Human Epidermal Growth Factor Receptor 2-Positive Duodenal Adenocarcinoma: A Case Report and Review of the Literature

Duodenal adenocarcinoma is a rare malignancy and carries a poor prognosis. The role of adjuvant therapy and the optimal chemotherapy regimen remain largely unclear. Treatment with trastuzumab results in prolonged survival in gastroesophageal cancer if human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified in tumor cells. However, unlike gastric adenocarcinomas, duodenal cancers seem to rarely harbor HER2 amplification or overexpression. We report the case of a patient with HER2-positive stage III duodenal adenocarcinoma who has received adjuvant chemotherapy including trastuzumab.Key Words: Duodenal adenocarcinoma, Trastuzumab, Human epidermal growth factor receptor 2 amplification     

MODIS BRDF effects over Brazilian tropical forests and savannahs: a comparative analysis

Bidirectional reflectance distribution function (BRDF) effects over Brazilian tropical forests (Amazon) and savannahs (Cerrado) were inspected for differences in high-quality pixel retrievals, view direction, view zenith angle (VZA), solar zenith angle (SZA) and relative azimuth angle (RAA). By comparing Moderate Resolution Imaging Spectroradiometer (MODIS) data, corrected and non-corrected for BRDF effects (2000–2014), we evaluated the magnitude of such effects over reflectance and vegetation indices (VIs). The VIs were the Enhanced Vegetation Index (EVI) and the Normalized Difference Vegetation Index (NDVI). From the Amazon to the Cerrado, we observed a higher frequency of high-quality pixel retrievals, a decrease in VZA, and an increase in seasonal SZA amplitude. Brightness increased in the backscattering direction and with shifts in RAA over tropical forests toward the BRDF hotspot at the end of dry season (September). Compared to the savannahs from the Cerrado or those from northern Amazon, stronger BRDF effects were observed for Amazonian tropical forests and for the EVI. BRDF changes in the dry season NDVI amplitude (NDVI_Sept minus NDVI_June) were lower than 5% for both biomes. For the EVI amplitude, we observed changes up to 20% over the savannahs and close to 60% for most of the Amazon. However, even after BRDF correction and in spite of the observed differences close to 0.02, EVI values from June and September were still statistically different from each other.     

Input on monitoring and evaluation practices of government management of Brazilian Municipal Health Departments

What do the leaders of the Municipal Health Service (SMS) report and say about the systematic monitoring and evaluation of their own government management? The purpose of this paper is to provide input for the formulation of plausible hypotheses about such institutional processes and practices based on information produced in an exploratory study. This is a multiple case study with quantitative and qualitative analysis of answers to a semi-structured questionnaire given to government officials of a systematic sample of 577 Municipal Health Services (10.4% of the total in Brazil). They were selected and stratified by proportional distribution among states and by the population size of municipalities. In general, it shows that approximately half of the respondents use information from Health Monitoring Evaluations to orient decision-making, planning and other management approaches. This proportion tends to decrease in cities with smaller populations. There are specific and significant gaps in financial, personnel and crisis management. The evidence from the hypotheses highlights the fact that these processes are still at an early stage.     

Vaccine-elicited Human T Cells Recognizing Conserved Protein Regions Inhibit HIV-1

Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4⁺ cells and inhibited HIV-1 replication by up to 5.79 log₁₀. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8⁺ T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.     

Postoperative complications in the treatment of rectal neoplasia by transanal endoscopic microsurgery: a prospective study of risk factors and time course

Purpose

Transanal endoscopic microsurgery (TEM) is a safe and efficient minimally invasive treatment for rectal benign and early malignant neoplasia, but postoperative complications may be severe. We aimed to evaluate the risk factors related to the incidence, severity, and time course of postoperative complications of TEM.

Methods

This is a prospective study of postoperative complications in 53 patients (>18 years old) with benign or early rectal neoplasia who underwent TEM with curative intention or, for higher stages, palliation. Outcome measures included age, sex, American Society of Anesthesiologists score, neoadjuvant chemoradiotherapy, lesion height and size, pathologic margins, tumor histology, and suture type.

Results

Overall morbidity was 50 %. Temporary fecal incontinence was the most frequent complication (17.3 %). Complication rates of Clavien–Dindo grades I and II were 21.1 % and those of grades III and IV 3.8 %. Of patients with complications, more had lesions under the first rectal valve than over the first valve (61.54 % vs 38.46 %, p?=?0.04). Patients submitted to chemoradiotherapy had a 24-fold greater chance of presenting grade II complications (p?=?0.002). When the surgical defect was treated using the TEM device to perform the suture, the chance of having grade III complications was reduced 16-fold (p?=?0.04). Fifty-three percent of complications occurred in the first 10 days and 95 % within 20 days.

Conclusions

Postoperative complications after transanal endoscopic microsurgery for the treatment of rectal neoplasia are frequent, acceptable, and usually controllable with pharmacologic treatment. Over time the nature of complications is continuous, centered on the first 20 days after surgery.

     

Multicentre randomized trial of sotalol vs amiodarone for chronic malignant ventricular tachyarrhythmias

Sotalol was compared with amiodarone in this open randomizedmulticentre study of patients with ventricular tachycardia orfibrillation not associated with acute myocardial infarctionrefractory to or intolerant of Class I drugs. 16 of 30 patientstreated with amiodarone completed 12 months on therapy, fivewere withdrawn because of recurrent ventricular tachycardiaand nine because of presumed adverse drug reactions, complianceproblems or protocol violation. Four of those who were withdrawndied within 12 months. Sixteen of 29 patients completed 12 months on sotalol, one waswithdrawn because of ventricular tachycardia and nine becauseof presumed adverse drug reactions, poor compliance or the needfor coronary artery surgery. Three died on treatment and twoafter withdrawal but within 12 months of entering the study. When the results are analysed by intention to treat there wasno significant difference in antiarrhythmic efficacy or in theincidence of side-effects severe enough to warrant withdrawalfrom the trial. There was an increase in left ventricular ejectionfraction in those treated with sotalol, which, because of itspharmacokine-tics, is an attractive alternative to amiodaronefor patients with malignant ventricular arrhythmias who cantolerate ß-adrenergic blockade.     

Automatic adjustment of pacing output in the clinical setting

Background

AutoCapture (AC) is a programmable feature that enables the pacemaker to both track the capture threshold and automatically adjust the output on a beat-by-beat basis. Although AC safely and significantly reduces the current drainage, some authors have argued that the longevity benefit of such a system is overstated. This study aims to estimate the longevity extension that can be obtained, in the clinical routine, by turning the AC on in comparison to pacemakers programmed to operate at the shipped and manually optimized output.

Methods

We selected 83 consecutive patients who received implanted St Jude's Affinity pacemakers >6 months earlier. Eight patients died or were lost to follow-up and in 9 subjects the AC could not be turned on. In the remaining 66 patients, current drain and estimated longevity were compared in 3 situations: (1) AC on; (2) AC off, optimized programming (100%-150% voltage threshold); (3) AC off, shipped output (3.5 V).

Results

Five patients had large variations (>1 V) of the AC threshold. Current drainage was 8.0 ± 0.9 mA in the AC group, 8.7 ± 1.8 mA with AC off and optimized programming, and 11.3 ± 2.3 mA at shipped output (P < .01). Estimated longevity was significantly extended (P < .01) by AC (12.1 ± 1.0 years) when compared to shipped (8.9 ± 1.7 years) and optimized programming (11.3 ± 1.4 years).

Conclusion

Reprogramming the pacemaker output significantly enhanced its estimated longevity; AC added a moderate but significant extension over manual reprogramming and was associated with increased safety in patients with large ventricular threshold variations.     

Autoantibodies against platelet membrane glycoproteins in children with acute and chronic immune thrombocytopenic purpura

The autoimmune nature of chronic immune thrombocytopenic purpura (ITP) in adults is widely accepted. In contrast, the pathogenetic mechanism in acute and chronic ITP in children is not known. In this report, we studied 39 children with destructive thrombocytopenia, 15 patients with acute ITP and 24 patients with chronic ITP. Platelet autoantibodies to platelet glycoprotein IIb/IIIa were detected in 14 of 24 patients (58.3%) in the chronic ITP group and in four of 15 (26.7%) with acute ITP. Binding ratios (+/- SD) of positive patients were significantly greater (P = .01) in chronic ITP (8.0 +/- 9.1) when compared with those of acute ITP where the binding ratios were only slightly above the normal range (1.9 +/- 0.4). The results show that autoantibodies against platelet glycoproteins are present in the majority of children with chronic ITP confirming the autoimmune nature of this disorder. The minimal elevation seen in the positive children with acute ITP suggests a different pathogenetic mechanism. These data suggest that this approach may be useful in differentiating acute from chronic ITP patients.