Impact of CD34/CD309 expression in circulating endothelial progenitor cells on prognosis and response to bortezomib therapy in multiple myeloma.

Multiple myeloma (MM) is a prevalent yet incurable hematologic malignancy. Despite the proven efficacy of proteasome inhibitors in treating MM, resistance to Bortezomib-based treatments persists in a subset of patients. This case control study explores the potential of circulating endothelial progenitor cells (EPCs) as biomarkers for predicting response to Proteasome Inhibitor based therapy combined with Dexamethasone in MM patients.

Psychiatric sequelae of thromboangiitis obliterans: a case report and review of the literature.

Background: Peripheral manifestations secondary to progressive vascular occlusions are characteristic of the rare condition termed thromboangiitis obliternas (TAO) or Buerger's disease. The central manifestations of this disease are however poorly characterized, particularly those of psychiatric nature, and their prevalence is largely unknown. Speculations have been made around the polymorphic nature and triggers of observed psychopathology in TAO; much however remains to be unraveled in this area.

Reflex and reflective laboratory interventions for adding value to test results; an integral part of laboratory stewardship.

Post-analytical reflexive (automated) and/or reflective (patient tailored and thought driven) interventions (PARRI), have played a subsidiary role in many diagnostic laboratories, despite mounting evidence of their clinical value. The ever-pervasive demand for greater quality healthcare while curbing costs mandates laboratory stewardship utilizing the most robust testing strategies, including PARRI, to guide patient management. Clinical and medical biochemists are well positioned to guide such additive testing strategies by performing such maneuvers as scrutiny of selected test results, determination of potential adjunctive testing and provision of result interpretation.

Targeting NAD Synthesis to Potentiate CD38-Based Immunotherapy of Multiple Myeloma.

Antibodies targeting CD38, a NAD-degrading enzyme, have emerged as a promising immunotherapy against multiple myeloma (MM). Currently, the mechanisms by which anti-CD38 antibodies establish their therapeutic effects are poorly understood. Here, we advocate for the depletion of NAD to enhance the efficacy of anti-CD38-based immunotherapies in MM.

Low-depth sequencing for copy number abnormalities in multiple myeloma supersedes fluorescent in situ hybridization in scope and resolution.

Multiple myeloma (MM) is an incurable hematological malignancy that relies on cytogenetic determination of copy number abnormalities (CNAs) for prognosis and management. Low-depth whole genome sequencing (LD-WGS) is a cost-effective alternative to targeted genomics for CNA detection, but its value has yet to be explored in MM. DNA from CD138+ cells from MM patients were sequenced using an Illumina NextSeq at <1x depth (ultralow-depth).

Late Onset First Episode Psychosis Emerging as Delusional Misidentification of Familiar Sacred Places During a Holy Pilgrimage: A Case Report and Literature Review.

Background: The delusional misidentification syndromes (DMS) include a myriad of discrete but related syndromes, which have wide spectrum anomalies of familiarity. Several misidentification syndromes have been described in the psychiatric literature, the most common of these delusions are: the Capgras syndrome; the Fregoli syndrome; the syndrome of inter-metamorphosis; reduplicative paramnesia; and environmental reduplication.

Case Presentation: The reported case highlights the emergence of late onset first episode psychosis in a Middle Eastern 65-year-old female who has no previous psychiatric history.

Multiple pre- and post-analytical lean approaches to the improvement of the laboratory turnaround time in a large core laboratory.

Background: Core laboratory (CL), as a new business model, facilitates consolidation and integration of laboratory services to enhance efficiency and reduce costs. This study evaluates the impact of total laboratory automation system (TLA), electric track vehicle (ETV) system and auto-verification (AV) of results on overall turnaround time (TAT) (phlebotomy to reporting TAT: PR-TAT) within a CL setting.

Methods: Mean, median and percentage of outlier (OP) for PR-TAT were compared for pre- and post-CL eras using five representative tests based on different request priorities.

Evaluation of the impact of a total automation system in a large core laboratory on turnaround time.

Background: Growing financial and workload pressures on laboratories coupled with user demands for faster turnaround time (TAT) has steered the implementation of total laboratory automation (TLA). The current study evaluates the impact of a complex TLA on core laboratory efficiency through the analysis of the In-lab to Report TAT (IR-TAT) for five representative tests based on the different requested priorities.

Methods: Mean, median and outlier percentages (OP) for IR-TAT were determined following TLA implementation and where possible, compared to the pre-TLA era.

An effective utilization management strategy by dual approach of influencing physician ordering and gate keeping.

Objectives: There is increasing recognition of the importance of appropriate laboratory test utilization. We investigate the effect of a multifaceted educational approach that includes physician feedback on individual test ordering, in conjunction with targeted restriction, on the utilization of selected laboratory tests.

Design And Methods: Scientific evidence was compiled on the usefulness and limitations of tests suspected of being over utilized in our laboratories.

Predicting refeeding hypophosphataemia: insulin growth factor 1 (IGF-1) as a diagnostic biochemical marker for clinical practice.

Background: Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH).

Adherence to the National Institute of Clinical Excellence guidance on parenteral nutrition screening is not enough to improve outcomes.

Background & Aim: Majority of the National Institute of Clinical Excellence (NICE) nutrition guidance recommendations were based on Grade D evidence due to absence of randomised controlled trials. The aim was to assess outcomes of parenteral nutrition (PN) administration when the guidance was adhered to.

Methods: The prospective study included patients referred for PN.

Rapid cycling bipolar affective disorder and recurrent strokes secondary to high blood homocysteine.

Introduction: The interface between psychiatric disorders and organicity has been a matter for contentious debate.

Aim: To report an interesting clinical case of moderate homocystinuria presenting with significant psychiatric and neurological deficits.

Method: A case report highlighting the impact of homocystinuria on producing intractable rapid cycling bipolar affective disorder.

Life-threatening hyperkalaemia and multisystem toxicity following first-time exposure to cocaine.

Cocaine is a drug notorious for its ability to adversely affect almost any organ in the body and cause a plethora of biochemical abnormalities secondary to its severe vasoconstrictive properties. These abnormalities are not exclusively seen in habitual users or cases of overdose, and may sometimes cause confusion as to the underlying pathology. We describe a case of a young female who presented to the Accident and Emergency department in the early hours of the morning complaining of muscle weakness following the inhalation of a small quantity of an 'unknown substance' the previous night.

Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.

Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included.

Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation.

Inter-individual response differences to vitamin D and Ca supplementation may be under genetic control through vitamin D and oestrogen receptor genes, which may influence their absorption and/or metabolism. Metabolomic studies on blood and urine from subjects supplemented with Ca and vitamin D reveal different metabolic profiles that segregate with genotype. Genotyping was performed for oestrogen receptor 1 gene (ESR1) and vitamin D receptor gene (VDR) in fifty-six postmenopausal women.

Postprandial bone turnover is independent of calories above 250 kcal.

Background: The mechanisms causing bone turnover after food intake have not yet been elucidated. Several gut hormones are secreted in the postprandial phase, proportional to meal calorie content, and possibly one or more of these could influence bone turnover. The aim of this study was to investigate bone turnover in proportion to graded-calorie and fixed calcium containing meals.

Gene abnormalities in multiple myeloma; the relevance of TP53, MDM2, and CDKN2A.

Background And Objectives: Disruption of either the p14ARF- mdm2- p53 or p16INK4A- Rb1 pathways produces a breakdown of regulatory mechanisms and creates a gateway for tumorigenesis. Since the incidence and clinical implications of abnormalities of TP53, CDKN2A (encoding for p16 and p14) and MDM2 genes (chromosome 12) in multiple myeloma (MM) is not clear, we investigated allelic loss at the former two loci and gain at the latter locus in a series of 82 MM patients.

Design And Methods: Dual color fluorescence in situ hybridization (FISH) was applied to bone marrow samples to establish the incidence of changes at the above mentioned loci.

Delineation of the minimal region of loss at 13q14 in multiple myeloma.

Previous studies have focused on the incidence and prognostic implications of 13q14 deletions in multiple myeloma (MM), but none has sought to delineate the minimal common deleted region (CDR). In an effort to do so, dual-color interphase fluorescence in situ hybridization (FISH) was applied on 82 myeloma cases, initially by use of three probes for 13q14 (RB1, D13S319, and D13S25). Deletions were detected in 29/82 (35.

Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia.

Background And Objectives: A female patient presented with splenomegaly and lymphocytosis with atypical lymphoid cell morphology. We identified t(2;7)(p12;q21) prompting studies of the translocation breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG k genes in the t(2;7) leading to over-expression of CDK6 protein.

Design And Methods: A variety of clinical and laboratory techniques including cell marker, cytogenetic and histologic studies were applied in order to establish the diagnosis.

Unusual case of leukemic mantle cell lymphoma with amplified CCND1/IGH fusion gene.

We describe a case of leukemic mantle cell lymphoma (MCL) with complex karyotype and amplification of the CCND1/IGH fusion gene. Testing for the presence of t(11;14), the hallmark of MCL, revealed multiple copies of the fusion signals. We therefore conducted extensive molecular cytogenetic studies to delineate the nature and consequences of such an abnormality.