The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12–17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50–800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817.

Background Atypical hemolytic uremic syndrome is an exceedingly rare thrombotic microangiopathy caused by accelerated activation of the alternative complement pathway. Case presentation Here, we report two cases of patients presenting with suspected atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 infection. The first patient, a 25-year-old Hispanic male, had one prior episode of thrombotic microangiopathy presumed to be atypical hemolytic uremic syndrome precipitated by influenza A, and re-presented with thrombocytopenia, microangiopathic hemolytic anemia, nonoliguric renal failure, and normal ADAMTS13 activity, with confirmed coronavirus disease 2019 positivity. The second patient, a 31-year-old Caucasian female, had no personal history of thrombotic microangiopathy, though reported a family history of suspected atypical hemolytic uremic syndrome. She presented with similar laboratory derangements, oliguric renal failure requiring hemodialysis, and confirmed coronavirus disease 2019 positivity. Both patients were treated with eculizumab with complete resolution of their hematologic and renal complications. Conclusion To our knowledge, this represents the largest case series of atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 in adults.

BackgroundPatient reports of health related quality of life can provide important information about the long-term impact of prostate cancer. Because patient symptoms and function can differ by age of the survivor, the aim of our study was to examine patient-reported quality of life and prostate symptoms by age at diagnosis among a registry of Dutch prostate cancer survivors.MethodsA population of 617 individuals from the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) database was surveyed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) and prostate symptom (EORTC QLQ-PR25) scales. Age at diagnosis was the main independent variable, with three age categories: 60 years and younger, 61–70 years, and 71 years and older. Dependent variables were the EORTC-QLQ-C30 and EORTC QLQ-PR25 scales, divided into positive and negative outcomes. Positive measures of health-related quality of life included global health, physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning. Negative outcomes included fatigue, nausea, pain, dyspnea, insomnia, appetite, constipation, and diarrhea. We also assessed sexual activity, and urinary, bowel and hormonal symptoms. Descriptive analyses included frequencies with chi-square tests and medians with Kruskal-Wallis tests. Multivariable adjusted analyses were conducted by median regression modeling.ResultsAmong the numerous scales showing some unadjusted association with age group, only two scales demonstrated significant differences between prostate cancer patients age 71+ compared to the youngest group (age < 61) after multivariable adjustment. On average, the oldest patients experienced an 8.3-point lower median physical functioning score (β = − 8.3; 95% CI = − 13.9, − 2.8; p = 0.003) and a 16.7-point lower median sexual activity score (β = − 16.7; 95% CI = − 24.7, − 8.6; p < 0.001) while controlling for BMI, marital status, time since diagnosis, comorbidities (heart condition), Gleason score, and treatment (prostatectomy).ConclusionsResults suggest that patient age at diagnosis should be considered among factors that contribute to health-related quality of life outcomes for prostate cancer survivors. Implications for Cancer Survivors: A possible reevaluation of screening recommendations may be appropriate to acknowledge age as a factor contributing to health-related quality of life outcomes for prostate cancer survivors.

Background Hemophilia A is an X‐linked inherited bleeding disorder caused by deficiency of coagulation factor VIII. Factor VIII is activated as part of the intrinsic coagulation cascade. It plays a crucial role as the cofactor in the intrinsic “tenase” complex activating factor X to assist in clot formation. Absence or mutation of this coagulation factor leads to excessive bleeding. Clinical manifestations of hemophilia relate to bleeding from impaired hemostasis, sequelae from bleeding, or complications of coagulation factor infusion. Diagnostic criteria for Hemophilia A include factor VIII activity level below 40% of normal, presence of a mutated F8 gene, and the absence of von Willebrand disease (F8 gene ‐ Genetics Home Reference ‐ NIH. https://ghr.nlm.nih.gov/gene/F8). Patients who have this intrinsic defect in the coagulation cascade have a characteristically prolonged PTT. It is theorized that the majority of factor VIII is synthesized mainly in the liver, by way of liver sinusoidal endothelial cells (Arruda VR. Haematologica. 2015;100(7):849–850). Extrahepatic production also occurs in the endothelial cells, kidneys, and lymphatic tissue. In 1969, Marchioro et al showed that transplantation of normal liver to hemophilia dog could normalize plasma factor VIII levels (Marchioro T L, Science. 1969;163(3863):188–190). These results were subsequently proven in humans. Liver transplantation from hemophilia A donors without factor VIII inhibitor is not commonly performed due to the perceived risk of developing hemophilia A in the recipient. There is currently limited literature aimed at elucidating this risk. We present a case of liver transplantation in a hemophilia A donor to a recipient with no history of hemophilia A with literature reviewis a case report, objective and method do not apply. Objective and method We did a case report and literature review of a liver transplant receipient fro ma hemohpila A donor. Results The receipient of the liver from hemophilia A donor did not develop hemophilia post transplant and had normal factor VIII levels. conclusion To our knowledge, this is only the second case in humans of hemophilia A patient as a donor in liver transplantation. As the indications for liver transplantation have expanded, there is a need to expand the donor list, and possibly not exclude this population as viable donor option.

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