Translating in vitro prediction of cytotoxic T cell alloreactivity to hematopoietic stem cell transplantation outcome

IntroductionPreviously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT).MethodsWe selected patients transplanted with a 9/10 single HLA class I mismatched graft (n = 171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor–recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis.ResultsWe observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest.ConclusionFurther investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.     

Influences of Gender on Complication Rate and Outcome after Roux-en-Y Gastric Bypass: Data Analysis of More Than 10,000 Operations from the German Bariatric Surgery Registry

Background

Since 1 January 2005, bariatric surgery has been monitored in Germany. All related data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University Magdeburg.

Methods

Data collection regarding obesity and metabolic surgery was started in an online database in 2005. Follow-up data are collected once a year. Participation in the quality assurance study is voluntary.

Results

Since 2005, 10,330 Roux-en-Y gastric bypass (RYGB) procedures have been performed in Germany. In total, 8,013 patients were female and 2,317 were male. Male patients suffered significantly more comorbidities than female patients. The men also had higher body mass indexes (BMIs) and ages than the women at the time of operation. Data on the gender-specific aspects of RYGB from the Nationwide Survey of Bariatric Surgery in Germany (GBSR) showed a significant difference in anastomotic insufficiency at the gastro-entero-anastomosis. The leakage rate was 2.37 % (55/2,317) in men and 1.68 % (135/8,013) in women. Additionally, specific complication and mortality rates were significantly higher in male than in female patients.

Conclusions

Metabolic and obesity surgery is becoming increasingly popular in Germany. Data from the GBSR show significant differences in preoperative comorbidities and postoperative complication and mortality rates between male and female patients. There is a need for further evaluation of gender-specific aspects to optimize patient selection and reduce specific postoperative complications.     

Total spondylectomy for solitary bone plasmacytoma of the lumbar spine in a young woman: a case report and review of literature

Abstract

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Introduction

Solitary bone plasmacytoma (SP) is a rare diagnosis for which the primary treatment is local radiotherapy. There is no established consensus suggesting a total spondylectomy in spinal SP.

Materials and Methods

We report the case of a 43-year-old woman with solitary plasmacytoma of the lumbar spine treated with complete vertebral resection. Radiographs, CT scan and MRI showed a single osteolytic lesion of the third lumbar vertebra. Further diagnostics following recommended algorithm for tumour screening were negative. Two times, biopsy showed no histological pathologies. Due to the instability of the spine with suspicious unknown lesion, we decided to perform a dorsal lumbar approach and instrumentation with complete resection of the posterior parts to prepare for a complete resection if mandatory. Resamples were taken and the bone surfaces sealed. Consecutive findings were positive for plasma cell infiltration of the respective vertebra, however not on the first pass, but after diagnostic pathological reference. Surgery was completed by total spondylectomy. Reference histological findings with restaging and cytogenetic risk analysis confirmed a non-high-risk solitary bone plasmacytoma, and the patient was scheduled for localized radiotherapy with 40 Gy.

Results

Follow-up examinations (53 months) showed no local recurrence or disease progression.

Discussion

There is no consensus in the literature regarding appropriate surgical approach and perioperative strategies in the treatment of solitary plasmacytoma. The finding of a solitary plasmacytoma of the spine was the determining factor for our decision to perform radical surgery with subsequent radiotherapy. The rationale for the chosen approach was to minimize the risk of local recurrence and to avoid conversion into multiple myeloma. The follow-up with 53 months is limited. However, discussion remains, if radical surgery in addition to local radiotherapy could be an alternative therapeutic approach depending on paraclinical parameters, age and cytogenetic risk analysis.     

Construct and predictive validity of a self-reported measure of preclinical mobility limitation

OBJECTIVES: To validate self-reported preclinical mobility limitation concept and self-report assessment method against muscle power and walking speed, and to study the predictive validity of preclinical mobility limitation with respect to future risk of manifest mobility limitation. DESIGN: Observational prospective cohort study and cross-sectional analysis. SETTING: Research laboratory and community. PARTICIPANTS: A total of 632 community-living (age range, 75-81 y) women and men took part in the baseline assessments and 302 persons in the semi-annual interviews on mobility limitation over 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking speed, muscle power, and self-reported preclinical and manifest mobility limitation. Preclinical mobility limitation was defined as self-reported tiredness or modification of task performance without task difficulty. At baseline, 4 subgroups were created according to self-reported preclinical mobility limitation in any of 3 mobility tasks (walking 2 km, walking 0.5 km, climbing up stairs): no limitation, preclinical limitation, and minor and major manifest limitation. RESULTS: At baseline, participants with preclinical mobility limitation showed intermediate levels of walking speed and muscle power, compared with those with no limitation or manifest mobility limitation. Participants reporting baseline preclinical mobility limitation had 3- to 6-fold higher age- and sex-adjusted risk of progressing to major manifest mobility limitation during the 2-year follow-up compared with participants with no limitation at baseline, whereas the risk among those with minor limitation at baseline was 14- to 18-fold higher compared with those with no limitation. CONCLUSIONS: The self-report assessment tool proved to be a valid measure to capture the early signs of disability and may serve as an inexpensive tool for identifying those nondisabled persons at high risk for future disability.     

Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues

Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and “liquid biopsies” for patients with CNS metastases.     

Automated segmentation of the left ventricle in cardiac MRI

We present a fully automated deformable model technique for myocardium segmentation in 3D MRI. Loss of signal due to blood flow, partial volume effects and significant variation of surface grey value appearance make this a difficult problem. We integrate various sources of prior knowledge learned from annotated image data into a deformable model. Inter-individual shape variation is represented by a statistical point distribution model, and the spatial relationship of the epi- and endocardium is modeled by adapting two coupled triangular surface meshes. To robustly accommodate variation of grey value appearance around the myocardiac surface, a prior parametric spatially varying feature model is established by classification of grey value surface profiles. Quantitative validation of 121 3D MRI datasets in end-diastolic (end-systolic) phase demonstrates accuracy and robustness, with 2.45 mm (2.84 mm) mean deviation from manual segmentation.     

Morbidity and Mortality after Pancreaticoduodenectomy in Patients with Borderline Resectable Type C Clinical Classification

Background

We previously described the clinical classification of patients with resectable pancreatic tumor anatomy but marginal performance status (PS) or reversible comorbidities as “borderline resectable type C” (BR-C). This study was designed to analyze the incidence and risk factors for post-pancreaticoduodenectomy (PD) morbidity/mortality in a multi-institutional cohort of BR-C patients.

Methods

Elective PDs were evaluated from the 2005-10 ACS-NSQIP database. BR-C was defined as age?≥?80, poor PS, weight loss?>?10 %, pulmonary disease, recent myocardial infarction/angina, stroke history, and/or preoperative sepsis. Variables associated with 30-day postoperative major complications (PMC) and mortality were analyzed.

Results

A total of 3,033/8,266 (36.7 %) patients were BR-C. BR-C patients were more likely to suffer PMC (31.3 vs. 26.2 %) and mortality (4.1 vs. 2.3 %). BR-C patients with PMC suffered 50 % higher mortality versus non-BR-C patients with PMC (11.5 vs. 7.7 %) (all p?<?0.001). For BR-C patients, multivariate analysis identified the following risk factors for PMC or mortality: albumin?<?3.5 g/dL, dyspnea, preoperative sepsis, age?≥?80, poor PS, anesthesia score?≥?4, and intraoperative transfusion?≥?4 units.

Conclusions

Nationwide, one third of patients undergoing PD are medically borderline. These BR-C patients are at higher risk for and less able to be rescued from PMC. Surgeons should identify and optimize comorbidities and utilize prehabilitation to address functional deficits before elective PD.