A Phase 1 Study of ABI-009 (Nab-sirolimus) in Combination With Temozolomide and Irinotecan in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors-A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study ADVL1514.

Background: Nab-sirolimus (ABI-009, nab-rapamycin; Aadi Bioscience Inc. [Aadi]) is a human albumin-bound form of sirolimus nanoparticles, a potent mTOR inhibitor. This phase I trial was conducted to define dose-limiting toxicities (DLT), maximum tolerated or recommended phase II dose (MTD/RP2D), and pharmacokinetics of Nab-sirolimus in combination with temozolomide and irinotecan.

Diverse Phenotypic Presentation of the Welander Distal Myopathy Founder Mutation, With Myopathy and Amyotrophic Lateral Sclerosis in the Same Family.

Welander distal myopathy is a rare myopathy with prominent and early involvement of distal upper extremity muscles, prevalent in individuals of Scandinavian origin, and caused by a founder mutation in the cytotoxic granule-associated RNA-binding protein (T-cell intracellular antigen-1; TIA1), E384K. Different pathogenic variants in the TIA1 gene, distinct from the founder 1, have recently been associated with frontotemporal dementia and amyotrophic lateral sclerosis (ALS), suggesting that TIA1-related disorders belong to the group of multisystem proteinopathies. We describe the first case of a two-generation family with the founder E384K TIA1 mutation demonstrating phenotypic variability; the mother manifested as Welander myopathy, whereas 2 daughters manifested as ALS.

Kidney transplant outcomes in children with simultaneous versus sequential heart-kidney transplants.

Background: Heart transplant recipients frequently require kidney transplantation for concomitant advanced chronic kidney disease. Data on simultaneous (heart and kidney transplants performed simultaneously) versus sequential (heart transplant performed before kidney) heart-kidney transplants in children are limited. Herein, we compare kidney transplant outcomes between the two groups.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

Importance: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety.

Possible Concomitant Aggressive NK Cell Leukemia and EBV-positive T-cell lymphoma; Using the online beta version of WHO-HAEM5 and videoconferencing software to make diagnoses accessible in an emerging economy.

Background: Using the World Health Organization Classification 5th edition (beta version online; WHO-HAEM5bv) in emerging economies is key to global healthcare equity. Although there may be ongoing updates, hesitancy in accepting and reporting these diagnoses in publication conflicts with the WHO's commitment to global accessibility. Aggressive NK cell leukemia (ANKL) and systemic EBV-positive T-cell lymphoma of childhood (SEBVTCL) with CD4-positive immunophenotype are both rare entities, are most described in Asians and East Asians, are associated with prior systemic chronic active EBV disease (CAEBV), and presentation with Hemophagocytic Lymphohistiocytosis (HLH).

Time since primary transplant and poor functional status predict survival after redo lung transplant.

Background: In previous studies, lower functional status measured by Karnofsky Performance Status (KPS) correlated with worse survival after redo lung transplant. We hypothesize that combining reduced functional status and time from primary lung transplant will correlate with the etiology of lung allograft failure after primary lung transplant and more accurately predict survival after redo lung transplant.

Methods: This retrospective study was approved by University of Minnesota Institutional Review Board.

Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia: A Report From the Children's Oncology Group AAML1331 Trial.

Importance: All-trans retinoic acid (ATRA) and arsenic trioxide therapy without the use of maintenance therapy has been found to be beneficial for the treatment of adults with standard-risk acute promyelocytic leukemia (APL). However, it is unclear whether similar regimens are safe and beneficial for the treatment of high-risk APL or pediatric patients with standard-risk APL.

Objective: To assess whether treatment with an ATRA and arsenic trioxide-based regimen is safe and allows for the elimination or substantial reduction of chemotherapy use among pediatric patients with standard-risk or high-risk APL, respectively.

Myeloid Sarcoma Expressing Keratins and Mimicking Carcinoma-Case Report and Literature Review.

Unusual presentations of otherwise common hematopoietic neoplasms are a well-recognized diagnostic challenge. Herein, we present a case study of a previously healthy 64 year old woman with myeloid sarcoma whose diagnosis was delayed by an unusual immunohistochemical staining pattern, including cytokeratin expression, by the neoplastic cells and by possible anchoring bias introduced by radiographic and flow cytometric immunophenotyping reports. This case study emphasizes the need to integrate clinical, radiographic, histologic, and immunophenotyping data for rapid and accurate tissue diagnoses while being wary of the lack of specificity for many common immunophenotypic markers.

Lung Transplant Recipients With Prior Coronary Artery Bypass Grafting Are at Increased Risk of Death and Early Perioperative Hemorrhage.

Prior coronary artery bypass grafting (CABG) has been considered a relative contraindication to lung transplantation due to the atherosclerotic disease burden and technical challenges. We hypothesized that lung transplant recipients with prior CABG have increased mortality compared to recipients without prior CABG. Further, the causes of death are different for lung transplant recipients with prior CABG vs without CABG.

Registry-Managed Care Coordination and Education for Patients With Co-occurring Diabetes and Serious Mental Illness.

Objective: Longitudinal changes in health outcomes of patients with serious mental illness and co-occurring diabetes were examined after introduction of an intervention involving electronic disease management, care coordination, and personalized patient education.

Methods: This observational cohort study included 179 patients with serious mental illness and diabetes mellitus type 2 at a behavioral health home in Chicago. The intervention employed a care coordinator who used a diabetes registry to integrate services; patients also received personalized diabetes self-management education.

Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development.

Background: Skeletal development and maintenance are complex processes known to be coordinated by multiple genetic and epigenetic signaling pathways. However, the role of long non-coding RNAs (lncRNAs), a class of crucial epigenetic regulatory molecules, has been under explored in skeletal biology.

Results: Here we report a young patient with short stature, hypothalamic dysfunction and mild macrocephaly, who carries a maternally inherited 690 kb deletion at Chr.

Patients with Gaucher disease display systemic oxidative stress dependent on therapy status.

Gaucher disease is an autosomal recessive metabolic disorder caused by mutations in , which encodes for the lysosomal hydrolase enzyme, β-glucocerebrosidase. The resulting misfolded protein can trigger endoplasmic reticulum stress and an unfolded protein response within the affected cells. The enzyme deficiency leads to accumulation of its substrates, glucosylceramide and glucosylsphingosine, within macrophage lysosomes and with prominent disease manifestations in macrophage rich tissues.

Psychosocial Impact and Disease Management in Patients with Congenital Factor VII Deficiency.

Purpose: Congenital factor VII (FVII) deficiency is a rare bleeding disorder of variable phenotype with predominantly mucocutaneous bleeding. The aim of this study was to identify the burden of FVII deficiency on patients and caregivers through a better understanding of the management and psychosocial impact of this disease.

Materials And Methods: A rare disease specialty recruiter from Comprehensive Health Education Services recruited participants for this online survey, which was conducted from January 31 to March 12, 2019.

Disease Burden in Patients with Glanzmann's Thrombasthenia: Perspectives from the Glanzmann's Thrombasthenia Patient/Caregiver Questionnaire.

Purpose: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder caused by a mutation in the αIIbβ3 integrin essential for optimal platelet function and hemostasis. The aim of this study was to identify the burden of GT on patients and caregivers through better understanding of the management and psychosocial impact of this disorder.

Patients And Methods: Participants for this online survey were recruited using a rare disease specialty recruiter from Comprehensive Health Education Services.

Effects of monitoring versus blunting on the public's preferences for information in a hypothetical cancer diagnosis scenario.

Monitoring and blunting are coping styles that characterize how people respond when faced with personally threatening situations. High monitors tend to pay more attention to, scan for, and amplify threatening cues; high blunters tend to avoid information and seek distractions when faced with a threatening event. This study sought to investigate possible differential effects of monitoring and blunting coping styles on information preferences in a hypothetical cancer diagnosis scenario in the adult general public of Minnesota.

The Effect of Infectious Diseases Consultation on Mortality in Hospitalized Patients With Methicillin-Resistant , , and Bloodstream Infections.

We evaluated the association between infectious disease consultation and bloodstream infection outcomes, including methicillin-resistant , , and No infectious diseases consultation was associated with over 4-fold increased hazard of death at 3 months and 6-fold increased hazard of death in hospital.

Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy.

Type 1 Gaucher disease (GD1), a glycosphingolipid storage disorder caused by deficient activity of lysosomal glucocerebrosidase, is classically considered non-neuronopathic. However, current evidence challenges this view. Multiple studies show that mutations in GBA1 gene and decreased glucocerebrosidase activity are associated with increased risk for Parkinson disease.

Diagnosis of epidermodysplasia verruciformis: Two cases highlighting the role of direct HPV L1 gene sequencing.

Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by the development of multiple flat warts with the potential for malignant transformation. Patients are susceptible to human papillomavirus (HPV) infection that develops in a background of either a genetic or acquired immunodeficiency predisposing patients to infection with specific HPV types that are ubiquitous but generally non-pathogenic in healthy individuals. There is no standard clinical methodology for determining the causative HPV from patients with suspected EV.

Does adjuvant chemotherapy dose modification have an impact on the outcome of patients diagnosed with advanced stage ovarian cancer? An NRG Oncology/Gynecologic Oncology Group study.

Purpose: To determine the relationship between chemotherapy dose modification (dose adjustment or treatment delay), overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC) who receive carboplatin and paclitaxel.

Methods: Women with stages III and IV EOC and PPC treated on the Gynecologic Oncology Group phase III trial, protocol 182, who completed eight cycles of carboplatin with paclitaxel were evaluated in this study. The patients were grouped per dose modification and use of granulocyte colony stimulating factor (G-CSF).

Optimization of a microfluidics-based next generation sequencing assay for clinical oncology diagnostics.

Background: Massively parallel, or next-generation, sequencing is a powerful technique for the assessment of somatic genomic alterations in cancer samples. Numerous gene targets can be interrogated simultaneously with a high degree of sensitivity. The clinical standard of care for many advanced solid and hematologic malignancies currently requires mutation analysis of several genes in the front-line setting, making focused next generation sequencing (NGS) assays an effective tool for clinical molecular diagnostic laboratories.

Metabolic Syndrome and Neurocognition Among Diverse Middle-Aged and Older Hispanics/Latinos: HCHS/SOL Results.

Objective: Hispanics/Latinos have the highest risks for metabolic syndrome (MetS) in the U.S. and are also at increased risk for Alzheimer disease.

Cumulative Doses to Brain and Other Critical Structures After Multisession Gamma Knife Stereotactic Radiosurgery for Treatment of Multiple Metastatic Tumors.

Purpose: Repeat stereotactic radiosurgery (SRS) is an attractive alternative to whole brain radiation therapy (WBRT) for treatment of recurrent brain metastases (BM). The purpose of this study is to determine the cumulative doses to the brain and critical normal structures in patients who underwent repeat courses of Gamma Knife (GK) SRS.

Materials And Methods: We retrospectively identified ten patients who received at least three GK-SRS sessions for multiply recurrent BM at our institution from 2013 to 2016.