Computed tomography-guided stereotactic biopsy of intracranial lesions in pediatric patients

Purpose  

The primary objective of this study was to report the results of author’s 18-year experience of diagnostic stereotactic biopsy procedures in children with intracranial lesions.     

Systemic juvenile xanthogranuloma with multiple central nervous system lesions

Juvenile xanthogranulomatosis (JXG) is an uncommon histiocytic disorder that is usually benign and limited to the skin. The systemic form of JXG is rare and may be associated with severe morbidity and mortality especially in central nervous system (CNS) involvement. Here, we describe a six-year-old boy with disseminated skin lesions and neurological signs and symptoms. Diagnostic work up revealed multiple brain lesions. A skin biopsy and a stereotactic brain biopsy considered suggestive of systemic JXG. Treatment with prednisolone, vinblastine and methotrexate was successful with regression of skin and CNS lesions. The patient has been in remission for almost three years.     

Genetically Engineered Cancer Models,But Not Xenografts,Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

Background.

Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed.

Methods.

In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs).

Results.

Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors.

Conclusions.

The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors.     

Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis

Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ～97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism-detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35-9.878, P=0.011) and 3.19 (95% confidence interval, 1.06-9.57, P=0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes.     

Electroconvulsive therapy and venous angiomas: two case reports and review of the literature

According to the American Psychiatric Association, the risk for complications related to the electroconvulsive therapy (ECT) treatment of patients with cerebrovascular malformations is small. The literature contains a number of case studies presenting the uneventful treatment of patients with cerebral aneurysms with ECT. However, there is a paucity of cases presenting ECT in the context of a cerebral venous angioma. In this article, we present 2 cases of patients treated with ECT who were found to have documented venous angiomas. This is followed with a brief review of the literature.     

Purification and characterization of α-amylase in Moroccan locust,Dociostaurus maroccanus Thunberg (Orthoptera: Acrididae) and its inhibition by inhibitors from Phaseolus vulgaris L.

An α-amylase with molecular weight of 73?kDa was purified from midgut of Dociostaurus maroccanus using ammonium sulfate precipitation, gel filtration, and ion exchange chromatography. The optimal pH and temperature were 6 and 45?°C, respectively. As calculated using Lineweaver–Burk plots, the Km was about 0.62?mM and the Vmax was 1.113 (μmol/min/mg protein). Mn²⁺, Hg⁺, Zn²⁺ and ethylene diamine tetraacetic acid (EDTA) decreased α-amylase activity of D. maroccanus, whereas the addition of K⁺, Na⁺, Fe²⁺, Ba⁺, Mg²⁺, Ca²⁺ and Co²⁺ increased enzyme activity. Alpha-amylase inhibitors (AI1, AI2) with molecular weights of 43?kDa and 29?kDa, respectively, were purified from the seeds of Phaseolus vulgaris and its inhibitory effect on purified α-amylase of D. maroccanus was investigated. These inhibitors inhibited the D. maroccanus gut α-amylase activity significantly.     

Effects of the addition of low-dose ketamine to propofol-fentanyl anaesthesia during diagnostic gynaecological laparoscopy

Objectives

Diagnostic gynaecological laparoscopy (DGL) is a brief procedure, generally performed on an outpatient basis. Propofol-fentanyl is often used for anaesthesia in minor outpatient procedures because of its rapid onset, short duration of action and smooth patient awakening. However, propofol has various cardiovascular effects such as reduced arterial pressure, cardiac output and cardiac index. Ketamine is an intravenous anaesthetic and short-acting analgesic that could alleviate the haemodynamic effects of propofol due to its sympathomimetic activity. The aim of this placebo-controlled trial was to evaluate the effects of the addition of low-dose ketamine to propofol-fentanyl anaesthesia in DGL.

Study design

In this double-blind randomized trial, 60 healthy women undergoing gynaecological laparoscopy to investigate infertility were studied. Following injection of midazolam and fentanyl in all patients, the study group (n = 30) received ketamine 0.5 mg/kg and propofol 1–2.5 mg/kg, and the placebo group (n = 30) received saline 0.9% and propofol 1–2.5 mg/kg. Propofol was subsequently infused for the maintenance of anaesthesia.

Results

Patients in the study group had a significantly lower incidence of pain than patients in the placebo group during propofol injection (13% vs 87%, respectively; p < 0.0001). After induction of anaesthesia, 16 (53%) patients in the placebo group and three (10%) patients in the study group had a decreased heart rate (p < 0.001). The decrease in mean arterial pressure was greater in the placebo group compared with the study group (37% vs 7%, respectively; p < 0.001). During the procedure, the total mean ± standard deviation dose of propofol was 420 ± 65 mg in the placebo group and 330 ± 35 mg in the study group (p < 0.001). Pain scores for the first 3 h after the operation were significantly lower in the study group (p < 0.001).

Conclusion

Use of low-dose ketamine with propofol-fentanyl anaesthesia in patients undergoing DGL was associated with less pain during propofol injection, lower incidence of haemodynamic changes, lower total dose of propofol and improved postoperative analgesia.     

Robust-Deep: A Method for Increasing Brain Imaging Datasets to Improve Deep Learning Models’ Performance and Robustness

A small dataset commonly affects generalization, robustness, and overall performance of deep neural networks (DNNs) in medical imaging research. Since gathering large clinical databases is always difficult, we proposed an analytical method for producing a large realistic/diverse dataset. Clinical brain PET/CT/MR images including full-dose (FD), low-dose (LD) corresponding to only 5 % of events acquired in the FD scan, non-attenuated correction (NAC) and CT-based measured attenuation correction (MAC) PET images, CT images and T1 and T2 MR sequences of 35 patients were included. All images were registered to the Montreal Neurological Institute (MNI) template. Laplacian blending was used to make a natural presentation using information in the frequency domain of images from two separate patients, as well as the blending mask. This classical technique from the computer vision and image processing communities is still widely used and unlike modern DNNs, does not require the availability of training data. A modified ResNet DNN was implemented to evaluate four image-to-image translation tasks, including LD to FD, LD+MR to FD, NAC to MAC, and MRI to CT, with and without using the synthesized images. Quantitative analysis using established metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), and joint histogram analysis was performed for quantitative evaluation. The quantitative comparison between the registered small dataset containing 35 patients and the large dataset containing 350 synthesized plus 35 real dataset demonstrated improvement of the RMSE and SSIM by 29% and 8% for LD to FD, 40% and 7% for LD+MRI to FD, 16% and 8% for NAC to MAC, and 24% and 11% for MRI to CT mapping task, respectively. The qualitative/quantitative analysis demonstrated that the proposed model improved the performance of all four DNN models through producing images of higher quality and lower quantitative bias and variance compared to reference images.