Metabolomic Phenotyping of Gliomas: What Can We Get with Simplified Protocol for Intact Tissue Analysis?

Glioblastoma multiforme is one of the most malignant neoplasms among humans in their third and fourth decades of life, which is evidenced by short patient survival times and rapid tumor-cell proliferation after radiation and chemotherapy. At present, the diagnosis of gliomas and decisions related to therapeutic strategies are based on genetic testing and histological analysis of the tumor, with molecular biomarkers still being sought to complement the diagnostic panel. This work aims to enable the metabolomic characterization of cancer tissue and the discovery of potential biomarkers via high-resolution mass spectrometry coupled to liquid chromatography and a solvent-free sampling protocol that uses a microprobe to extract metabolites directly from intact tumors. The metabolomic analyses were performed independently from genetic and histological testing and at a later time. Despite the small cohort analyzed in this study, the results indicated that the proposed method is able to identify metabolites associated with different malignancy grades of glioma, as well as IDH and 1p19q codeletion mutations. A comparison of the constellation of identified metabolites and the results of standard tests indicated the validity of using the characterization of one comprehensive tumor phenotype as a reflection of all diagnostically meaningful information. Due to its simplicity, the proposed analytical approach was verified as being compatible with a surgical environment and applicable for large-scale studies.

Urgent excision of primary intracardiac Burkitt Lymphoma in a child

We present the case of a 9-year-old girl who was referred to our service with a recent history of shortness of breath on exertion and fatigue in addition to visual disturbances and gastrointestinal symptoms. A Transthoracic Echocardiography demonstrated the presence of 3 large intracardiac masses in both the right and left atrium protruding into the mitral and tricuspid valve orifices causing bilateral inflow obstruction. The patient underwent urgent surgical excision of the masses which was uncomplicated. Histological testing was consistent with a rare intracardiac location of Burkitt’s Lymphoma.

Erdheim-Chester disease – case report

Summary Erdheim-Chester disease (ECD) belongs to the malignant polyostotic sclerotic forms of non-Langerhans histiocytosis. During abnormal prolipheration of pathologic histiocytes (foam cells), involved structures become hypertrophic with increased density followed by scarring. Mostly the diaphysis and metaphysis of long bones of lower limbs with typical pain are involved. According to the WHO, the disease is classified as histiocytic neoplasia. We refer on a 74-year-old female patient with expansive process in the region of upper clivus and sphenoidal bone on the right side. Histological testing confirmed this very rare disease that affects about 600 patients over the world. Key words Erdheim-Chester – foamy histiocytes – sclerosis – fibrosis

Bone Union Assessment with Computed Tomography (CT) and Statistical Associations with Mechanical or Histological Testing: A Systematic Review of Animal Studies

Objective and accurate assessment of bone union after a fracture, arthrodesis, or osteotomy is relevant for scientific and clinical purposes. Bone union is most accurately imaged with computed tomography (CT), but no consensus exists about objective assessment of bone union from CT images. It is unclear which CT-generated parameters are most suitable for bone union assessment. The aim of this review of animal studies is to find which CT-generated parameters are associated most strongly with actual bone union. Scientific databases were systematically searched. Eligible studies were studies that (1) were animal studies, (2) created a fracture, (3) assessed bone union with CT, (4) performed mechanical or histological testing as measure of actual bone union, and (5) associated CT-generated outcomes to mechanical or histological testing results. Two authors selected eligible studies and performed risk of bias assessment with QUADAS-2 tool. From 2567 studies that were screened, thirteen studies were included. Most common CT parameters that were investigated were bone mineral density, bone volume, and total callus volume. Studies showed conflicting results concerning the associations of these parameters with actual bone union. CT-assessed torsional rigidity (assessed by three studies) and callus density (assessed by two studies) showed best results. The studies investigating these two parameters reported moderate to strong associations with actual bone union. CT-assessed torsional rigidity and callus density seem the most promising parameters to represent actual bone union after a fracture, arthrodesis, or osteotomy.Prospero trial registration number: CRD42020164733

Assessment of compliance with national guidelines in genetic testing and tumor profiling in patients diagnosed with pancreatic adenocarcinoma: A retrospective review.

e16260 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of poor prognosis, portending a 5-year survival rate of 9% when considering all stages. Although the mainstay of treatment of PDAC remains cytotoxic chemotherapy in both the early and advanced stages, recent advances in tumor profiling and germline testing have allowed for the incorporation of poly-ADP-ribose polymerase (PARP) inhibitors, immune checkpoint inhibitors and targeted therapy to be utilized in the maintenance and subsequent-line settings for metastatic PDAC, respectively. We sought to identify our institutional compliance rate in germline testing and tumor profiling in all patients diagnosed with PDAC. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 171 patients reviewed, 121 received and completed treatment in our institution, and were included in the analysis. Median age was 69 years. 55 patients (45%) were male and 66 (55%) were female. Germline testing was done in 28 patients (23%) and tumor molecular profiling was done in 25 patients (21%). Testing for microsatellite instability was performed in 28 patients (23%). Testing for programmed death-ligand (PD-L1) expression was done in 16 patients (13%). On univariate analysis, family history of malignancy was a predictor for germline testing (OR 5.3; 95% CI 1.4-2.01; p=0.01). No predictors were identified in association with tumor molecular profiling likely due to low sample size. Conclusions: Our analysis reveals an institutional compliance rate of 20-23% in adherence to national guidelines with respect to germline testing and tumor profiling in the management of PDAC. A family history of malignancy demonstrated predictive association with germline testing. Factors which may limit pathological evaluation of microsatellite stability status, assessment of PD-L1 expression and molecular profiling include lack of institutional protocol for reflex histological testing, financial or insurance constraints, and lack of adequate tissue. As part of our Quality improvement project, we identified that incorporation of reflex histological testing based on tumor-type, standardization of tissue biopsy to optimize yield, and utilization of support staff, such as Oncology Navigators, to facilitate scheduling for germline testing may increase compliance rates.

Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

The effect of a probiotic preparation containing Enterococcus faecium DSM 7134 for chickens on growth performance, immune status, and the histology and microbiological profile of the jejunum

The aim of the study was to determine whether and in what dosage and duration of administration a probiotic containing live cultures of Enterococcus faecium, enriched with vitamin D3 and ascorbic acid, affects the histological and microbiological profile of the intestine, as well as the immunity and growth performance of chickens. The jejunum together with its contents was also collected for microbiological and histological testing. The results obtained indicate that the birds receiving the probiotic preparation in the amount of 0.25 g/L of water during the entire fattening period attained significantly higher bodyweight than the Control, with significantly lower feed conversion. Furthermore, this dosage and duration was most efficient in reducing the total count of fungi, aerobic bacteria and coliform bacteria in the intestinal contents, in addition to increasing the height of the jejunal villi and depth of the crypts. The probiotic administered in the amount of 0.25 g/L of water during the entire fattening period also significantly increased lysozyme activity and the content of IgA in the blood serum as compared with the Control, while decreasing the content of IL-6, and thus most efficiently stimulated non-specific immunity in the chickens.

High pressure–low flow remodeling of the rat saphenous vein wall

Objective To better understand factors that may play a role in the development of varicosities. Methods We induced combined flow-pressure disturbance in the saphenous system of the rat by performing chronic partial clipping of the main branch. Biomechanical and quantitative histological testing was undertaken. Results A rich microvenous network developed. Bloodflow decreased to 0.65 ± 0.18 µl/s (control side, 3.5 ± 1.4 µl/s) and pressure elevated to 6.8 ± 0.7 mmHg (control side, 2.3 ± 0.2 mmHg, p < 0.05). Involution of the wall and lumen was observed (16.5%, 28.7% and 35.5% reduction in outer diameter, wall thickness and wall mass respectively, p < 0.05). Elevated macrophage (CD68) and cell division (Ki67) activity was observed. Elastic tissue and smooth muscle actin became less concentrated in the inner medial layers. Conclusions Low-flow induced morphological shrinking of the lumen in veins may override pressure-induced morphological distension. Loosening of the force-bearing elements during flow-induced wall remodeling may be an important pathological component in varicosity.

Refractory Rheumatic Disorder: Atypical Postpregnancy Osteoporosis

This is a case report on a young patient with severe osteoporosis that was initially revealed when she presented with polyarthralgia during her second pregnancy. Postpartum, the pain increased and her X-ray did not show any abnormalities. A bone scintigraphy was performed. It indicated an inflammatory rheumatic disorder. Six months after partum, an investigation of right coxalgia revealed a spontaneous basicervical fracture. Given the persistent polyarthralgia, the patient underwent a new scintigraphy, which revealed areas of what looked to be old rib and L1 fractures. A subsequent full body magnetic resonance imaging (MRI) scan revealed signal abnormalities that could indicate multiple lower limb bone fractures. Despite exhaustive biological, radiological, and histological testing, no secondary cause for the osteoporosis was found. The patient was started on teriparatide. We finally concluded that, despite the atypical presentation, the patient was suffering from postpregnancy osteoporosis. It is possible that the frequency of occurrence of this still poorly understood disease is underestimated.