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  1. Singam P, Thanabalan J, Mohammed Z
    Biomed Imaging Interv J, 2011 01 01;7(1):e3.
    PMID: 21655112 MyJurnal DOI: 10.2349/biij.7.1.e3
    Traumatic intractable epistaxis following fractures of the facial and base of skull rarely may be life-threatening. Common sites of injury are the internal carotid and maxillary artery. When conventional methods of arresting haemorrhage fail, the choices are then an open arterial ligation or superselective embolisation. This paper presents a patient with life-threatening epistaxis from a Le Fort type II fracture. Angiography revealed a maxillary artery injury in which superselective embolisation was performed and the haemorrhage was successfully arrested. A literature review of this technique is discussed, including its advantages and the relationship of the internal maxillary artery to facial fractures.
  2. Tuang GJ, Zahedi FD, Husain S, Hamizan AKW, Kew TY, Thanabalan J
    Int J Med Sci, 2023;20(2):211-218.
    PMID: 36794158 DOI: 10.7150/ijms.68095
    Introduction: The fundament of forensic science lies in identifying a body. The morphological complexity of the paranasal sinus (PNS), which varies greatly amongst individual, possess a discriminatory value that potentially contributes to the radiological identification. The sphenoid bone represents the keystone of the skull and forms part of the cranial vault. It is intimately associated with vital neurovascular structures. The sphenoid sinus, located within the body of the sphenoid bone, has variable morphology. The sphenoid septum's inconsistent position and the degree, as well as the direction disparities of sinus pneumatization, have indeed accorded it a unique structure in providing invaluable information in forensic personnel identification. Additionally, the sphenoid sinus is situated deep within the sphenoid bone. Therefore, it is well protected from traumatic degradation from external causes and can be potentially utilized in forensic studies. The authors aim to study the possibility of variation among the race, and gender in the Southeast Asian (SEA) population, using volumetric measurements of the sphenoid sinus. Materials and methods: This is a retrospective cross-sectional analysis of computerized tomographic (CT) imaging of the PNS of 304 patients (167 males, 137 females) in a single centre. The volume of the sphenoid sinus was reconstructed and measured using commercial real-time segmentation software. Result: The total volume of sphenoid sinus of male gender had shown to be larger, 12.22 (4.93 - 21.09) cm3 compared to the counterpart of 10.19 (3.75 - 18.72) cm3 (p = .0090). The Chinese possessed a larger total sphenoid sinus volume, 12.96 (4.62 - 22.21) cm3) than the Malays, 10.68 (4.13 - 19.25) cm3 (p = .0057). No correlation was identified between the age and volume of the sinus (cc= -.026, p = .6559). Conclusion: The sphenoid sinus volume in males was found to be larger than those of females. It was also shown that race influences sinus volume. Volumetric analysis of the sphenoid sinus can potentially be utilized in gender and race determination. The current study provided normative data on the sphenoid sinus volume in the SEA region, which can be helpful for future studies.
  3. Teik CK, Basri NI, Abdul Karim AK, Azrai Abu M, Ahmad MF, Abdul Ghani NA, et al.
    Arch Iran Med, 2019 06 01;22(6):340-343.
    PMID: 31356101
    Cerebral arteriovenous malformation (AVM) is a rare entity with an estimated prevalence of 0.01-0.05% in the general population. We reviewed hospital obstetric records during 2010-2017 and reported a case series of six patients with cerebral AVM in pregnancy, of which five patients had successful pregnancy, and one maternal mortality.
  4. Soon BH, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, Thanabalan J, et al.
    Front Physiol, 2017;8:231.
    PMID: 28484394 DOI: 10.3389/fphys.2017.00231
    The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.
  5. Soon BH, Abu N, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, et al.
    Per Med, 2022 01;19(1):25-39.
    PMID: 34873928 DOI: 10.2217/pme-2021-0033
    Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.
  6. Sprigg N, Flaherty K, Appleton JP, Al-Shahi Salman R, Bereczki D, Beridze M, et al.
    Health Technol Assess, 2019 07;23(35):1-48.
    PMID: 31322116 DOI: 10.3310/hta23350
    BACKGROUND: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage.

    OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH).

    DESIGN: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial.

    SETTING: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK).

    PARTICIPANTS: Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset.

    EXCLUSION CRITERIA: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy  4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK.

    CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events.

    FUTURE WORK: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed.

    TRIAL REGISTRATION: Current Controlled Trials ISRCTN93732214.

    FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland.

  7. Law ZK, Desborough M, Roberts I, Al-Shahi Salman R, England TJ, Werring DJ, et al.
    J Am Heart Assoc, 2021 02;10(5):e019130.
    PMID: 33586453 DOI: 10.1161/JAHA.120.019130
    Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH-2 (Tranexamic Acid in Intracerebral Hemorrhage-2) double-blind, randomized, placebo-controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre-ICH antiplatelet therapy, and 24-hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre-ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no-antiplatelet group. Pre-ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01-1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32-1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25-2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62-0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41-0.91) with no significant interaction between pre-ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.
  8. Law ZK, Appleton JP, Scutt P, Roberts I, Al-Shahi Salman R, England TJ, et al.
    Stroke, 2022 Apr;53(4):1141-1148.
    PMID: 34847710 DOI: 10.1161/STROKEAHA.121.035191
    BACKGROUND: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial.

    METHODS: Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours.

    RESULTS: Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38-93) minutes for doctor consent, 55 (37-95) minutes for 2-stage patient, 69 (43-110) minutes for 2-stage relative, 75 (48-124) minutes for 1-stage patient, and 90 (56-155) minutes for 1-stage relative consents (P<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5-2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5-3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03-0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up.

    CONCLUSIONS: The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays.

    REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.

  9. Sprigg N, Flaherty K, Appleton JP, Al-Shahi Salman R, Bereczki D, Beridze M, et al.
    Lancet, 2018 May 26;391(10135):2107-2115.
    PMID: 29778325 DOI: 10.1016/S0140-6736(18)31033-X
    BACKGROUND: Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage.

    METHODS: We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214.

    FINDINGS: We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]).

    INTERPRETATION: Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect.

    FUNDING: National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.

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