Real-world data on the use of emicizumab in patients with haemophilia A with and without inhibitors in Singapore.

Introduction: Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures.

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH).

Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.

Impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) gene testing in invasive breast cancers: A single center study.

The study aimed to evaluate the impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) testing in invasive breast cancer compared with previous 2013 guidelines. Between Jan 2014 and May 2020, 3364 consecutive invasive breast carcinomas with concurrent HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results were retrospectively reviewed for HER2 status. Both 2013 and 2018 testing criteria were applied to establish the HER2 status.

Assessment of transient changes in oxygen diffusion of single red blood cells using a microfluidic analytical platform.

Red blood cells (RBCs) capability to deliver oxygen (O) has been routinely measured by P50. Although this defines the ability of RBCs to carry O under equilibrium states, it cannot determine the efficacy of O delivery in dynamic blood flow. Here, we developed a microfluidic analytical platform (MAP) that isolates single RBCs for assessing transient changes in their O release rate.

Implementation of cytogenomic microarray with plasma cell enrichment enables better abnormality detection and risk stratification in patients with plasma cell neoplasia than conventional cytogenetics and fluorescence in situ hybridization.

The detection of chromosomal abnormalities is important in the diagnosis, prognosis and disease monitoring in plasma cell neoplasia (PCN). However, the gold standard diagnostic techniques of conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) are hampered by culture difficulties and probe availability. Cytogenomic microarray (CMA), however, is able to surmount such limitations and generate a comprehensive genomic profile with the implementation of plasma cell (PC) enrichment.

Chromosomal microarray analysis is superior in identifying cryptic aberrations in patients with acute lymphoblastic leukemia at diagnosis/relapse as a single assay.

Introduction: Conventional cytogenetics (CC) is important in diagnosis, therapy, monitoring of post-transplant bone marrow, and prognosis assessment of acute lymphoblastic leukemia (ALL). However, due to the nature of ALL, CC often encounters difficulties of complex karyotype, poor chromosome morphology, low mitotic index, or normal cells dividing only. In contrast, chromosomal microarray analysis (CMA) showed a specificity >99% and a sensitivity of 100% in chronic lymphocytic leukemia (CLL) patients.

Symmetry recovery of cell-free layer after bifurcations of small arterioles in reduced flow conditions: effect of RBC aggregation.

Heterogeneous distribution of red blood cells (RBCs) in downstream vessels of arteriolar bifurcations can be promoted by an asymmetric formation of cell-free layer (CFL) in upstream vessels. Consequently, the CFL widths in subsequent downstream vessels become an important determinant for tissue oxygenation (O2) and vascular tone change by varying nitric oxide (NO) availability. To extend our previous understanding on the formation of CFL in arteriolar bifurcations, this study investigated the formation of CFL widths from 2 to 6 vessel-diameter (2D-6D) downstream of arteriolar bifurcations in the rat cremaster muscle (D = 51.

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer.

Context: Human epidermal growth factor receptor 2 (HER2/neu) amplification is used as a predictive marker for trastuzumab treatment in breast cancer. Both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) testing algorithms have been based on the 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. In late 2013, the guidelines were updated with new scoring criteria.

Amplification of 1q21 and other abnormalities in multiple myeloma patients from a tertiary hospital in singapore.

Much effort has been made to stratify multiple myeloma patients for targeted therapy. However, responses have been varied and improved patient stratifications are needed. Forty-five diagnostic samples from multiple myeloma patients (median age 65 years) were stratified cytogenetically as 15 having non-hyperdiploidy, 20 having hyperdiploidy and 10 having a normal karyotype.

CpG Oligonucleotide and Interleukin 2 stimulation enables higher cytogenetic abnormality detection rates than 12-o-tetradecanolyphorbol-13-acetate in Asian patients with B-cell chronic lymphocytic leukemia (B-CLL).

The present study was designed to compare abnormality detection rates using DSP30 + IL2 and 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Asian patients with B-CLL. Hematological specimens from 47 patients (29 newly diagnosed, 18 relapsed) were established as 72 h-DSP30 + IL2 and TPA cultures. Standard methods were employed to identify clonal aberrations by conventional cytogenetics (CC).

The road to memory: an early rest for the long journey.

Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA(+), CD127(+), CCR7(+), CD62L(+), CXCR3(+)) first developed into effector T cells (CD45RA(+/-), CD127(+/-), CCR7(+/-), CD62L(+), CXCR3(+)), followed by three intermediate stages: intermediate T cells 1 (CD45RO(+), CD127(+/-), CCR7(+), CD62L(+), CXCR3(+)), intermediate T cells 2 (CD45RO(+), CD127(-), CCR7(-), CD62L(+), CXCR3(+)), and intermediate T cells 3 (CD45RO(+/-), CD127(+), CCR7(+), CD62L(-), CXCR3(+)) before reverting to stable CD45RA(+) central memory T cells (CD45RA(+), CD127(+), CCR7(+), CD62L(+), CXCR3(+)). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO(+), CD127(-), CCR7(-), CD62L(-), CXCR3(+)).

Cytogenetic and molecular aberrations of multiple myeloma patients: a single-center study in Singapore.

Background: Much is known about the cytogenetic lesions that characterize multiple myeloma (MM) patients from the USA, Europe, and East Asia. However, little has been published about the disease among Southeast Asians. The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population.

Differential outcomes in an extended family with constitutional t(11;22)(q23.3;q11.2).

The t(11;22) rearrangement is the most common recurrent familial reciprocal translocation in man. Heterozygote carriers are phenotypically normal but are at risk of subfertility in the male, miscarriages, and producing chromosomally unbalanced offspring. The unbalanced progeny usually results from an extra der(22) chromosome resulting from a 3:1 malsegregation.

Synovial sarcoma of the kidney: a report of 4 cases with pathologic appraisal and differential diagnostic review.

Background: Synovial sarcoma of the kidney is rare. It is clinicoradiologically indistinguishable from the more frequently encountered renal cell carcinoma. Histologically it needs to be differentiated from other spindle cell lesions occurring within the kidney, including a spectrum of benign to malignant tumors.

HER2/neu revisited: quality and interpretive issues.

Background: Immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) are the only tests currently approved by the US Food and Drug Administration for classifying which patients will benefit from trastuzumab therapy. The accuracy of these two testing methods can be adversely affected by a variety of pre-analytical, analytical and post-analytical factors. According to the latest published recommendations of the panel of the Joint Committee of the American Society of Clinical Oncology and College of American Pathologists for HER2/neu testing, laboratories performing IHC and FISH for HER2/neu status in breast cancer are now required to have a high concordance of at least 95% between IHC and FISH, significantly higher than that in the published literature.

Outpatient-based therapy of oral fludarabine and subcutaneous alemtuzumab for asian patients with relapsed/refractory chronic lymphocytic leukemia.

Background. Intravenous alemtuzumab and fludarabine are effective in combination for the treatment of chronic lymphocytic leukemia (CLL), but require hospital visits for intravenous injection. We performed a pilot study to assess the safety and efficacy of outpatient-based oral fludarabine with subcutaneous alemtuzumab (OFSA) for the treatment of relapsed/refractory CLL.

Holoprosencephaly: an antenatally-diagnosed case series and subject review.

Introduction: Holoprosencephaly (HPE) is an uncommon congenital failure of forebrain development. Although the aetiology is heterogeneous, chromosomal abnormalities or a monogenic defect are the major causes, accounting for about 40% to 50% of HPE cases. At least 7 genes have been positively implicated, including SHH, ZIC2, SIX3, TGIF, PTCH1, GLI2, and TDGF1.

Loss of the extra chromosome 21 in a patient with Down syndrome and myelodysplasia.

Monosomy 21 is a rare acquired karyotypic abnormality associated with myeloid disorders. Occurrence of loss of one chromosome 21 in the background of trisomy 21 in Down syndrome, resulting in the pseudo-normalization of trisomy 21, is a novel finding. The case is described of a patient with Down syndrome who acquired such a genetic abnormality as a result of myelodysplastic syndrome.

In vivo liver electroporation: optimization and demonstration of therapeutic efficacy.

Adverse effects (death and leukemogenesis) from viral vector-mediated gene therapy have renewed interest in plasmids as safer, more scalable, simple, and cost-effective vectors. Electroporation and hydrodynamic delivery are two techniques that improve the efficiency of plasmid-mediated gene transfer. The liver is a good tissue platform for targeted transfer of therapeutically relevant genes for correction of metabolic disorders, for example, hemophilia A.

Acute promyelocytic leukemia with PML-RARA fusion on i(17q) and therapy-related acute myeloid leukemia.

We describe a patient with acute promyelocytic leukemia (APL) and the karyotype 46,XX,i(17)(q10) with PML-RARA fusion gene detected by fluorescence in situ hybridization (FISH) and nested reverse transcriptase-polymerase chain reaction (RT-PCR). FISH using dual-color translocation probes for PML (promyelocytic leukemia) and RARA (retinoic acid receptor-alpha) showed fusion signal for PML-RARA on both arms of i(17q). The patient attained complete remission (CR) with all-trans retinoic acid treatment and became PML-RARA negative.

FVIII gene delivery by muscle electroporation corrects murine hemophilia A.

Background: Hemophilia A treatment relies on costly factor VIII (FVIII) replacement that may transmit iatrogenic viral diseases. Viral vectors and cell implants are being developed as improvements. We investigated in vivo electroporation of naked DNA as a safe and simple method for correcting FVIII deficiency.