography imaging. The patient had intralesional STS injections several times, which significantly decreased the size of the lesion and eliminated the related symptoms. The effectiveness of STS as a non-surgical therapy option for children’s oral hemangiomas is demonstrated by this report.
Peripheral Neuronal NPTX2 Exacerbates Chronic Itch in an Atopic Dermatitis Model via...
Zhi-Jun Zhang
Xue-Qiang Bai

Zhi-Jun Zhang

and 10 more

June 07, 2025
Background and Purpose Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions, primarily characterized by intense itching that leads to scratching and presents a challenging clinical issue with incompletely mechanisms. Neuronal pentraxin 2 (NPTX2) is associated with neurodevelopment, synaptic plasticity, and neuroinflammation in the central nervous system (CNS). This study aimed to thoroughly investigate the peripheral role of NPTX2 in mediating chronic itch under the condition of AD. Experimental Approach Real-time PCR, immunohistochemistry, ELISA assay, Western blot and siRNA intervention were performed to explore the peripheral role of NPTX2 in an Atopic Dermatitis Model. Key Results We demonstrated that NPTX2 was selectively up-regulated in small- and medium-sized trigeminal ganglion (TG) neurons in the MC903-induced AD model, and transported to peripheral nerve terminals. Importantly, protein expression of NPTX2 was significantly elevated in the skin nerves of AD patients. Intriguingly, NPTX2 intradermal administration alone provoked moderate scratching behavior in mice. However, Nptx2 siRNA intra-TG injection significantly attenuated scratching behaviors in AD mice. Mechanistically, NPTX2 synergizes with interleukin-31 (IL-31), a well-known pruritic cytokine in AD, to potentiate p-ERK signaling in primary sensory neurons. PD98059, the inhibitor of p-ERK, significantly alleviated the scratching induced by the combination of NPTX2 and IL-31. Additionally, PD98059 also significantly reduced the up-regulation and release of Nptx2 caused by IL-31 stimulation. Conclusion and Implications Our results offers a new understanding of the molecular mechanisms underlying chronic pruritus in the MC903-induced AD model, for targeting NPTX2-dependent signaling as a key therapeutic strategy for refractory itch disorders.
Secondary Amenorrhea Mimicking PCOS Following Severe Dietary Restriction and Moringa...
Maha Ahmed
Manahil Abbasi

Maha Ahmed

and 4 more

June 07, 2025
Secondary Amenorrhea Mimicking PCOS Following SevereDietary Restriction and Moringa Supplementation: A Case Report
Feasibility of a stepped-care intervention for those at clinical high risk for psycho...
Daniel Shapiro
Rebecca Grattan

Daniel Shapiro

and 18 more

June 07, 2025
Aim This study assessed feasibility of a stepped-care model for those at clinical high-risk for psychosis (CHRp) within a coordinated specialty care clinic in the United States. Methods Youth aged 12-30 completed a 12-month, three-step intervention where persistent or worsening symptoms received increasingly intensive treatment including Supportive Problem Solving, Cognitive Behavioral Case Management and a Selective Serotonin Reuptake Inhibitor. Results Of 32 CHR youth admitted to the clinic over 18 months, 12 were eligible for the study, ten consented, eight participated, and five completed. Major reasons for ineligibility were loss to follow-up during engagement, pressing comorbid concerns that required other specialty care, and medication preferences. Those who completed treatment showed clinically significant improvements in multiple domains and no worsening. Three discontinued due to medication needs (more intensive care, perceived side effects) with the remainder of the sample showing small-to-moderate and moderate-to-large effect sizes in social functioning, depression, and attenuated psychosis symptoms by 12-month follow-up. Conclusions This preliminary study supports larger scale trials of stepped-care interventions for CHRp in the US, but also illuminates key features of the US healthcare system that must shape implementation. The stepped-care intervention appeared tolerable and feasible in those who engaged, but comorbid treatment needs in this heterogenous population, including medication needs/preferences, and disengagement during referral to psychosis specialty care precluded participation for many. Future studies will need to evaluate larger samples, account for needs and preferences for medication, and should place screening and early steps in general outpatient mental health services to evaluate real-world effectiveness.
Rare hummingbird mimicry: urban nesting by a male-plumaged female Veraguan mango
Dallas R. Levey
Gretchen Daily

Dallas Levey

and 1 more

June 07, 2025
Male plumage mimicry by adult females of sexually dimorphic hummingbird species provides an intriguing system for understanding social and ecological selection mechanisms. However, our understanding of female male-mimicry is limited by a lack of behavioral observations of wild hummingbirds with male plumage, such as in giving parental care. Using photos and 2.5 min of video taken at close proximity, we documented a Veraguan mango (Anthracothorax veraguensis) with male plumage both incubating eggs and later feeding young in the town of Palmar Norte in southern Costa Rica. Based on plumage characteristics and range, we ruled out the similar green-breasted mango (A. prevostii) that occurs in close geographic proximity. Using Google Earth imagery, we characterized the landscape surrounding the nest as a heterogeneous mix of urban, residential, and agricultural land. We speculated on potential mechanisms that may maintain female-limited polymorphisms in the Veraguan mango and related species, including the interaction of social and ecological selection pressures. This observation provides the first empirical evidence of male-mimicry polymorphism in the Veraguan mango, contributing valuable information to the species’ natural history and to the broader understanding of male-plumaged females in hummingbirds.
Feasibility of Atezolizumab in Combination with Chemotherapy for Children with Relaps...
Matthew E. Campbell
Sonja Stutzman

Matthew E. Campbell

and 16 more

June 07, 2025
Background : Combining immune checkpoint inhibitors (ICI) with chemotherapy may improve treatment response in children with solid tumors. We sought to determine the feasibility of combining v incristine, i rinotecan, and t emozolomide with the ICI a tezolizumab in children with relapsed or refractory s olid tumors (VITAS). Methods: Patients ≥ 6 months and ≤ 18 years old with a relapsed or refractory solid tumor, no prior ICI, and evaluable disease per RECIST v1.1 were eligible for the Phase I cohort (NCT04796012). Patients received atezolizumab 15 mg/kg on day 1, vincristine 1.5 mg/m 2 on day 1, irinotecan 50 mg/m 2 on days 1-5, and temozolomide 100 mg/m 2 on days 1-5 in 21-day cycles. Primary endpoint was the number of patients with dose-limiting toxicities (DLT) in the first two cycles of therapy. Results : Six patients (median age: 14 years) with rhabdomyosarcoma (n=3), osteosarcoma (n=2), and Ewing sarcoma (n=1) received therapy and were evaluable for toxicity. Patients received a median of 7 (range: 2 to 20) cycles of treatment. No patients experienced a DLT. One patient experienced Grade 2 immune-related colitis. Four patients experienced Grade ≥ 3 adverse events (decreased neutrophil count, febrile neutropenia, weight loss, anorexia). One patient with rhabdomyosarcoma had a sustained partial response through 16 cycles. One patient with relapsed pulmonary osteosarcoma has ongoing stable disease through 20 cycles. Conclusions : Atezolizumab combined with vincristine, irinotecan, and temozolomide was feasible and well tolerated in children with solid tumors. Efficacy of this regimen is now being assessed in relapsed and refractory rhabdomyosarcoma in an ongoing Phase II cohort.
A Survey of Machine Learning Approaches for Predictive Software Quality Assurance: Tr...
Mohd Rizal Zolkepli
Norain Jaine

Mohd Rizal Zolkepli

and 3 more

June 07, 2025
Machine learning (ML) has emerged as a transformative force in predictive software quality assurance (PSQA), offering data-driven techniques for early defect detection, test case prioritization, and code quality analysis. This survey explores the current landscape of ML-driven approaches in PSQA, emphasizing the use of supervised learning, deep learning, and natural language processing (NLP) to enhance automation and precision in software testing. The paper compares traditional quality assurance methods with modern ML-based techniques, highlighting their advantages and limitations. Key trends such as the integration of ML models into CI/CD pipelines, the adoption of transformer-based models, and the application of ensemble learning are examined in depth. Additionally, challenges related to data quality, model interpretability, and scalability are discussed. The paper concludes by identifying future research directions, including the need for explainable AI, domain-specific datasets, and adaptive learning frameworks. This review aims to guide researchers and practitioners in leveraging machine learning to build more efficient, scalable, and intelligent quality assurance systems.
Neuroblastoma, as if that were not enough!
Criss Koba
Christian TAGUE

Criss Koba

and 3 more

June 07, 2025
A document by Criss Koba. Click on the document to view its contents.
“So what will my next cancer be?” Low-grade brain tumour diagnosed through nurse coor...
Andrew Grant
Meera Warby

Andrew Grant

and 11 more

June 07, 2025
A document by Andrew Grant. Click on the document to view its contents.
The Threat of Medical Misinformation: A Case of Ivermectin Toxicity in a Pediatric On...
Stephen Gilene
Lindsay Haacker

Stephen Gilene

and 3 more

June 07, 2025
The Threat of Medical Misinformation: A Case of Ivermectin Toxicity in a Pediatric Oncology PatientStephen Gilene1, Lindsay Haacker1, Hillary Rutan1, Joseph G. Pressey1,2Affiliations: 1Cincinnati Children’s Hospital Medical Center, Division of Oncology and 2University of Cincinnati College of MedicineAddress correspondence to: Joseph G. Pressey, Division of Oncology, Cincinnati Children’s Hospital, 3333 Burnett Ave, MLC 7018, Cincinnati OH, 45209, joseph.pressey@cchmc.org, 513-636-4200.Word Count: 803Number of Tables, Figures, and Supporting Information Files: noneShort Title: Ivermectin Toxicity in Pediatric OncologyKeywords : misinformation, ivermectin, pediatric oncology, preventative medicine
“Neutropenic Colitis in Paediatric Lymphoma: Distinguishing Typhlitis from Pancolitis...
Rohini Sahay
Simon Bomken

Rohini Sahay

and 3 more

June 07, 2025
Background: Neutropenic colitis (NC), commonly manifesting as typhlitis, is a serious gastrointestinal complication of chemotherapy. Pancolitis represents a more severe form with higher morbidity. This case series highlights the clinical course and outcomes of pediatric patients with pancolitis requiring surgical intervention. Methods: Retrospective review of 47 pediatric lymphoma patients treated at a UK CCLG center (2020–2023). Patients with NC were identified and categorized based on extent of colonic involvement. Data were collected on clinical presentation, management, and outcomes. Results: 7 patients developed NC (14.8%), 5 (10.6%) had pancolitis. One patient died following delayed surgery. Four patients with early surgical intervention recovered and resumed chemotherapy. Early surgery correlated with improved outcomes. Conclusions: Pancolitis in neutropenic pediatric patients requires prompt diagnosis and early surgical intervention. Delay may increase mortality. A standardized approach and national database are recommended.
ECMO as salvage therapy for neutropenic enterocolitis with refractory septic shock an...
Michal Frelich
Filip Burša

Michal Frelich

and 5 more

June 07, 2025
ECMO as salvage therapy for neutropenic enterocolitis with refractory septic shock and abdominal compartment syndrome in a patient with acute lymphoblastic leukemiaMichal Frelich1,2, Filip Burša1,2,3*, Peter Sklienka,1,23 Jan Máca1,2,3, Iveta Laryšová4 and Jaroslav Štěrba51Department of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava, Ostrava, Czech Republic2Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic3Institute of Physiology and Pathophysiology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic4Department of Pediatrics, Faculty of Medicine, University Hospital Ostrava, Ostrava University, Ostrava, Czech Republic.5Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic* 17.listopadu 1790, Ostrava, Czech Republic, filip.bursa@fno.cz, +420777806460Word count: 1117Number of tables: 0, number of figures: 1Running title: ECMO as salvage therapy in a patient with acute lymphoblastic leukemiaKeywords: neutropenic enterokolitis, ECMO, refractory septic shock, acute lymphoblastic leukemiaConflict of interest: noneTo the Editor:Infectious complications, including neutropenic enterocolitis (NE), are a serious consequence of immunosuppressive therapy for children with cancer. NE is characterised by a variety of non-specific symptoms, including fever, abdominal pain, diarrhoea and vomiting These symptoms typically manifest one to three weeks after chemotherapy. (1) Although this syndrome has been recognised for over 60 years, its pathophysiology remains unclear. The primary insults are immune deficiency and coagulation disturbances associated with the underlying malignancy, as well as damage to the intestinal mucosa caused by the administration of chemotherapy. This is followed by bacterial invasion of the intestine in neutropenic, immunosuppressed patients. The proliferating bacteria produce endotoxins that damage enterocytes further and cause microvascular thrombosis, leading to subsequent intestinal ischaemia. (2) In some patients, the translocation of bacteria into the bloodstream can lead to sepsis. (1,2)The patient (a 8-year-old girl) was diagnosed with acute lymphoblastic leukaemia (B-ALL, IKZF1del) in May 2023. She was treated according to the AEIOP BFM 2017 protocol, which resulted in the rapid clearance of blast cells and bone marrow MRD negativity after 33 days of treatment. (3) On D35, the patient developed diffuse abdominal pain, nausea and vomiting. A CT scan of the abdomen showed distension of the bowel and a small amount of fluid in the small pelvis. Blood tests revealed severe neutropenia and elevated inflammatory parameters (CRP 237 mg/L, PCT 2.83 ng/L and Il-6 18870 ng/L). Given her condition and medical history, the patient was admitted to the pediatric intensive care unit (PICU).According to the Nesher and Rolston criteria, the diagnosis of neutropenic enterocolitis as the primary clinical manifestation of her febrile neutropenia was made. (2) The patient’s general condition deteriorated rapidly, resulting in altered consciousness and respiratory failure, which required intubation and mechanical ventilation. Despite the early initiation of combined empirical antibiotic therapy (meropenem, metronidazole, amikacin, biseptol and amphotericin B), the patient developed refractory (catecholamine-resistant) septic shock within hours of admission to the PICU, requiring excessive doses of vasopressors (norepinephrine 2.5 µg/kg/min and epinephrine 0.05 µg/kg/min in combination with vasopressin at a dose of 0.11 IU/h). Repeated boluses of methylene blue only stabilised the circulation in the short term, after which the catecholamine dose had to be increased. Anuria necessitated continuous renal replacement therapy (CRRT), to which a CytoSorb cartridge was added.Although the 2020 Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children recommend venoarterial exracorporal membrane oxygenation (hereinafter referred to as va ECMO) as a rescue therapy in patients with refractory septic shock (with a low level of evidence and a weak recommendation), its use in children with cancer is still controversial.(4,5) However, as the prognosis of children with malignant disease has improved significantly over the last 20 years, ECMO may be a viable and ethically justifiable support for these critically ill patients. (5) Furthermore, in our patient, echocardiography revealed severe sepsis-induced myocardial dysfunction (SMD) with low cardiac output (1,7l/min), and thus a greater effect of va ECMO on haemodynamic stabilisation can be expected in this case compared to refractory vasoplegic shock.(6) Consistent with the above, the effect of ECMO was immediate in our patient, because within 2 hours of its initiation, it was possible to reduce the norepinephrine to half the original dose and to completely stop the continuous administration of epinephrine and vasopressin. In addition, the heart rate decreased (from 200 to 140/min) and spontaneous diuresis occurred at a rate of 0.5-1 ml/kg/hr. The administration of levosimendan led to progression of hypotension, so therapy was stopped and milrinone was started at a dose of 0.75 µq/kg/min.This case illustrates the need for measurement of cardiac output (CO) in children with septic shock, as 32-47 % of them have some degree of SMD. (7) Echocardiography should be performed especially in children who do not achieve a satisfactory mean arterial pressure despite adequate fluid resuscitation and increasing doses of vasopressors. The pathophysiology of SMD is still not fully understood, although it was first described by Parker in 1984. The myocardium is functionally and structurally damaged by endotoxin, inflammatory cytokines and mitochondrial dysfunction. NO production plays an important role in the pathophysiology of SMD, which, in addition to exacerbating mitochondrial dysfunction, leads to a reduced myofibril response to calcium and a downregulation of β-adrenergic receptors. In surviving patients, normalisation of CO is achieved within 7-10 days. (8) The contribution of four standard doses of anthracyclines to cardiac dysfunction during the induction phase of leukaemia treatment remains speculative.After 30 hours of uneventful ECMO run, the ECMO flow began to deteriorate. After ruling out all the usual causes (hypovolemia, cannula malposition, thrombosis in circuit), the patient’s intra-abdominal pressure (IAP) was measured and a diagnosis of abdominal compartment syndrome (ACS) was made with an IAP consistently above 22 mmHg, anuria, decrease in ECMO flow and circulatory instability. This was surprising, as ACS is a rare complication of NE that has only been described in adult patients. (9) Managing this condition in patients on ECMO is difficult because negative fluid balance, the basic therapeutic measure, is usually not tolerated. These patients are also usually deeply anaesthetised and paralysed. Desufflation colonoscopy with lavage did not decrease IAP. The patient was taken to the operating theatre, where a decompressive laparotomy and a VAC (Vacuum Assisted Closure) system were performed (Figure 1). A recent study has shown that decompressive laparotomy is an effective and safe treatment for paediatric ACS, even in patients receiving ECMO (10). The patient’s condition improved rapidly, and she was weaned from ECMO after nine days. The laparotomy was closed one week later.The further treatment course for her acute leukaemia was strictly individualised, balancing the biology of the leukaemia, MRD dynamics, and tolerance of treatment.Antineoplastic treatment was resumed 50 days after admission to the ICU with septic shock, with blinatumomab chosen as the initial treatment. Further treatment consisting of additional blinatumomab and high-dose methotrexate was well tolerated. However, obstructive ileus occurred during reinduction therapy, requiring open surgery and resection of the stenotic part of the small intestine. The patient has made a full recovery, however standard protocolar reinduction was not completed as planned and she uneventfully continues maintenance chemotherapy in a 1st CCR 24 months from her severe, life threatening complication.This case study illustrates the potential of ECMO support for selected patients with refractory septic shock and SMD, including children with cancer. It also highlights the importance of regularly measuring intra-abdominal pressure to enable the early diagnosis and management of ACS in children with severe NE. This condition can lead to critical reductions in ECMO blood flow and systemic hypoperfusion. The case also documents the need for meticulous supportive care measures, including the availability of advanced intensive care facilities, for children with cancer.Figure 1 Decompression laparotomy and VAC system in ECMO-supported patient
Bone Marrow Response Assessment in Pediatric Neuroblastoma: Strengths and Pitfalls of...
Surabhi Jain
Lavleen Singh

Surabhi Jain

and 11 more

June 07, 2025
Background: Neuroblastoma (NB) is the most common extracranial solid tumor in young children, with bone marrow (BM) involvement critically impacting prognosis. The International Neuroblastoma Response Criteria Bone Marrow Working Group (INRC-BMWG) has proposed standardized guidelines for BM response assessment. However, the practical utility, limitations, and role of immunohistochemistry (IHC) and maturation changes within these criteria remain underexplored. Methods: This study retrospectively analyzed 36 consecutive cases of NB with BM metastasis at presentation or post-induction. BM response categories were assigned using INRC-BMWG criteria. Quantitative assessment included tumor area, differentiation, and stroma composition. A minimum of two IHC markers (synaptophysin/chromogranin and PHOX2B) were routinely used, with S100 applied selectively to identify Schwannian stroma. Functional imaging (MIBG/FDG PET) was performed at diagnosis, midway, and therapy completion, with concordance to histopathological response calculated. Results: Of 257 BM biopsies, 110 (42.8%) showed tumor infiltration; 36 cases were evaluable pre- and post-therapy. According to INRC-BMWG, 4 were categorized as complete response, 8 as minimal disease, 6 as progressive disease, and 17 as stable disease. IHC improved minimal disease detection and prevented misclassification. Maturation features were observed in over a third of minimal/stable disease cases, though not currently included in response criteria. Imaging-pathology concordance was highest in complete and progressive response categories, but lower in minimal disease (33.3%). Conclusion: INRC-BMWG guidelines provide a robust framework for BM response assessment in NB, but may benefit from inclusion of maturation features and refined necrosis interpretation. Integration of IHC and imaging with histology offers more accurate, clinically relevant response evaluation.
Anything to Help
Harmony Farner

Harmony Farner

June 07, 2025
Anything to HelpHarmony Farner, MA, CCRP11Research Division of Quality of Life and Palliative Care, Department of Oncology, St. Jude Children’s Research Hospital, USACorrespondence to:Harmony Farner, MA, CCRP /St. Jude Children’s Research Hospital / 262 Danny Thomas Pl, MS 1121, Memphis, TN 38105 / 901-595-7457 / Email: harmony.farner@stjude.orgText word count: 1236Brief running title: Anything to HelpKey words: pediatric oncology, quality of life, palliative careTables: 0Figures: 0I typed the patient’s phone number into my phone multiple times and immediately deleted it, too nervous to make the recruitment call. After several aborted attempts, suddenly the phone was ringing. I remember thinking to myself, “don’t pick up, don’t pick up - please go to voicemail.” And then, a young man answered. Immediately a knot formed in my throat.I had spent the better part of a day leaving voicemails for adolescent and young adult patients and parents eligible for a research study about prognostic communication preferences in the setting of advanced pediatric cancer. When C answered the phone, I stumbled over my words, shocked that someone had answered. Faltering, I explained that I was calling to ask if he might be interested in participating in a research study that sought to understand how patients with cancer want to hear information about prognosis. I felt like my body was collapsing in on itself, trying to make myself as small as possible in an attempt to avoid the tongue lashing that was surely coming for bothering a cancer patient. But to my surprise, C immediately replied yes, even before I had a chance to fully describe what the study entailed. He told me, “Anything to help.”When I started my job as a researcher within the palliative care division, I felt squarely outside of my comfort zone. Who was I to ask childhood cancer patients for their time, especially when they may have little time left in this world? Even worse, how could I ask them to talk about their poor prognosis? As an anthropologist, I’ve approached and interviewed participants living in abject poverty in Baltimore, women serving time in a correctional facility in Memphis, and members of the Makah Tribe in Washington state, just to name a few. Walking into a pod of inmates at a correctional facility didn’t scare me, but this sure did. My training taught me to be respectful of participants’ time, their words, their feelings, and their story. We were to cause them no harm. I worried that asking patients to talk about their illness could cause distress, and I couldn’t bear the thought of adding another stressor in their lives.I remember waiting for C at the clinic, nervously watching the clock and reviewing the interview guide for the umpteenth time.  He had suggested that we meet at 7am, before his full day of appointments. He bounded in, leading the nurse to the room instead of the other way around. He was dressed in comfortable jeans, sneakers, and a hoodie. His sparkling eyes, broad smile, and positive energy filled the room – it was the kind of energy that was infectious, lifting your mood just by being in his presence. This was a young man who was living and eager to enjoy every moment of it.I remember asking C to take me back to the beginning, and he started by recounting, “Well, the first time they cracked my skull open…” knocking twice on his head with his fist and a mischievous smile on his face. I must have looked shocked, because he reassured me, explaining, “I was really excited about [the craniotomy] because they were going to keep me awake, and I was like, ‘Cool, I want to be awake while people are cracking open my head!’ ” As we laughed together, any nervousness I had quickly dissipated.At the end of the interview, I thanked C profusely for his time and his candor. I was taken aback when C thanked me in return for asking his questions that he had never been asked before and for encouraging him to speak about his cancer journey unfiltered. He noted that, despite the excellent medical care that he had received, no one had ever asked him to reflect on his cancer journey, his poor prognosis, and his preferences for talking about how cancer would affect his future life. He was genuinely grateful to have been given this opportunity to speak his mind, and he apologized for talking too much. I assured him that there was no such thing.I left the interview both relieved and elated to know that the experience had been so beneficial for C. I found myself wondering if he was a rare example, or was there a chance that other patients might feel similarly? I would later discover that while C was an exceptional human being, he wasn’t the only one excited to tell their story.Many months later, I had the chance to reach back out to study participants to ask if they might be interested in joining a focus group to review the study findings and collaborate to create an intervention to improve prognostic communication. This time, I was excited to call C, and once again he agreed to participate with enthusiasm and no hesitation. He shared with me that he was working full-time, had enrolled in college courses, and had recently married the love of his life – and yet he still wanted to prioritize being a part of this research study despite his busy schedule. Over the next few months, C participated in all four focus groups, offering valuable insights into his cancer journey. He was never shy about speaking his mind, and he frequently helped encourage other more timid patients to share their perspectives. At times, he appeared tired, but he was always actively present and committed to the research process. After each focus group, part of my job entailed emailing participants to thank them for attending the session. Each time, I was deeply moved when C emailed me, expressing his sincere thanks to our research team for including him in this important work.Since meeting C, my perspective as a researcher has profoundly evolved. I no longer view recruitment and data collection as a burden imposed on cancer patients, but rather as a potential opportunity to enable those who are interested to tell their story, in their own words. I no longer fret over the process of describing our research study, as C taught me that just because a topic is emotionally charged does not mean that it’s disrespectful to invite people to share their thoughts about it. Rather, I’ve learned that I can show the utmost respect by creating space for patients to speak their mind. Not asking the hard questions doesn’t mean that people aren’t thinking about them – conversely, asking these questions can be a gift, empowering them to reflect aloud on this very real, very hard experience that otherwise is rarely addressed.Even as C approached the end of his life, he continued to express enthusiasm and gratitude for the opportunity to participate in research. He was thrilled to receive a copy of a recently published manuscript that reported on findings from the study, and as they encircled his bedside, his family reflected together with him on the powerful legacy that his research contributions would make on the world.I now know that, by speaking with patients about difficult topics related to their cancer, we can learn how to better treat the whole individual. Perhaps even more importantly, we can honor their personhood by centering their voices and elevating their stories. Our research participants, like all of us, contain multitudes – and we will never see the whole story unless we ask.Acknowledgement: I would like to thank Dr. Trisha Paul for her guidance and support in drafting and revising this essay.
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