1.Exploring Neonatal NaV1.5 Voltage-Gated Sodium Channel as a Therapeutic Target in Cancer
Mohd Redhuan Mohd Noor ; Siti Yusrina Nadihah Jamaludin ; Mohd Harizal Senik ; Farizan Ahmad ; Noor Fatmawati Mokhtar ; Izuddin Fahmy Abu ; Muhammad Yusran Abdul Aziz
The International Medical Journal Malaysia 2026;25(No. 1):30-40
Voltage-gated sodium channels (VGSCs) play pivotal roles in cancer progression and
have emerged as promising therapeutic targets and biomarkers. VGSCs comprise
multiple subtypes with distinct tissue distributions, influencing tumour characteristics in
different ways. Among these, the tetrodotoxin-sensitive α-subunits and the β1 subunit,
commonly found in breast cancer, have been implicated in metastasis and tumour
aggressiveness. The NaV1.5 channel and its neonatal variant (nNaV1.5) are
overexpressed in aggressive cancers such as breast, prostate, colorectal, and lung cancers,
thereby enhancing their invasive capacity. nNaV1.5 is particularly significant due to its
tumour-specific expression and strong association with poor prognosis, especially
in breast cancer, where it regulates cell proliferation, invasion, and tumour
microenvironment remodelling. This review highlights nNaV1.5 as a critical ion channel
that drives metastasis through ion regulation, extracellular acidification, and cytoskeletal
remodelling. We further evaluate current therapeutic strategies, including siRNA,
monoclonal antibodies, and small-molecule inhibitors, while addressing translational
challenges such as tumour heterogeneity, drug delivery limitations, and off-target
cardiotoxicity due to its similarity with the adult isoform. In addition, we explore the
potential of nNaV1.5 as a biomarker subject to epigenetic regulations by factors
including RE1-silencing transcription factor (REST) and histone deacetylase 2 (HDAC2),
which may facilitate patient stratification and treatment optimization. By integrating
mechanistic insights, therapeutic opportunities, and translational challenges, this review
goes beyond descriptive summaries to provide a framework for advancing nNaV1.5
research from preclinical studies toward clinical application in cancer therapy.
2.Liver hypertrophy post-Yttrium-90 versus portal vein embolization: A systematic review and meta-analysis
Sehar Salim VIRANI ; Kaleem Sohail AHMED ; Omar MAHMUD ; Sheza SAQIB ; Mustafa Ali KHAN ; Leslie CHRISTENSEN ; Syed Nabeel ZAFAR
Annals of Hepato-Biliary-Pancreatic Surgery 2026;30(1):35-41
Background:
s/Aims: Portal vein embolization (PVE) and Yttrium-90 (Y-90) radioembolization are used to induce liver hypertrophy, increasing future liver remnant volume and reducing the risk of post-resection liver failure. This systematic review compares the effectiveness of PVE and Y-90 radioembolization in promoting liver hypertrophy in patients undergoing liver resection.
Methods:
A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase, Cochrane, and Web of Science were searched for studies published between January 2000 and August 2023. Studies comparing PVE and Y-90 radioembolization with respect to liver hypertrophy were included. Risk of bias was assessed using the Newcastle–Ottawa Scale. Pooled mean differences were calculated using an inverse-variance random-effects model.
Results:
Of 1,965 studies identified, three retrospective cohort studies met inclusion criteria, comprising 125 patients. Among these, 67.3% underwent PVE and 32.7% received Y-90 radioembolization. Hepatocellular carcinoma was the most common diagnosis (55.9%), followed by metastatic disease (32.3%) and cholangiocarcinoma (11.8%). PVE was more commonly used as a preoperative strategy for liver resection, while Y-90 radioembolization was primarily employed for palliative intent. One study reported greater hypertrophy with Y-90 compared to PVE (63% vs. 36%); however, hypertrophy was assessed over a longer interval (150 vs. 30 days). In pooled analysis, PVE was associated with significantly greater hypertrophy (mean difference 23.75%; 95% CI 12.02–35.48; p < 0.0001; I 2 = 48%).
Conclusions
Evidence directly comparing PVE and Y-90 radioembolization for liver hypertrophy remains limited. While pooled results favor PVE, procedure selection should be individualized based on clinical context.
3.Anesthesia management for dental procedures in a patient with aromatic L-amino acid decarboxylase deficiency: a case report
Edvin BIHORAC ; Akkan MAHMUD ; Ahmed USLU ; Nedim ÇEKMEN
Journal of Dental Anesthesia and Pain Medicine 2025;25(1):77-82
Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare autosomal recessive neurometabolic synthesis disease with sympathetic autoregulation deficiency. Perioperative management of AADCD presents unique challenges due to autonomic dysfunction, impaired sympathetic regulation of heart rate, and potential airway complications. Herein, we report the successful anesthetic management of a 14-year-old male patient with AADCD under total intravenous anesthesia during extensive dental procedures. We applied the rapid sequence induction and intubation method with cricoid pressure to minimize the risk of pulmonary aspiration due to the potential difficulty in mask ventilation and intubation, limited mouth opening, microcephaly, micrognathia, and poor cooperation. Intubation was performed without any complications. Due to the autonomic dysfunction, potential airway complications, and developmental, mental, and motor delays in this disorder, perioperative management requires a multidisciplinary approach with comprehensive preoperative evaluation.
4.Theory of Planned Behavior Constructs for Covid-19 Booster Dose Vaccination Among Malaysian Adults’ Population: An Exploratory Analysis
Norsuhana Emilinadiah Husin1,2 ; Rabiatul Adawiyah Abdul Rohim1 ; Rosliza Yahaya1,2 ; Harmy Mohamed Yusoff1 ; Azizul Fadzli Wan Jusoh1,3 ; Nik Ahmad Shaiffudin Nik Him1,3 ; Aniza Abd Aziz1
Malaysian Journal of Medicine and Health Sciences 2025;21(No. 1):126-133
Introduction: The Theory of Planned Behavior (TPB) construct is recommended by the World Health Organization to
assess intention for vaccination; however, there is yet a validated instrument in the context of booster dose Covid-19
vaccination in Malaysia. The purpose of the present study is to translate and investigate the factorial validity and
internal reliability of the TPB construct for booster dose Covid-19 vaccination (TPB-BDV) questionnaire in Malaysia.
Materials and methods: In the pre-testing of the study, five experts and 40 Malaysian adults respectively rated the
content and validity index of all 11 items of the translated questionnaire in Malay version. Next, 160 Malaysian
adults completed the Malay version of Theory of Planned Behavior- Booster Dose Vaccination (TPB-BDV) questionnaire via online. Results: In the pre-testing phase, Content Validity and Face Validity Index for 10 items in Malay
version of TPB-BDV achieved cutoff mean score >3.0 for relevancy, clarity, ambiguity, and simplicity. Meanwhile,
Item 8 scored low on relevancy. In the main study, exploratory factor analysis suggested three factors consisting of
a final 10 items (without Item 8) which accounted for 74.0% of the total variance. The three factors were Attitude (5
items), Subjective Norms (3 items), and Perceived Behavioral Control (2 items). The internal reliability ranged from a
= 0.83 to a = 0.93, with an overall value of a = 0.90. Conclusion: The findings suggest that the 10-items Malay version of TPB-BDV is valid and reliable to measure the individual decision in taking the Covid-19 booster-dose vaccine
among Malaysian adult population.
5.Anesthesia management for dental procedures in a patient with aromatic L-amino acid decarboxylase deficiency: a case report
Edvin BIHORAC ; Akkan MAHMUD ; Ahmed USLU ; Nedim ÇEKMEN
Journal of Dental Anesthesia and Pain Medicine 2025;25(1):77-82
Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare autosomal recessive neurometabolic synthesis disease with sympathetic autoregulation deficiency. Perioperative management of AADCD presents unique challenges due to autonomic dysfunction, impaired sympathetic regulation of heart rate, and potential airway complications. Herein, we report the successful anesthetic management of a 14-year-old male patient with AADCD under total intravenous anesthesia during extensive dental procedures. We applied the rapid sequence induction and intubation method with cricoid pressure to minimize the risk of pulmonary aspiration due to the potential difficulty in mask ventilation and intubation, limited mouth opening, microcephaly, micrognathia, and poor cooperation. Intubation was performed without any complications. Due to the autonomic dysfunction, potential airway complications, and developmental, mental, and motor delays in this disorder, perioperative management requires a multidisciplinary approach with comprehensive preoperative evaluation.
6.Anesthesia management for dental procedures in a patient with aromatic L-amino acid decarboxylase deficiency: a case report
Edvin BIHORAC ; Akkan MAHMUD ; Ahmed USLU ; Nedim ÇEKMEN
Journal of Dental Anesthesia and Pain Medicine 2025;25(1):77-82
Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare autosomal recessive neurometabolic synthesis disease with sympathetic autoregulation deficiency. Perioperative management of AADCD presents unique challenges due to autonomic dysfunction, impaired sympathetic regulation of heart rate, and potential airway complications. Herein, we report the successful anesthetic management of a 14-year-old male patient with AADCD under total intravenous anesthesia during extensive dental procedures. We applied the rapid sequence induction and intubation method with cricoid pressure to minimize the risk of pulmonary aspiration due to the potential difficulty in mask ventilation and intubation, limited mouth opening, microcephaly, micrognathia, and poor cooperation. Intubation was performed without any complications. Due to the autonomic dysfunction, potential airway complications, and developmental, mental, and motor delays in this disorder, perioperative management requires a multidisciplinary approach with comprehensive preoperative evaluation.
7.The Effects of Tirzepatide on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Muhammad Umar MAHAR ; Omar MAHMUD ; Salaar AHMED ; Saleha Ahmed QURESHI ; Wasila Gul KAKAR ; Syeda Sadia FATIMA
Journal of Obesity & Metabolic Syndrome 2024;33(4):348-359
Background:
Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP)-glucagon-like peptide 1 (GLP-1) receptor agonist being evaluated for the treatment of various metabolic disorders. We performed a meta-analysis of randomized data on the effects of tirzepatide on serum lipid levels.
Methods:
We systematically searched the PubMed and ClinicalTrials.gov databases for relevant data from randomized controlled clinical trials. All articles were screened, reviewed, and extracted by at least two independent authors, with conflicts resolved by consensus. Four hundred and thirty-three records were identified in the initial literature search; 18 of them were identified for full-text review, and 14 of those were systematically reviewed and included in the analysis. The meta-analysis was performed using an inverse variance random-effects model.
Results:
Fourteen articles that reported data from 13 randomized controlled clinical trials were included in the review. Nine trials had a low risk of bias, two had a moderate risk, and two had a high risk of bias. The pooled analysis showed that tirzepatide was efficacious at improving all lipid markers, including cholesterol and triglycerides.Moreover, a clear dose response trend was visible across results from groups taking 5, 10, and 15 mg of tirzepatide.
Conclusion
There is growing evidence to support the use of tirzepatide in patients with metabolic diseases such as type 2 diabetes mellitus, metabolic syndrome, and obesity. Our results demonstrate that tirzepatide significantly improves all aspects of patient metabolism and might be superior in this regard to conventional agents such as insulin formulations or traditional GLP-1 agonists.
8.Efficacy and Safety of Valganciclovir in Congenital Cytomegalovirus Infection with Isolated Intrahepatic Cholestasis:A Randomized Controlled Trial
Salahuddin MAHMUD ; Tanzila FARHANA ; Ataul Mustufa ANIK ; Fayaza AHMED ; Mashud PARVEZ ; Madhabi BAIDYA ; Rafia RASHID ; Farhana TASNEEM ; Ahmed Rashidul HASAN ; Mohammad Jahangir ALAM ; Shafi Ahmed MUAZ
Pediatric Gastroenterology, Hepatology & Nutrition 2024;27(5):298-312
Purpose:
Cytomegalovirus (CMV) infection affects the hepatic, neurologic, hematopoietic, respiratory, gastrointestinal, and other organs, resulting in a high mortality rate and longterm sequelae. It may cause acute or chronic hepatitis, or even lead to hepatic cirrhosis.Valganciclovir (VGCV) is an effective, safe, and well-tolerated treatment for congenital CMV infection, without any serious adverse effects. This study was conducted to evaluate the clinical, biochemical, and virological profiles of infants with CMV with intrahepatic cholestasis and to determine the outcomes with or without treatment with VGCV.
Methods:
Twenty infants aged <6 months diagnosed with congenital CMV infection with evidence of intrahepatic cholestasis were included in this study. Randomization was used to divide the study participants into 2 groups. The control group (n=10) was treated with only supportive management, and the intervention group (n=10) was treated with oral VGCV at 16 mg/kg/dose 12 hours a day for 6 weeks plus supportive treatments. Physical examinations and biochemical, serological, and virological tests were performed at the time of diagnosis and at the end of 6 weeks and 6 months.
Results:
The control and intervention groups were compared in terms of clinical and laboratory parameters such as jaundice, dark urine, pale stool, hepatomegaly, total bilirubin, aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, and CMV polymerase chain reaction load, which showed a significant reduction after treatment in the intervention group (p<0.05) with oral VGCV, with very few side effects, whereas the control group showed no significant changes.
Conclusion
Oral VGCV can be used to effectively treat CMV infection with intrahepatic cholestasis without notable side effects.
9.Efficacy and Safety of Valganciclovir in Congenital Cytomegalovirus Infection with Isolated Intrahepatic Cholestasis:A Randomized Controlled Trial
Salahuddin MAHMUD ; Tanzila FARHANA ; Ataul Mustufa ANIK ; Fayaza AHMED ; Mashud PARVEZ ; Madhabi BAIDYA ; Rafia RASHID ; Farhana TASNEEM ; Ahmed Rashidul HASAN ; Mohammad Jahangir ALAM ; Shafi Ahmed MUAZ
Pediatric Gastroenterology, Hepatology & Nutrition 2024;27(5):298-312
Purpose:
Cytomegalovirus (CMV) infection affects the hepatic, neurologic, hematopoietic, respiratory, gastrointestinal, and other organs, resulting in a high mortality rate and longterm sequelae. It may cause acute or chronic hepatitis, or even lead to hepatic cirrhosis.Valganciclovir (VGCV) is an effective, safe, and well-tolerated treatment for congenital CMV infection, without any serious adverse effects. This study was conducted to evaluate the clinical, biochemical, and virological profiles of infants with CMV with intrahepatic cholestasis and to determine the outcomes with or without treatment with VGCV.
Methods:
Twenty infants aged <6 months diagnosed with congenital CMV infection with evidence of intrahepatic cholestasis were included in this study. Randomization was used to divide the study participants into 2 groups. The control group (n=10) was treated with only supportive management, and the intervention group (n=10) was treated with oral VGCV at 16 mg/kg/dose 12 hours a day for 6 weeks plus supportive treatments. Physical examinations and biochemical, serological, and virological tests were performed at the time of diagnosis and at the end of 6 weeks and 6 months.
Results:
The control and intervention groups were compared in terms of clinical and laboratory parameters such as jaundice, dark urine, pale stool, hepatomegaly, total bilirubin, aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, and CMV polymerase chain reaction load, which showed a significant reduction after treatment in the intervention group (p<0.05) with oral VGCV, with very few side effects, whereas the control group showed no significant changes.
Conclusion
Oral VGCV can be used to effectively treat CMV infection with intrahepatic cholestasis without notable side effects.
10.The Effects of Tirzepatide on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Muhammad Umar MAHAR ; Omar MAHMUD ; Salaar AHMED ; Saleha Ahmed QURESHI ; Wasila Gul KAKAR ; Syeda Sadia FATIMA
Journal of Obesity & Metabolic Syndrome 2024;33(4):348-359
Background:
Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP)-glucagon-like peptide 1 (GLP-1) receptor agonist being evaluated for the treatment of various metabolic disorders. We performed a meta-analysis of randomized data on the effects of tirzepatide on serum lipid levels.
Methods:
We systematically searched the PubMed and ClinicalTrials.gov databases for relevant data from randomized controlled clinical trials. All articles were screened, reviewed, and extracted by at least two independent authors, with conflicts resolved by consensus. Four hundred and thirty-three records were identified in the initial literature search; 18 of them were identified for full-text review, and 14 of those were systematically reviewed and included in the analysis. The meta-analysis was performed using an inverse variance random-effects model.
Results:
Fourteen articles that reported data from 13 randomized controlled clinical trials were included in the review. Nine trials had a low risk of bias, two had a moderate risk, and two had a high risk of bias. The pooled analysis showed that tirzepatide was efficacious at improving all lipid markers, including cholesterol and triglycerides.Moreover, a clear dose response trend was visible across results from groups taking 5, 10, and 15 mg of tirzepatide.
Conclusion
There is growing evidence to support the use of tirzepatide in patients with metabolic diseases such as type 2 diabetes mellitus, metabolic syndrome, and obesity. Our results demonstrate that tirzepatide significantly improves all aspects of patient metabolism and might be superior in this regard to conventional agents such as insulin formulations or traditional GLP-1 agonists.


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