Recurrent Nontraumatic Subgaleal Hematomas in a Pediatric Patient With Sickle Cell Disease

Spontaneous subgaleal hematoma in pediatric patients with sickle cell disease (SCD) is a rare occurrence that can present with symptoms mimicking ischemic stroke, a known complication of SCD. However, unlike ischemic stroke, subgaleal hematoma is nonlethal and can be managed conservatively without major sequelae. Here, we present the case of an adolescent with SCD who presented with 2 episodes of subgaleal and epidural hematomas, 2 years apart. The latter episode occurred while on crizanlizumab, an anti-P-selectin antibody, approved for use in SCD in 2019 to reduce the number of acute pain crises. We demonstrate the diagnosis of subgaleal hematoma and outline steps to conservative management which were safe and did not lead to focal neurologic deficits

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Formulating adjuvant therapy of rHDL nanoparticles with saquinavir to combat high-risk neuroblastoma.

Research Appreciation Day Award Winner - 2015 2nd Place Children's Health Research Award - Pediatrics DepartmentPurpose: Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (HRNB). Current chemotherapy regimens have a serious limitation due to off target toxicity. The purpose of our project is to evaluate the effectiveness of a drug delivery platform with reconstituted/synthetic high density lipoprotein nanoparticles (rHDL) using rHDL-saquinavir formulation for the treatment of HRNB. It is anticipated that upon establishing an improved chemotherapeutic regimen for HRNB, the rHDL technology could be extended to enhance the chemotherapy for other pediatric cancers. Materials and Methods: The rHDL-Saquinavir nanoparticles were prepared by cholate dialysis method. The entrapment efficiency of Saquinavir was determined by Fluorimetric measurements. The chemical composition of rHDL/Saquinavir particles was estimated by standard kits. The average size of the particles was measured by DeLsa Nano particle size analyzer. The stability of particles was estimated by dialyzing the particles at 37°C, for 48 hours at pH 7.4. The cytotoxic effectiveness of the formulation was tested against two HRNB cell lines (SJNKP and IMR-5 obtained from Dr F. Temius, Regina Margherita Children’s Hospital, Turin, Italy)) as compared to that of the free Saquinavir using CCK-8 kit. The Inhibitory concentration to kill 50% of the cells (IC50) was determined. Results: The entrapment efficiency of the rHDL-SAQ particles was determined to be 70%. The chemical composition study indicated that the rHDL-SAQ nanoparticles were composed of 60% phospholipids, 24% protein, 9% cholesterol, and 7% of Saquinavir. The average diameter of the particle was 7.3 nm. The stability of the nanoparticle formulation measured as retention of the drug under experimental conditions indicated that 71% of the drug was preserved. When testing the survival of the IMR-5 cell lines in presence of Free and rHDL-Saquinavir, it was found that the rHDL particles were 10 times more effective than free Saquinavir. The effect on the SJNKP cells was observed to be 2 fold greater when using the rHDL particles compared to the free drug. Moreover, the rHDL-SAQ particles were both able to achieve 100% killing while the free SAQ did not achieve 100% killing effect in the given range. Conclusions: The rHDL-Saquinavir nanoparticles were successfully formulated. The particles appeared to be small, stable and non-leaking. In vitro survival studies suggested that rHDL-Saquinavir formulation is more effective than the free saquinavir. Thus, these studies support the potential of this novel drug delivery platform for treating HRNB. These studies could be extended to other types of cancers as well

Prevalence of Sleep Disturbances in Pediatric Cancer Patients and Their Diagnosis and Management

Sleep disturbances represent an understudied yet common source of distress among pediatric cancer patients and survivors, with deleterious effects on quality of life. Sleep issues stem from multiple risk factors, yet individual contributors are difficult to isolate, consequently impeding the identification of targets for intervention. In many pediatric cancer patients, disrupted sleep and its negative impact on quality of life continue into adulthood and may affect various functional domains. This literature review highlights the types and prevalence of sleep disturbances in pediatric cancer patients during active treatment and through survivorship. Potential etiological and risk factors for disturbed sleep are summarized, including the effects of cancer and its treatment, psychosocial and family factors, as well as individual-patient aspects, such as genetics, mood and coping skills. While existing assessment and management strategies are reviewed, the literature is incomplete, and significant gaps emerge in our understanding of sleep disturbances in pediatric cancer patients and survivors. The review concludes with recommendations of areas where further research is needed. The aims of this review include increasing clinicians’ awareness of sleep disturbances as a significant source of poor quality of life in pediatric cancer patients and survivors and directing researchers to gaps in our understanding of sleep disturbances in pediatric cancer patients and survivors

Prevalence of Sleep Disturbances in Pediatric Cancer Patients and Their Diagnosis and Management

Sleep disturbances represent an understudied yet common source of distress among pediatric cancer patients and survivors, with deleterious effects on quality of life. Sleep issues stem from multiple risk factors, yet individual contributors are difficult to isolate, consequently impeding the identification of targets for intervention. In many pediatric cancer patients, disrupted sleep and its negative impact on quality of life continue into adulthood and may affect various functional domains. This literature review highlights the types and prevalence of sleep disturbances in pediatric cancer patients during active treatment and through survivorship. Potential etiological and risk factors for disturbed sleep are summarized, including the effects of cancer and its treatment, psychosocial and family factors, as well as individual-patient aspects, such as genetics, mood and coping skills. While existing assessment and management strategies are reviewed, the literature is incomplete, and significant gaps emerge in our understanding of sleep disturbances in pediatric cancer patients and survivors. The review concludes with recommendations of areas where further research is needed. The aims of this review include increasing clinicians’ awareness of sleep disturbances as a significant source of poor quality of life in pediatric cancer patients and survivors and directing researchers to gaps in our understanding of sleep disturbances in pediatric cancer patients and survivors.</jats:p

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective

Non-Hodgkin lymphoma (NHL) is a broad entity which comprises a number of different types of lymphomatous malignancies. In the pediatric and adolescent population, the type and prognosis of NHL varies by age and gender. In comparison to adults, pediatric and adolescent patients generally have better outcomes following treatment for primary NHL. However, relapsed/refractory (R/R) disease is associated with poorer outcomes in many types of NHL such as diffuse large B cell lymphoma and Burkitt lymphoma. Newer therapies have been approved in the use of primary NHL in the pediatric and adolescent population such as Rituximab and other therapies such as chimeric antigen receptor T-cell (CAR T-cell) therapy are under investigation for the treatment of R/R NHL. In this review, we feature the characteristics, diagnosis, and treatments of the most common NHLs in the pediatric and adolescent population and also highlight the differences that exist between pediatric and adult disease. We then detail the areas of treatment advances such as immunotherapy with CAR T-cells, brentuximab vedotin, and blinatumomab as well as cell cycle inhibitors and describe areas where further research is needed. The aim of this review is to juxtapose established research regarding pediatric and adolescent NHL with recent advancements as well as highlight treatment gaps where more investigation is needed.</jats:p

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective

Non-Hodgkin lymphoma (NHL) is a broad entity which comprises a number of different types of lymphomatous malignancies. In the pediatric and adolescent population, the type and prognosis of NHL varies by age and gender. In comparison to adults, pediatric and adolescent patients generally have better outcomes following treatment for primary NHL. However, relapsed/refractory (R/R) disease is associated with poorer outcomes in many types of NHL such as diffuse large B cell lymphoma and Burkitt lymphoma. Newer therapies have been approved in the use of primary NHL in the pediatric and adolescent population such as Rituximab and other therapies such as chimeric antigen receptor T-cell (CAR T-cell) therapy are under investigation for the treatment of R/R NHL. In this review, we feature the characteristics, diagnosis, and treatments of the most common NHLs in the pediatric and adolescent population and also highlight the differences that exist between pediatric and adult disease. We then detail the areas of treatment advances such as immunotherapy with CAR T-cells, brentuximab vedotin, and blinatumomab as well as cell cycle inhibitors and describe areas where further research is needed. The aim of this review is to juxtapose established research regarding pediatric and adolescent NHL with recent advancements as well as highlight treatment gaps where more investigation is needed

Withdrawn: Biomarkers in Disease Diagnosis and the Role of LC-MS and NMR: A Review

The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Design. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication. </jats:sec

Cerebral Sinus Venous Thrombosis in Children with Inherited Bleeding Disorders -- a Case Series

In patients with inherited bleeding disorders, thrombus development poses a challenge in balancing the management of thrombosis and bleeding. Pediatric antithrombotic therapy guidelines do not address the treatment of a thrombus in the setting of a bleeding disorder. We present a case series of four children with inherited bleeding disorders presenting with cerebral sinus venous thrombosis and bleeding, in order to summarize the different therapeutic approaches and outcomes of these patients.</jats:p