Progressive multifocal leukoencephalopathy post ibrutinib therapy in relapsed chronic lymphocytic leukaemia.

Progressive multifocal leukoencephalopathy (PML) is a generally fatal infection of the cerebrum by the JC virus. It occurs in a range of primary and secondary immunosuppressed states and has become more common with AIDS and increasing the use of immunosuppressive therapies. Recently, Ibrutinib, a Bruton's Tyrosine Kinase Inhibitor (BTKi), has also been associated with PML. Here, we describe the case of a 77-year-old man treated for relapsed Chronic Lymphocytic Leukemia (CLL) with Ibrutinib, who eventually developed a fatal cerebellar granule cell variant of PML confirmed on autopsy. The case adds to the growing body of literature finding such an association with BTKis and highlights the importance of clinical vigilance in patients receiving such therapy.

Composite phaeochromocytomas-a systematic review of published literature.

INTRODUCTION: Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a single centre's records and presents a systematic literature review of composite phaeochromocytomas. METHODS: In addition to describing 2 case reports, a systematic search of the Medline database from inception up to April 2020 was done for human case reports on composite phaeochromocytomas. Relevant titles and/or abstracts were screened, and full texts were reviewed to identify appropriate studies. Data was extracted and a descriptive analysis of presentation, clinical features, management strategies and outcomes was performed. The quality of included studies was assessed using a critical appraisal checklist. RESULTS: There were 62 studies included, with a total of 94 patients. Of 91 patients where data was available, the median (range) age of patients was 48 (4-86) years. Of 90 patients where information was provided, 57% were female. In at least 28% of patients, a genetic cause was identified. Common presenting features include abdominal pain, palpable mass, cardiovascular and gastrointestinal symptoms. The most common tumour component with phaeochromocytoma is ganglioneuroma; other components include ganglioneuroblastoma, neuroblastoma and malignant peripheral nerve sheath tumours. In patients with follow-up data (n=48), 85% of patients were alive and well at a median (range) follow-up time of 18 (0.5-168) months. CONCLUSION: Composite phaeochromocytoma is a rare tumour, with a significant genetic predisposition. This review summarises available epidemiological data, which will be useful for clinicians managing this rare condition.

Toxic adenoma: to biopsy or not to biopsy?

Toxic adenoma nodules rarely harbour cancer. Fine-needle aspiration (FNA) is often not done because of the rarity of these lesions being cancer, the difficulty in interpreting cytology in hyperthyroid patients and the rare precipitation of thyrotoxicosis. We present two young, Caucasian female patients aged 29 and 13 years who were each diagnosed with a toxic nodule categorised as benign and indeterminate respectively. They underwent hemithyroidectomy after being rendered euthyroid, however their histology unexpectedly revealed differentiated follicular cancer. Despite thyroid cancer being rare in patients with toxic adenomas, it should be considered when planning treatment, especially if there are risk factors for cancer, or suspicious features on ultrasound examination. A review of the literature shows that compared with adenomas in euthyroid patients, patients in this group are generally younger and predominately female. If an FNA is considered, it should be performed after the patient is rendered euthyroid.

Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition.

In 1960 researchers reported that balanced translocation between chromosomes 22 and 9 resulted in the generation of Philadelphia chromosome. This breakthrough revolutionized our knowledge related to leukemia biology and contemporary studies revealed that chromosomal translocation resulted in the fusion between the 5' segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene. Research over the years has progressively and systematically improved our understanding of the genetic and proteomic basis of Leukemia. Genome-wide profiling studies, including genome sequencing and microarray analysis, have helped us in identification of different intracellular signaling cascades that are frequently mutated in Leukemia.  We partition this multi-component review into different sections related to biochemical characteristics of BCR-ABL+ cells, underlying mechanism of generation of mutations and crosstalk of BCR-ABL with various intracellular signaling cascades. We also summarize how BCR-ABL encoding mRNA is negatively regulated by different miRNAs and the strategies which are currently being used to effectively target BCR-ABL protein. We also provide an overview of the natural products which have been used for targeting of BCR-ABL protein. Better understanding of the protein network of Philadelphia positive leukemic cells will prove to be helpful in getting a step closer to personalized medicine.

Elemental Quantification and Residues Characterization of Wet Digested Certified and Commercial Carbon Materials.

Inductively coupled plasma optical emission spectroscopy (ICP-OES) is a common, relatively low cost, and straightforward analytical technique for the study of trace quantities of metals in solid materials, but its applicability to nanocarbons (e.g., graphene and nanotubes) has suffered from the lack of efficient digestion steps and certified reference materials (CRM). Here, various commercial and certified graphitic carbon materials were subjected to a "two-step" microwave-assisted acid digestion procedure, and the concentrations of up to 18 elements were analyzed by ICP-OES. With one exception (Sm), successful quantification of all certified elements in the two reference nanocarbons studied was achieved, hence validating the sample preparation approach used. The applicability of our "two-step" protocol was further confirmed for a commercial single-walled carbon nanotube sample. However, the digestion was markedly incomplete for all other commercial materials tested. Where possible, the digestion residues of the carbon materials analyzed (CRM included) were characterized to understand the structural changes that take place and how this may explain the challenge of disintegrating graphitic carbon. In this respect, it was found that solid state nuclear magnetic resonance holds considerable promise as a nonlocalized, easily interpretable, and reliable tool to access the efficient disintegration of these materials.

An evaluation of microwave-assisted fusion and microwave-assisted acid digestion methods for determining elemental impurities in carbon nanostructures using inductively coupled plasma optical emission spectrometry.

It is common for as-prepared carbon nanotube (CNT) and graphene samples to contain remnants of the transition metals used to catalyze their growth; contamination may also leave other trace elemental impurities in the samples. Although a full quantification of impurities in as-prepared samples of carbon nanostructures is difficult, particularly when trace elements are intercalated or encapsulated within a protective layer of graphitic carbon, reliable information is essential for reasons such as quantifying the adulteration of physico-chemical properties of the materials and for evaluating environmental issues. Here, we introduce a microwave-based fusion method to degrade single- and double-walled CNTs and graphene nanoplatelets into a fusion flux thereby thoroughly leaching all metallic impurities. Subsequent dissolution of the fusion product in diluted hydrochloric and nitric acid allowed us to identify their trace elemental impurities using inductively coupled plasma optical emission spectrometry. Comparisons of the results from the proposed microwave-assisted fusion method against those of a more classical microwave-assisted acid digestion approach suggest complementarity between the two that ultimately could lead to a more reliable and less costly determination of trace elemental impurities in carbon nanostructured materials.

Investigation of the probable causes of specific childhood disabilities in eastern Afghanistan (preliminary report).

To identify risk factors likely to cause developmental disabilities and to generate hypotheses for a further study of risk factors predisposing to disability and slow mental and physical development. Mothers and children attending/visiting the Sandy Gall's Afghanistan Appeal (SGAA) clinics in the East Zone of Afghanistan. The main outcome measures, developmental disabilities, cerebral palsy (CP), club foot, CDH and polio. Results, 37.5% of the disabilities were present at birth, 46% of the disabled children were born from parents who are 1st cousin which was confirmed by computing chi2 value, which is 10.87 with one degree of freedom. 58.3% of the disabled children were born from parents who lack antenatal care. 22.4% of the pregnant women in the defined population had antenatal checkups, and 97% of the mothers in the defined population are illiterate, 52% of the children found with CP specific and mental retardation. 25% were with delayed physical and mental development. 13% were with CP specific and 10% were club foot. 2% of the children were visually handicapped, 9% with hearing impairment. 61% of children were from Nangarhar, 25% from Laghman and 14% from Kunar.

Oligospermia and its relation with hormonal profile.

Serum of 161 oligospermic men was analysed for pituitary hormones LH and FSH and the androgen testosterone. The hormonal analysis indicated normal levels of LH and testosterone, while the FSH levels showed negative correlation to the sperm concentration.