Acute leukemia and lymphoma in pregnancy, a retrospective study from a tertiary center in Malaysia.

INTRODUCTION: Most evidence about the management of cancer and hematological malignancy in pregnancy are derived from retrospective observational studies with a small sample size. Availability of sufficiently large data has enabled evidence-based decision-making in this clinical dilemma. MATERIALS AND METHODS: Retrospective study looking into patients diagnosed with acute leukemia or lymphoma in pregnancy from 1st January 2014 to 1st January 2020 in Ampang General Hospital including newly or previously diagnosed and relapsed disease RESULTS: 37 cases of acute leukemia or lymphoma in pregnancy occurred in 34 patients. Majority of acute leukemia or lymphoma in pregnancy diagnosed in 1st trimester or in the setting of previously established or relapsed disease was therapeutically terminated. Thirteen pregnancies treated with antenatal chemotherapy resulted in livebirths except one stillbirth. More adverse obstetric outcomes are observed in pregnancies that did not receive antenatal chemotherapy, but association did not reach statistical significance. There was no significant difference in fetal outcome between cohort with and without antenatal chemotherapy. No treatment related mortality was observed in pregnancies with antenatal chemotherapy. Overall survival for newly diagnosed acute leukemia in pregnancy is significantly better with antenatal chemotherapy versus no antenatal chemotherapy. CONCLUSION: Treatment with chemotherapy in 2nd trimester of pregnancy onwards appears to have tolerable risks with favorable obstetric and fetal outcome. Deferment of treatment for acute leukemia in pregnancy to after delivery may cause increased risk of maternal and fetal adverse outcome.

MJP going green.

No abstract available.

ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia.

INTRODUCTION: Acute myeloid leukaemia (AML) is a heterogeneous malignant disease with a high degree of treatment failure using chemotherapy. Leukaemia stem cells (LSCs) are CD34+CD38- early progenitors associated with poor prognosis in AML. A unique LSC phenotype that excludes rare normal haematopoietic stem cells (HSC) is still elusive. This study aimed to determine expression of selected potential LSC markers in normal and leukaemic myeloid cells and correlate prognosis in AML patients. MATERIALS AND METHODS: Flow cytometry and RT-qPCR measured expressions of ALDH, IL3RA/CD123, CLEC12A/CLL-1/CD371, HOXA3 and ENPP4. Normal cord blood (n=3) and blood monocytes (n=5) represented HSC and mature cells, respectively. Myeloid leukaemia cell lines (THP-1, KG-1a, K562 and HL-60) represented progenitor cells at various stages of maturation. AML samples included chemo-resistant (n=8), early relapse (n=2) and late relapse (n=18). RESULTS: Combining protein/gene expressions, CD34+CD38- was a feature of immature cells seen in cord blood, KG-1a, and K562 but not more mature cells (blood monocytes and HL-60). Normal cells expressed CD371 while mature cells (blood monocytes and HL-60) lacked CD123. ENPP4 was not expressed on normal cells while HOXA3 was expressed only on cord blood and THP-1. In AML, CD123, HOXA3, ENPP4 (but not CD371) were significantly increased in the CD34+CD38- fraction of chemo-resistant patients while ALDH was associated with chemo-resistance. CONCLUSION: CD34+CD38- presented an immature phenotype and with ALDH were associated with poor prognosis. CD123, HOXA3 and ENPP4 further enriched the LSC population. ENPP4 has not been reported and has the advantage of not being expressed on HSC and normal monocytes.

Therapeutic potential of mesenchymal stem cells and their derivatives in sarcopenia.

Sarcopenia is a common condition in the geriatric population. It refers to age-related and progressive decline in muscle mass and function, which has a great impact on one's mobility and quality of life. Patients with sarcopenia are mainly treated with nutritional therapy, exercise therapy, or a combination of both. Since the identification of mesenchymal stem cells (MSCs) several decades ago, many studies have explored the application of MSCs in the field of regenerative medicine. MSCs are popular candidates for cell-based therapy owing to their multipotent nature and immunomodulatory properties. Even though MSCs do not naturally differentiate into myogenic cells, they are important players in skeletal muscle health, as MSCs support myogenic differentiation of other cells and promote recovery of injured skeletal muscle. Recent studies have found that MSCs may be of benefits in the treatment of sarcopenia. This article gives an overview of sarcopenia and the role of MSCs in skeletal muscle homeostasis. It also discusses the therapeutic potential of MSCs and their derivatives, as well as the underlying mechanisms of the therapeutic effects of MSCs and MSC-based products in sarcopenia.

Medical record archives in the era of digitalisation.

No abstract available.

Guidelines on retention of pathology records and materials (Version 2/2022).

No abstract available.

Role of circular RNAs in determining the fate of mesenchymal stem cells.

Ribonucleic acid (RNA) has been well-understood for its linear form for many years. With advances in high-throughput sequencing, there is an increasing focus on circular RNAs (circRNAs) recently. Although they were previously regarded as splicing error by-products, research has shown that they play a pivotal role in many cellular processes, one of which is the control of stem cell differentiation and fate. On the other hand, decades of research have demonstrated the promising therapeutic potential of mesenchymal stem cells (MSCs). To this end, there is a growing body of research on the role of circRNAs in the determination of the fate of MSCs. This review critically examines the current evidence and consolidates key findings from studies that explore the involvement of circRNAs in the regulation of MSC differentiation.

Challenges of Covid-19 testing.

No abstract available.

Therapeutic potentials of neural stem cells in Alzheimer's disease.

The commonest cause of dementia among the elderly population is Alzheimer's disease (AD). It is a health concern globally as the number of people affected by dementia worldwide is rapidly increasing. Several genes have been linked to AD and the pathogenesis of the disease has been extensively and vigorously examined. Thus far, only a few drugs have been approved by the Food and Drug Administration (FDA) for the pharmacological treatment of AD and a growing body of research has turned to alternative options such as stem cell therapy. This review will give an overview of the pathological and clinical aspects of AD. Although researchers have explored the suitability and feasibility of using various types of stems cells to treat AD, this review will focus mainly on neural stem cells (NSCs)/ neural progenitor cells (NPCs). The behaviour and properties of NSCs will be described, accompanied by a comprehensive discussion of the therapeutic strategies involving the use of NSCs/NPCs in the treatment of the disease.

Reprogramming human dermal fibroblast into induced pluripotent stem cells using nonintegrative Sendai virus for transduction.

INTRODUCTION: Induced pluripotent stem cells (iPSC) that exhibit embryonic stem cell-like properties with unlimited self-renewal and multilineage differentiation properties, are a potential cell source in regenerative medicine and cell-based therapy. Although retroviral and lentiviral transduction methods to generate iPSC are well established, the risk of mutagenesis limits the use of these products for therapeutic applications. MATERIALS AND METHODS: In this study, reprogramming of human dermal fibroblasts (NHDF) into iPSC was carried out using non-integrative Sendai virus for transduction. The iPSC clones were characterised based on the morphological changes, gene expression of pluripotency markers, and spontaneous and directed differentiation abilities into cells of different germ layers. RESULTS: On day 18-25 post-transduction, colonies with embryonic stem cell-like morphology were obtained. The iPSC generated were free of Sendai genome and transgene after passage 10, as confirmed by RT-PCR. NHDF-derived iPSC expressed multiple pluripotency markers in qRT-PCR and immunofluorescence staining. When cultured in suspension for 8 days, iPSC successfully formed embryoid body-like spheres. NHDF-derived iPSC also demonstrated the ability to undergo directed differentiation into ectoderm and endoderm. CONCLUSION: NHDF were successfully reprogrammed into iPSC using non-integrating Sendai virus for transduction.

End-of-life care preferences of nursing home residents: Results of a cross-sectional study.

BACKGROUND: Palliative care services were not available in nursing homes in Singapore. Project CARE (Care At the end-of-life for Residents in homes for the Elderly) was a pilot programme that aimed to promote advance care planning and improve end-of-life care in nursing homes. AIM: We aimed to examine end-of-life care preferences among nursing home residents, and identify factors associated with preference for medical intervention, cardiopulmonary resuscitation and place of death. DESIGN AND SETTING/PARTICIPANTS: A cross-sectional study using data from advance care planning discussions was conducted from September 2009 to April 2012 across seven nursing homes. The advance care planning discussion was conducted with the resident (with a prognosis of 6 months or 1 year), their families and staff from the nursing home and hospital. RESULTS: A total of 600 residents and their families completed the advance care planning discussion. Majority (93.2%) preferred not to proceed with cardiopulmonary resuscitation, 52.3% opted for limited additional intervention at the nursing home with escalation to the hospital if necessary and 77.0% preferred to die at the nursing home. Residents 85+ years (relative risk ratio: 3.34, 95% confidence interval: 1.13-9.93, p = 0.030) were more likely to prefer medical intervention at the nursing home only. No associations were found with the preference for cardiopulmonary resuscitation. Residents who were single, or who were Christians or Catholics (adjusted odds ratio: 2.09, 95% confidence interval: 1.04-4.19, p = 0.039), were more likely to prefer to die at the nursing home. CONCLUSION: Preferences for medical interventions in nursing homes provide support to extend palliative care services to nursing homes, which may benefit residents who are older, single, or Christians or Catholics.

Temporal response properties of koniocellular (blue-on and blue-off) cells in marmoset lateral geniculate nucleus.

Visual perception requires integrating signals arriving at different times from parallel visual streams. For example, signals carried on the phasic-magnocellular (MC) pathway reach the cerebral cortex pathways some tens of milliseconds before signals traveling on the tonic-parvocellular (PC) pathway. Visual latencies of cells in the koniocellular (KC) pathway have not been specifically studied in simian primates. Here we compared MC and PC cells to "blue-on" (BON) and "blue-off" (BOF) KC cells; these cells carry visual signals originating in short-wavelength-sensitive (S) cones. We made extracellular recordings in the lateral geniculate nucleus (LGN) of anesthetized marmosets. We found that BON visual latencies are 10-20 ms longer than those of PC or MC cells. A small number of recorded BOF cells (n = 7) had latencies 10-20 ms longer than those of BON cells. Within all cell groups, latencies of foveal receptive fields (<10° eccentricity) were longer (by 3-8 ms) than latencies of peripheral receptive fields (>10°). Latencies of yellow-off inputs to BON cells lagged the blue-on inputs by up to 30 ms, but no differences in visual latency were seen on comparing marmosets expressing dichromatic ("red-green color-blind") or trichromatic color vision phenotype. We conclude that S-cone signals leaving the LGN on KC pathways are delayed with respect to signals traveling on PC and MC pathways. Cortical circuits serving color vision must therefore integrate across delays in (red-green) chromatic signals carried by PC cells and (blue-yellow) signals carried by KC cells.

Cellular mechanisms of emerging applications of mesenchymal stem cells.

Mesenchymal stem cells (MSC) are multipotent, self-renewing cells that can be found mainly in the bone marrow, and other post-natal organs and tissues. The ease of isolation and expansion, together with the immunomodulatory properties and their capability to migrate to sites of inflammation and tumours make them a suitable candidate for therapeutic use in the clinical settings. We review here the cellular mechanisms underlying the emerging applications of MSC in various fields.

Recurrent multiple myeloma presenting as a breast plasmacytoma.

We describe a patient with multiple myeloma, who initially responded to chemotherapy and went into remission. She presented 10 months later with a right breast lump which was confirmed by core biopsy to be a plasmacytoma. Further treatment with radiotherapy, thalidomide and later second line chemotherapy appeared unsuccessful and she showed rapid disease progression with rising paraproteins and new extramedullary plasmacytoma lesions in the forehead, supraclavicular region, nasopharynx, liver, spleen, pancreas and paraaortic lymph nodes.

Childhood idiopathic myelofibrosis: a case report and review of literature.

Idiopathic myelofibrosis occurs predominantly in older adults. It is very rarely seen in children. We describe a 3-year-old girl with Down's syndrome who presented with recurrent chest infections associated with anaemia and easy bruising. There was mild hepatosplenomegaly. Full blood picture revealed pancytopaenia with leucoerythroblastosis with absence of circulating blast cells. Repeated attempts at bone marrow aspiration and trephine biopsy were unsuccessful. A trephine biopsy from the tibia showed depressed myelopoiesis and erythropoiesis, megakaryocytes with atypical morphology and increased bone marrow reticulin fibres, findings compatible with idiopathic myelofibrosis. She was treated symptomatically as she was clinically stable. Review of the English literature online yielded 46 reported cases of childhood idiopathic myelofibrosis with variable outcome from spontaneous remission to an indolent course with shortened survival. 6 cases evolved to another malignancy. 5 cases were associated with Down's syndrome.

Effect of pyridostigmine (Mestinon) on human platelet aggregation.

INTRODUCTION: Normal platelet functions are critical for achieving primary haemostasis. Numerous medications have been shown to affect platelet functions. Pyridostigmine (Mestinon), an orally active cholinesterase inhibitor that is commonly used to treat myasthenia gravis has been documented to cause epistaxis and prolonged bleeding after a cut in anectodal reports. This study was initiated after a patient diagnosed to have myasthenia gravis, developed multiple bruises a week after being started on Mestinon. The objective of this study was to investigate the effect of Mestinon on platelet aggregation stimulated with various agonists in vitro. MATERIALS AND METHODS: A stock solution of Mestinon was prepared by dissolving Mestinon tablet in normal saline. A serial dilution of Mestinon solutions was then prepared from this stock solution. Fresh whole blood from a normal healthy individual was added to this series of diluted Mestinon solutions. These samples were then tested for platelet aggregation using Chrono-log platelet impedance aggregometer with various platelet agonists. Mestinon-free whole blood sample was used for control. The patient's whole blood sample taken at the time of bruises was also tested for platelet aggregation using the same method. RESULTS: The results showed that in the presence of pyridostigmine (Mestinon), platelet aggregation was inhibited in response to ADP and collagen stimulations. However, when agonists such as ristocetin and arachidonic acid were used, aggregation of platelets was detectable even though the degree of aggregation was relatively reduced when compared with control samples. This pattern of anti-platelet aggregation was also seen in the patient sample. CONCLUSION: Pyridostigmine interferes with human platelet aggregation and uncommonly in susceptible patient may result in bleeding tendency. Thus, healthcare workers need to be aware of this uncommon side effect of pyridostigmine.

In vitro expression of erythropoietin by transfected human mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cells (MSC) are pluripotent progenitor cells that can be found in human bone marrow (BM). These cells have low immunogenicity and could suppress alloreactive T-cell responses. In the current study, MSC were tested for their capacity to carry and deliver the erythropoietin (EPO) gene in vitro. METHODS: Expanded BM MSC was transfected with EPO-encoded plasmid pMCV1.2 and EPO-encoded MIDGE (minimalistic immunologically defined gene expression) vector by electroporation. The expressed EPO was used to induce hematopoietic stem cells (HSC) into erythroid colonies. RESULTS: The results showed that the MIDGE vector was more effective and stable than the plasmid (pMCV1.2) in delivering EPO gene into MSC. The supernatants containing EPO obtained from the transfected cell culture were able to induce the differentiation of HSC into erythroid colonies. DISCUSSION: MSC hold promise as a cell factory for the production of biologic molecules, and MIDGE vector is more effective and stable than the plasmid in nucleofection involving the EPO gene.

In-vitro differentiation study on isolated human mesenchymal stem cells.

Mesenchymal stem cells are pluripotent progenitors that could be found in human bone marrow. Mesenchymal stem cells are capable of renewing themselves without differentiation in long-term culture. These cells also have low immunogenicity and can suppress alloreactive T cell responses. In the current study, mesenchymal stem cells isolated and propagated previously from the bone marrow of a megaloblastic anaemia patient were tested for their capabilities to differentiate into adipocytes, chondrocytes and osteoblasts in vitro. The differentiated cells were determined by Oil Red O, Alcian Blue-PAS and Alizarin Red S staining, and reverse transcriptase-polymerase chain reaction to determine the expression of mRNA specific for adipogenesis, chondrogenesis and osteogenesis. The results showed that the fibroblast-like cells were capable of differentiating into adipocytes, chondrocytes and osteoblasts upon chemical induction. The adipocytes, chondrocytes and osteoblasts were stained positively to Oil Red O, Alcian Blue-PAS and Alizarin Red S respectively. The differentiated cells were also found to express mRNA specific for adipogenesis ('peroxisome proliferation-activated receptor gamma2' and lipoprotein lipase), chondrogenesis (collagen type II) and osteogenesis (osteocalcin, osteopontin and alkaline phosphatase). In conclusion, this research has successfully isolated fibroblast-like cells from human bone marrow and these cells demonstrated morphological, cytochemical and immunochemical characteristics similar to mesenchymal stem cells. These cells maintain their proliferative properties and could be differentiated into the mesoderm lineage. The success of this study is vital because mesenchymal stem cells can be used in cellular therapy to regenerate or replace damaged tissues, or as a vehicle for therapeutic gene delivery in the future.

Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience.

INTRODUCTION: Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies. OBJECTIVE: To evaluate the purity, recovery and viability of CD34+ cells selected from harvested peripheral blood stem cells using the CliniMACS device, as well as to evaluate the T and B cell contents of these products. METHOD: Eight adult patients with malignant haematological diseases (5 non-Hodgkin's lymphomas in 2nd complete remission (CR) and 3 acute myeloid leukaemias in 1st CR) were mobilised with granulocyte colony-stimulating factor (G-CSF) with or without chemotherapeutic regimens. A total of nine leukaphereses for peripheral blood stem cell harvest using the Cobe Spectra cell separator (Cobe BCT Lakewood, CO) were performed. The harvested PBSC were then positively selected for CD34+ cells using the CliniMACS device (Milteny Biotech, Germany). RESULTS: A total of nine leukapheresis products from eight adults with a median pre-selection total CD34+ cell count of 282.2 x 10(6) (range 103.7 - 738.2 x 10(6)) were positively selected with CliniMACS. The median post-selection total CD34+ cell count was 99.5 x 10(6) (range 7.7 - 443.9 x 10(6)) with the median recovery was 66.0% (range 2 - 94%) and median purity of products of 79% (range 18 - 86%). The median total T cell count was reduced dramatically from 3.1 x 10(9) pre-selection to 7.9 x 10(6) post-selection. The selection did not affect the viability of selected cells that was tested with trypan blue exclusion method with a median pre and post selection viabilities of 98% (range 95 - 98%). CONCLUSION: We conclude that positive selection of CD34+ cells using magnetic separation technology by CliniMACS device results in low T-cell content stem cell with acceptable purity and recovery for autologous peripheral blood stem cell transplantation.