Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.     

Bone mineral density: Methods of measurement and its influence on primary stability of miniscrews

Objective:To verify whether bone mineral density (BMD) of cortical bone, trabecular bone, and total bone influence the primary stability of orthodontic miniscrews and to verify whether there is a correlation between the measurement of BMD by cone-beam computed tomography (CBCT) and central dual-energy x-ray absorptiometry (DEXA).Materials and Methods:Twenty bovine bone sections were extracted from the pubic and iliac bones from regions with cortical thicknesses of approximately 1 mm. The BMD of the total bone block was evaluated using two methods: CBCT and DEXA. The BMD of cortical, trabecular, and total bone in the region of interest (ROI) were also evaluated by CBCT. After scanning the bone blocks, 20 self-drilling miniscrews (INP®) 1.4 mm in diameter and 6 mm long were inserted into them. The peak implant insertion torque (IT) was registered. After this, the pull-out test (PS) was performed and the maximum force registered. The Pearson correlation test was applied to verify the correlations between variables.Results:The BMD of the total bone block verified by CBCT and DEXA showed a positive and strong correlation (r  =  0.866, P  =  .000). The BMD of the ROI for cortical bone influenced the IT (r  =  0.518, P  =  .40) and the PS of miniscrews (r  =  0.713, P  =  .001, Table 2). However, the total bone BMD (verified by CBCT and DEXA) and trabecular bone BMD presented weak and not statistically significant correlations with primary stability.Conclusions:There was a positive correlation between total bone block BMD measured by DEXA and CBCT. The cortical BMD influenced the IT and PS.     

Effects of chemical composition on the corrosion of dental alloys

The aim of this study was to determine the effect of the oral environment on the corrosion of dental alloys with different compositions, using electrochemical methods. The corrosion rates were obtained from the current-potential curves and electrochemical impedance spectroscopy (EIS). The effect of artificial saliva on the corrosion of dental alloys was dependent on alloy composition. Dissolution of the ions occurred in all tested dental alloys and the results were strongly dependent on the general alloy composition. Regarding the alloys containing nickel, the Ni-Cr and Ni-Cr-Ti alloys released 0.62 mg/L of Ni on average, while the Co-Cr dental alloy released ions between 0.01 and 0.03 mg/L of Co and Cr, respectively.The open-circuit potential stabilized at a higher level with lower deviation (standard deviation: Ni-Cr-6Ti = 32 mV/SCE and Co-Cr = 54 mV/SCE). The potenciodynamic curves of the dental alloys showed that the Ni-based dental alloy with >70 wt% of Ni had a similar curve and the Co-Cr dental alloy showed a low current density and hence a high resistance to corrosion compared with the Ni-based dental alloys. Some changes in microstructure were observed and this fact influenced the corrosion behavior for the alloys. The lower corrosion resistance also led to greater release of nickel ions to the medium. The quantity of Co ions released from the Co-Cr-Mo alloy was relatively small in the solutions. In addition, the quantity of Cr ions released into the artificial saliva from the Co-Cr alloy was lower than Cr release from the Ni-based dental alloys.     

Spinocerebellar ataxia type 3/Machado–Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions

Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta‐CAGexp from parent–offspring pairs, and delta‐CAGexp between siblings were obtained. One hundred and fifty‐nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta‐CAGexp among 115 direct parent–offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta‐CAGexp between 269 siblings correlated with their delta‐of‐age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.     

Father’s obesity programs the adipose tissue in the offspring via the local renin–angiotensin system and MAPKs pathways,especially in adult male mice

Purpose

Studies demonstrated the influence of mother’s obesity on offspring. However, the father is also related to programming the future generation. The study aimed to evaluate the effects of father’s obesity upon white adipose tissue (WAT) remodeling, resulting in activation of signaling pathways and inflammation in male and female offspring.

Methods

Male C57BL/6 mice received control diet (lean father group; 17% energy from lipids) or high-fat diet (obese father group; 49% energy from lipids) for 8 weeks before mating. The mothers received control diet throughout the experiment. Mice were mated: lean mother and lean father, and lean mother and obese father. Offspring received control diet from weaning until 3 months of age when they were studied.

Results

In the offspring, father’s obesity led to decreased QUICKI with impairment of the insulin signaling pathway in both sexes. In line with these findings, in white adipose tissue, male offspring demonstrated hypertrophied adipocytes, enhanced proinflammatory cytokines, overactivation of components of the local renin–angiotensin system (RAS) and extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of peroxisome proliferator-activated receptors (alpha and gamma).

Conclusions

We observed that father’s obesity influences the offspring in adult life, with an impairment in insulin homeostasis, adipocyte remodeling, and adipose tissue overexpression of IL-6 and TNF-alpha in male offspring. The activation of local RAS and ERK1/2, a concomitant PPAR diminishing, and impairment in phosphorylation of AKT and IRS-1 could explain at least in part the findings regardless of the increase in body mass in the offspring.

     

Impact of multidrug resistance on the management of bacterial infections in cirrhosis

Patients with cirrhosis have an increased risk of infection and differently from other complications, that over the years are improving in their outcomes, infections in cirrhotic patients are still a major cause of hospitalization and death (up to 50% in-hospital mortality). Infections by multidrug-resistant organisms (MDRO) have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact. About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years. MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution. An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects, such as the type of infection (spontaneous bacterial peritonitis, pneumonia, urinary tract infection and spontaneous bacteremia), bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition (community acquired, healthcare associated or nosocomial). Furthermore, regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology. Antibiotic treatment is the most effective measure to treat infections caused by MDRO. Therefore, optimizing antibiotic prescribing is critical to effectively treat these infections. Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality. On the other hand, the supply of new agents to treat these infections is very limited. Thus, specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.     

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady- state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.