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B-cell lymphoma research in Malaysia - A narrative review
Lymphomas are a diverse group of malignant proliferations that arise as discrete tissue masses. The most widely accepted taxonomy for lymphoma is the World Health Organization classification of tumours of haematopoietic and lymphoid tissues, the 5th edition of which was released in June 2022. Most (85% to 90%) lymphoid neoplasms are of B cell origin. Mature B-cell neoplasms are a heterogeneous group of malignancies with similar disease courses and treatment paradigms. This review focuses on the various mature B-cell lymphomas in Malaysia, including Hodgkin lymphoma. A literature search was performed in various bibliographic databases. A total of 64 papers were included in this review. We found 15 papers on Hodgkin lymphoma, 14 on follicular lymphoma, 12 on Burkitt lymphoma, 5 on mucosa-associated lymphoid tissue (MALT) lymphoma, 4 on plasmablastic lymphoma, 3 on mantle cell lymphoma, 1 each on primary mediastinal large B-cell lymphoma, B-lymphoblastic lymphoma, and 3 on other unspecified B-cell lymphomas. The site, age, distribution, prognostic markers, and the various subclassification of B cell lymphomas were studied from these papers. Prognostic genetic markers in B-cell lymphomas include C-MYC, BCL2 and BCL6 as they are the most prevalent mutations in this condition. Anecdotal outcomes range from rapid fatality to unexplained spontaneous remission. This review adds to the existing literature on lymphoma in Malaysia by compiling the evidence that may lead to further research on the diagnosis and treatment of lymphoma in Malaysia and worldwide
Ethnic density and first episode psychosis in the British Pakistani population: findings from the East Lancashire Early Intervention Service
Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups. To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire. Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas. A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased. Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence
Strategies for optimising early detection and obstetric first response management of postpartum haemorrhage at caesarean birth: a modified Delphi-based international expert consensus
Objective There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert’s consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth.
Design Systematic review and three-stage modified Delphi expert consensus.
Setting International.
Population Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance.
Outcome measures Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth.
Results Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman’s haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman’s haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach.
Conclusion These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step
Experimental and numerical analysis of microfluids Y-micromixer fabrication using CO2 laser
Microfluidic devices (MFD) have several applications in the chemical and biomedical analysis field such as mixing two different drugs prescribed to inpatients. Micromixer can be fabricated using laser beam to ablate microchannel on the surface of polymeric substrate. In this work, CO2 laser was used to manufacture MFD on polymethyl methacrylate substrate with straight and zigzag profiles by investigating the effect of processing parameters (scanning speed, laser power and depth of focus) on the ablated microchannel width, depth, aspect ratio (AR) and wettability. The focus is to produce channel with depths from around 50 µm to 1600 µm using one system, hence producing large microchannels which were not studied in most of the report work. Then a CFD model was developed to characterize the effect of channel geometry and liquid diffusivity and speed on the fluids mixing efficiency. The results showed that the crater width, depth, AR, surface hydrophilicity and surface temperature increased with increasing line energy, and the effect of the process dynamics at constant fluences was also investigated. Various channel profiles such as V-shaped and U-shaped cross sections were produced by shifting the focal position of the beam. This is important in the design phase of the channels, since our single pass method of machining offers a full range of AR from around 0.3 up to 2.25, and a channel depth of 47–1600 µm. The results also showed that the mixing efficiency significantly relies on the channel geometry and fluid flow characteristics, with a maximum mixing efficiency of 99.9% was recorded using a squared shaped MFD
Dietary Interventions in Autism: A Critical Appraisal and Commentary on Systematic Review Findings
An estimated 1% of the global population is believed to be autistic. Clinical focus is often on interventions that target social functioning, sensory processing and communication. Dietary interventions are often explored as a means of targeting these core symptoms. However, research findings are often inconclusive due to small sample sizes. This commentary critically examines a meta-analysis focused on dietary interventions - including omega-3, vitamins, and other supplements - in the treatment of autism. It evaluates the study's findings and contextualizes their implications for neurological nursing practice
Integrating compression therapy into heart failure and lymphoedema management
Heart failure (HF) and lymphoedema often co-exist, significantly affecting the quality of life and requiring complex management. Heart Failure, characterised by reduced cardiac function, affects around 1 million people in the UK. Lymphoedema, involving lymphatic failure, affects 4 to 29 per 1000 individuals, particularly older adults. Traditionally heart failure management focuses on medication, while lymphoedema relies on compression therapy (CT). The article examines the integration of CT to treat lymphoedema with coexisting HF. Evidence suggests that with careful management and multidisciplinary collaboration, CT can be safely used in stable HF patients to manage lymphoedema, improving overall treatment outcomes and patient wellbeing. This approach requires adherence to guidelines and a holistic, patient-centred care model. Debates about CT for lymphoedema in the presence of HF highlight the need for patient-focused and all-encompassing care. Practitioners must consider the broader context of both conditions and collaborate with colleagues and patients to make informed treatment decisions
Establishing an Evidence Based Technique for Mucosal Landmarks’ measurement, Ethnic Disparity in Segment Length and Biopsy Technique In Barrett’s Oesophagus and Gastrointestinal Endoscopy
Barrett’s Oesophagus (BO) is a metaplastic condition affecting 1-2% of the UK population with propensity to evolve into dysplasia and Adenocarcinoma of Oesophagus (ACO). Early detection of dysplasia by tissue biopsies is dependent on regular surveillance which is reliant on measuring the correct length of BO and microscopic examination of biopsy specimens. The length of BO is dependent on the position of gastroesophageal junction (GOJ) from incisors, which could be measured in both intubation and extubation of endoscope. However, it is not clear if there is any difference in the position when measured during both phases. Furthermore, it is not clear if taking biopsies in a certain way i.e., single (SBB), or double bite (DBB) affects the histological quality of specimens. Moreover, BO is a global disease and in racial terms there are clinical, demographic, and prognostic differences between White British (WBP) and South Asian populations (SAP). One such specific difference is the progression of BO to ACO. It is noteworthy that segment length strongly correlates with ACO progression, yet literature lacks clarity on segment length differences between the populations.
MD Aim
To assess the quality of histological specimens collected through SBB and DBB, comparing size, orientation, crush artefacts and overall effect on histological diagnosis. It is also aimed to identify oesophageal landmarks in relation to BO in both phases of endoscopy as well as to chart and compare the length of BO segment SAP and WBP using statistical approaches. To achieve these aims, the MD was divided into three studies.
Methods
In study I Patients (>18 years) were assigned randomly to SBB or DBB groups and biopsies were collected prospectively. In addition, patients were also prospectively included for the assessment of oesophageal landmarks (Study II) and finally, segments length of the BO was analysed based on ethnicity, and difference was compared statistically (Study III).
Results:
Study I (n=135, 54% males), aged ranged from 20 to 91 (M 54± 15.8) and 144 procedures were performed. The time taken to collect sets of SBB (n=72) was 74 to 286 seconds (M = 180, SD±55.9) and DBB (n=72) ranged from 39 to 149 seconds (M = 88.5, SD±28.5, IQR = 71-111) with significant difference, suggesting SB takes longer time (P0.05).
Study II I (n=259, 46.7% males) age for the population ranged from 18 to 95 years (M = 58.9, SD±17.2). GOJ on insertion was located distal in comparison to Intubation (M =40 ±2.8, n =259, IQR=38-42) and extubation (Mdn = 40, M =40 ±2.9, n =258, IQR=38-42), z = -3.9, p<.01). The length of HH was compared Intubation (Mdn = 1, M =1.44 ±.92, n =137, IQR=1-2) and extubation (Mdn = 1, M =1.48 ±.87, n =175, IQR=1-2), z = -2.0 p=.03) and found shorter in intubation.
Study III: 249 cases of BO were identified in both sets of data. Landmarks and biopsy data and age ranged from 18 to 95 years (M = 58.2, SD±17.3, IQR = 25-75). SAP has short MBO as compared to WBP, and this was true for SAP males on subgroup analysis. To assess for significance, both segments were compared and significant difference was observed in both MBO (WBP (Median = 2, n = 221, IQR=2-3) and SAP (Median = 2, n = 28, IQR=1-2), U = 2247, z = -2.4, p =0.01)) and CBO (WBP (Median = 1, n = 219, IQR=1-2) and SAP (Median = 1, n = 28, IQR=1-1), U = 2407, z = -2.0, p <0.01))
Discussion and conclusion:
We show here that there is no significant difference between SBB and DBB biopsies in terms of histological quality however when considering time, SB takes significantly longer to complete number of biopsies per cycle. Therefore, we suggest that when taking large number of biopsies DBB technique should be used. In relation to landmarks, there is proximal displacement of GOJ during the extubation and this changes the number of diagnosed HH, hence it is suggested that for the purpose of standardisation all measurements should be taken in the extubation. This research further suggests that there is a significant difference between WBP and SAP in relation to BO segment length nevertheless comprehensive research to assess BO in different ethnicities in holistic fashion is needed. Such a project may form basis for new guidelines where ethnicity may also be a relevant factor in surveillance of BO
A thematic analysis of the involvement of children and families in Child Safeguarding Practice Reviews in England
The need to involve children and families in Child Safeguarding Practice Reviews (CSPRs) is set out within the current statutory guidance. However, there remains limited guidance that sets out how this should be done and the available research indicates that children and families are often excluded or choose not to be involved. The aim of this study was to explore how children and families are currently being involved in CSPRs in order to support the development of best practice approaches. The study was conducted by undertaking a thematic analysis of the involvement of children and families in the CSPRs published on the National Society for the Prevention of Cruelty to Children (NSPCC) repository since the implementation of the guidance in 2018. The analyses identified four themes: ‘reports do not mention family involvement’, ‘children and families were excluded’, ‘children and families were invited but were not involved’ and ‘children and families were invited and at least one member was involved’. The study concludes that there is a necessity for clearer guidance regarding how, when and who will engage with the children and families, taking an individualised approach that offers flexibility, provides support and addresses trauma
TARGETING RESIDUAL CANCER FROM THE INVASIVE MARGIN OF GLIOBLASTOMA USING COMPUTATIONAL TOOLKITS
AIMS Infiltrative margin GBM, as a proxy for residual disease post-surgery, can be identified by 5-aminolevulininc acid (5ALA) to facilitate the discovery of uniquely expressed or upregulated molecular pathways. Complementary bioinformatics approaches offer reproducible ways to enable interoperability of heterogenous data sources towards identification of therapeutic targets associated with GBM infiltration. METHOD RNA-seq primary tumour data was first categorised as: 5ALA+ (infiltrative margin) vs tumour core and 5ALA+ vs 5ALA- (reactive brain). Two levels of filtration (genes with adjusted p-value &lt;0.05; degree of fold change with log2&gt;1.5) were applied to genes, creating two separate gene lists. Cross-referencing gene lists identified transcripts upregulated in both 5ALA+ vs core and 5ALA+ vs 5ALA-. This candidate gene list was inputted into STRING to generate an uncurated protein-protein interaction (PPI) network, which returned a significant PPI enrichment p-value to confirm network connectivity, and next inputted into Metascape to elucidate biological processes associated with tumour infiltration. RESULTS Of 141 upregulated 5ALA+ genes TCP10L3, HELT, MGAM, ALOX5 and FOXI1 exhibited the greatest fold change. The most prevalent 5ALA+ biological processes were primitive streak formation, disaccharide metabolic process and sodium ion transmembrane transport. LOC157273, LINC00200, LINC00656, LOC285626 and LINC01568 were identified as long non-coding RNAs (lncRNA) most abundant in the infiltrative margin of GBM relative to tumour core and reactive brain. Regulatory associations between candidate 5ALA+ lncRNA and genes, and in silico drug repurposing via molecular docking, are being investigated. CONCLUSION The plasticity of GBM warrants analysis of the GBM infiltrative margin via computational toolkits to enhance understanding of upregulated molecular pathways, functionally associated with an invasive phenotype
SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF COMPLICATIONS ASSOCIATED WITH SURGICAL DEBULKING OF BRAIN METASTASIS
AIMS Surgical resection of brain metastasis is associated with complications, which worsen patient’s quality of life, results in oncological treatment delays and death. Surgical complication data aids decision making, leads to objective risk benefit analysis and informed consent. The aim of this study is to quantify rates, types and risk factors for complications related to surgical debulking of brain metastasis. METHOD Retrospective analysis on adult patients with brain metastasis, who underwent surgical debulking between 2017 and 2023 at Royal Preston Hospital. Data collected included demographics, diagnosis, 30-days post-operative complications, 30-days mortality, 30-days post-operative palliation, primary tumour, Karnofsky-Performance Score (KPS), first vs. repeat resection, use of drain and type of suture materials etc. Univariate analysis was carried out using Graphpad software. RESULTS Two-hundred and twenty-seven patients qualified. The most common primaries were lung (n=93, 41%), breast (n=43, 18.9%), and skin (n=31, 13.7%). The most common complications were Hospital-acquired pneumonia (HAP) (n=27, 11.9%), surgical site infection (SSI) (n=19, 8.4%), wound dehiscence (n=14, 6.2%), thromboembolic events (n=12, 5.3%) and CSF leak (n=8, 3.5%). Thirty days mortality and post-operative palliation (due to surgical complications) were both 3.5% each (n=8). Two-hundred and six (93.2%) had KPS ³70 whilst 15 (6.8%) had KPS &lt; 70 [range 30-60 pre-operatively (median 60)). KPS &lt; 70 was statistically significant for post-operative palliation (p=0.01), HAP (0=0.02) and urine infection (p=0.002), but not for 30-day mortality. Twenty-five (11.1%) patients undergoing repeat resections, experienced higher wound infections (p=0.002). CONCLUSION Surgical debulking is associated with significant post-operative complications, with 7% either dying or not receiving any further treatment, 18.1% percent developing serious wound complications (SSI, CSF leak, Wound dehiscence) and 19.4% experiencing significant medical complications (HAP/UTI/Thromboembolism). Pre- operative KPS &lt; 70 and repeat resections are associated with statistically increased risk of complications