Neonatal and Pediatric Organ Donation: Ethical Perspectives and Implications for Policy

The lifesaving processes of organ donation and transplantation in neonatology and pediatrics carry important ethical considerations. The medical community must balance the principles of autonomy, nonmaleficence, beneficence, and justice to ensure the best interest of the potential donor and to provide equitable benefit to society. Accordingly, the US Organ Procurement and Transplantation Network (OPTN) has established procedures for the ethical allocation of organs depending on several donor-specific and recipient-specific factors. To maximize the availability of transplantable organs and opportunities for dying patients and families to donate, the US government has mandated that hospitals refer potential donors in a timely manner. Expedient investigation and diagnosis of brain death where applicable are also crucial, especially in neonates. Empowering trained individuals from organ procurement organizations to discuss organ donation with families has also increased rates of consent. Other efforts to increase organ supply include recovery from donors who die by circulatory criteria (DCDD) in addition to donation after brain death (DBD), and from neonates born with immediately lethal conditions such as anencephaly. Ethical considerations in DCDD compared to DBD include a potential conflict of interest between the dying patient and others who may benefit from the organs, and the precision of the declaration of death of the donor. Most clinicians and ethicists believe in the appropriateness of the Dead Donor Rule, which states that vital organs should only be recovered from people who have died. The medical community can maximize the interests of organ donors and recipients by observing the Dead Donor Rule and acknowledging the ethical considerations in organ donation

Persistent elevation of fetal hemoglobin following chemotherapy in sickle cell disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92111/1/24106_ftp.pd

Screening of high risk infants for metabolic disease in a metropolitan hospital

Screening of symptomatic infants for metabolic diseases is described which led to an improved detection rate because of better awareness and case selection, as well as the use of a test for urinary organic acids.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147121/1/jimd0081.pd

Transfusional Iron Overload in Sickle Cell Anemia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72471/1/j.1749-6632.1989.tb24225.x.pd

Stability over time of hematological variables in 197 children with sickle cell anemia

One hundred ninety-seven children with sickle cell anemia were followed for 4 years at the Wayne State Comprehensive Sickle Cell Center to evaluate the stability of the hematological variables (Hb, Hct, RBC count, MCV, %HbF and %HBA 2 ) over time. The mean values of the hematological measurements taken during three separate 16-month intervals were used to represent an individual's values. The correlations of the hematological variables between intervals ranged from a low of 0.46 for %HBA 2 to a high of 0.91 for %HbF. Correlations that spanned two intervals (an average of 32 months) were of the same magnitude as those that spanned only one interval (an average of 16 months), suggesting that there was no decrease in the degree of stability of these variables as the time between measurements increased. The stability of the correlations between variables within intervals, and the stability of the coefficients of the first two principal components of the six hematological variables over time suggested that the relationships among variables were also stable. In a recent report [Odenheimer et al, 1983], we used the values of the six hematological variables collected at an individual's first visit to the sickle cell center to identify four hematologically distinct subgroups of children. In the current report, we found that as many as 83% of the individuals remained in the same subgroup in at least two of the three follow-up intervals, suggesting that the factors that contributed to this classification were the result of stable, rather than transient phenomena.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38236/1/1320180316_ftp.pd

Essential role of HDAC6 in the regulation of PD-L1 in melanoma

Indexación: Web of Science; Scopus.Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been deMonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples and cell lines, down-regulates the expression of PD-L1, an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T-cells. Our data suggests that this novel mechanism of PD-L1 regulation is mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Additionally, we observed that selective HDAC6 inhibitors impairs tumor growth and reduce the in vim expression of several inhibitory checkpoint molecules and other regulatory pathways involved in immunosurveillance. Most importantly, these results provide a key pre-clinical rationale and justification to further study isotype selective HDAC6 inhibitors as potential immuno-modulatory agents in cancer. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.http://onlinelibrary.wiley.com/doi/10.1016/j.molonc.2015.12.012/abstract;jsessionid=DB86CF943DA7FD358A75C2CEEAD4D7C4.f03t0

Address correspondence to Vernon K. Sondak, MD, Cutaneous Oncol-ogy Program

Background: Surgery is currently the primary treatment modality for metastatic melanoma involving the inguinal lymph nodes. However, inguinal lymph node dissections are associated with substantial morbidity including infection, wound dehiscence, lymphedema, seroma, and deep venous thromboembolism (DV

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Abusive Head Trauma and Mortality-An Analysis From an International Comparative Effectiveness Study of Children With Severe Traumatic Brain Injury

Objectives: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. Design: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial—a comparative effectiveness study using an observational, cohort study design. Setting: PICUs in tertiary children’s hospitals in United States and abroad. Patients: Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). Interventions: None. Measurements and Main Results: Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). Conclusions: In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines