A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report

Introduction: Chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries, is a mature B-cell chronic lymphoproliferative disorder characterized by the accumulation of neoplastic CD5+ B lymphocytes, functionally incompetent and usually monoclonal in origin, in bone marrow, lymph nodes and blood. Diagnosis occurs predominantly in elderly patients, with a median age reported between 67 and 72 years. CLL has a heterogeneous clinical course, which can vary from indolent to, less frequently, aggressive forms. Early-stage asymptomatic CLL patients do not require immediate therapeutic intervention, but only observation; treatment is necessary for patients with advanced disease or when “active disease” is observed. The most frequent autoimmune cytopenia (AIC) is autoimmune haemolytic anaemia (AHIA). The main mechanisms underlying the appearance of AIC in CLL are not fully elucidated, the predisposition of patients with CLL to suffering autoimmune complications is variable and autoimmune cytopenia can precede, be concurrent, or follow the diagnosis of CLL. Case presentation: A 74-year-old man was admitted to the emergency room following the finding of severe macrocytic anaemia during blood tests performed that same day, in particular the patient showed a profound asthenia dating back several months. The anamnesis was silent and the patient was not taking any medications. The blood examination showed an extremely high White Blood Cell count and findings of AIHA in CLL-type mature B-cell lymphoproliferative neoplasia. Genetic investigations: Conventional karyotyping was performed and it obtained a trisomy 8 and an unbalanced translocation between the short arm of chromosome 6 and the long arm of chromosome 11, concurrent with interstitial deletions in chromosomes 6q and 11q that could not be defined in detail. Molecular cytogenetics (FISH) analyses revealed Ataxia Telangiectasia Mutated (ATM) monoallelic deletion (with loss of ATM on derivative chromosome 11) and retained signals for TP53, 13q14 and centromere 12 FISH probes. TP53 and IGHV were not mutated. Array-CGH confirmed trisomy of the entire chromosome 8 and allowed us to resolve in detail the nature of the unbalanced translocation, revealing multiple regions of genomic losses on chromosomes 6 and 11. Discussion: The present case report is an unusual CLL case with complex karyotype and refinement of all breakpoints at the gene level by the genomic array. From a genetic point of view, the case under study presented several peculiarities. Conclusions: We report the genetic findings of a CLL patient with abrupt disease onset, so far responding properly to treatments despite the presence of distinct genetic adverse traits including ATM deletion, complex karyotype and chromosome 6q chromoanagenesis event. Our report confirms that interphase FISH alone is not able to provide an overview of the whole genomic landscape in selected CLL cases and that additional techniques are required to reach an appropriate cytogenetic stratification of patients

Improvement of sperm morphology after surgical varicocele repair

Background: A causative relationship between varicocele and impairment of semen quality has been largely investigated in the context of male infertility, although its clinical benefit remains controversial. Objective: To investigate the effect of varicocele correction on detailed morphologic microscopic semen parameters in a large homogeneous cohort of patients and to evaluate which factors could predict semen improvement after the surgical treatment. Materials and methods: An observational, retrospective cohort study was carried out including all patients undergoing surgical treatment for varicocele from September 2011 to March 2020 in the same clinical centre. Enrolled males performed at least one semen analysis before and one after surgical varicocele correction. Primary outcome was the detailed morphologic microscopic sperm evaluation. Secondary outcomes were conventional semen analyses. Results: A total of 121 males (mean age 24.6 \ub1 6.1 years) were enrolled. Using detailed morphologic microscopic sperm evaluation, a significant morphological improvement was recorded, with a reduction in head and tail abnormalities. Moreover, a significant increase in sperm concentration (p = 0.015) and percentage of progressive and total motility (p = 0.022 and p = 0.039) were observed after surgery. The multivariate logistic analysis identified the ultrasonography varicocele degree before surgery as a main predictor of the sperm concentration improvement (p = 0.016), with the highest improvement for varicocele of I and II degree. Discussion: For the first time, the detailed morphologic microscopic sperm evaluation highlights a relevant reduction in sperm abnormalities after varicocele surgery, showing its potential application in clinical practice

British III done: recent work on Shakespeare and British, English, Irish, Scottish and Welsh identities

This contribution to <i>Literature Compass</i> has a three-fold purpose. First, it aims to do what it says in the title, and flag up recent approaches to British identities in Shakespeare studies. Secondly, it seeks to remind readers of an earlier and now largely forgotten tradition of nationalist criticism and scholarship preoccupied with the place of Britain – nation, state and empire – that flourished in the 1920s and 1930s. Thirdly, it endeavours to excavate some of the more obscure material on the subject that, because of its place of publication, may have been overlooked. The material collected here covers issues of borders, colonialism, culture, genre, identity, invasion, language, mapping, monarchy, plantation, union, and the matter of Britain, especially in the histories, though as will be seen this work encompasses most of Shakespeare's corpus. The short introductions to each section and the accompanying bibliography of over 300 items, ranging from notes and queries to substantial essays, is divided into six sections, beginning with a brief overview of the historical debate, then focusing on criticism dealing broadly with Britain, then embracing material ordered by constituent nation: England, Ireland, Scotland and Wales. That there is an even spread of material under this handful of headings suggests that each and every nation within this multi-nation state, as well as the problematic and often contested whole, has attracted its fair share of critical concern