Small lymphocytic lymphoma with florid perniosis-like features: a case report.

BACKGROUND: Small lymphocytic lymphoma is a relatively rare B-cell non-Hodgkin lymphoma that is considered to be the tissue equivalent of the much more common entity chronic lymphocytic leukemia. Cutaneous manifestations of small lymphocytic lymphoma are infrequent and the literature regarding them sparse. We describe here a case of a patient with a history of small lymphocytic lymphoma who developed perniosis-like features of the digits. CASE PRESENTATION: An 86-year old male patient with previously diagnosed small lymphocytic lymphoma developed painful erythematous swelling of the periungual area of his fingers and toes. This was associated with a dense dermal infiltration of CD5-positive B-lymphoid cells consistent with his low-grade B-cell lymphoma. Although partially refractory to local radiotherapy, the painful swelling of the fingers and toes resolved fully following systemic therapy with chlorambucil and rituximab. CONCLUSIONS: This unusual cutaneous manifestation of a lymphoma and the favourable response to systemic therapy may be instructive for the management of other patients who develop similar perniosis-like features.

Genomics of sablefish (Anoplopoma fimbria): expressed genes, mitochondrial phylogeny, linkage map and identification of a putative sex gene.

BACKGROUND: The sablefish (order: Scorpaeniformes) is an economically important species in commercial fisheries of the North Pacific and an emerging species in aquaculture. Aside from a handful of sequences in NCBI and a few published microsatellite markers, little is known about the genetics of this species. The development of genetic tools, including polymorphic markers and a linkage map will allow for the successful development of future broodstock and mapping of phenotypes of interest. The significant sexual dimorphism between females and males makes a genetic test for early identification of sex desirable. RESULTS: A full mitochondrial genome is presented and the resulting phylogenetic analysis verifies the placement of the sablefish within the Scorpaeniformes. Nearly 35,000 assembled transcript sequences are used to identify genes and obtain polymorphic SNP and microsatellite markers. 360 transcribed polymorphic loci from two sablefish families produce a map of 24 linkage groups. The sex phenotype maps to sablefish LG14 of the male map. We show significant conserved synteny and conservation of gene-order between the threespine stickleback Gasterosteus aculeatus and sablefish. An additional 1843 polymorphic SNP markers are identified through next-generation sequencing techniques. Sex-specific markers and sequence insertions are identified immediately upstream of the gene gonadal-soma derived factor (gsdf), the master sex determinant locus in the medaka species Oryzias luzonensis. CONCLUSIONS: The first genomic resources for sablefish provide a foundation for further studies. Over 35,000 transcripts are presented, and the genetic map represents, as far as we can determine, the first linkage map for a member of the Scorpaeniformes. The observed level of conserved synteny and comparative mapping will allow the use of the stickleback genome in future genetic studies on sablefish and other related fish, particularly as a guide to whole-genome assembly. The identification of sex-specific insertions immediately upstream of a known master sex determinant implicates gsdf as an excellent candidate for the master sex determinant for sablefish.

Influence of preoperative frailty on quality of life after cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of increased mortality after cardiac surgery, but its association with quality of life (QoL) and patient-centered outcomes is not fully understood. We sought to evaluate the association between frailty and such outcomes in older patients undergoing cardiac surgery. METHODS: This systematic review included studies evaluating the effect of preoperative frailty on QoL outcomes after cardiac surgery amongst patients 65 years and older. The primary outcome was patient's perceived change in QoL following cardiac surgery. Secondary outcomes included residing in a long-term care facility for 1 year, readmission in the year following the intervention, and discharge destination. Screening, inclusion, data extraction, and quality assessment were performed independently by two reviewers. Meta-analyses based on the random-effects model were conducted. The evidential quality of findings was assessed with the GRADE profiler. RESULTS: After the identification of 3105 studies, 10 observational studies were included (1580 patients) in the analysis. Two studies reported on the change in QoL following cardiac surgery, which was higher for patients with frailty than for patients without. Preoperative frailty was associated with both hospital readmission (pooled odds ratio [OR] 1.48 [0.80-2.74], low GRADE level) as well as non-home discharge (pooled OR 3.02 [1.57-5.82], moderate GRADE level). CONCLUSION: While evidence in this field is limited by heterogeneity of frailty assessment and non-randomized data, we demonstrated that baseline frailty may possibly be associated with improved QoL, but with increased readmission as well as discharge to a non-home destination following cardiac surgery. These patient-centered outcomes are important factors when considering interventional options for older patients. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).

Influence of preoperative frailty on quality of life after cardiac surgery: Protocol for a systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of adverse outcomes after cardiac surgery, but evidence regarding its ability to predict quality of life after cardiac surgery is currently lacking. Whether frail patients derive the same quality of life benefit after cardiac surgery as patients without frailty remains unclear. METHODS: This systematic review will include interventional studies (RCT and others) and observational studies evaluating the effect of preoperative frailty on quality-of-life outcomes after cardiac surgery amongst patients 65 years and older. Studies will be retrieved from major databases including the Cochrane Central Register of Controlled Trials, Embase, and Medline. The primary exposure will be frailty status, independent of the tool used. The primary outcome will be change in quality of life, independent of the tool used. Secondary outcomes will include readmission during the year following the index intervention, discharge to a long-term care facility and living in a long-term care facility at one year. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Meta-analysis based on the random-effects model will be conducted to compare the outcomes between frail and non-frail patients. The evidential quality of the findings will be assessed with the GRADE profiler. CONCLUSION: The findings of this systematic review will be important to clinicians, patients and health policy-makers regarding the use of preoperative frailty as a screening and assessment tool before cardiac surgery. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).

Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer.

Patients with lung cancers harboring an activating anaplastic lymphoma kinase (ALK) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely used screening tests for ALK rearrangements but both methods have limitations. The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay for high throughput and automated interpretation of ALK expression. In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR test (diagnostic cut-off ΔCt of ≤8) was shown to be highly sensitive (100%) when compared to FISH and IHC. Sequencing of RNA detected full-length ALK transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in which ALK expression was detected by the ALK RT-PCR test but negative by FISH and IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases without full-length ALK expression was 94% in comparison to FISH and sequencing. These data support the ALK RT-PCR test as a highly efficient and reliable diagnostic screening approach to identify patients with non-small cell lung cancer whose tumors are driven by oncogenic ALK.

Detection of a TRAF1-ALK fusion in an anaplastic large cell lymphoma patient with chemotherapy and ALK inhibitor-resistant disease.

BACKGROUND: The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, which was first identified as the fusion partner of the nucleophosmin (NPM1) gene in the recurrent t(2;5)(p23;q35) found in a subset of anaplastic large cell lymphoma (ALCL). Several distinct, non-NPM1, ALK fusions have subsequently been described in lymphomas and other tumor types. All of these fusions result in the constitutive expression and activation of ALK and ALK signaling pathways, ultimately leading to the malignant phenotype. CASE REPORT: A non-NPM1 fusion partner of ALK was identified in a 32-year-old Caucasian male ALCL patient whose disease was refractory to standard chemotherapy and autologous stem cell transplantation, and exhibited a poor response to a first-generation ALK inhibitor. Non-allele-specific ALK RT-qPCR revealed ALK overexpression and 5' RACE PCR revealed that the patient's lymphoma expressed a TRAF1-ALK fusion. CONCLUSIONS: We report the case of an ALCL patient whose tumor harbored the newly recognized TRAF1-ALK fusion and describe the clinical outcome after treatment with an ALK inhibitor. The short survival of our patient may reflect a propensity toward aggressive behavior in lymphomas that express this ALK fusion.