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Although there is an agreement that liver grafts from pediatric donors (PDs) should ideally be used for pediatric patients, there remain situations when these grafts are turned down for pediatric recipients and are then offered to adult recipients. The present study aimed to investigate the outcomes of using these grafts for liver transplantation (LT) in adult patients. Data from all patients undergoing LT between 2002 and 2014 were obtained from the United Network for Organ Sharing Standard Analysis and Research file. Adult recipients undergoing LT were divided into 2 groups: those receiving a pediatric liver graft (pediatric‐to‐adult group) and those receiving a liver graft from adult donors (adult‐to‐adult group). A separate subgroup analysis comparing the PDs used for adult recipients and those used for pediatric recipients was also performed. Patient and graft survival were not significantly different between pediatric‐to‐adult and adult‐to‐adult groups (P = 0.08 andP = 0.21, respectively). Hepatic artery thrombosis as the cause for graft loss was higher in the pediatric‐to‐adult group (3.6%) than the adult‐to‐adult group (1.9%;P < 0.001). A subanalysis looking at the pediatric‐to‐adult group found that patients with a predicted graft‐to‐recipient weight ratio (GRWR) < 0.8 had a higher 90‐day graft loss rate than those with a GRWR ≥ 0.8 (39% versus 9%;P < 0.001). PDs used for adult recipients had a higher proportion of donors with elevated aspartate aminotransferase/alanine aminotransferase (20% vs. 12%;P < 0.001), elevated creatinine (11% vs. 4%;P < 0.001), donation after cardiac death donors (12% vs. 0.9%;P < 0.001), and were hepatitis B virus core positive (1% vs. 0.3%;P = 0.002) than PDs used for pediatric recipients. In conclusion, acceptable patient and graft survival can be achieved with the use of pediatric liver grafts in adult recipients, when these grafts have been determined to be inappropriate for usage in the pediatric population.Liver Transplantation 22 1099–1106 2016 AASLD

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non‐Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS‐R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population‐based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.

Abstract Background In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1 DM , T2 DM ) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1 DM vs T2 DM gastroparesis patients. Methods Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1 DM and T2 DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow‐up differences between diabetes subtypes. Key Results At baseline, T1 DM patients ( N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2 DM patients ( N = 59). Independent discriminators of patients with T1 DM vs T2 DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities ( p ≤ 0.05). On follow‐up, gastrointestinal ( GI ) symptom scores decreased only in T2 DM ( p < 0.05), but not in T1 DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks ( p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life. Conclusions & Inferences Baseline symptoms were similar in T1 DM and T2 DM patients, even though T1 DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2 DM , but not T1 DM patients, despite increased medical and surgical treatment utilization by T1 DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

Aims: Heme derived from hemolysis is pro-oxidative and proinflammatory and promotes vaso-occlusion in murine models of sickle cell disease (SCD), suggesting that enhanced detoxification of heme may be beneficial. Nuclear factor erythroid-2-related factor-2 (Nrf2) transcription pathway is the principal cellular defense system responding to pro-oxidative and proinflammatory stress. Dimethyl fumarate (DMF), a drug approved for treatment of multiple sclerosis, provides neuroprotection by activating Nrf2-responsive genes. We hypothesized that induction of Nrf2 with DMF would be beneficial in murine SCD models. Results: DMF (30 mg/kg/day) or vehicle (0.08% methyl cellulose) was administered for 3–7 days to NY1DD and HbSS-Townes SCD mice. Vaso-occlusion, a hallmark of SCD, measured in sickle mice with dorsal skinfold chambers, was inhibited by DMF. The inhibitory effect of DMF was abrogated by the heme oxygenase-1 (HO-1) inhibitor tin protoporphyrin. DMF increased nuclear Nrf2 and cellular mRNA of Nrf2-responsive genes in livers and kidneys. DMF increased heme defenses, including HO-1, haptoglobin, hemopexin, and ferritin heavy chain, although plasma hemoglobin and heme levels were unchanged. DMF decreased markers of inflammation, including nuclear factor-kappa B phospho-p65, adhesion molecules, and toll-like receptor 4. DMF administered for 24 weeks to HbSS-Townes mice decreased hepatic necrosis, inflammatory cytokines, and irregularly shaped erythrocytes and increased hemoglobin F, but did not alter hematocrits, reticulocyte counts, lactate dehydrogenase, plasma heme, or spleen weights, indicating that the beneficial effects of DMF were not attributable to decreased hemolysis. Innovation: These studies identify Nrf2 activation as a new therapeutic target for the treatment of SCD. Conclusion: DMF activates Nrf2, enhances antioxidant defenses, and inhibits inflammation and vaso-occlusion in SCD mice. Antioxid. Redox Signal . 26, 748–762.

Study Design Retrospective clinical study of a prospectively collected, national database. Objective Determine the 30-day incidence, timing, and risk factors for venous thromboembolism (VTE) following thoracolumbar spine surgery. Methods The American College of Surgeons National Surgical Quality Improvement Program Participant Use File identified 43,777 patients who underwent thoracolumbar surgery from 2005 to 2012. Multiple patient characteristics were identified. The incidence and timing (in days) of deep vein thrombosis (DVT) and pulmonary embolus (PE) were determined. Multivariable regression analysis was performed to identify significant risk factors. Results Of the 43,777 patients identified as having had thoracolumbar surgery, 202 cases of PE (0.5%) and 311 cases of DVT (0.7%) were identified. VTE rates were highest in patients undergoing corpectomy, with a 1.7% PE rate and a 3.8% DVT rate. Independent risk factors for VTE included length of stay (LOS) ≥ 6 days (odds ratio [OR] 4.07), disseminated cancer (OR 1.77), white blood cell count > 12 (OR 1.76), paraplegia (OR 1.75), albumin < 3 (OR 1.73), American Society of Anesthesiologists class 4 or greater (OR 1.54), body mass index > 40 (OR 1.49), and operative time > 193 minutes (OR 1.43). LOS < 3 days was protective (OR 0.427). Conclusions We report an overall 30-day PE rate of 0.5% and DVT rate of 0.7% following thoracolumbar spine surgery. Patients undergoing corpectomy were at highest risk for VTE. Multiple VTE risk factors were identified. Further studies are needed to develop algorithms to stratify VTE risk and direct prophylaxis accordingly.

Pseudomyogenic hemangioendothelioma (PMH) is a well-recognized neoplasm that usually arises in the soft tissue; concurrent bone involvement occurs in 24% of cases. PMH of bone without soft tissue involvement is rare. We describe the clinicopathologic findings of 10 such cases, the largest series reported to date. The study included 9 male and 1 female patient; their ages ranged from 12 to 74 years (mean 36.7 y). All patients had multiple tumors with a distinct regional distribution: 45% restricted to the lower extremity; 25% to the spine and pelvis; and 15% to the upper extremity. On imaging studies the tumors were well circumscribed and lytic. The neoplasms were composed of spindled cells arranged in intersecting fascicles with scattered epithelioid cells; epithelioid cells predominated in 3 cases. The neoplastic cells contained abundant densely eosinophilic cytoplasm and vesicular nuclei. There was limited cytologic atypia and necrosis, few mitoses (0 to 2/10 high-power fields), and inconspicuous stroma. Unique findings included abundant intratumoral reactive woven bone and hemorrhage with numerous osteoclast-like giant cells. Immunohistochemically, most tumors were positive for keratin, ERG, and CD31; CD34 was negative. The balanced t(7:19)(q22;13) translocation was documented in 3 cases. Follow-up is limited, but no patient developed documented visceral dissemination, and all have stable or progressive osseous disease. PMH exclusively involving bone is rare. It is multicentric, often involves the lower extremity, and has unusual morphology. The differential diagnosis includes epithelioid vascular neoplasms, giant cell tumor, bone forming neoplasms, and metastatic carcinoma. Because of its rarity, unusual presentation, and morphology, accurate diagnosis can be challenging.

ObjectivesTo investigate the dose‐dependent effect of androgen deprivation therapy on community‐acquired respiratory infections in patients with localized prostate cancer.MethodsWe identified 52 905 men diagnosed with localized prostate cancer within the Surveillance, Epidemiology and End Results‐Medicare database between 1991 and 2006. We compared those who did not receive androgen deprivation therapy with those who received androgen deprivation therapy within 2 years of diagnosis, calculated as monthly equivalent doses (<7, 7–11, >11 doses), or orchiectomy. Adjusted Cox hazard models were fitted to predict the risk of community‐acquired respiratory infections (acute sinusitis, acute bronchitis, [severe] pneumonia) in patients treated with medical androgen deprivation therapy versus orchiectomy versus none.ResultsOverall, 43.4% received medical androgen deprivation therapy. These patients more likely experienced respiratory events compared with those who did not receive androgen deprivation therapy or who underwent orchiectomy (62.2% vs 54.5% vs 47.8%, P < 0.001). The risk of experiencing any respiratory event increased with the number of doses received. For example, men receiving >11 doses of androgen deprivation therapy were at greatest risk of acute sinusitis, acute bronchitis and pneumonia (HR 1.13, 1.26 and 1.15, respectively, all P < 0.001), except severe pneumonia. Furthermore, we did not detect any relationship between orchiectomy and respiratory events. Study limitations include the utilization of a retrospective population‐based dataset.ConclusionsIncreased exposure to medical androgen deprivation therapy for men with localized prostate cancer is associated with a higher risk of community‐acquired respiratory infections. Our results suggest that respiratory complications represent potentially underreported complications of medical androgen deprivation therapy.