CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor V beta genes

CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown etiology characterized by clonal proliferation of T cells that usually express T-cell receptor (TCR) alpha beta heterodimers. The purpose of this study was to identify the variable (V), joining (J), and diversity (D) region TCR beta-chain genes expressed by CD3+ LGL leukemic cells in an attempt to gain insights into the etiology of this disorder. Twelve patients with LGL leukemia were studied, including seven with both LGL leukemia and rheumatoid arthritis (RA). RA is also a disease of unknown etiology that occurs frequently in patients with LGL leukemia. Clonally expanded T cells that express specific TCR V beta genes have been identified in fluid and tissue specimens from the joints of patients with RA. In this study, V beta expression was determined by PCR using a panel of 22 unique V beta primers to amplify cDNA prepared from peripheral blood mononuclear cells (PBMC). A dominant V beta gene product was readily apparent in all patients. To confirm that the dominant V beta gene originated from a clonal expansion, DNA fragments corresponding to the dominant V beta genes were subcloned into plasmids and independently isolated recombinants were sequenced. V-D-J region sequences that occurred repeatedly indicated clonality. The V beta and J beta genes expressed by the leukemic cells showed a pattern of distribution that followed the frequency with which these genes are represented in the peripheral blood. The residues corresponding to the third complementarity-determining region of the TCR beta chain were different in all cases. A specific pattern of VDJ usage was not identified for those patients with both LGL leukemia and RA; however, utilization of V beta-6 by LGL clones (N = 3) was observed only in the setting of RA. These data suggest that leukemic CD3+ LGL cells have been clonally transformed in a random fashion with respect to the TCR beta chain.     

Genetic heterogeneity among Saint Louis encephalitis virus isolates of different geographic origin

A series of 57 Saint Louis encephalitis (SLE) virus isolates from humans, birds, rodents, and mosquitoes showed extensive variability in their RNase T₁ oligonucleotide fingerprints. The fingerprints of virion RNA did not contain an obvious poly(A) tract and were identical when the virus was grown in either mosquito or mammalian cells. Analysis and comparison of long oligonucleotides, representing approximately 10% of the genome of SLE isolates from the Central and Atlantic states, indicated the viruses share at least 80% of their long oligonucleotides. Analysis of the large T₁-resistant oligonucleotides by RNase A digestion revealed chemical similarities in the composition of common oligonucleotides derived from the genomes of four isolates. Analysis of 57 SLE strains from North America indicated that on the basis of the similarity of the oligonucleotide fingerprints, SLE isolates could be divided into genotypic sets representing different geographic regions in North America. These geographic varieties, designated “topotypes,” represent isolates from: (1) the Central/Atlantic states, (2) Florida, (3) and the Western United States. Variants of each “topotype” have been characterized whose oligonucleotide fingerprints are similar to that of the “topotype” but are sufficiently distinct to permit separation of the highly and less virulent SLE strains.     

Is rural radiation oncology practice quality as good as the big smoke? Results of the Australian radiotherapy single machine unit trial

Radiotherapy utilization rates in rural Australia are suboptimal, with one solution being the building of single machine units (SMUs). One concern raised with such an approach is the quality of care delivered in SMUs. The Australian and Victorian governments have established two SMUs in the state of Victoria, with each SMU operated as a satellite service of a major ‘hub’ site. We report on the planned evaluation of practice quality. Radiation oncologist (RO) clinical practice was externally audited using the Royal Australian and New Zealand College of Radiologists Peer Review Audit instrument. This tool splits RO clinical practice into documentation/quality assurance (QA) criteria and decision‐making criteria. Over the four sites, 130 patients were randomly selected for audit. At hub sites, 79.6% of all criteria audited were adequate, compared with 84.4% of criteria audited at SMUs (P = 0.0002). This difference was largely because of better adherence to documentation/QA criteria at the SMU sites. RO decision‐making and protocol adherence were routinely very high and consistent with other clinical practice audits. There were no significant differences between hubs and SMUs for adherence to decision‐making criteria; however, the few potential deficiencies in patient care identified occurred only at the hub sites. In at least one of these cases, potential suboptimal management was as a direct result of inadequate documentation. This audit found that SMUs provide as high a standard of radiotherapeutic care as larger hub departments. The findings also emphasize the need for all departments to target clinical documentation.     

Dashboard (in the) Knee

We present the case of a 19-year-old individual presenting to an orthopaedic outpatient clinic several months following a dashboard knee injury during a road traffic accident with intermittent mechanical symptoms. Despite unremarkable examination findings and normal magnetic resonance imaging, the patient was identified subsequently as having an intra-articular plastic foreign body consistent with a piece of dashboard on arthroscopic knee assessment, the retrieval of which resulted in a complete resolution of symptoms.     

Uterine artery embolization for symptomatic fibroids with imaging follow up

The aim of this study was to determine the effectiveness of uterine artery embolization (UAE) as a primary treatment method in treatment of symptomatic fibroids, whether there are any preembolization MRI characteristics of fibroid predictive of reduction in volume and assess reduction in uterine and dominant fibroid volumes using ultrasound (US) and MRI. Study was carried out in total of 32 patients aged 25–49 years (mean 40.9 years). Uterine and dominant fibroid volume were determined using US and MRI before UAE, MRI and US at 3 months and US alone at 6 and 12 months post‐UAE, supplemented by clinical evaluation at interval of 3, 6 and 12 months. Procedure was carried out through unilateral femoral puncture using poly vinyl alcohol (PVA) particles 355–500 μm in size. All 32 patients had successful procedures. Overall, 25 patients responded, giving a clinical success rate of 78.12%. Mean reduction in volume of uterus and fibroid was 33 and 59.7% and 48.9 and 75.5% on US at 3 and 12 months respectively, and 33.3 and 58.6% on MRI at 3 months. Volume reduction on US and MRI at 3 months was highly correlative. There was no statistical difference in size reduction in volume of fibroids, which were hypointense or hyperintense on T2‐weighted image (T2WI) on pre‐UAE MRI. Uterine artery embolization leads to good technical success and fibroid volume reduction. Ultrasound alone may be used for follow up of patients post‐UAE. Preprocedure signal characteristics on T2WI are not predictors of volume reduction after UAE.     

Severity of diabetic retinopathy and its relationship with age at onset of diabetes mellitus in India: A multicentric study

Purpose:To present clinical profile and risk factors of sight-threatening diabetic retinopathy (STDR) among people with age of onset of diabetes (AOD) <25 versus ≥25 years.Methods:A retrospective chart analysis of consecutive patients with diabetic retinopathy (DR) n = 654) treated at 14 eye care centers across India between 2018 and 2019 was performed. Patients were divided into two groups, Group 1: AOD <25 years and Group 2: AOD ≥25 years. DR and diabetic macular edema (DME) were classified using the International Clinical Classification of DR severity scale. STDR included severe nonproliferative DR (NPDR), proliferative DR (PDR), and moderate to severe DME. A multilevel mixed-effects model was used for comparison between two groups: 1) Patients with DR and AOD <25 years and 2) Patients with DR and AOD ≥25 years. Bivariate and multivariate regression analyses were used to evaluate risk factors between the two groups.Results:A total of 654 patients were included, 161 (307 eyes) in AOD <25 and 493 (927 eyes) in AOD >25 group. There was a higher prevalence of PDR with high-risk characteristics in AOD <25 group (24% vs. 12%) at baseline and 12-month follow-up (25% vs. 6%); P < 0.001. Systolic hypertension and poor glycemic control were risk factors in both groups, with no difference in these modifiable risk factors between groups.Conclusion:People with youth-onset DM are likely to present with severer form of STDR despite similar modifiable risk factors. Therefore, strict control of systolic blood pressure, glycemic status, and regular screening for DR are recommended to reduce the risk of STDR irrespective of the age of onset of diabetes.