English Journal Articles: Recent submissions
Now showing items 1-20 of 36
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T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.Relapse after allogeneic hematopoietic cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) entering HCT with poor-risk features1-3. When HCT does produce prolonged relapse-free survival, it commonly reflects graft-versus-leukemia effects mediated by donor T cells reactive with antigens on leukemic cells4. As graft T cells have not been selected for leukemia specificity and frequently recognize proteins expressed by many normal host tissues, graft-versus-leukemia effects are often accompanied by morbidity and mortality from graft-versus-host disease5. Thus, AML relapse risk might be more effectively reduced with T cells expressing receptors (TCRs) that target selected AML antigens6. We therefore isolated a high-affinity Wilms' Tumor Antigen 1-specific TCR (TCRC4) from HLA-A2+ normal donor repertoires, inserted TCRC4 into Epstein-Bar virus-specific donor CD8+ T cells (TTCR-C4) to minimize graft-versus-host disease risk and enhance transferred T cell survival7,8, and infused these cells prophylactically post-HCT into 12 patients ( NCT01640301 ). Relapse-free survival was 100% at a median of 44 months following infusion, while a concurrent comparative group of 88 patients with similar risk AML had 54% relapse-free survival (P = 0.002). TTCR-C4 maintained TCRC4 expression, persisted long-term and were polyfunctional. This strategy appears promising for preventing AML recurrence in individuals at increased risk of post-HCT relapse.
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Anaplastic thyroid carcinoma transformation in a lateral neck node metastasis - A case report and a review of the literatureAnaplastic thyroid carcinoma is thought to be derived from previous existing papillary or follicular thyroid carcinoma that dedifferentiates into its anaplastic counterpart. We present a case where this type of dedifferentiation occurs at a metastatic site in a regional lymph node, years after the primary papillary thyroid tumor had metastasized.
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Towards an Individualized Nutrition Treatment: Role of the Gastrointestinal Microbiome in the Interplay Between Diet and Obesity.Dietary treatments for obesity have relatively low long-term success. Recent studies have identified the gastrointestinal microbiome as a factor of high relevance. The current knowledge on the interplay between diet, obesity, and the gastrointestinal microbiome and the potential for individualized dietary treatment will be discussed. Studies indicate that each individual digests and metabolizes identical food substances differently depending on their gastrointestinal microbiome composition. Factors related to this crosstalk may improve our understanding of weight homeostasis and treatment of obesity. Long-time dietary intake is the key in the composition of the gastrointestinal microbiome which seems to be an important factor for energy balance, resulting in emerging opportunities for increasingly varied obesity treatment. Compliance to dietary treatment is critical for long-term success as enduring changes in gastrointestinal microbiome seem to slow over time. More research is urgently needed to investigate this missing link in our understanding of obesity.
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Giant gastric lipoma successfully removed by endoscopic submucosal dissection: case report and systematic review.Gastric lipomas are rare adipose tumors that constitute less than 1% of gastric tumors. While lipomas generally do not need removal unless symptomatic, endoscopic resection has been proposed as safe for gastric lipomas smaller than 2 cm. Yet, there is no consensus on the optimal treatment method for larger lipomas. We report a case of a giant 7-cm gastric lipoma successfully removed by endoscopic submucosal dissection (ESD) and systematically review the literature for gastric lipomas removed by ESD. Systematic review was conducted by searching PubMed and Scopus databases, up to 15 February 2018, using combinations of relevant terms. We report a 55-year-old male with known gastroesophageal reflux disease and asthma, who sought medical attention due to chronic heartburn and asthma exacerbations. These symptoms were attributed to a large 7 cm × 3 cm gastric lipoma that caused gastric outlet obstruction. The lipoma was safely removed by ESD, allowing quick recovery and alleviation of symptoms. In our review, we identified 20 gastric lipomas treated with ESD, with 15 (75%) being 2 cm or larger. The average size of the lipomas was 4 cm (range: 1.2-9 cm). All lipomas were limited to the submucosa, with 80% of the tumors located in the antrum. Three lipomas were removed by submucosal tunneling. All tumors were successfully removed en bloc and no major complications were reported. Our findings support the conclusion that ESD may be a safe alternative to conventional surgery for removal of large symptomatic gastric lipomas.
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Editor's Choice - The Impact of Centralisation and Endovascular Aneurysm Repair on Treatment of Ruptured Abdominal Aortic Aneurysms Based on International Registries.Current management of ruptured abdominal aortic aneurysms (RAAA) varies among centres and countries, particularly in the degree of implementation of endovascular aneurysm repair (EVAR) and levels of vascular surgery centralisation. This study assesses these variations and the impact they have on outcomes. RAAA repairs from vascular surgical registries in 11 countries, 2010-2013, were investigated. Data were analysed overall, per country, per treatment modality (EVAR or open aortic repair [OAR]), centre volume (quintiles IV), and whether centres were predominantly EVAR (≥50% of RAAA performed with EVAR [EVAR(p)]) or predominantly OAR [OAR(p)]. Primary outcome was peri-operative mortality. Data are presented as either mean values or percentages with 95% CI within parentheses, and compared with chi-square tests, as well as with adjusted OR. There were 9273 patients included. Mean age was 74.7 (74.5-74.9) years, and 82.7% of patients were men (81.9-83.6). Mean AAA diameter at rupture was 7.6 cm (7.5-7.6). Of these aneurysms, 10.7% (10.0-11.4) were less than 5.5 cm. EVAR was performed in 23.1% (22.3-24.0). There were 6817 procedures performed in OAR(p) centres and 1217 performed in EVAR(p) centres. Overall peri-operative mortality was 28.8% (27.9-29.8). Peri-operative mortality for OAR was 32.1% (31.0-33.2) and for EVAR 17.9% (16.3-19.6), p < .001, and the adjusted OR was 0.38 (0.31-0.47), p < .001. The peri-operative mortality was 23.0% in EVAR(p) centres (20.6-25.4), 29.7% in OAR(p) centres (28.6-30.8), p < .001; adjusted OR = 0.60 (0.46-0.78), p < .001. Peri-operative mortality was lower in the highest volume centres (QI > 22 repairs per year), 23.3% (21.2-25.4) than in QII-V, 30.0% (28.9-31.1), p < .001. Peri-operative mortality after OAR was lower in high volume centres compared with the other centres, 25.3% (23.0-27.6) and 34.0% (32.7-35.4), respectively, p < .001. There was no significant difference in peri-operative mortality after EVAR between centres based on volume. Peri-operative mortality is lower in centres with a primary EVAR approach or with high case volume. Most repairs, however, are still performed in low volume centres and in centres with a primary OAR strategy. Reorganisation of acute vascular surgical services may improve outcomes of RAAA repair.
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Adrenergic and metabolic effects of electrical weapons: review and meta-analysis of human data.Electronic control with the CEW (conducted electrical weapon) has gained widespread acceptance as the preferred force option due to its significant injury reduction. However, a CEW application does stress the human body. In the case of the CEW, the human body response is similar to the challenge of physical exercise combined with emotional stress over a very short time interval. There has been concern whether the tension of the skeletal-muscle system together with the emotional stress of being exposed to the effects of a CEW, can lead to severe metabolic dysfunction. A systematic and careful search of the MedLine database was performed to find publications describing pathophysiological effects of CEWs. Additional publications were collected through a manual search of reference lists in retrieved articles. After preliminary exclusions, we carefully reviewed the remaining publications and found 24 papers reporting prospective human clinical research data on adrenergic, ventilation, or metabolic effects. Where there were multiple studies on the same endpoints, we performed meta-analyses. A CEW exposure provides a clinically insignificant increase in heart rate (7.5 BPM) and a drop in both systolic and diastolic blood pressure. Alpha-amylase goes down but cortisol levels increase-both epinephrine and norepinephrine levels are increased by levels similar to mild exercise. A CEW exposure increases ventilation but does not appear to interfere with gas exchange. Lactate is increased slightly while the pH is decreased slightly with changes equivalent to mild exercise. The lactate and pH changes appear quickly and do not appear to be affected by increasing the exposure duration from 5 to 30 s. Thorough review and meta-analyses show that electrical weapon exposures have mixed and mild adrenergic effects. Ventilation is increased and there are metabolic changes similar to mild exercise.
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Cardiac and skeletal muscle effects of electrical weapons : A review of human and animal studies.Conducted Electrical Weapons (CEWs) are being used as the preferred non-lethal force option for police and special forces worldwide. This new technology challenges an exposed opponent similarly to the way they would be challenged by physical exercise combined with emotional stress. While adrenergic and metabolic effects have been meta-analyzed and reviewed, there has been no systematic review of the effects of CEWs on skeletal and cardiac muscle. A systematic and careful search of the MedLine database was performed to find publications describing pathophysiological cardiac and skeletal muscle effects of CEWs. For skeletal muscle effects, we analyzed all publications providing changes in creatine kinase, myoglobin and potassium. For cardiac effects, we analyzed reported troponin changes and arrhythmias related to short dart-to-heart-distances. Conducted electrical weapons satisfy all relevant electrical safety standards and there are, to date, no proven electrocution incidents caused by CEWs. A potential cardiovascular risk has been recognized by some of the experimental animal data. The effects on the heart appear to be limited to instances when there is a short dart-to-heart-distance. The effect on the skeletal muscle system appears to be negligible. A responsible use of a CEW on a healthy adult, within the guidelines proposed by the manufacturer, does not imply a significant health risk for that healthy adult.
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Inflammatory Breast Cancer: What surgeons need to know.Strict criteria to identify Inflammatory Breast Cancer (IBC) have been made available - these are based on pathological as well as clinical observations. It is mandatory to confirm the criteria used in any further report. Scientific evidence accumulated so far is confusing, and unclear therefore no hard conclusion can be drawn from the available literature on the management of IBC. The advent of new medications results into an up-to-date management and different outcomes. It is mandatory to follow these criteria if reliable guidelines are to be made available in the next future.
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Self-reported exposure to traffic pollution in relation to daytime sleepiness and habitual snoring: a questionnaire study in seven North-European cities.Little is known about associations between traffic exposure and sleep disturbances. We examined if self-reported exposure to traffic is associated with habitual snoring and daytime sleepiness in a general population.
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Decreased postural control in adult survivors of childhood cancer treated with chemotherapy.The objective of cancer treatment is to secure survival. However, as chemotherapeutic agents can affect the central and peripheral nervous systems, patients must undergo a process of central compensation. We explored the effectiveness of this compensation process by measuring postural behaviour in adult survivors of childhood cancer treated with chemotherapy (CTS). We recruited sixteen adults treated with chemotherapy in childhood for malignant solid (non-CNS) tumours and 25 healthy age-matched controls. Subjects performed posturography with eyes open and closed during quiet and perturbed standing. Repeated balance perturbations through calf vibrations were used to study postural adaptation. Subjects were stratified into two groups (treatment before or from 12 years of age) to determine age at treatment effects. Both quiet (p = 0.040) and perturbed standing (p ≤ 0.009) were significantly poorer in CTS compared to controls, particularly with eyes open and among those treated younger. Moreover, CTS had reduced levels of adaptation compared to controls, both with eyes closed and open. Hence, adults treated with chemotherapy for childhood cancer may suffer late effects of poorer postural control manifested as reduced contribution of vision and as reduced adaptation skills. These findings advocate development of chemotherapeutic agents that cause fewer long-term side effects when used for treating children.
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Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome.The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines.
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Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort.Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations.
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Association between healthy maternal dietary pattern and risk for gestational diabetes mellitus.Gestational diabetes mellitus (GDM) is associated with negative health effects for mother and child. The aim was to investigate the association between maternal dietary patterns and GDM.
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Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients.To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients.
